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H Levavi

Publications and source records attributed to H Levavi.

At least 19 recordsLinked to original sources
PubMed2005

A multicenter study of CA 125 level as a predictor of non-optimal primary cytoreduction of advanced epithelial ovarian cancer.

AIMS: To provide a large database of pre-operative CA 125 levels which may predict inappropriate cytoreductive surgery in patients with advanced epithelial ovarian cancer. METHODS: A multicenter review of the records of 424 patients with FIGO stage III and IV epithelial ovarian cancer of patients who underwent primary cytoreductive surgery was performed. The validity of pre-operative CA 125 level measurement as a single predictor of the possibility to achieve only suboptimal cytoreduction was evaluated by calculating the sensitivity and the specificity of various cut-off values. The relative importance of different cut-off values in achieving the best predictive validity was assessed by a receiver operating characteristics (ROC) curve. RESULTS: Optimal cytoreduction (largest diameter of residual tumour < or =1 cm) was achieved in 242 patients. The median CA 125 level in optimally cytoreduced patients was lower than in those patients suboptimally debulked (304 vs 863 U/mL; p<0.001). The area under the ROC curve was 0.65 (95% confidence interval, 0.60-0.71) and the CA 125 threshold derived from the ROC was 400 U/mL. The accuracy of the test at this level was 62%. CONCLUSIONS: The clinical applicability of the ROC derived CA 125 threshold is limited. The data accrued in the study provides a basis for decision-making regarding the place of primary surgery various CA 125 levels.

Biomarkers, Tumor↗
PubMed2005

Screening for cervical cancer--an evidence-based approach.

INTRODUCTION: The Papanicolau (Pap) smear is widely accepted by both the public and health authorities as a useful tool for detection of cervical cancer and its precursors. In Israel only opportunistic screening exists and still the incidence of invasive cervical cancer is among the lowest in the world. OBJECTIVES: To examine the existing evidence for the effectiveness of cervical cancer screening by Pap smears; to apply the findings to Israeli data, and to assess the implications for the current cervical cancer screening policy. METHODS: Search of Medline (1966-June 2003) and the Cochrane Library for relevant systematic reviews, controlled trials and cohort studies. RESULTS: There have been no trials of screening for cervical cancer and its precursors and therefore, no direct evidence that screening improves outcomes. A single retrospective cohort study estimated the age-adjusted RR for invasive cervical cancer in women with at least one Pap smear, whether normal or abnormal, compared to women with no smear at 0.4 (95% CI 0.2-0.9). In Israel some 27,800 (range: 20,800-167,000) women need to be screened in order to prevent one case of cervical cancer. The cost of preventing a single case of invasive cervical is approximately 1.288 million NIS (range: 1.643-13.193 million NIS). CONCLUSIONS: An evidence-based approach to the question of the effectiveness of cervical cancer screening using Pap smears has yielded weak evidence. Based on this weak evidence and rough estimations of the effectiveness and cost of mass screening for cervical cancer in Israel, we conclude that the current policy should be maintained.

Adult↗
PubMed2003

Frequency of BRCA mutations in primary peritoneal carcinoma in Israeli Jewish women.

OBJECTIVE: The aim of the present study was to compare demographic and clinical characteristics of primary peritoneal carcinoma (PPC) to ovarian carcinoma (OvC) with regard to BRCA mutation frequencies. METHODS: 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 an ongoing nationwide epidemiological study of these neoplasms in Israel. The present study comprises 609 (81.5% of 747) Jewish women with epithelial stage III-IV OvC and 68 (77.3% of 88) Jewish women with PPC who were genetically tested for the BRCA mutations. Data from each patient were collected by the aid of a prestructured questionnaire and medical records. Blood samples or tumor tissue was tested for the 185delAG and 5382insC mutations in BRCA1 and the 6174delT mutations in BRCA2. RESULTS: A carrier rate of 28% of any BRCA 1/2 mutation was observed among the PPC group and of 30% among the invasive stage III-IV OvC. No differences were found between PPC and OvC neither in the overall distribution of BRCA1/2 mutation carrier rates nor according to type of mutation, age, ethnic origin, and histologic subtype. Among women with a positive family history, a higher rate of mutation carriers was observed in the PPC group compared to the OvC group (72.7 vs 43.8%, respectively, P = 0.07). CONCLUSIONS: The similar frequency distribution of BRCA1/2 mutations in PPC and OvC observed in the present study indicates that these mutations may predispose to PPC as well and that this neoplasm is part of the hereditary breast-ovarian cancer syndrome.

Adult↗
PubMed2003

A mobile aerosol cryotherapy device (Histofreezer) for treatment of cervical contact bleeding: a pilot study.

This study aims to evaluate the efficacy of the Histofreezer (a mobile aerosol cryotherapy device) treatment for women with cervical contact bleeding. Ten healthy women aged 22-50 years referred to our outpatient colposcopy clinic for recurrent postcoital or contact bleeding, and who suffered from mild to wide ectropion with bleeding on contact were studied. All women had a normal pelvic examination and ultrasound and a normal colposcopy and PAP smear. They were treated with the Histofreezer, which freezes the tissue to a temperature of -55 degrees C. A picture of the cervix was taken by a cervical camera before, after the procedure and during follow-up visits 4 and 8 weeks afterwards. There was a complete resolution of bleeding ectropion with a good healing of squamous metaplasia in seven patients. Two women showed partial improvement. Based on this initial study, this short and simple ambulatory treatment shows good results, both subjectively and on follow-up colposcopy.

Adult↗
PubMed2003

Failure of sentinel node identification following neo-adjuvant chemo-radiotherapy for locally advanced squamous cell carcinoma of the vulva.

A case of a 70-year-old patient with advanced local vulvar cancer is presented. Treatment with neo-adjuvant chemo-radiotherapy for two courses was administered and two weeks after completion of treatment the patient underwent wide local excision with bilateral inguino-femoral lymph node dissection through three separate incisions. Two methods for the evaluation of sentinel nodes--lymphoscintigraphy and intraoperative gamma hand-held probe and blue dye injection, did not detect any sentinel node on either side. Groin-node dissection revealed 23 negative nodes. It is our hypothesis that the non-visualization of sentinel nodes in this patient was due to post-irradiation damage to the lymph channels.

Aged↗
PubMed2003

BRCA susceptibility genes--a review of current conservative management of BRCA mutation carriers.

Three options for the management of a patient carrying a deleterious mutation in the BRCA gene exist: close surveillance, chemoprevention and prophylactic surgical procedures. We aimed at reviewing the current knowledge on the conservative management of patients who are found to be carriers of the BRCA susceptibility genes. Recent literature in the English language was reviewed for publications containing the conservative management of BRCA mutation-carriers. Close surveillance for the breasts includes breast self-examination, clinical examination by a specialist and breast imaging techniques--mammography and magnetic resonance imaging. Ovarian surveillance includes pelvic examination, transvaginal ultrasonography and blood CA-125 measurements. Age at beginning of examinations and their frequency are discussed. Chemoprevention includes tamoxifen and oral contraceptives for breast and ovarian cancer prevention, respectively.

Breast Neoplasms↗
PubMed2002

Effect of BRCA mutations on the length of survival in epithelial ovarian tumors.

PURPOSE: To study the role of BRCA mutations in ovarian cancer survival. PATIENTS AND METHODS: Blood samples and specimens of ovarian tumors (whenever blood samples were not available) at the time of the primary surgery were obtained in the course of a nationwide case-control study of women with ovarian cancer in Israel. The three common BRCA mutations in Israel (185delAG, 5382insC, and 6174delT) were analyzed with a multiplex polymerase chain reaction to amplify the exons containing the three mutations using fluor-labeled primers in a single reaction. Because each mutation is a small insertion or deletion, they can be detected as length polymorphisms. Patients were followed for up to 5 years (range, 20 to 64 months). Statistical analysis was performed using the Kaplan-Meier method and the log-rank test. Stepwise Cox regression analysis was used for determination of independent prognostic factors. RESULTS: This report is based on 896 blood or tumor specimens analyzed for the presence of the BRCA mutations. Of these, 234 women (26.1%) were found to be positive. A significant difference in survival pattern was found between BRCA1/BRCA2 carriers and noncarriers among the women with invasive ovarian cancer (median survival, 53.4 months v. 37.8 months; 3-year survival, 65.8% v. 51.9%, respectively). These differences were independent of age at diagnosis or stage of the disease. CONCLUSION: Our data indicate that the survival of patients with ovarian cancer is affected by BRCA germline mutation, at least in the early years after diagnosis.

Case-Control Studies↗
PubMed2001

The polymorphic CAG repeat in the androgen receptor gene in Jewish Israeli women with endometrial carcinoma.

BACKGROUND: Endometrial carcinoma is considered a hormonal-dependent tumor; estrogen induces endometrial cellular proliferation, whereas progestins display an antiproliferative effect on endometrial tissue. The role that androgen and its receptor (androgen receptor [AR]) play in the pathogenesis of endometrial carcinoma is less clear. Although androgen has an in vitro inhibitory effect on endometrial cell proliferation, up to 75% of endometrial carcinoma express AR somatically. A polymorphic CAG repeat within exon 1 of the AR encodes for a polyglutamine tract, with length range of 8 to 33 repeats, which is inversely correlated with the transcriptional activity of the AR. METHODS: To gain insight into the role of AR in endometrial carcinoma, the authors analyzed the polymorphic CAG repeat in 79 Jewish Israeli patients with endometrial carcinoma as compared with 44 healthy Jewish women serving as controls. Analysis was conducted using germline DNA as template and using polymerase chain reaction primers flanking the CAG repeat with subsequent fluorescent determination of allele sizes. RESULTS: Allele size range of the longer of the two alleles in the patients was 11-33 (mean, 19.8 +/- 2.7) and in the controls 10-22 (mean, 17.9 +/- 1.9), a statistically significant difference (P < 0.01). Allele size variation within the patient group did not correlate with disease stage, grade, reproductive history, or age at diagnosis. CONCLUSIONS: The authors conclude that AR-CAG repeat length differs in Jewish patients with endometrial carcinoma as compared with healthy individuals in Israel, and this finding increases the possibility that the AR is involved in the predisposition to this neoplasm.

Aged↗
PubMed2001

A single nucleotide polymorphism in the 5' untranslated region of RAD51 and risk of cancer among BRCA1/2 mutation carriers.

RAD51 colocalizes with both BRCA1 and BRCA2, and genetic variants in RAD51 would be candidate BRCA1/2 modifiers. We searched for RAD51 polymorphisms by sequencing 20 individuals. We compared the polymorphism allele frequencies between female BRCA1/2 mutation carriers with and without breast or ovarian cancer and between population-based ovarian cancer cases with BRCA1/2 mutations to cases and controls without mutations. We discovered two single nucleotide polymorphisms (SNPs) at positions 135 g-->c and 172 g-->t of the 5' untranslated region. In an initial group of BRCA1/2 mutation carriers, 14 (21%) of 67 breast cancer cases carried a "c" allele at RAD51:135 g-->c, whereas 8 (7%) of 119 women without breast cancer carried this allele. In a second set of 466 mutation carriers from three centers, the association of RAD51:135 g-->c with breast cancer risk was not confirmed. Analyses restricted to the 216 BRCA2 mutation carriers, however, showed a statistically significant association of the 135 "c" allele with the risk of breast cancer (adjusted odds ratio, 3.2; 95% confidence limit, 1.4-40). BRCA1/2 mutation carriers with ovarian cancer were only about one half as likely to carry the RAD51:135 g-->c SNP. Analysis of the RAD51:135 g-->c SNP in 738 subjects from an Israeli ovarian cancer case-control study was consistent with a lower risk of ovarian cancer among BRCA1/2 mutation carriers with the "c" allele. We have identified a RAD51 5' untranslated region SNP that may be associated with an increased risk of breast cancer and a lower risk of ovarian cancer among BRCA2 mutation carriers. The biochemical basis of this risk modifier is currently unknown.

Adult↗
PubMed2000

Connective tissue activating peptide III expression disappears progressively with increased dysplasia in human cervical epithelium.

OBJECTIVE: The aim of this study was to explore the possible involvement of CTAP-III in the development of cervical cancer as it progresses through several cervical intraepithelial neoplasia (CIN) stages. MATERIAL AND METHODS: Twenty-four cervical specimens were obtained by direct punch biopsy, conization, or hysterectomy. Diagnosis of CIN I to CIN III was based on standard morphological criteria in 12 specimens. Tissue specimens were also obtained from 4 normal uteri and 8 cases of invasive squamous cell cervical carcinoma. RT-PCR, using CTAP-III-specific primers, was used to identify CTAP-III mRNA and polyclonal antibodies, directed against the N-terminus of CTAP-III, for immunostaining of the CTAP-III protein. RESULTS: RT-PCR yielded amplified fragments in RNA derived from normal cervical tissue, while no PCR product was detected in the invasive cervical carcinoma tissue. The PCR product corresponded to a CTAP-III plasmid PCR product. Both tissues expressed the same amounts of GAPDH mRNA as the control for the integrity and equal amounts of the isolated RNA. In each of the 16 specimens of normal cervices and of CIN tissues, epithelial cells were stained with the anti-CTAP-III antibodies. In normal epithelium, CTAP-III staining was homogeneously distributed in all epithelial layers, except in the highly active and proliferating basal cells. CTAP-III was localized at the epithelial cell membrane or between adjacent epithelial cells in a granular, chain-like pattern of staining. In the CIN specimens, CTAP-III staining was no longer seen in the deep epithelial layers, consistent with the dysplastic appearance of the cells, and remained in the seemingly normal superficial epithelial layers. Cells of invasive cervical carcinoma did not stain for CTAP-III and were detected in endothelial cells of capillary blood vessels. CONCLUSION: The specific localization of CTAP-III between adjacent epithelial cells suggests a possible role of this chemokine in maintaining the normal architecture of epithelial tissues. Its progressive disappearance in increasingly severe CIN may be applied to distinguish between specific stages in the progression of cervical carcinoma.

Amino Acid Sequence↗
PubMed1996

Conservative management of postmenopausal pelvic echo-free findings--preliminary results.

OBJECTIVES: To develop a conservative protocol for the treatment of echo-free findings in the pelvis, diagnosed by sonography in post-menopausal women, in order to avoid unnecessary surgical intervention. METHODS: A prospective study where each post-menopausal-patient underwent sonographic evaluation of the pelvic mass, serum Ca-125 levels, ambulatory aspiration of the cyst, and operative laparoscopy if necessary. RESULTS: One hundred and eighty-two women were included in the 3 years of the study. Only two cases of malignancy were diagnosed. There were no false-negative results. CONCLUSION: Although the results of our protocol of conservative management look promising, we cannot draw final conclusions because of the small sample size. Perhaps as our knowledge increases, physicians will feel more confident in handling adnexal findings conservatively.

Adnexa Uteri↗
PubMed1996

The biology of ovarian cancer of epithelial origin.

Ovarian cancer of epithelial origin is associated with the highest mortality rate of all gynecologic malignancies. Since no symptoms or signs are manifested at the early stages of the disease, it is no surprise that in 75% of patients peritoneal metastases are found during primary surgery. Despite advances in conservative treatment methods (invasive and noninvasive), screening for early detection of the disease is not yet available, and the overall survival rate is as low as 5-15%. Recent studies in molecular biology have drawn attention to different research directions in ovarian cancer and have contributed much to our understanding of this disease and its underlying pathologic mechanisms. This review is intended to highlight some of the new aspects of this research, specifically: hereditary ovarian cancer, genetic background in terms of chromosomal changes, DNA anomalies, oncogenes, tumor-suppressor genes, peptide growth factors and cytokines, invasiveness and metastasis, and finally, drug resistance. No breakthrough has as yet occurred in any of the subjects screened in this review, but results are promising. The clinical application of the steadily increasing knowledge in the biology of ovarian cancer may assist in the development of new treatment modalities that will improve survival.

Cell Transformation, Neoplastic↗
PubMed1995

Laser versus loop electrosurgical excision in vulvar condyloma for eradication of subclinical reservoir demonstrated by assay for 2'5' oligosynthetase human papillomavirus.

We studied, in an open clinical trial, 28 women with giant solitary human papillomavirus (HPV) lesions of the vulva that were treated by both laser and the loop electrosurgical excision procedure (LEEP), and analyzed the biopsy specimens of normal skin adjacent to the lesions for papillomavirus sequences by Southern blot hybridization and 2'-5' oligo-A synthetase (interferon) activity. The patients were reexamined after 3 weeks when a second treatment to the still infected areas was reapplied. They were reexamined for recurrence after 3 months: 4 patients harbored HPV-DNA genomes on the laser-treated side, adjacent to the original lesion, compared to 1 patient who developed recurrence on the LEEP side in a more distant, previously untreated, area. The optimal extent of laser or LEEP treatment necessary to reduce recurrence of vulvar condyloma remains to be established. Good in situ hybridization tests combined with the polymerase chain reaction and measurements of oligosynthetase activity to determine the types of cells involved at different sites of infection and to assess harboring of latent HPV genomes in histologically normal tissue are necessary in order to plan proper HPV treatment modality strategies.

2',5'-Oligoadenylate Synthetase↗
PubMed1994

Three-dimensional modelling of tumor-induced ovarian angiogenesis.

It is now well established that unrestricted growth of tumors is dependent upon angiogenesis. However, previous studies on tumor growth have not yet revealed how the transition to an angiogenetic state in ovarian malignancy is reflected in the vascular architecture of the ovary. We report here our preliminary observations based upon three-dimensional imaging of normal and tumor-induced ovarian angiogenesis created with a computer-assisted three-dimensional interactive application. The findings suggest that tumor-induced angiogenesis creates a bizarre vascular architecture, with a possible link to chaotic behavior.

Cystadenocarcinoma, Serous↗