Benjamin Piura

Parity, Oral Contraceptives, and the Risk of Ovarian Cancer among Carriers and Noncarriers of a BRCA1 or BRCA2 Mutation

BACKGROUND Multiparity and the use of oral contraceptives reduce the risk of ovarian cancer, but their effects on this risk in women with a BRCA1 or BRCA2 mutation are unclear. METHODS We conducted a population-based case-control study of ovarian cancer among Jewish women in Israel. Women were tested for the two founder mutations in BRCA1 and the one founder mutation in BRCA2 that are known to be common among Jews. We estimated the effects of parity and oral-contraceptive use on the risk of ovarian cancer in carriers and noncarriers in separate analyses that included all control women, who did not have ovarian cancer. RESULTS Of 751 controls who underwent mutation analysis, 13 (1.7 percent) had a BRCA1 or BRCA2 mutation, whereas 244 of 840 women with ovarian cancer (29.0 percent) had a BRCA1 or BRCA2 mutation. Overall, each additional birth and each additional year of use of oral contraceptives were found to lower the risk of ovarian cancer, as expected. Additional births were protective in separate analyses of carriers and noncarriers, but oral-contraceptive use appeared to reduce the risk only in noncarriers; among carriers, the reduction in the odds of ovarian cancer was 12 percent per birth (95 percent confidence interval, 2.3 to 21 percent) and 0.2 percent per year of oral-contraceptive use (-4.9 to 5.0 percent). CONCLUSIONS The risk of ovarian cancer among carriers of a BRCA1 or BRCA2 mutation decreases with each birth but not with increased duration of use of oral contraceptives. These data suggest that it is premature to use oral contraceptives for the chemoprevention of ovarian cancer in carriers of such mutations.

Management of primary melanoma of the female urogenital tract

Primary melanoma of the urogenital tract in women is rare, but biologically aggressive. They usually affect elderly women and account for less than 10% of all cancer of the urogenital tract in women and less than 10% of all melanoma diagnosed in women. Tumours originate from melanocytes that are present in the urogenital mucosal epithelium of about 3% of women. Tumour staging can be challenging; however, the American Joint Committee on Cancer melanoma staging system has been recommended for use in vulvar and vaginal melanoma. Surgery is the treatment of choice; less-extensive surgery can be a sensible approach because satisfactory locoregional control might be obtained from wide local excision and radiotherapy, without the morbidity and disfigurement associated with radical surgery. Complete regional lymphadenectomy does not seem necessary if a sentinel lymph-node biopsy sample is negative; however, this decision should be made with caution. Various chemotherapy and biotherapy (ie, immunotherapy and biological-response modifiers) regimens have been used in advanced or metastatic melanoma. However, the role of chemotherapy for women with urogenital-tract melanoma has not been established, and biotherapy methods presented to date have been anecdotal.

Matrix metalloproteinases 2 and 9, E-cadherin, and β-catenin expression in endometriosis, low-grade endometrial carcinoma and non-neoplastic eutopic endometrium

OBJECTIVES Endometriosis and endometrial endometrioid carcinoma are both capable of invasion and metastasis, but their biological behavior is strikingly different. Matrix metalloproteinases (MMPs) and changes in adhesion molecules have a role in the pathogenesis of various physiological and pathological processes, as well as in the development of endometriosis and endometrioid endometrial carcinoma. We hypothesized that endometriosis, being a benign process, will show different MMPs and adhesion molecules expressions, compared to endometrioid endometrial carcinoma, a disease with potential of malignant behavior. STUDY DESIGN We performed an immunohistochemical study to investigate expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), E-cadherin and beta-catenin in endometriosis, low-grade endometrial endometrioid carcinoma, and eutopic proliferative endometrium. Endometriotic tissues (n=15), low-grade endometrial endometrioid carcinomas (n=15), and unremarkable proliferative endometrium from women without endometriosis or carcinoma (n=10) were examined. RESULTS Endometriotic tissues showed statistically significantly stronger staining for MMP-9 and reduced beta-catenin expression when compared with proliferative endometrium. Endometrial endometrioid carcinoma showed decreased E-cadherin expression in comparison with proliferative endometrium. MMP-2 and MMP-9, and E-cadherin expressions were significantly higher and beta-catenin expression was significantly lower in endometriosis as compared to endometrioid carcinoma. CONCLUSIONS We suggest that increased MMPs and altered beta-catenin may play a role in the pathogenesis of endometriosis. Decreased E-cadherin may be important in the development of endometrial endometrioid carcinoma. The changes in MMPs, E-cadherin and beta-catenin differ in endometriosis from those in endometrioid carcinoma, an interesting finding in view of the fact that both these diseases are capable of invasion and metastasis, but have different biological behavior.

Abnormal uterine bleeding as a presenting sign of metastases to the uterine corpus, cervix and vagina in a breast cancer patient on tamoxifen therapy.

Metastases to the female genital tract from extragenital cancers are uncommon. The ovaries are most often affected with the breast and gastrointestinal tract being the most common sites of the primary malignancy. Metastases to the uterus from extragenital cancers are significantly rarer than metastases to the ovaries and in the majority of cases the ovaries are also involved. A case of metastases restricted to the uterine corpus, cervix and vagina from breast carcinoma, without involvement of the ovaries, is described. The patient who had been on tamoxifen therapy presented with postmenopausal bleeding. The diagnosis of uterine metastases was established during endometrial ablation and confirmed by total abdominal hysterectomy and bilateral salpingo-oophorectomy. This case illustrates that abnormal uterine bleeding in a breast cancer patient, regardless of whether she is receiving or not receiving tamoxifen, should always alert the physician to consider the possibility of uterine metastases from breast carcinoma.

Serum IgG and IgA antibodies specific for Chlamydia trachomatis in salpingitis patients as determined by the immunoperoxidase assay

The feasibility of applying elevated Chlamydia trachomatis specific IgG antibody and serum IgA antibodies as a non-invasive screening test for C. trachomatis associated salpingitis was analysed in 54 salpingitis patients and 294 apparently healthy women by the single antigen (L2) immunoperoxidase assay (IPA). The prevalence rate of C. trachomatis IgG antibody (titre ≥64) was significantly higher in the salpingitis patients in comparison to control (67% versus 23%). The prevalence rate of elevated C. trachomatis IgG titres (≥128, ?256 and ≥542) was significantly higher in the salpingitis patients as compared to the controls. For example, at an IgG titre of ? 128 the prevalence rate was 57% in the salpingitis patients and 8% in the healthy controls (p < 0.0001).The prevalence of C. trachomatis IgA antibodies (titre ≥16) was significantly higher in salpingitis patients in comparison to controls (37% versus 4%). The prevalence of elevated IgA titres (≥32 and ≥64) was found to be significantly higher in salpingitis patients as compared to controls. All the IgA seropositive salpingitis patients were also found to have C. trachomatis IgG antibodies. It appears that testing for IgG antibodies at a serum dilution of 1:128, and for IgA antibodies at a dilution of 1:16 by the IPA test comprises the best combination for the differentiation between the salpingitis patients and apparently healthy controls, and it is suggested that this be used as a marker of active C. trachomatis infection.

Autoantibodies to tumor-associated antigens in breast carcinoma.

Autoantibodies (AAbs) to tumor-associated antigens (TAAs) have been identified in the circulation of patients with cancer. This paper will focus on recent knowledge related to circulating AAbs to TAAs in breast carcinoma. So far, the following TAAs have been identified to elicit circulating AAbs in breast carcinoma: p53, MUC-1, heat shock proteins (HSP-27, HSP-60, and HSP-90), HER2/neu/c-erb B2, GIPC-1, c-myc, c-myb, cancer-testis antigens (NY-ESO-1), BRCA1, BRCA2, endostatin, lipophilin B, cyclin B1, cyclin D1, fibulin, insulin-like growth factor binding protein 2 (IGFBP-2), topoisomerase II alpha (TOPO2α), and cathepsin D. Measurement of serum AAbs to one specific TAA only is of little value for screening and early diagnosis of breast carcinoma; however, assessment of AAbs to a panel of TAAs may have promising diagnostic potential.

Peritoneal tuberculosis--an uncommon disease that may deceive the gynecologist.

OBJECTIVES To document women with peritoneal tuberculosis mimicking ovarian malignancy and to review pertinent literature. STUDY DESIGN The records of women with peritoneal tuberculosis who were managed at the Soroka Medical Center, Beer-Sheva, Israel between January 2000 and December 2001 were reviewed. RESULTS Four patients with peritoneal tuberculosis mimicking ovarian malignancy were encountered. Two presented with the classical symptomatology of advanced-stage ovarian carcinoma including ascites, abdominopelvic masses and elevated serum CA-125, and two presented with lower abdominal pain and adnexal mass. Laparoscopy in one patient and laparotomy in three patients revealed peritoneal tuberculosis and no malignancy. Of the three patients who had laparotomy, two underwent unnecessary extended surgery including total hysterectomy, bilateral salpingo-oophorectomy, omentectomy and bilateral pelvic lymphadenectomy, and one had conservative surgery including unilateral salpingo-oophorectomy. All patients were postoperatively treated with quadruple anti-tuberculosis chemotherapy. CONCLUSIONS Medical awareness of peritoneal tuberculosis is still lacking and many women with this disease are initially thought to have ovarian malignancy and undergo unnecessary extended surgery. Laparoscopy including biopsies seems to be a sufficient and safe method to provide diagnosis of peritoneal tuberculosis. If laparoscopy is not feasible, laparotomy should be performed. If no malignancy is detected and the diagnosis of peritoneal tuberculosis is confirmed, unnecessary extended surgery is avoided and anti-tuberculosis treatment is started.

Can parametrectomy be avoided in early cervical cancer? An algorithm for the identification of patients at low risk for parametrial involvement

AIMS To assess the rate of parametrial involvement in a large cohort of patients who underwent radical hysterectomy for cervical cancer and to suggest an algorithm for the triage of patients to simple hysterectomy or simple trachelectomy. METHODS Multicenter retrospective study of patients with cervical cancer stage I through IIA who underwent radical hysterectomy and pelvic lymphadenectomy. The patients were divided into 2 groups according to whether or not the parametrium was involved. The two groups were compared with regard to the clinical and histopathological variables. Logistic regression of the variables potentially assessable prior to definitive hysterectomy such as age, tumor size, lymph-vascular space invasion (LVSI) and nodal involvement was performed. RESULTS Five hundred and thirty patients had specific histological data on parametrial involvement and in 58 (10.9%) patients, parametria was involved. Parametrial involvement was significantly associated with older age, tumors larger than 2 cm, deeper invasion, LVSI, involved surgical margins, and the presence of nodal metastasis. By triaging patients with a tumor ≤ 2 cm and no LVSI, the parametrial involvement rate was 1.8% (2/112 patients). With further triage of patients with negative nodes, the rate of parametrial involvement was 0% (0/107 patients). CONCLUSION Using a pre-operative triage algorithm, patients with early small lesions, no LVSI and no nodal involvement may be spared radical surgical procedures and parametrectomy. Further prospective data are urgently needed.

Autoantibodies to Tailor-Made Panels of Tumor-Associated Antigens in Breast Carcinoma

Autoantibodies (AAbs) to tumor-associated antigens (TAAs) have been identified in the sera of cancer patients. In a previous review published in this journal, we have focused on recent knowledge related to circulating AAbs to individual TAAs in breast carcinoma. This review will focus on recent knowledge related to AAb assays to tailor-made panels of TAAs in breast carcinoma. So far, AAb assays to the following tailor-made panels of TAAs have been assessed in breast carcinoma: (1) p53, c-myc, HER2, NY-ESO-1, BRCA2, and MUC1, (2) IMP1, p62, Koc, p53, c-MYC, cyclin B1, and survivin, (3) PPIA, PRDX2, FKBP52, HSP-60, and MUC1, (4) MUC1, HER2, p53, and IGFBP2, (5) p53, HER2, IGFBP-2, and TOPO2α, (6) survivin and livin, (7) ASB-9, SERAC1, and RELT, and (8) p16, p53, and c-myc. Assessment of serum AAbs to a tailor-made panel of TAAs provides better sensitivity to diagnosis of breast carcinoma than measuring serum AAbs to a single TAA. Nevertheless, measurement of serum AAbs to a panel of TAAs for screening and early diagnosis of breast carcinoma is still investigational and should be carried out along with traditional diagnostic studies.

Basal cell carcinoma of the vulva

Vulvar basal cell carcinoma (BCC) accounts for 7% of all vulvar cancers at two hospitals in the south of Israel. The purpose of this study was to investigate the clinical findings, treatment and outcome of patients with vulvar BCC treated at these institutions.