Asher Shushan

Human menopausal gonadotropin and the risk of epithelial ovarian cancer

OBJECTIVE To determine whether women with epithelial ovarian cancer are more likely to have been exposed to fertility drugs, and in particular hMG, than healthy population controls. DESIGN A nationwide case-control study. PATIENTS Two hundred living women 36 to 64 years of age, with a histologically confirmed diagnosis of primary invasive or borderline epithelial ovarian cancer that was first diagnosed and reported to the Israel Cancer Registry between January 1, 1990 and September 1, 1993 were enrolled. There were 164 (82%) invasive and 36 (18%) borderline epithelial ovarian tumors among the 200 cases. The controls were 408 women from the same dialing areas selected by random digit dialing. Cases and controls were interviewed using a standard questionnaire. A multivariate logistic model was used to assess the association of fertility drug use and ovarian cancer, controlling for variables found to be statistically associated with this outcome on univariate analysis. RESULTS Twenty-four women with epithelial ovarian cancer (12%) and 29 healthy controls (7.1%) reported that they had used any fertility drug (adjusted odds ratio [OR] 1.31; 95% confidence interval [CI] 0.63 to 2.74). Among cases and controls, respectively, 22 and 24 reported that they had used hMG alone or in combination with clomiphene citrate (adjusted OR 1.42, 95% CI 0.65 to 3.12), and 11 and 6 reported that they had used hMG alone (adjusted OR 3.19, (95% CI 0.86 to 11.82). The risk was increased particularly in the subgroup of women with borderline ovarian tumors who had used hMG (adjusted OR 9.38, 95% CI 1.66 to 52.08). CONCLUSIONS We conclude that the use of ovulation induction agents, in particular hMG, may increase the risk of epithelial ovarian tumors.

How Often Are Endometrial Polyps Malignant

Objective: Endometrial polyps are a frequent pathology encountered during pelvic sonography and diagnostic hysteroscopies. The true incidence of malignant endometrial polyps is unknown. The estimations range from 0.5 to 4.8%. The objective of this study was to investigate the frequency of malignant endometrial polyps, and to characterize the hysteroscopic image of these polyps. Methods: The study included 300 consecutive women with endometrial polyps who underwent hysteroscopic polypectomy. Patients’ characteristics, operative findings, and pathology reports were analyzed. Results: Four of the 300 endometrial polyps removed by operative hysteroscopy were malignant (1.3%). Patients with malignant polyps were symptomatic peri- or postmenopausal women. All asymptomatic polyps in this series were found to be benign. We could not identify any distinct hysteroscopic feature of malignancy. Conclusions: Our study shows that about 1.5% of endometrial polyps may be malignant. This finding reinforces the indication for removal of symptomatic endometrial polyps, preferably by a hysteroscopic procedure. The significance of asymptomatic uterine polyps has still to be determined.

Ovarian cysts in premenopausal and postmenopausal tamoxifen-treated women with breast cancer

OBJECTIVE Our purpose was to investigate the frequency of ovarian cysts in tamoxifen-treated breast cancer patients. STUDY DESIGN The study population included 95 consecutive tamoxifen-treated premenopausal and postmenopausal women with breast cancer who were followed up by the outpatient clinic at the Hadassah University Hospital between September 1990 and June 1992. Tamoxifen was administered orally (20 mg/day). All patients underwent a pelvic examination and vaginal ultrasonography with a 5 MHz vaginal probe. RESULTS During the study 11 of 95 tamoxifen-treated breast cancer patients (11%) had ovarian cysts. Five cysts were detected in postmenopausal women (6.3% of the postmenopausal women) and six in premenopausal women (37.5% of the premenopausal women). In postmenopausal and premenopausal women the mean tamoxifen treatment interval was 19.4 +/- 7.8 months (range 4 to 48 months) and 28 +/- 6.1 months (range 12 to 54 months), respectively (p = 0.41). In 8 of the 11 patients the ovarian cystic enlargement disappeared after cessation of tamoxifen treatment. Two patients underwent laparotomy because of persistent cysts and the third because of a rapidly growing myoma. The three cysts were found to be benign. CONCLUSION Ovarian cysts are a common side effect of tamoxifen treatment. The ovarian cysts can develop in tamoxifen-treated premenopausal as well as postmenopausal women with breast cancer. Most of the tamoxifen-associated cysts disappear after tamoxifen treatment is abandoned.

Behcet's disease and pregnancy

Background.  Behçets disease (BD) is a multisystem inflammatory chronic disorder, which is characterized by relapsing oral and genital ulceration and iridocyclitis. While being of unknown etiology, vasculitic changes of possible autoimmune origin are common to all involved organs, and thrombotic complications, which may adversely affect gestation, are frequently seen. Very little is known to date about the reciprocal influence of BD and pregnancy. We have undertaken to explore the mutual effect of BD and pregnancy with emphasis on maternal and fetal complications.

Changes related to phosphatidylinositol 3-kinase/Akt signaling in leiomyomas: possible involvement of glycogen synthase kinase 3α and cyclin D2 in the pathophysiology

OBJECTIVE To identify changes in the expression and phosphorylation of phosphatidylinositol 3-kinase (PI3K)/Akt protein kinases controlling survival and/or apoptosis of in vitro cell cultures of uterine leiomyomas. DESIGN Establishment of paired cell cultures of leiomyoma and myometrial specimens. SETTING Hadassah gynecology research laboratory. PATIENT(S) Eleven white premenopausal women, 35 to 50 years of age, undergoing hysterectomy because of symptomatic uterine leiomyomas. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Immunochemical analysis of expression and phosphorylation of relevant PI3K/Akt and BCL2 proteins. RESULT(S) Analysis of total phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and of nonphosphorylated and phosphorylated (p) PDK1, Akt, glycogen synthase kinase 3 (GSK3), FKHR, tuberin (TSC2) and hamartin (TSC1) complex, and cyclin D2 proteins indicated that [1] the level of pGSK3alpha and cyclin D2 proteins was elevated significantly in the leiomyoma compared with the normal myometrium, [2] there was a significant interaction between PTEN- PDK1 and between pAkt-pGSK3beta in the leiomyoma compared with the myometrial cells, and [3] there was a significant interaction between pAkt-pGSK3alpha in the paired leiomyoma and myometrial cultures. CONCLUSION(S) Our study suggests that the downstream signaling components of the PI3K/Akt pathway, GSK3 (a regulator of apoptosis), and cyclin D2 (a promoter of G1/S progression), as well as the significant interaction between PTEN-PDK and between pAkt-pGSK3beta, are involved in the survival and proliferation of leiomyomas.

Subfertility in the era of assisted reproduction: changes and consequences

OBJECTIVE To review the major changes that have occurred during the last decade of assisted reproduction technology (ART) practice, looking at the various conditions that cause subfertility. DESIGN A short review describing the progress that has been made during the last decade of ART practice, analyzing the various conditions that cause subfertility, is presented. The efficacy of ART as a treatment of these conditions is discussed. CONCLUSIONS Assisted reproductive technology currently is used for a wide range of indications and has become an acceptable tool in the treatment of subfertile couples. Yet, there is an ongoing debate regarding the effectiveness of ART versus conventional treatment for the various conditions that cause subfertility. The effectiveness of IVF in terms of pregnancy rate (PR) was demonstrated only for patients with severe bilateral tubal disease and male subfertility. For couples with other causes of infertility the differences in PRs do not reach statistical significance, and the efficacy of IVF has not been demonstrated clearly to date. Moreover, much of the discussion about management of subfertility has centered on costs of ART and the cost-benefit of ART versus conventional therapy for subfertility. It has been shown that, in women with unexplained infertility, menotropin treatment is as successful, less expensive, and carries a smaller risk than the surgical approach used in ART. However, the exact role of ART in the management of polycystic ovarian syndrome, immunological infertility, and endometriosis still is to be determined. Yet, as embryo implantation after ART still is considerably lower than that of fertile couples who conceive naturally, we expect that the next major thrust improving the effectiveness of ART will occur after future elucidation of factors influencing embryonic implantation.

Hysteroscopic treatment of intrauterine lesions in premenopausal and postmenopausal women.

STUDY OBJECTIVE To compare the safety and efficacy of hysteroscopic surgery in the management of intrauterine lesions in premenopausal and postmenopausal women and, in particular, to investigate whether glycine absorption is different between these populations. DESIGN Comparative study (Canadian Task Force classification II-2). SETTING Tertiary care university hospital. PATIENTS Thirty postmenopausal and 78 premenopausal women with intrauterine polyps or myomas. INTERVENTION Hysteroscopic myomectomy or polypectomy. MEASUREMENTS AND MAIN RESULTS One hundred eight procedures were completed successfully by hysteroscopy; in two cases myomectomy was completed in a second operation for a deeply embedded myoma. No major complications occurred in either group. Median operating time, mean glycine absorption, and median postoperative hospital stay were not significantly different between groups. During mean follow-up of 15 months (range 1-39 mo), four women underwent hysterectomy (1 for endometrial cancer, 1 for complex hyperplasia with atypia, 2 for pelvic pain and menorrhagia). CONCLUSION Hysteroscopic surgery is an effective and safe therapeutic option for intrauterine lesions regardless of a womans menopausal status.

Umbilical cord blood for use in transplantation

Bone marrow transplantation has rapidly progressed over the last two decades offering cure and prolonged disease-free survival for patients suffering from certain hemato-oncological malignancies or metabolic disorders. However, bone marrow transplantation is limited by the paucity of major histocompatibility loci antigen (HLA)-matched donors, and the morbidity and mortality due to graft-versus-host disease. Recently it has been shown, that umbilical cord blood represents a unique source of transplantable hematopoietic progenitor cells. Currently, human umbilical cord blood from a newborn sibling has been used successfully for hematopoietic reconstitution of approximately 40 children with congenital or malignant diseases. Establishment of umbilical cord blood banks might alleviate some of the problems associated with bone marrow transplantation. The developments in this field which have occurred during the last decade, as well as the importance of cooperation between the obstetric and transplantation staff, are discussed in this review. Certain ethical problems remain surrounding the issue of using human umbilical cord blood for allogeneic transplantation which must be addressed.

Septate Uterus with Cervical Duplication: Rethinking the Development of Müllerian Anomalies

We present a case of a septate uterus with duplication of the cervix and a vaginal septum, which challenges the embryologic concept of unidirectional caudad to cephalad müllerian ducts fusion. This unique case is, to the best of our knowledge, the seventh reported case of this müllerian anomaly. It challenges the classic theory of unidirectional caudad to cephalad fusion of the müllerian ducts, and might be additional evidence to support the hypothesis suggested by Musset et al. Accurate diagnosis and reports of such cases are important not only for the benefit of treatment, but to reflect the true incidence of this anomaly, and consolidate the embryologic concept.

Acetaldehyde differentially affects the growth of uterine leiomyomata and myometrial cells in tissue cultures

OBJECTIVE To examine the effect of alcohol and its derivatives on leiomyomata versus normal myometrium in cell culture. DESIGN A study on human tissue cultures. SETTING A tertiary-care university hospital. PATIENT(S) Premenopausal women with uterine myomas. INTERVENTION(S) Obtaining paired cultures of normal myometrium and myomas from women undergoing hysterectomy. MAIN OUTCOME MEASURE(S) Analysis of the effect of ethanol and acetaldehyde on cell growth and the expression of relevant proteins. RESULT(S) Acetaldehyde statistically significantly inhibited the growth of myoma cells compared with normal myometrium. The level of alcohol dehydrogenase 1 (ADH1) protein was lower in myoma than in myometrial cells. The acetaldehyde dehydrogenase 1 (ALDH1) protein level was higher in myoma cells. Treatment with acetaldehyde resulted in a relative reduction of ALDH1 level in the myoma cells. CONCLUSION(S) Acetaldehyde has an inhibitory effect on cell growth of myoma compared with normal myometrium. The reduced level of ADH1 and the increased level of ALDH1 proteins observed in myoma cell culture reduces the acetaldehyde level and thus may be involved in myoma cell growth.