The impact of a nationwide hands-on workshop on the diagnostic rates and management of obstetrical anal sphincter Injuries in Israel.

AIM: The aim was to evaluate the influence of a half day, hands-on, workshop on the detection and repair of obstetric anal sphincter injuries (OASIs). METHOD: Starting in February 2011, hands-on workshops for the diagnosis and repair of OASIs were delivered by trained urogynaecologists in departments of tertiary medical centres in Israel. The structure of the hands-on workshop resembles the workshop organized at the International Urogynecological Association annual conferences. Participants included medical staff, midwives and surgical residents from each medical centre. We collected data regarding the rate of OASIs, 1 year before and 1 year following the workshop, in 11 medical centres. The study population was composed of parturients with the following inclusion criteria: singleton pregnancy, vertex presentation and vaginal delivery. Pre-viable preterm gestations (< 24 weeks), birth weight < 500 g, stillborn, and those with major congenital anomalies, multifoetal pregnancies, breech presentations and caesarean deliveries were excluded from the analysis. RESULTS: In the reviewed centres, 70 663 (49.3%) women delivered prior to the workshop (pre-workshop group) and 72 616 (50.7%) women delivered following the workshop (post-workshop group). Third- or fourth-degree perineal tears occurred in 248 women (0.35%) before the workshop, and in 328 (0.45%) following the workshop, a significant increase of 28.7% (P = 0.002). The increase in diagnosis was significant also in women with third-degree tears alone, 226 women (0.32%) before the workshop and 298 (0.41%) following the workshop, an increase of 28.3% (P = 0.005). CONCLUSION: The detection rate of OASIs has significantly increased following the hands-on workshop. The implementation of such programmes is crucial for increasing awareness and detection rates of OASI following vaginal deliveries.

Can syndromic macrocephaly be diagnosed in utero?

OBJECTIVES: To compare the outcomes of fetuses with apparently isolated macrocephaly and those with associated findings, and to compare prenatal findings with postnatal diagnoses in children with syndromic macrocephaly. METHODS: We reviewed the files of all patients referred for suspected fetal macrocephaly, during a 10-year period from 2000, to a large prenatal diagnosis unit with expertise in fetal neurology counseling. Macrocephaly was defined as head circumference (HC) > 2 SDs of the norm. Patients with confirmed HC > 2 SD were identified and contacted, and their development was evaluated. RESULTS: Adequate data for analysis were available for 98 patients, in 82 of whom the fetal macrocephaly was considered isolated (Group A), and in 16 of whom associated fetal anomalies were identified (Group B). Macrocephaly was diagnosed earlier in Group B patients (28.4 vs. 32.3 weeks, P = 0.069), and the HC in Group B patients was larger (Z-score 2.95 vs. 2.3, P < 0.001). From Group A there were 81 liveborn; one of whom was diagnosed as having infantile autism. From Group B, there were nine liveborn. The associated central nervous system findings, as demonstrated by ultrasound and magnetic resonance imaging, included mild ventriculomegaly, malformations of cortical development, callosal abnormalities, overdeveloped sulcation, large cavum septi pellucidi, large subarachnoid spaces, mega cisterna magna, periventricular pseudocyst, open operculum and vermian dysgenesis. Syndromic diagnosis was made in utero in five fetuses and after birth in three. In eight patients, associated malformations were confirmed after birth but a specific diagnosis was not reached. CONCLUSIONS: When fetal macrocephaly is associated with other brain or systemic anomalies, syndromic macrocephaly can be diagnosed in utero. Fetuses with syndromic macrocephaly have a significantly larger HC, usually > 2.5 SD above the mean. Isolated macrocephaly, particularly when the HC is < 2.5 SD above the norm, may be clinically benign.

Expression of heparanase, Mdm2, and erbB2 in ovarian cancer.

Ovarian cancer is the most lethal of gynecological malignancies. Yet early diagnosis and prognosis are far from being satisfactory. Degradation of heparan sulfate proteoglycans by heparanase appears to play an important role in the invasiveness of tumor cells through the basement membrane and into the extracellular matrix. Recent cloning of the heparanase gene and generation of monoclonal antibodies against the enzyme permit to examine tumor cell expression of the enzyme. The aim of the present study was to assess heparanase activity and localization in various subtypes of epithelial ovarian cancer in correlation with oncogene expression. Histologically confirmed malignant ovarian tissue from ten women and tissue from 2 benign ovarian tumors and 4 normal ovaries were assessed for heparanase presence, activity and localization, incidence of apoptosis and expression of the oncogenes erbB2 and Mdm2. Heparanase immunohistostaining and activity were present in mucinous carcinomas and were more intense than in endometrioid and in serous carcinomas. The lowest activity was observed in benign ovarian tumors and normal ovaries. In ovarian carcinomas the enzyme was intensely concentrated in the cytoplasm of the cancerous cells. In contrast, in normal ovaries and benign tumors the enzyme was predominantly localized in endothelial cells lining blood capillaries. The rate of apoptosis was considerably higher in mucinous and endometrioid carcinomas, and was lower in serous and primary peritoneal carcinomas. Extremely high concentration of heparanase was often demonstrated in apoptotic cells. Endometrioid and serous carcinomas showed high expression of Mdm2 and erbB2 while mucinous carcinomas showed low expression. In benign ovarian tumors and normal ovaries the expression of both oncoproteins was extremely low. In conclusion ovarian carcinomas demonstrate higher levels of heparanase than benign tumors and normal ovaries suggesting that the enzyme may play an important role in metastatic spread of the cancerous cells. Apoptosis may be a significant part of the mechanism of the enzyme release into the extracellular space. Although heparanase activity seems to play an essential role in tumor progression, expression of oncogenes, such as erbB2 and Mdm2 seems to play the dominant role in the development of ovarian cancer.

Timing of testicular sperm retrieval procedures and in vitro fertilization-intracytoplasmic sperm injection outcome.

OBJECTIVE: To compare the outcome of IVF-intracytoplasmic sperm injection (ICSI) using testicular spermatozoa obtained on the day of ovum pick-up (OPU) or on the day before OPU. DESIGN: Retrospective study. SETTING: An IVF clinic in a university hospital. PATIENT(S): Forty-seven IVF-ICSI cycles using testicular spermatozoa in 28 couples with the male partner suffering from nonobstructive azoospermia. INTERVENTION(S): Sperm retrieval was performed either on the OPU day (23 cycles in 19 patients; group A) or on the day before OPU (24 cycles in 15 patients; group B). Testicular sperm aspiration (TESA) was performed and followed by testicular sperm extraction (TESE) if no spermatozoa could be found. MAIN OUTCOME MEASURE(S): The presence of motile spermatozoa at the time of ICSI and fertilization and clinical pregnancy rates. RESULT(S): A similar proportion of motile spermatozoa (60.9% vs. 62.5%), fertilization rate (61.7% vs. 58.9%), and clinical pregnancy rate per transfer (34.8% and 29.2%) were obtained for groups A and B, respectively. CONCLUSION(S): Testicular sperm retrieval can be performed on the day before OPU without compromising success. Considerable medical and practical advantages may be offered by further advancement of testicular sperm retrieval procedures to 48 hours before OPU. This approach should thus be further evaluated.

The role of tamoxifen in the treatment of symptomatic uterine leiomyomata -- a pilot study.

OBJECTIVES: To determine the efficacy of tamoxifen in patients with leiomyomata complaining of abdominal pains and vaginal bleeding. STUDY DESIGN: Prospective, randomized, double blind study. A total of 10 patients received for 6 months 20 mg tamoxifen daily, and 10 women received placebo. All patients underwent serial pelvic and ultrasound exams and endometrial sampling was performed prior to initiation of treatment. After 5 years, the patients were interviewed again. RESULTS: Uterine size was not affected by the use of tamoxifen. Patients reported a blood loss decrease of 40--50% at the end of the study (P=0.0001). In the control group a slight increase in blood loss was reported. Hemoglobin levels remained unchanged in both groups. In the study group patients reported after 4 months of treatment a substantial decrease in the intensity of pain (P=0.018). Seven patients in the study group and one patient in the control group developed ovarian cysts. CONCLUSIONS: Treatment with tamoxifen added only marginal benefit while causing unacceptable side effects. Tamoxifen does not seem to be a useful adjunct in the treatment of symptomatic uterine leiomyomata and its use for this indication should be discouraged.

Ovarian carcinoma associated thrombocytosis. Correlation with prognostic factors and with survival.

OBJECTIVE: To assess the prevalence of thrombocytosis (platelets > or = 400,000 microliters) in ovarian cancer of epithelial origin as compared to benign controls consisting of benign ovarian cysts of epithelial origin and to correlate it with prognostic factors of ovarian cancer and survival. METHOD: Hospital records of 82 consecutive patients with ovarian carcinoma, 12 with low malignant potential tumors and 70 with invasive carcinoma, and of 32 patients with benign cysts of epithelial origin were reviewed. The clinical data and preoperative platelet counts were recorded. RESULTS: The prevalence of thrombocytosis in invasive ovarian carcinoma of epithelial origin was significantly higher than in benign controls (24.3% vs 2.9%; p = 0.006). No statistically significant correlation was found between thrombocytosis with age, grade and residual disease. A statistically non-significant excess of thrombocytosis was found among patients with advanced disease, but the survival of patients with thrombocytosis was significantly less favorable (p = 0.04). CONCLUSIONS: Thrombocytosis is significantly more prevalent in ovarian cancer patients than in benign controls and has a statistically significant correlation with poorer survival. The prevalence of thrombocytosis in ovarian carcinoma and its significance in various studies is inconsistent and should be elucidated in large prospective studies.

Demonstration of cranial sutures and fontanelles at 15 to 16 weeks of gestation: a comparison between two-dimensional and three-dimensional ultrasonography.

OBJECTIVE: The purpose of this study was to evaluate the feasibility of obtaining good quality three-dimensional ultrasound pictures of the cranial sutures and fontanelles and to compare between two-dimensional and three-dimensional ultrasound in identifying the normal appearance of cranial sutures and fontanelles by the transvaginal approach at 15 to 16 weeks of gestation. METHODS: Fifty fetuses were prospectively evaluated by two-dimensional and three-dimensional transvaginal sonography between 15 and 16 weeks of gestation. The sagittal, coronal, lambdoidal, and metopic sutures, as well as anterior and posterior fontanelles, were inspected. RESULTS: Three-dimensional ultrasound enabled visualization of all sutures in 37 (74%) fetuses compared to 28 (56%) fetuses examined by two-dimensional ultrasonography (p = NS). The visualization of the sagittal suture was significantly superior by three-dimensional ultrasonography compared to two-dimensional ultrasonography (50 (100%) vs 35 (70%), p < 0.001). No significant difference between the two modalities was found in visualization of the fontanelles. CONCLUSION: Sutures and fontanelles are usually satisfactorily demonstrated by two-dimensional and three-dimensional ultrasound at 15 to 16 weeks of gestation. The sagittal suture is difficult to visualize using two-dimensional ultrasound, and three-dimensional ultrasound appears to be the best method for its demonstration.

Tissue and serum CA125 expression in endometrial cancer.

Serum CA125 is elevated in some endometrial cancer patients. The purpose of the present study was to assess the correlation between the presence of CA125 in endometrial cancer tissue and elevated CA125 serum levels. Serum levels of CA125 were examined in 39 patients with endometrial cancer prior to definitive surgery. After diagnosis reconfirmation, additional slides were prepared from each case for immunohistochemical staining for anti-CA125 antigens. Of the 39 patients, 28 had endometrioid endometrial carcinoma (EEC) and 11 had mixed mesodermal sarcoma (MMS). In EEC, 21.4% of the patients had an elevated CA125 serum level, and that correlated with stage (P = 0.02) but not with grade. The percentage of EEC patients with positive tissue staining was significantly higher than the percentage with elevated serum levels (89.3% vs. 21.4%, P < 0.0001). No correlation between positive tissue staining and stage or grade was observed. In MMS the percentage of positive tissue staining was also higher than that with elevated serum CA125 levels and the percentage with elevated serum levels was higher than in EEC. However, the differences were statistically not significant. Our study indicates that the majority of EEC tissues contain CA125 and that the percentage of positive CA125 tissue staining is significantly higher than that of elevated CA125 serum levels. This indicates the presence of some mechanism that prevents the access of CA125 into the circulation. This mechanism is probably less effective in more advanced EEC's and in MMS.

Methotrexate versus hyperosomolar glucose in the treatment of extrauterine pregnancy.

The aim of this prospective, randomized, double blind study was to compare the efficacy of methotrexate and hyperosmolar glucose injected directly into the extra-uterine gestational sac under laparoscopic vision. The study included twenty women with ectopic pregnancy. Inclusion criteria were intact tubal pregnancy, not exceeding 4 cm in diameter, rising or plateauing betahCG levels, and no evidence of intra-abdominal bleeding. The patients were treated by laparoscopically guided injection of 3 mL fluid into the area containing the tubal pregnancy. The fluid contained either 25 mg methotrexate (n=9) or 50% glucose (n=9). Daily decrease in betahCG levels was faster in patients treated by methotrexate (median 8.7%) than in those treated by hyperosmolar glucose (median 4.8%), p=0.17. The study was discontinued due to a higher failure rate in the group treated by hyperosmolar glucose. In conclusion, local injection of methotrexate is superior to hyperosmolar glucose. It can be used as an alternative to salpingostomy or salpingotomy whenever laparoscopy is performed for the diagnosis and treatment of extra-uterine pregnancy.

Bipolar electrical energy in physiologic solution--a revolution in operative hysteroscopy.

STUDY OBJECTIVE: To evaluate the feasibility and efficiency of operative hysteroscopy in physiologic saline solution. DESIGN: Prospective observational study (Canadian Task Force classification II-2). SETTING: Tertiary university hospital. PATIENTS: One hundred sixteen women (56% menopausal) with intrauterine pathology with or without symptoms, in whom malignancy was excluded by endometrial sampling. INTERVENTION: Operative hysteroscopy for resection of uterine septa, lysis of adhesions, and resection of myomas or polyps using a bipolar electrical energy system (VersaPoint) developed for this purpose. MEASUREMENTS AND MAIN RESULTS: Polyps were significantly more common in menopausal than in premenopausal women. Symptoms (mainly bleeding) occurred in 66.9% of premenopausal and 74.5% of menopausal patients. Endometrial polyps and submucous myomata were associated with symptoms in 68% and 70%, respectively. Operating time was less than 25 minutes. Two specimens revealed malignancy. One uncomplicated uterine perforation occurred. CONCLUSION: This new technique has the potential to replace monopolar-based intrauterine interventions and may become the treatment of choice for benign intrauterine pathology.

The fetal cerebellar vermis: normal development as shown by transvaginal ultrasound.

OBJECTIVE: To determine the normal appearance and development of the fetal cerebellar vermis using mid-sagittal planes obtained by transvaginal sonography. SUBJECTS AND METHODS: A total of 101 fetuses were evaluated by transvaginal sonography between 21 and 39 weeks of gestation. The mid-sagittal antero-posterior and cranio-caudal vermian diameters, circumference and surface area were measured and calculated. Nomograms were produced. RESULTS: The vermis was observed in 96% of the cases and all the measurements were performed in 92%. The vermis grows in a linear fashion throughout pregnancy. The growth pattern correlates well with gestational age, biparietal diameter, head circumference and transverse cerebellar diameter. CONCLUSION: Transvaginal sonography is a valuable tool in the study of the fetal vermis during the second half of pregnancy. Knowledge of its normal appearance may help identify developmental anomalies and enable accurate prenatal counseling.

Premalignant lesions of the uterine cervix in a large cohort of Israeli Jewish women.

Israeli Jewish women are at low risk for cancer of the uterine cervix. In view of absent screening programs in Israel, there are only scarce data available with regard to results of PAP smears. The aim of this study was to assess the incidence of premalignant cervical lesions in the largest sample of PAP smears reported so far from Israel. We retrospectively analyzed the results of 297,849 PAP smears, which had been examined in a single laboratory, during 9 years (1991-1999). The incidence of low- and high-grade squamous intraepithelial was 0.69% and 0.29%, respectively. Our data indicate similar incidence rates for premalignant lesions in Jewish Israeli women as observed in Western countries, but no increase during the study period. In spite of relatively high incidence rates for premalignant lesions of the uterine cervix, the incidence rate for invasive cervical cancer remains conspicuously low. For unknown reason the conversion rate from premalignant cervical lesions to invasive cancer is lower in Israeli Jewish women than in European and North American women. We discuss possible reasons for this phenomenon and suggest that at this time mass screening for cervical cancer in Israel may probably not be justified.