Double heterozygosity in the BRCA1 and BRCA2 genes in the Jewish population.

BACKGROUND: The frequency and characteristics of disease in individuals who concomitantly harbor pathogenic mutations in both BRCA1 and BRCA2 genes are not established. MATERIALS AND METHODS: Data were collected from the database of Clalit Health Services National Familial Cancer Consultation Service. Probands referred to this clinical service and their family members are routinely tested for the three Jewish founder mutations (BRCA1: 185delAG, 5382insC, BRCA2: 6174delT). In addition, carriers identified in a population-based cohort of all cases diagnosed with breast cancer in Israel in 1987-1988 allowed the estimation of the population frequency of this phenomenon. RESULTS: In the clinic-based series of 1191 carriers of mutations in BRCA1 or BRCA2 belonging to 567 families, 22 males and females (1.85%) from 17 different families (3.0%) were found to harbor two different mutations. These included 18 individuals (1.51%) who concomitantly carried the 185delAG BRCA1 and the 6174delT BRCA2 mutations and four individuals (0.34%) who carried the 5382insC BRCA1 and the 6174delT mutations. All individuals were heterozygote carriers and none had a double mutation of both founder mutations in the BRCA1 gene itself. Seven of the 16 double carrier women (46.7%) had a personal history of breast carcinoma, diagnosed at a mean age of 44.6, compared with 372/926 (40.2%) carriers of a single mutation diagnosed with a mean age at diagnosis of 48.1 [odds ratio (OR)=1.3, 95% confidence interval (CI) 0.4-4.0]. One case (6.7%) had a personal history of ovarian carcinoma diagnosed at the age of 53 compared with 55/926 (5.9%) of the women with single mutation (OR=1.1, CI=0.2-7.6). The frequency of double mutations in the population-based national breast cancer cohort was 2.2% of all carriers, and 0.3% of all breast cancer cases in the Ashkenazi population in the cohort. The mean age at diagnosis of breast cancer was younger in the carriers of two mutations. CONCLUSION: Double carriers of mutations in the BRCA genes are rare and seem to be carrying a similar probability of developing breast and ovarian cancers as carriers of single mutations.

The outcome of patients with stage I endometrial cancer involving the lower uterine segment.

The objective of this study was to evaluate whether lower uterine segment involvement (LUSI) correlates with recurrence and survival in women with stage I endometrial adenocarcinoma and whether it is associated with poor prognostic histopathologic features. Three hundred seventy-five consecutive patients with endometrial carcinoma stage I compromised the study population. The patients were divided into two groups according to the presence of LUSI with endometrial carcinoma. The two groups were compared with regard to prognostic factors and outcome measures by using the Pearson chi(2) test, log-rank test, and Cox proportional hazards model. LUSI was present in 89 (24%) patients with stage I endometrial carcinoma. LUSI was significantly associated with grade 3 tumor (P = 0.022), deep myometrial invasion (P < 0.0001), and the presence of capillary space-like involvement (CSLI) (P = 0.003). Kaplan-Meier survival curves demonstrated that patients with LUSI had a lower recurrence-free survival (log-rank test; P = 0.009) and a worse overall survival (log-rank test; P = 0.0008). In the Cox proportional hazards model, only a trend toward higher recurrence rate (HR = 2.4, 95% CI 0.7, 8.2; P = 0.16) and a trend toward poorer overall survival (HR = 1.54, 95% CI 0.82, 2.91; P = 0.18) were noted when LUSI was present. In patients with stage I endometrial cancer, the presence of LUSI is associated with grade 3 tumor, deep myometrial invasion, and the presence of CSLI. A larger group of patients is necessary to conclude whether higher recurrence rate and poorer overall survival are associated with the presence of LUSI.

Does hysteroscopy affect prognosis in apparent early-stage endometrial cancer?

The objective of the study was to compare the outcome measures of patients with endometrial adenocarcinoma diagnosed by endometrial biopsy, uterine curettage, or hysteroscopy. Medical records of 392 women diagnosed with apparent early-stage endometrial adenocarcinoma were reviewed. Data concerning the mode of diagnosis, histologic type and grade, surgical stage, peritoneal washings and lymph nodes status, and patient's outcome were retrieved. During the study period, 99 (25.3%) cases were diagnosed by endometrial biopsy, 193 (49.2%) by uterine curettage, and 100 (25.5%) by hysteroscopy. There were 347 (88.5%) cases of endometrioid adenocarcinoma and 45 (11.5%) of poor histologic types, including serous papillary, clear cell, and small cell cancer. Three hundred and sixteen (80.6%) patients had stage I disease, 8 (2.0%) stage II, and 68 (17.4%) stage III. Peritoneal cytology was positive in only one case. Recurrent disease occurred in 6.9% patients, of which 50% had local recurrence and 50% had distant. Recurrent disease was found in 15.2% patients diagnosed by endometrial biopsy, in 4.7% where uterine curettage was used, and in 5% when hysteroscopy was applied. No statistically significant difference in the survival rate between the different diagnostic methods applied was found, although a higher recurrence rate was noted following endometrial biopsy. After a median follow-up time of 25 months for patients undergoing hysteroscopy, there was no difference in recurrence rates and/or overall survival compared to other diagnostic procedures implying that hysteroscopy can be safely used in the diagnosis of endometrial cancer.

Lymphvascular space involvement compromises the survival of patients with stage I endometrial cancer: results of a multicenter study.

AIMS: To quantify the relative risk associated with lymphvascular space involvement (LVSI) on outcome measures in patients with apparent stage I endometrial cancer. METHODS: Six hundred and ninety nine consecutive patients with endometrial carcinoma apparent stage I, who underwent surgery in one of four gynecological oncology centers in Israel, comprised the study population. Forty cases with and 659 without LVSI were followed for a median time of 39 months. Recurrence free, disease specific and overall survival was compared between the two groups. The effect of LVSI, adjusted for other clinical and histo-pathological prognostic factors, was assessed by multivariate analysis. RESULTS: The univariate Kaplan-Meier procedure for survival analysis showed that patients with LVSI had lower recurrence free survival (p=0.0003), worse disease specific (p=0.0007) and overall survival (p<0.0001). Cox proportional hazards model demonstrated a trend toward shorter recurrence free survival (HR=2.0, 95% CI 0.9, 4.5; p=0.08), a worse disease specific survival (HR=2.8, 95% CI 1.1, 7.4; p=0.04) and decreased overall survival (HR=2.0, 95% CI 1.1, 3.8; p=0.03) in cases with LVSI. CONCLUSIONS: In patients with apparent stage I endometrial cancer the presence of LVSI, an independent poor prognostic factor, is associated with a two fold increased risk of death. The presence of LVSI warrants consideration when deciding upon post operative management.

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.

[Role of intercellular adhesion molecule-1 and E-selectin in the pathogenesis of ovarian hyperstimulation syndrome].

OBJECTIVE: To explore the ICAM-1 and E-selectin in patients with OHSS and clarifying its role in pathogenesis of the syndrome. MATERIALS AND METHODS: 20 patients were included in the research and 20 control patients with stimulating ovarian cycle for the purposes of ART, during the period from 01.01.2004 till 01.01.2005 years in the center of ART-MU-Varna and Department of Obstetrics and Gynecology-IVF-ward-MU-Ben-Gurion, Israel. The patients were divided into 3 subgroups according to the degree of OHSS by the classification of Golan- mild, moderate, severe. The method of ELISA was used to record the values of the factors under research. RESULTS: Six patients with severe OHSS, showed increase in the value of the ICAM-1 and somebody of them, showed low level of E-selectin testing in serum and ascitic fluid in comparison with the control group and the rest of the patient with OHSS. CONCLUSION: OHSS is a life-threatening complication in which the main pathophysiology factor is the increased of capillary permeability. ICAM-1 are expressed on human granulosa cells and by the vascular endothelium after the stimulation by inflammatory cytokines and acts as a mediator of the cohesion with the lymphoid cells. E-selectin is produced by the endothelium after cytokine activation. The soluble forms of these molecules are found in serum, follicular fluid during the COH, as well as in ascitic fluid in severe OHSS. In our research adhesion molecules- ICAM-1 are correlated to the OHSS, especially in the severe forms of the syndrome.

Adrenocortical oncocytoma in pregnancy.

BACKGROUND: Adrenal oncocytomas are uncommon, nonfunctioning tumors occurring most often in endocrine organs. CASE: A 32-year-old woman presented at 25 weeks' gestation complaining of right flank pain. Abdominal ultrasonography and computed tomography revealed a 9 x 10-cm solid right-sided adrenal mass. Endocrine evaluation was normal. At 36 weeks' gestation, she underwent cesarean followed by resection of the adrenal mass. Histopathologic and ultrastructural studies revealed a benign adrenocortical oncocytoma. CONCLUSION: Although rare, adrenocortical oncocytomas should be included in the differential diagnosis of solid, nonfunctioning, adrenal tumors in pregnancy.

Acanthosis nigricans and hyperandrogenism in a pregnancy complicated by diabetes.

BACKGROUND: Acanthosis nigricans and hyperandrogenism have been associated with diabetes mellitus accompanied by insulin resistance. However, these manifestations have rarely been reported to occur as a result of the insulin resistance of pregnancy. CASE: A 31-year-old woman with diabetes mellitus exhibited severe insulin resistance during pregnancy. At 32 weeks, daily administration of 500 U insulin was required to maintain glycemic control. Skin lesions typical of acanthosis nigricans appeared, and free testosterone levels were elevated (10.3 pg/mL). These manifestations resolved after delivery. CONCLUSION: This case may demonstrate a correlation between reversible gestational insulin resistance and acanthosis nigricans.

Oral sustained-release ritodrine as a substitute for prolonged intravenous tocolysis.

Prolonged administration of intravenous ritodrine is necessary in some pregnant women with recurrent preterm labor as serum levels achieved by oral administration of ritodrine are insufficient to prevent recurrent contractions. New oral sustained-release ritodrine at 320 mg/day was given to 38 women with recurrent preterm labor. Serum levels of the drug at this dosage are considered comparable with levels achieved by i.v. treatment. The average duration of treatment was 8 days (range, 1-22). Patient tolerance was acceptable, and major maternal complications did not occur. We conclude that in selected cases, it may be possible to substitute oral sustained-release ritodrine at 320 mg/day for prolonged i.v. treatment.

Reproductive outcome after expectant management of ectopic pregnancy.

OBJECTIVE: To study fertility rates following expectant management of clinically stable ectopic pregnancies. STUDY DESIGN: Twenty of 33 patients with laparoscopically confirmed aborting tubal pregnancies managed expectantly were followed for a period of 1-5 years (mean 2.7 years). Excluded were the patients not desiring pregnancy, and patients with known impediments to fertility, such as age > 40 years and previous infertility, as well as patients lost to follow-up. RESULTS: Successful pregnancies occurred in 16 patients (80%); one patient (5%) had a repeat ectopic pregnancy. CONCLUSIONS: Expectant management is associated with a favorable reproduction outcome.

Prevalence of hydronephrosis in patients with genital prolapse.

OBJECTIVE: To determine the prevalence of hydronephrosis in patients with genital prolapse and evaluate contributing factors. METHODS: Retrospective study of the records of 189 patients with pelvic organ prolapse who underwent preoperative renal imaging studies. RESULTS: Of the 189 patients 31 (17.4%) had hydronephrosis; in 20 (10.6%) patients the hydronephrosis was mild, in 7 (3.7%) it was moderate and in 4 (2.7%) it was severe. The patients with hydronephrosis were older (mean age 68+/-9.5 SD vs. 60.5+/-10.8 SD, P<0.001) had a higher creatinine levels (0.84+/-0.4 SD vs. 0.78+/-0.3 SD P<0.005) and had a higher degree of uterine prolapse (mean 2.6+/-0.9 SD vs. 1.1+/-1.2 SD, P<0.005). After adjusting for age and type of prolapse, only patients with uterine prolapse remained significantly more likely to suffer from hydronephrosis (adjusted odds ratio 1.9, 95% CI 1.1, 3.2). CONCLUSION: The prevalence of hydronephrosis in patients with genital prolapse is appreciable and is related primarily to degree of uterine prolapse.

Thyroid hormone levels in cord blood of infants with acidemia at birth.

OBJECTIVE: To study the funic thyroid hormone levels in cases were fetal distress during labor resulted in acidemia at birth. MATERIAL AND METHODS: Arterial and venous levels of TSH, total T4, free T4 and total T3 obtained from cord blood at birth of twelve acidemic fetuses were compared with normal controls. RESULTS: Acidemic fetuses had a significanly higher TSH levels than controls (16.5+/-2. 1 microI/dl vs. 9.6+/-1.4 microI/dl, P=0.01). Total T3 levels were significantly lower in acidemic fetuses (49.2+/-2.9 ng/dl vs. 63+/-5. 5 ng/dl, P=0.04). Total and free T4 levels were similar and there was no difference between arterial and venous levels of the hormones. CONCLUSIONS: Birth acidemia from fetal distress during labor is associated with higher TSH levels and lower T3 levels.

Budd-Chiari syndrome complicating severe preeclampsia in a parturient with primary antiphospholipid syndrome.

A 27-year-old primipara with severe preeclampsia and primary antiphospholipid syndrome developed right upper quadrant pain, massive ascites, HELLP syndrome, and disseminated intravascular coagulation shortly following vaginal delivery. Computed tomography and color Doppler studies were compatible with complete thrombosis of the right hepatic veins, the Budd-Chiari syndrome. Anticoagulation was initiated, along with supportive measures, and the patient recovered completely. Imaging studies 6 months later were normal. This case demonstrates that nearly fatal forms of venous thrombosis may complicate preeclampsia in women with antiphospholipid syndrome; Doppler studies of the hepatic vein are of value in establishing the diagnosis.

Incidence and contribution of predisposing factors to transverse lie presentation.

OBJECTIVES: Reassessment of predisposing factors to transverse lie presentation. METHODS: Retrospective analysis of delivery data on 92 women with transverse lie presentation, using ultrasonography, and 92 randomly chosen control vertex deliveries. RESULTS: The association between transverse lie and multiparity, prematurity, placenta previa, polyhydramnios and uterine anomalies is reaffirmed. Predisposing factors were found in 66% of primiparas but in only 33% of multiparas. CONCLUSIONS: Known predisposing factors to transverse lie presentation withstood a closer and more accurate assessment of their incidence.

Sonographically diagnosed pelvic hematomas and postcesarean febrile morbidity.

OBJECTIVE: To evaluate the incidence of ultrasonographically-diagnosed postcesarean hematomas and correlate their presence with febrile morbidity. METHODS: Prospective study of 111 consecutive patients who had a pelvic ultrasound 4-6 days post-operatively. Ultrasonographic findings were correlated with clinical data. RESULTS: Postoperative fever was diagnosed in 28 (25%) patients. Fifteen (13.5%) women had hematomas; 10 (9%) had bladder-flap and five (4.5%) had subfascial hematomas. Only subfascial hematomas were significantly associated with post-operative fever (P = 0.01). CONCLUSIONS: Postcesarean bladder-flap hematomas are not predictive of post-operative fever. The presence of subfascial hematomas should be specifically sought in the evaluation of a febrile postcesarean patient.

Thrombocytopenia with the HELLP syndrome. Report of two cases with reversal in normotensive and nonproteinuric gravidas.

BACKGROUND: In the absence of hypertension and proteinuria, pregnant women with hemolysis, elevated liver enzymes and low platelet count (HELLP syndrome) present a diagnostic and therapeutic problem. CASES: Two atypical cases occurred of HELLP syndrome diagnosed by hemolysis, elevated liver enzymes and low platelet count. The patients presented early in the third trimester with epigastric pain and lacked the usual signs of preeclampsia, such as hypertension and proteinuria. The patients were managed expectantly; during this time they became hypertensive, but the thrombocytopenia resolved. CONCLUSION: Pregnant women with hemolysis, elevated liver enzymes and thrombocytopenia who do not have hypertension or proteinuria should undergo complete diagnostic evaluation. If other etiologies are ruled out, the patient should be managed as appropriate for severe preeclampsia complicated by the HELLP syndrome.

Sweeping of membranes vs. intracervical prostaglandin E2 gel for cervical ripening. Randomized trial.

OBJECTIVE: To compare intracervical prostaglandin E2 gel and membrane sweeping for cervical ripening. STUDY DESIGN: Fifty patients were randomized to either intracervical prostaglandin E2 or membrane sweeping. A Bishop score was assigned by a blinded examiner prior to and 24 hours following the procedure. RESULTS: The Bishop scores assigned 24 hours after prostaglandin instillation and membrane sweeping were not significantly different (3.4, SE 0.42, vs. 3.3, SE 0.37, respectively; P > .05). The proportions of women entering active labor or delivering within 24 hours were similar in the prostaglandin and membrane groups (21% and 19%, respectively; P > .05). CONCLUSION: When both intracervical prostaglandin insertion and membrane sweeping are feasible, their salutary effects are comparable.

Preoperative diagnosis of intestinal intussusception in pregnancy. A case report.

BACKGROUND: Intestinal intussusception is a rare event during pregnancy. The diagnosis of intestinal obstruction from any cause in pregnancy is made more difficult by the common overlapping complaints of nausea, vomiting and abdominal pain, which may persist during the second trimester. CASE: Intestinal obstruction occurred at 17 weeks' gestation. A preoperative diagnosis of intussusception was made by ultrasound by demonstrating multiple ecodense and ecolucent rings in the right lower quadrant of the abdomen. CONCLUSION: Ultrasonography may support the diagnosis of intussusception in pregnant women with intestinal obstruction.

Retroperitoneal abscess after normal delivery. A report of two cases.

BACKGROUND: Retroperitoneal abscess is a rare complication of normal labor and delivery, and no apparent etiology is evident. CASES: We report on two patient who presented with back and leg pain soon after normal deliveries. While the condition was initially clinically misdiagnosed, ultrasonography and computed tomography demonstrated retroperitoneal collections and aided in guided percutaneous drainage. After a protracted course of antibiotic treatment and daily irrigation, the collections resolved. CONCLUSION: Ultrasonography and computed tomography were invaluable in the diagnosis and guided drainage of rare psoas abscesses complicating delivery.

Primary breast carcinoma of the vulva: case report and review of literature.

The occurrence of ectopic breast tissue within the vulva is uncommon and the development of breast carcinoma within vulvar ectopic breast tissue is very rare. To date, only 12 cases of primary vulvar breast carcinoma have previously been reported in the English literature. This paper presents the 13th reported case of primary breast carcinoma of the vulva. The patient presented with a vulvar ulcerated lump and the diagnosis was based on a morphologic pattern consistent with breast carcinoma and the presence of estrogen and progesterone receptors. Primary surgery consisted of radical vulvectomy and bilateral groin dissection. The groin lymph nodes were involved bilaterally. Adjuvant therapy consisted of systemic chemotherapy (4 cycles of adriamycin and cyclophosphamide followed by 4 cycles of paclitaxel) and pelvic radiotherapy. Oral tamoxifen 20 mg/day was started for the next five years. It is concluded that the management of primary breast carcinoma of the vulva should be modeled after that for primary carcinoma of the orthotopic breast with primary surgery followed by systemic chemotherapy and pelvic radiotherapy. Chemotherapy should be similar to that employed for breast carcinoma. Tamoxifen should be prescribed for patients whose tumors contain estrogen receptors.