The natural history of pericardial tamponade secondary to recurrent ovarian carcinoma - A case report and review of the literature.

•We report a case of malignant cardiac tamponade secondary to ovarian carcinoma•We emphasize the quick and fatal outcome of such a complication•It seems that aggressive treatment offers the longest overall survival.

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.

Temporal pattern of recurrence of stage I endometrial cancer in relation to histological risk factors.

OBJECTIVE: To study the temporal pattern of endometrial cancer recurrence in relation to histological risk factors in a large multicenter setting. METHODS: 843 patients with apparent stage I endometrial cancer were followed for a median time of 38 months, documenting all recurrences. Patients were stratified as high risk based on the presence of at least one of the established histological risk factors: high tumor grade, penetration to the outer half of the myometrium, lymphvascular space involvement, lower uterine segment involvement and non endometroid histology. Survival analysis, including Kaplan-Meier curves, log-rank tests and multi-variate Cox proportional hazard regression were used to evaluate the equality of recurrence-free distributions for different levels of risk. RESULTS: Recurrence was documented in 66 cases. The presence of one or more of the histological risk factors was associated with significantly shorter recurrence free survival, not attenuating over time (p < 0.001). Age-adjusted Cox regression model demonstrated a significantly decreased recurrence-free survival (HR = 2.8 95% CI 1.5, 5.1) in the presence of risk factors. CONCLUSIONS: In patients with stage I endometrial cancer, the presence of histological risk factors is associated with a significantly higher recurrence rate, which does not attenuate over follow up time. This may allow for a selective approach in the follow- up of endometrial cancer patients.

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.

A multicenter validation of computerized tomography models as predictors of non- optimal primary cytoreduction of advanced epithelial ovarian cancer.

AIMS: To compare the validity of four predictive models of preoperative computerized tomography (CT) scans in predicting suboptimal primary cytoreduction in patients treated for advanced ovarian cancer. PATIENTS AND METHODS: Preoperative CT scans of patients with stage III/IV epithelial ovarian cancer who underwent primary cytoreductive surgery at one of four medical centers were reviewed by radiologists blinded to surgical outcome. The validity of each set of CT criteria previously published by Nelson, Bristow, Dowdy, and Qayyum as predictors of suboptimal cytoreduction was assessed. RESULTS: Data of 123 patients were evaluated. Optimal cytoreduction (largest diameter of residual tumor < or =1cm) was obtained in 90 (73.2%) patients. All CT models were able to significantly predict surgical outcome (p<0.02). The respective sensitivity, specificity, and accuracy of the CT models to predict sub-optimal cytoreduction was 64%, 64% and 64% for Nelson's criteria, 70%, 64% and 66% for Bristow's criteria, 79%, 60%, and 65% for Dowdy's criteria, and 67% 57% and 60% for Qayyum's criteria. CONCLUSIONS: Apart from Dowdy's criteria, the accuracy rates of CT predictors of suboptimal cytoreduction in the original cohorts could not be confirmed in this cross validation. This study underscores the difficulty in devising universally applicable selection criteria or models that reliably predict surgical outcome across institutions and surgeons.

The reproducibility of histological parameters employed in the novel binary grading systems of endometrial cancer.

OBJECTIVE: To compare the interobserver reproducibility and prognostic value of the FIGO grading system with the histological parameters employed in the various recently proposed binary grading systems of endometrial cancer. METHODS: Seventy two consecutive stage I endometrioid endometrial carcinomas from hysterectomy specimens were independently graded by two pathologists. Clinical data and outcome were obtained from the patients' records. The following histological parameters were evaluated: FIGO grade (dichotomized to grades 1 and 2 vs. grade 3), nuclear atypia, presence of more than 50% solid growth, diffusely infiltrative rather than expansive growth pattern, presence of tumor cell necrosis, and mitotic count. Interobserver agreement was measured by the kappa (k) statistics. Kaplan-Meier survival analysis, log-rank tests and Cox proportional hazard regression were used to evaluate the equality of survival distributions and to model the overall effects of the various predictor variables on survival. RESULTS: The interobserver reproducibility was as follows: FIGO grade, k=0.65; nuclear atypia, k=0.63; solid growth, k=0.51; infiltrative growth pattern, k=0.38; tumor necrosis, k=0.52; and mitotic index, k=0.44. In the comparison of the Kaplan-Meier curves, the following parameters were associated with a significantly poorer survival: FIGO grade 3, p=0.02; presence of more than 50% solid growth, p=0.01; and a high mitotic index, p=0.01. The other binary histological parameters were not significantly predictive of survival. CONCLUSIONS: The proposed novel binary grading parameters are not advantageous in terms of interobserver reproducibility and prognostic significance over dichotomization to FIGO grades 1 and 2 vs. grade 3. A simple binary grade based solely on presence of more than 50% solid growth has a comparable reproducibility and prognostic value.

Lower uterine segment involvement is associated with adverse outcome in patients with stage I endometroid endometrial cancer: results of a multicenter study.

OBJECTIVE: To quantify the relative risk associated with lower uterine segment involvement (LUSI) on outcome measures in patients with apparent stage I endometroid endometrial cancer. METHODS: A cohort of 769 consecutive patients with endometroid endometrial carcinoma apparent stage I, who underwent surgery in five gynecological oncology centers in Israel; 138 patients with and 631 without LUSI were followed for a median time of 51 months. Local recurrence, recurrence-free and overall survival were compared between the two groups. RESULTS: LUSI was associated with grade 3 tumor (p=0.002), deep myometrial invasion (p<0.001), and the presence of lymphvascular space involvement (p=0.01). There were 22 cases of local recurrences, 40 cases of distal recurrences and 80 patients died. Univariate survival analysis showed that patients with LUSI had trend toward lower regional recurrence-free survival (p=0.09), and significant lower distant recurrence-free survival (p=0.04) and lower overall survival (p=0.002). The Cox proportional hazards model demonstrated a significantly decreased overall survival (HR=2.3; 95% CI 1.3, 3.9; p=0.003) in cases with LUSI. CONCLUSIONS: In patients with apparent stage I endometroid endometrial cancer, the presence of LUSI is a poor prognostic factor, associated with a significantly higher risk of distal recurrence and death. The presence of LUSI warrants consideration when deciding upon surgical staging or postoperative management.

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.

[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.

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.

The significance of the degree of myometrial invasion in patients with stage IB endometrial cancer.

OBJECTIVE: To study the validity of the FIGO staging classification of endometrial cancer Stage IB by correlating degree of myometrial invasion depth with outcome measures. STUDY DESIGN: Fifty patients with endometrial adenocarcinoma FIGO Stage IB who underwent hysterectomy between 1989 and 2001 were divided into two groups according to depth of myometrial invasion. The first group comprised of 31 patients with myometrial invasion of less than or equal to one-third. The second group included 19 patients with invasion greater than one-third but less than one-half. The two groups were compared with regard to prognostic factors and outcome measures. RESULTS: The overall 5-year recurrence-free survival, disease specific survival and overall survival rates were 87%, 94% and 77%, respectively. These outcome measures did not vary significantly between the two groups. There were no statistically significant differences between the two groups with regard to the following parameters: duration of follow-up, age, proportion of patients who underwent complete surgical staging and postoperative adjuvant radiotherapy. Histologic parameters of the two groups, such as histological type, grade and proportion of patients with capillary space-like involvement and lower uterine segment involvement were not significantly different. CONCLUSIONS: In patients with Stage IB endometrial cancer the amount of myometrial invasion defined as less than one third compared with invasion greater than one third does not appear to correlate with their outcome, thus validating the FIGO staging system.

Pregnancy outcome after laparoscopy or laparotomy in pregnancy.

STUDY OBJECTIVE: To assess obstetric performance and fetal outcomes after laparoscopy or laparotomy performed during pregnancy. DESIGN: Nationwide, multicenter, retrospective chart review (Canadian Task Force classification II-2). SETTING: Seventeen hospitals throughout Israel: 12 university or university-affiliated hospitals and 5 general hospitals. PATIENTS: Three hundred eighty-nine pregnant women. INTERVENTION: Laparoscopy or laparotomy for various indications. MEASUREMENTS AND MAIN RESULTS: Of 192 laparoscopies performed, 141 were during the first, 46 during the second, and 5 during the third trimester; respective figures for 197 laparotomies were 63, 110, and 24. No intraoperative complications were reported for either procedure. Six and 25 women had complications after laparoscopy and laparotomy, respectively. There was no significant difference in abortion rates between groups. Mean gestational age at delivery and mean birthweight were comparable between groups. No significant difference was found in frequency of fetal anomalies between groups or when compared with the Israel register of anomalies. CONCLUSION: Operative laparoscopy seems to be as safe as laparotomy in pregnancy.

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.

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.

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.

Comparative pharmacokinetics of once daily intravenous and intramuscular gentamicin in patients with post partum endometritis.

In patients with post partum endometritis once daily intramuscular administration of gentamicin may be convenient in certain clinical settings. However pharmacokinetic data on once daily intramuscular gentamicin are not reported. In this study 10 women with post partum endometritis were given once daily intravenous gentamicin (4 mg/kg ideal body weight) followed at a later day by a similar intramuscular dose. Gentamicin levels coincided at 30 min. Levels at 60 and 90 min were lower with the intravenous route. Further clinical studies are needed to confirm reduced nephrotoxicity and ototxicity with the intramuscular route.