Gad Sabah

Tumor microRNA expression patterns associated with resistance to platinum based chemotherapy and survival in ovarian cancer patients

BACKGROUND Ovarian cancer, the leading cause of gynecologic cancer deaths, is usually diagnosed in advanced stages. Prognosis relates to stage at diagnosis and sensitivity to platinum based chemotherapy. We aimed to assess the expression of microRNAs in ovarian tumors and identify microRNA expression patterns that are associated with outcome, response to chemotherapy and survival. METHODS Patients, who were surgically treated for ovarian cancer between January 2000 and December 2004 were identified. Patient charts were reviewed for clinicopathologic information, follow-up and survival. Total RNA was extracted from tumor samples and microRNA expression levels were measured by microarrays. Expression levels were compared between groups of samples and statistically analyzed. RESULTS Fifty-seven patients were identified to fit study criteria. Of them, 19 patients had stage I disease at diagnosis, and 38 patients, stage III. All patients received platinum based chemotherapy as first line treatment. 18 microRNAs were differentially expressed (p<0.05) between stage I and stage III disease. Seven microRNAs were found to be significantly differentially expressed in tumors from platinum-sensitive vs. platinum-resistant patients (p<0.05). Five microRNAs were associated with significant differences (p<0.05) in survival or recurrence-free survival. High expression of hsa-mir-27a identified a sub-group of patients with very poor prognosis. CONCLUSIONS We have found an array of tumor specific markers that are associated with response to platinum based first line chemotherapy. Expression of some of these miRNAs also correlated closely with prognosis. This approach can potentially be used to tailor chemotherapy and further management to specific patient needs.

Bacterial vaginosis in pregnancy treated with yoghurt

As various drugs might have an effect on the fetus during pregnancy, the use of drugs should be minimized in the pregnant woman. Since bacterial vaginosis (BV) can be associated with prematurity and postpartum complications, we searched for alternative therapy for its cure during pregnancy. Commercial yoghurt incorporates both factors necessary for maintaining the protective mechanism of the vagina, vaginal pH and lactobacilhis. A total of 32 women with BV in the first trimester of pregnancy were treated with intravaginal application of yoghurt. The result was favorable indicating that the continuous correction of vaginal pH and lactobaccillus flora is crucial for normal vaginal ecology. During pregnancy, a local treatment restoring the normal acidity and vaginal flora, without systemic effect, may be preferable to any other treatment.

The significance of paracardiac lymph-node enlargement in patients with newly diagnosed stage IIIC ovarian cancer.

OBJECTIVE Extra-abdominal metastases in epithelial ovarian cancer (EOC) are relatively rare. Interpreting computed tomography (CT) scans, during initial work-up, little attention is focused on enlargement of paracardiac lymph nodes (PCLN) and their significance is not clear. We aimed to examine whether the presence of PCLN during initial diagnosis of EOC influences prognosis. METHODS A retrospective study comparing patients with stage 3 EOC who were diagnosed with PCLN on CT scan during initial evaluation to stage 3C patients without PCLN. Scans were reviewed by a single radiologist for peritoneal involvement, distal metastases and presence of PCLN. Disease status at diagnosis, results of surgery, chemotherapy and response, disease-free interval (DFI) and overall survival (OS) were recorded. RESULTS Thirty one patients with stage 3C EOC with PCLN on initial CT scan were included and compared with 41 controls. There was no significant difference between groups in abdominal optimal cytoreduction rate. Lower rates of complete response (CR) to initial treatment were detected in the study group (45.2% vs. 78.0%, p=.004). In survival analysis, the DFI for patients with PCLN was shorter (median 9.0 vs. 24.0 months, p=.0097) and overall survival was shorter (median 31.7 vs. 61.3 months, p=.001). Multivariate analysis showed that PCLN was significantly associated with a lower rate of CR, a shorter DFI and a shorter OS. CONCLUSION The presence of enlarged PCLN at presentation appears to be associated with poor prognosis in stage 3C EOC. Further attention should be given to detection and follow-up of such findings when considering treatment.

The initial flare-up induced by gonadotropin releasing hormone agonist may serve as a predictor of ovarian response in the current IVF-ET treatment cycle in normogonadotropic women aged 40-48 years.

AbstractObjective: Our purpose was to assess the potential role of the baseline hormone profile in combination with the initial pattern of response to gonadotropin releasing hormone (GnRH) analogue in predicting ovarian function and hence reproductive outcome in normogonadotropic patients aged 40 years or older undergoing IVF treatment. Patients and Methods: A retrospective analysis of 394 controlled ovarian hyperstimulation (COH) cycles that reached the stage of oocyte retrieval was conducted. The study included 163 normogonadotropic (serum FSH ≤15 IU/L) patients aged between 40 and 48 years who had regular menstrual cycles. Superovulation was achieved using menotropins in combination with GnRH analog (short protocol, beginning on menstrual day 2). The ovarian response was monitored on the third cycle day, the day following the first GnRH analogue administration. Results: Cycle distribution by patient age was 175 (44.4%), 122 (30.9%), and 97 (24.7%), while the patient distribution was 85 (52.2%), 48 (29.5%), and 30 (18.3%) for age groups 40–41, 42–43, and 44–48 years, respectively. The mean total dose of menotropins needed for optimal COH was 1787 IU (range, 600–6000 IU). This dose increased with age, while the yield of oocytes and embryos declined (P<0.05; ANOVA). A positive correlation was demonstrated between the E2 level on day 3 (GnRH analogue flare effect) and the outcome of the treatment cycle (number of oocytes and embryos). Using multiple stepwise regression analysis, it was demonstrated that the initial (day 3) serum E2 levels, combined with baseline FSH levels, patients age and body mass index enabled early prediction of the ovarian response in the current IVF-ET treatment cycle (oocytes=8.2−0.18×Age+0.17×BMI−0.12×FSH+0.0042×E2). Conclusions: Multiple-parameter analysis demonstrated that the use of the initial E2 response to GnRH analogue stimulation combined with basic clinical data may assist in the prediction of ovarian function and hence the reproductive outcome in normogonadotropic IVF patients aged 40 years or older. This may serve as a clinical tool for improving patient selection and treatment outcome in IVF-ET.

Robotic blue-dye sentinel lymph node detection for endometrial cancer – Factors predicting successful mapping

OBJECTIVE Sentinel lymph node (SLN) mapping has emerged as a viable option for the treatment of patients with endometrial cancer. We report our initial experience with SLN mapping algorithm, and examine the factors predicting successful SLN mapping. METHODS We analyzed all data recorded in our institute on robotic blue-dye SLN detection mapping from the time it was first introduced to our department in January 2012-December 2014. Data included patient demographics, SLN allocation, operating room times, and pathology results. RESULTS During the study period, 74 patients had robotic assisted surgery for endometrial cancer with attempted SLN mapping. SLN was found overall in 46 patients (62.1%). At first, SLN was detected in only 50% of cases, but after performing 30 cases, detection rates rose to 84.6% (OR = 3.34, CI 1.28-8.71; p = 0.003). Univariate analysis showed a higher detection rate with methylene blue than patent blue dye, 74.3% vs. 52.3% (OR = 2.744, 95% CI 1.026-7.344; p = 0.042). In multivariate analysis, high body mass index (BMI) was associated with failed mapping (OR = 0.899; 95% CI 0.808-1.00), as was the presence of lymph-vascular space invasion (LVSI) (OR = 0.126; 95% CI 0.24-0.658) and few cases per surgeon (OR = 1.083, 95% CI 1.032-1.118). Factors related to uterine pathology itself, including tumor histology, grade, method of diagnosis, the presence of an endometrial polyp, and lower uterine segment involvement were not found to be associated with successful mapping. CONCLUSIONS Surgeon experience, BMI and LVSI may affect the success rate of SLN mapping for endometrial cancer. These factors should be investigated further in future studies.

Burkitt's lymphoma of the ovary: case report and review of the literature.

Primary Burkitt’s lymphoma of the ovary is extremely rare. We report the case of a 39-year-old woman who presented with a 1-month history complaints of night sweats, abdominal pain and dyspnea. Physical examination demonstrated pleural effusions, ascites and an abdominal mass. Imaging showed enlargement of both ovaries extending to the surrounding tissue. Frozen sections on explorative laparotomy suggested granulosa cell tumor of the ovary, and thus extensive debulking was carried out. The final pathological report was compatible with Burkitt’s lymphoma. A systematic literature review revealed another 16 cases of ovarian Burkitt’s lymphoma. Characteristics predictive for the diagnosis of Burkitt’s lymphoma were: younger age, bilateral ovarian involvement, a rapidly progressive course and high LDH levels.

Clinical course of patients treated for advanced ovarian carcinoma without surgical intervention.

Objective To describe the clinical course and outcome of patients with non-surgically-treated advanced ovarian cancer attending a single institute. Methodology/Principal Findings We reviewed the medical charts of all patients with advanced epithelial ovarian cancer who underwent chemotherapy at a tertiary medical center between January 2005 and December 2010 but were never operated. Data on patient characteristics, disease course, and outcome were collected from patient files. Sixteen patients met the inclusion criteria. Eight (50%) were diagnosed with apparent FIGO stage IIIC disease, and 8 with stage IV. Five patients (31%) achieved a complete clinical response, and 11 (69%) achieved a partial response. Among the complete responders, the median disease-free interval was 8 months (range 7–11 months). In all of them, the disease recurred and second-line chemotherapy was administered. Of them, four (80%) achieved a second complete response. Partial responders had up to four lines of chemotherapy, with continued disease progression. The median overall survival of the whole group was 19.5 months, and of the complete responders, 28 months. Conclusions/Significance Most patients with advanced ovarian carcinoma who will not undergo surgery respond only partially to first-line chemotherapy. Having no surgery is associated with a short disease-free interval.

Recurrent bilateral dermoid cysts in accessory ovaries

Ectopic ovarian tissue can be classified as either accessory or supernumerary. The first description of an accessory ovary was reported by Grohe in 1864 (1) and of a supernumerary ovary by Winckel in 1890 (2). Accessory ovaries arise from a splitting of the developing ovarian primordium on the germinal ridge and are supplied by vessels continuous with those of the normally placed ovaries, along the mesoovarium (2). They are located near the normally placed ovary, and they may be connected to the broad, utero-ovarian, or infundibulopelvic ligaments. Supernumerary ovaries, on the other hand, are entirely separated from the normally placed ovary and arise from an anlage separate from that of the normally placed ovaries (3). Since they develop from a transplantation of germinal ridge tissue or an early disruption of gonadocyte migration through the dorsal mesentery, they will have an independent blood supply (2).The true incidence of accessory ovary is difficult to determine. This finding is certainly very ra...

Uterine papillary serous carcinoma pre‐operatively diagnosed as endometrioid carcinoma: Is omentectomy necessary?

Uterine papillary serous carcinoma (UPSC) is a relatively rare but aggressive uterine malignancy comprising approximately 10% of endometrial cancers. Many women pre‐operatively misdiagnosed as having endometrioid carcinoma have ultimately UPSC on final pathology. These women receive inadequate surgical staging without omentectomy.

The use of Fluorouracil (5-FU) and leucovorin in women with heavily pretreated advanced ovarian carcinoma.

Background:Women suffering from recurrent platinum-resistant ovarian carcinoma go through several lines of chemotherapy, but eventually fail all conventional chemotherapy options. After failing multiple other regimens, we offer patients fluorouracil (5-FU) in a weekly regimen with leucovorin. For those women who failed to react to multiple lines of treatment, 5-FU has been shown to be a reasonable option with reported response rates of 10% to 33%. We report our experience with 5-FU+leucovorin in this patient population. Methods:This is a retrospective chart review of women treated for recurrent ovarian carcinoma between January 2003 and December 2009. Women with recurrent ovarian carcinoma who had been treated with at least 3 previous chemotherapy regimens and had received 5-FU were eligible for the study. 5-FU and leuocovorin are given at 600 mg/m2 weekly for 6 weeks of an 8-week cycle. Patient charts were reviewed for demographics and disease history relevant to the administration of 5-FU. Response was assessed clinically and by CA125 levels. Results:Fifty-three patients matching inclusion criteria received 5-FU during the study period. Twenty-five percent of patients achieved a partial response and 17% stable disease for an overall response rate of 42%. A median of 4 weekly doses was administered (range, 1 to 26). The median survival of the whole cohort was 10 weeks after the last dose of 5-FU was administered. Conclusions:In this population of heavily pretreated patients, a significant response to 5-FU can be achieved. Unfortunately, the response is short lived and mostly partial.