Comparison between the modified French AmbUlatory Cesarean Section and standard cesarean technique-a randomized double-blind controlled trial.

BACKGROUND: The French AmbUlatory Cesarean Section is a cesarean delivery technique, which includes a vertical fascial incision to the left of the linea alba and an extraperitoneal approach to the uterus. The presumed benefits of this technique are decreased postoperative pain and accelerated recovery. However, evidence supporting these impressions is scarce. OBJECTIVE: This study aimed to compare maternal recovery after French AmbUlatory Cesarean Section vs standard cesarean delivery technique. STUDY DESIGN: In this double-blind randomized controlled trial, women undergoing elective cesarean delivery at term were allocated into French AmbUlatory Cesarean Section vs standard cesarean delivery technique. A modified French AmbUlatory Cesarean Section technique was used, adhering to all French AmbUlatory Cesarean Section operative steps except for the extraperitoneal approach. In both groups, the use of intravenous hydration, intrathecal morphine, and bladder catheter was avoided, and all women were encouraged to stand and walk 3 to 4 hours after the operation. The primary adverse composite outcome included either of the following: a visual analog scale score of >6 at 3 to 4 hours after the operation, an inability to stand up and walk to the restroom 3 to 4 hours after the operation, and a 15-Item Quality of Recovery (QoR) questionnaire score of <90 at 24 hours after the operation. The women were followed up for 6 weeks. RESULTS: Overall, 116 women were included in the trial (58 in each group). The adverse composite outcome did not differ between the 2 groups (38.9% for the French AmbUlatory Cesarean Section group vs 53.8% for the regular cesarean delivery group; P=.172). In both groups, more than 90% of the women were able to get up and walk 3 to 4 hours after the operation. Compared with the standard cesarean delivery group, the French AmbUlatory Cesarean Section group had a longer duration of the operation (43.7±11.2 vs 54.4±11.3 minutes; P<.001), a higher rate of intraoperative complications (0.0% vs 13.8%; P=.006), and a higher rate of umbilical cord pH level of <7.2 (3.4% vs 17.2%; P=.029) were noted. Evaluation via phone call 1 week after the operation showed better quality of recovery scores in the French AmbUlatory Cesarean Section group than in the standard cesarean delivery group (27.1±8.4 vs 24.6±8.0; P=.043). Other secondary outcomes did not differ between the 2 groups. CONCLUSION: As excellent maternal recovery was noted in both groups, we believe that the main factor affecting this recovery is the perioperative management (including avoidance of the use of intraoperative intravenous hydration, intrathecal morphine, and bladder catheter, with early postoperative mobilization). The maternal and neonatal safety outcomes of the French AmbUlatory Cesarean Section technique remain to be proven by larger-scale high-quality randomized controlled trials.

The Maternal Age Cut-Off for an Increase in Composite Adverse Outcomes.

OBJECTIVE: To investigate whether there is a specific maternal age cut-off at which there is an increase in maternal and neonatal adverse outcomes. METHODS: A retrospective study comparing maternal and neonatal outcomes between nulliparous women of different ages. The receiver operating characteristic model with the Youden index was used to find the best age cut-off using cesarean delivery (CD) and composite adverse outcomes. A multivariable logistic regression analysis was calculated after adjusting for smoking, induction of labour, epidural use, hypertensive disorders, gestational diabetes, and birth weight. RESULTS: The study included 11 343 nulliparous women. Age 28 years was found to be the cut-off age at which we found a significant increase in adverse outcomes. Women older than age 28 years had a higher risk of CD than women younger than 28 years (35.7% vs. 21.3%, P < 0.0001). They were also more likely to deliver prematurely (11.9% vs. 7.9%; P < 0.0001) and had higher rates hypertensive disorders (2.3% vs. 1.1%; P < 0.0001) and gestational diabetes mellitus (0.4% vs. 0.1%; P = 0.001). Furthermore, their babies were more likely to be growth restricted (1.1% vs. 0.3%; P < 0.0001). There were no differences in the rates of induction of labour or macrosomia. After adjusting for confounders, we found that women older than 28 years had higher risks of CD and adverse outcomes than younger women (aOR 1.9 [95% CI 1.744-2.1] and aOR 1.6 [95% CI 1.6-1.77], respectively). CONCLUSION: Increasing maternal age is independently associated with adverse maternal and neonatal outcomes with an age cut-off of 28 years. Women older than age 28 years are at higher risk for composite adverse outcomes than younger women.

Is There a Survival Advantage in Diagnosing Endometrial Cancer in Asymptomatic Patients? A Systemic Review and Meta-analysis.

Data supporting a survival advantage of endometrial cancer diagnosed before the onset of postmenopausal bleeding are lacking. This study sought to compare overall survival and disease recurrence between women who were asymptomatic at diagnosis and women who were symptomatic at diagnosis. A systemic search was conducted in databases using the terms: "asymptomatic," "ultrasound," "screening," and "endometrial cancer." Only original research studies that compared characteristics of tumour advancement and survival measures were included. The six articles included in the meta-analysis comprised 2961 patients. Data were collected on study design and period, number and characteristics of participants, and outcomes in terms of tumour histology and survival measures. Higher rates of stage I tumours were shown among asymptomatic patients (relative risk 1.19). The proportion of high-grade histology did not differ between the two groups (relative risk 0.92). The crude pooled estimate for overall survival did not yield statistical significance, nor did recurrence-free survival (which was reported by three studies). In conclusion, endometrial cancer diagnosed in asymptomatic women is not associated with higher survival than in symptomatic women. Invasive procedures in asymptomatic women with incidental ultrasonographic findings should be carefully weighed because no survival advantage is expected.

Cervical Cancer with Intermediate Risk Factors: Is there a Role for Adjuvant Radiotherapy? A Systematic Review and a Meta-Analysis.

BACKGROUND: The yield of adjuvant radiotherapy in cervical cancer patients with intermediate risk factors is controversial. The objective of our meta-analysis was to shed light on this important issue. MATERIAL AND METHODS: Search was conducted in several databases. By independent screening of titles and abstracts, 2 investigators selected original researches examining the effect of adjuvant radiation treatment on overall survival and progression-free survival in cervical cancer patients with intermediate risk factors. RESULTS: Of the 5 articles included, a total of 591 patients with intermediate risk factors were encompassed. Statistical significance was noted in favor of radiation therapy in a subgroup of patients with 2 or more intermediate factors in terms of recurrence (OR 0.46 [95% CI 0.28-0.74, p = 0.001]) and overall survival (OR 1.86 [95% CI 1.03-3.36, p = 0.04]). After adding patients with one risk factor, radiation exerted a non-significant effect on recurrence rate, overall survival, disease-free survival, and 5-year cancer-specific survival, while increasing the rate of gastrointestinal side effects (2.4 vs. 0%, p = 0.0156). CONCLUSIONS: Adjuvant radiation therapy decreases the risk for recurrence and increases the overall survival in patients with 2 intermediate risk factors. These benefits were not shown after adding patients with one risk factor.

Primary Papillary Serous Carcinoma of the Fallopian Tube Presenting as a Vaginal Mass: A Case Report and Review of the Literature.

BACKGROUND There is now evidence to support that some cases of high-grade serous papillary carcinoma arise from the fallopian tubes rather than the ovaries. Common symptoms at presentation include abdominal pain and swelling, vomiting, altered bowel habit and urinary symptoms. To our knowledge, this is the first case of serous papillary carcinoma presenting as a vaginal mass lesion. CASE REPORT A 41-year-old woman was referred to the Bnai-Zion Medical Center with the main complaint of irregular vaginal bleeding, vaginal mucous discharge, and suspected pelvic mass. Physical examination showed a soft, painless mass, measuring about 10 cm in diameter located mainly in the recto-vaginal septum, but not involving the uterus. Ultrasound examination showed no abnormal ovarian or uterine findings. Transvaginal biopsies of the mass showed a poorly differentiated serous papillary carcinoma of ovarian, tubal, or peritoneal origin. The physical examination and imaging findings strongly indicated an inoperable tumor, and the patient was treated with neoadjuvant (pre-surgical) chemotherapy. Pre-operative computed tomography (CT) imaging showed the partial involvement of the colon, and so surgical treatment included total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, partial vaginectomy, anterior rectal resection, and lymph node dissection. Histopathology of the surgical specimens showed a poorly differentiated serous carcinoma originating from the fimbria of the right fallopian tube. CONCLUSIONS To the best of our knowledge, this is the first report to describe primary fallopian tube papillary serous carcinoma presenting as a vaginal mass. Therefore, physicians should be aware of this possible diagnosis.

Clinical Use and Optimal Cutoff Value of Ca15-3 in Evaluation of Adnexal Mass: Retrospective Cohort Study and Review of the Literature.

OBJECTIVE: To estimate the diagnostic performance and reference values of serum cancer antigen (Ca)15-3 levels in the triage of adnexal masses. MATERIALS AND METHODS: This retrospective cohort study was carried out in 481 patients referred to the Gynecology Department at Carmel Medical Center due to adnexal mass between years 2005 and 2012. All patients underwent surgery with histopathologically confirmed diagnosis and routine preoperative measurements of serum Ca125 and Ca15-3. RESULTS: Combination of Ca125 with Ca15-3 elevated the sensitivity of Ca125 alone (from 86.9% to 93.2%; P=0.029), along with reduction of its specificity (from 80.5% to 69.5%; P=0.005) in differentiation between malignant and benign cases. According to receiver operating characteristic curve, Ca15-3 level of 21 U/mL was shown to be the optimal reference value for malignancy detection. All cases with Ca15-3 levels above 44.5 U/mL were malignant, mostly of primary ovarian source. CONCLUSIONS: As Ca15-3 assessment allowed detection of significantly more malignancy cases, we believe that measurement of this marker in combination with Ca125 is worthwhile in patients presenting with adnexal masses. The cutoff of 21 U/mL seems to be the optimal value in this specific population. High Ca15-3 levels (above 44.5 U/mL) strongly direct to a diagnosis of malignancy, mostly of primary ovarian tumors rather than breast malignancy.

Pregnancy outcomes in oocyte recipients with fibroids not impinging uterine cavity.

OBJECTIVE: To examine the effects of fibroid uterus on pregnancy outcomes and endometrial features in ovum donation recipients. METHODS: Retrospective analysis of 744 ovum donation cycles was conducted in two private IVF centers between 2005 and 2012. All the recipients underwent transvaginal ultrasound examination, including endometrial thickness and grade measurements. Clinical pregnancy, spontaneous miscarriage, and live birth rates were regarded as the primary outcomes. RESULTS: Leimyomas not distorting the uterine cavity were diagnosed in 264 (35.5%) of the cycles. This group exhibited lower endometrial thickness (8.33 ± 1.8 vs. 8.73 ± 2.03 mm, p = 0.009), lower rates of Grade A (16.1 vs. 30.1%, p < 0.0001), and higher rates of grade C endometrium (10.2 vs. 5.5%, p < 0.0001), compared to the group with sonographically normal uterine cavity. In addition, significantly higher spontaneous miscarriage rates were found in fibroid uteri group (25 vs. 14.5%, p = 0.036). CONCLUSION: Our study results suggest that uterine fibroids not distorting the uterine cavity could constitute a risk factor for spontaneous miscarriage in oocyte donation cycles, possibly via their adverse effect on endometrial receptivity. Further well-designed trials should widely explore this subject, particularly focusing on impact of myomectomy on fertility rates in these patients.

The Effect of Paternal Age on Oocyte Donation Outcomes.

IMPORTANCE: In recent decades, a trend toward delayed childbearing is noted in developed countries. Whereas the effects of maternal age on fertility, pregnancy complications, and postnatal outcomes have been thoroughly explored, consequences of advanced paternal age are less well known. Oocyte donation cycles can be used as an optimal model to analyze the association between male ageing and reproductive outcomes with minimal confounding. OBJECTIVE: The purpose of this work was to summarize the updated and relevant literature dealing with the effect of paternal age on oocyte donation outcomes. RESULTS: According to the available evidence from oocyte donation cycles, it seems that no significant association exists between advanced paternal age and fertility. However, this evidence is based on few studies, many of which are of low quality, yielding conflicting results. In addition, the emerging evidence clearly indicates an increased risk of adverse postnatal manifestations of pregnancies conceived by older fathers, including de novo autosomal dominant disorders, impaired neurocognitive development, and increased risk of malignancy. CONCLUSIONS AND RELEVANCE: This review may be of aid to medical practitioners in counseling couples on the risks of delayed childbearing.

The effect of ozonated sterile saline irrigation on the endometrium - A preliminary study.

The objective of this study was to evaluate the effect of sterile ozonated saline endometrial irrigation on sonographic and histological endometrial parameters. This prospective investigation was performed in 12 healthy, ovulating women over three consecutive menstrual cycles: control cycle (endometrial irrigation with 10 cc of normal saline at day 10), no intervention cycle and study cycle (irrigation with 10 cc of sterile ozonated saline at day 10). Endometrial thickness was measured by transvaginal ultrasound at days 10 and 12 of the control and study cycles, and endometrial samplings were obtained from the participants two days after the irrigations (i.e. on day 12) for histological evaluation. Ozonated saline irrigation, compared to normal saline irrigation, resulted in a statistically significant elevation of the columnar epithelial height (30.30 ± 3.04 vs. 25.82 ± 3.28 µm, p < 0.003), increased number of endometrial blood vessels (30.48 ± 11.38 vs. 19.12 ± 8.74, p < 0.005) and increased number of stromal cells (191.30 ± 34.40 vs. 151.29 ± 29.98, p < 0.01). In conclusion, sterile ozonated saline irrigation of the endometrium has a significant favourable effect on various histological endometrial parameters. Further studies are needed to evaluate the effect of these changes on endometrial receptivity and pregnancy rates.

CEA in evaluation of adnexal mass: retrospective cohort analysis and review of the literature.

BACKGROUND: The aim of this study was to estimate the diagnostic accuracy of serum carcinoembryonic antigen (CEA) levels in conjunction with Ca125 in the triage of adnexal masses. METHODS: This retrospective cohort study was carried out in 495 patients referred to the Gynecology Department at Carmel Medical Center due to adnexal mass, between 2005 and 2012. All patients underwent surgery with histopathologically confirmed diagnosis and preoperative measurements of serum Ca125 and CEA. For each marker, sensitivity, specificity, positive predictive value, negative predictive value and risk ratio were calculated. RESULTS: Combination of CEA with Ca125, compared with Ca125 levels alone, yielded a nonsignificant effect on sensitivity (87.4% vs. 88.9%, respectively, p = 0.64) and specificity (79.3% vs. 74.3%, p = 0.18) in differentiating malignant from benign adnexal masses. CEA levels were higher in mucinous histological types, but were not helpful in detection of borderline tumors. Significantly higher CEA (21.4 ± 53.6 vs. 3.2 ± 11.9 ng/mL, p = 0.0002) and lower Ca125 values (103.9 ± 84.9 vs. 796 ± 1,331.5 U/mL, p = 0.0338) were demonstrated in the 17 metastatic cases compared with 181 primary ovarian malignancies. CONCLUSIONS: The combination of the tumor markers CEA and Ca125 did not contribute significantly to the detection of malignant adnexal masses compared with Ca125 alone. As our results suggest that higher CEA levels could be useful in differentiating metastatic tumors from primary ovarian malignancy and in diagnosis of mucinous histology, this issue should be investigated in large, well-designed, prospective cohort trials.

CA 19-9 in evaluation of adnexal mass: retrospective cohort analysis and review of the literature.

OBJECTIVE: The aim of this study was to estimate the diagnostic accuracy of serum marker CA 19-9 levels in the triage of adnexal masses. METHODS: This retrospective cohort study was carried out in patients referred to the Gynecology Department at Carmel Medical Center due to adnexal masses. All patients underwent preoperative measurements of serum CA 125 and CA 19-9 and surgery with histopathologically confirmed diagnosis. RESULTS: Between January 2005 and December 2012, 503 patients with adnexal masses were evaluated with serum tumor markers. Combination of CA 19-9 with CA 125, compared with CA 125 levels alone, suggested a nonsignificant effect on sensitivity (86.9% vs. 88.9%, respectively, p = 0.54) or specificity (79.5% vs. 73.5%, p = 0.1) in differentiating malignant from benign adnexal masses. CA 19-9 was not helpful in detecting mucinous histological types or borderline tumors. Mean CA 19-9 levels were higher in metastatic cases compared with primary ovarian malignancy (488.7 ± 1,457 vs. 46.3 ± 149.8 U/mL, respectively, p = 0.001). In mature cystic teratomas, mean CA 19-9 levels were higher and CA 125 levels were lower than in ovarian carcinoma (p = 0.049 and p = 0.0012, respectively). CONCLUSIONS: The combination of the tumor markers CA 19-9 and CA 125 did not contribute significantly to the detection of malignant adnexal masses compared with CA 125 alone. As our results suggest that higher CA 19-9 levels could be helpful in differentiating metastatic tumors from primary ovarian malignancy; this issue should be investigated in large well-designed prospective cohort trials.

Statins, aspirin and risk of thromboembolic events in ovarian cancer patients.

OBJECTIVES: Studies suggest that statins and low dose aspirin reduce risk of VTEs in the general population. We aimed to study the effect of these drugs on the incidence of VTEs in patients with ovarian cancer. METHODS: Patients diagnosed with ovarian cancer between 2000 and 2011 were identified through the Clalit Health Services (CHS) chronic disease registry. Data were extracted from CHS database and from computerized pharmacy records. Use of medications was analyzed as a time dependent covariate in a Cox regression model. RESULTS: Of 1746 patients 175 (10%) had a VTE during a median follow up of 3.13 years. 83 patients (5.6%) had a VTE within 2 years of diagnosis of ovarian cancer. Use of chemotherapy and stage 3 and 4 at presentation were associated with an increased risk for VTEs. Statins were used by 43.5% of the patients, and 32.3% used aspirin. Aspirin use was associated with a marginally significant reduction in incidence of VTEs within 2 years of diagnosis, HR 0.423 (95% CI 0.182-1.012, p-value 0.053). Statin use was not associated with risk of VTEs. CONCLUSION: This is the first study looking at the effect of statins and aspirin on the incidence of VTEs in ovarian cancer patients. In our cohort, statins did not decrease the risk for a VTE and aspirin use was associated with a reduced risk which was marginally significant. Our results might be explained by use of low potency statins and by alternate mechanisms for VTE formation in cancer patients.

Incomplete excision of cervical intraepithelial neoplasia and risk of treatment failure: a meta-analysis.

BACKGROUND: Over 60,000 women are treated for cervical intraepithelial neoplasia (CIN) each year in England, most by excision. Management of women who have incomplete excision is controversial and the subject of much debate. Consequently, the completeness of excision is often ignored in the planning of subsequent treatment. We aimed to assess the effect of completeness of excision on the risk of post-treatment disease. METHODS: We undertook a meta-analysis of studies published between Jan 1, 1960, and Jan 31, 2007, that studied the risk of post-treatment disease (ie, CIN of any grade or invasive cancer) in relation to completeness of excision. Studies were included if they described treatment of CIN by excision; numbers of women with involved margins; prevalence of and numbers of women with post-treatment disease in relation to margin status. Criteria for post-treatment disease had to be stated as a defined abnormal cytology or histology. Studies were excluded if they described treatment of cervical glandular intraepithelial disease (CGIN); if all or nearly all women had reflex hysterectomy done soon after initial treatment; if women were immunosuppressed (eg, if they were HIV-positive); or if no control group with disease-free margins was used. The endpoint of our analysis was the relative risk (RR) of post-treatment disease in those whose treatment histology suggested that excision was complete compared with those in whom excision was incomplete or uncertain. RR meta-analysis was done by use of a random effects model. FINDINGS: The initial Medline search identified 1756 publications, from which 125 publications were short-listed. Of these, 65 and one unpublished study met our inclusion criteria; therefore, 66 studies were included in this meta-analysis. These studies described findings in 35,109 women of whom 8091 (23%) had at least one margin of the excision biopsy involved with disease. After incomplete excision, RR of post-treatment disease of any grade was 5.47 (95% CI 4.37-6.83) and RR of high-grade disease (ie, CIN 2 or 3, or high-grade squamous intraepithelial lesion) was 6.09 (3.87-9.60) compared with the reference group who had complete excision. High-grade post-treatment disease occurred in 597 of 3335 (18%) women who had incomplete excision versus 318 of 12 493 (3%) women who had complete excision. INTERPRETATION: Incomplete excision of CIN exposes women to a substantial risk of high-grade post-treatment disease. Some of these women would be safer with a second treatment, especially if deep margins are involved, but most will need close follow-up for at least 10 years. Every effort should be made to avoid incomplete excision. Adding extensive ablation in the treatment crater to compensate for inadequate excision should be avoided because this might delay detection of inadequately treated invasive disease and because the effectiveness of additional ablation to destroy any residual CIN cannot be assessed. Furthermore, extensive ablation does not decrease any risk of preterm delivery in subsequent pregnancies.

Arsenic Trioxide inhibits the growth of human ovarian carcinoma cell line.

OBJECTIVE: To determine whether Arsenic Trioxide may be an effective treatment of human ovarian carcinoma, we examined if it induced apoptosis in human ovarian cancer cell line. METHODS: The human ovarian cell line SKOV3 was exposed to different concentrations of As2O3: 0 (control), 0.1 microM, 1 microM, 5 microM and 10 microM. The effect on cells proliferation and apoptotic parameters was examined. RESULTS: The most effective inhibitory Arsenic Trioxide concentrations were 5 microM and 10 microM, causing growth inhibition of 79% and 83%, respectively. The maximum inhibitory effect of Arsenic Trioxide on cellular proliferation was seen after 48 h. No morphological or molecular features of apoptosis have been observed. At the same time, there were no typical changes of cellular necrosis. CONCLUSIONS: The exact mechanism by which Arsenic Trioxide inhibits the growth of ovarian cancer cells is probably not by apoptosis. However, since As2O3 has been shown to inhibit ovarian cancer cellular growth, it should be further elucidated as a possible chemotherapeutic agent of ovarian cancer.

BRCA germline mutations in Jewish women with uterine serous papillary carcinoma.

OBJECTIVE: Our recent study determined the possible effects and incidence of BRCA1 and BRCA2 germline mutations in uterine serous papillary carcinoma (USPC). The purpose of this study was to determine the incidence of these mutations in an enlarged series of USPC. METHODS: We screened DNA from 27 women with USPC for BRCA1 and BRCA2 germline mutations common in the Jewish population (BRCA1-185delAG and 5382 insC,BRCA2-6174delT). In women with germline mutations, tumor DNA was screened for loss of heterozygosity (LOH) at the appropriate loci. RESULTS: Women (20) were of Jewish Ashkenazi origin and seven were non-Ashkenazi. Four of 20 (20%) Ashkenazi women were carriers of germline mutations: three 185delAG mutation and one 5382insC mutation. All carriers had strong family histories of breast-ovarian carcinoma. Seven out of 20 (35%) women had been diagnosed for breast carcinoma before diagnosis of USPC. Family histories of 12 women (60%) showed at least one first-degree relative with breast, ovarian, or colon carcinoma. Loss of heterozygosity analysis found a loss of the wild-type BRCA1 allele in three of the four primary uterine tumors that were examined. CONCLUSIONS: Our findings further support our previous published data suggesting a high incidence of BRCA carriers among USPC Ashkenazi Jewish patients. The loss of heterozygosity in the tumor tissue of carriers coupled with the high frequency of patient and family history of breast and ovarian malignancies suggest that USPC might be part of the manifestation of familial breast-ovarian cancer in Ashkenazi Jewish patients.