Prognostic significance of pretreatment thrombocytosis in endometrial cancer: an Israeli Gynecologic Oncology Group study.

OBJECTIVE: Endometrial cancer prognosis is related to stage, histology, myometrial invasion, and lymphovascular space invasion. Several studies have examined the association between pretreatment thrombocytosis and patient outcomes with contrasting results regarding prognosis. Our aim was to evaluate the association of pretreatment platelet count with outcomes in endometrial cancer patients. METHODS: This is an Israeli Gynecologic Oncology Group multicenter retrospective cohort study of consecutive patients with endometrial cancer, who underwent surgery between January 2002 and December 2014. Patients were grouped as low risk (endometrioid G1-G2 and villoglandular) and high risk (endometrioid G3, uterine serous papillary carcinoma, clear cell carcinoma, and carcinosarcoma). Those with stage I disease were compared with stages II-IV. Disease stages were reviewed and updated to reflect International Federation of Gynecology and Obstetrics (FIGO) 2009 staging. All patients underwent pelvic washings for cytology and total abdominal or laparoscopic hysterectomy with bilateral salpingo-oophorectomy. Pelvic lymph node assessment was performed in patients with tumors of moderate-high risk histology or deep myometrial invasion. Para-aortic sampling was performed at the surgeon's discretion. Patients were categorized by pretreatment platelet count into two groups: ≤400×109/L and >400×109/L (defined as thrombocytosis). Clinical and pathological features were compared using Student t-test, χ2 or Fisher's exact test. Survival measures were plotted with the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards model was used for multivariable comparison of associations. RESULTS: Of the 1482 patients included, most had stage I disease (961; 74.8%) and most had endometrioid histology (927; 64.1%). A total of 1392 patients (94%) had pretreatment platelet counts ≤400×109/L and 90 (6%) had pretreatment thrombocytosis. Patients with thrombocytosis had a significantly higher rate of high-grade malignancy, advanced stage, lymphovascular space invasion, low uterine segment involvement, and lymph node metastases. They also had shorter 5 year disease-free survival (65% vs 80%, p=0.003), disease-specific survival (63% vs 83%, p<0.05) and overall survival (59% vs 77%, p<0.05). On multivariate analysis, an elevated pretreatment thrombocyte count remained a significant independent predictor for disease-specific survival and overall survival. CONCLUSIONS: Pretreatment thrombocytosis is an independent prognostic factor for decreased disease-specific survival and overall survival among patients with endometrial cancer, and can serve as a predictor of poor outcome.

Age is an independent predictor of outcome in endometrial cancer patients: An Israeli Gynecology Oncology Group cohort study.

INTRODUCTION: Advanced age is considered an adverse factor in endometrial cancers but may be a surrogate for other conditions that impact outcomes. The study objective was to assess the association of age with endometrial cancer features, treatment and prognosis. MATERIAL AND METHODS: In this multicenter cohort study, consecutive women with endometrial cancer treated at 10 Israeli institutions between 2000 and 2014 were accrued in an assimilated database. Postmenopausal women were stratified into age groups with a cut-off of 80. Clinical, pathological and treatment data were compared using t test or Mann-Whitney test for continuous variables, and Chi-square Test or Fisher's Exact test for categorical variables. Main outcome measures included disease recurrence and disease-specific and overall survival; these were plotted using the Kaplan-Meier method and compared using the log-rank test. The association between age and recurrence and survival, adjusted for other clinical and pathological factors, was assessed using multivariable Cox regression modeling. RESULTS: A total of 1764 postmenopausal women with endometrial cancer were identified. Adverse pathological features were more prevalent in older women, including high-risk histologies (35% vs 27%, P = .025), deep myoinvasion (44% vs 29%, P = .001) and lymphovascular involvement (22% vs 15%, P = .024). Surgical staging was performed less frequently among older women (33% vs 56%; P < .001). Chemotherapy was less often prescribed, even for non-endometrioid histologies (72% vs 45%; P < .001). On multivariable analysis, age remained a significant predictor for recurrence (HR = 1.75, P = .007), death of disease (HR = 1.89, P = .003) and death (HR = 2.4, P < .001). CONCLUSIONS: Older age in women with endometrial cancer is associated with more adverse disease features, limited surgery and adjuvant treatment, and worse outcomes. On multivariable analysis, age remains an independent prognosticator in this population.

[INTRAPARTUM ULTRASOUND - THE FUTURE IS HERE].

INTRODUCTION: This review aims to present the different applications and benefits of intrapartum ultrasound (IPUS) compared to the traditional digital vaginal examination. IPUS is non-invasive, does not cause pain or discomfort to the woman and may reduce the rate of ascending infections. In comparison to the vaginal exam, IPUS is more accurate in diagnosing fetal head position and station, is easy to acquire and has a faster learning curve. Applications of IPUS include: 1. Diagnosing the fetal head position either by suprapubic or trans-perineal ultrasound when the fetal head is low, which is more accurate than the digital vaginal exam; 2. Measuring cervical dilatation and effacement by trans-perineal ultrasound. This may be of more value especially in patients with ruptured membranes or patients who have difficulty with invasive examinations; 3. Assessing fetal head station and labor progress by measuring the head-perineal distance (HPD) and the angle of progression (AOP); 4. Estimating the pelvic size relative to the fetal head by measuring the pubic arch angle and fetal head circumference; 5. Predicting the mode of delivery before and during the labor process; 6. Prior to deciding the mode of delivery in a prolonged second stage of labor; 7. Providing a visual biofeedback to improve pushing efforts and mother-baby connection.

Effect of Menopausal Status on the Diagnosis of Endometrial Polyp.

OBJECTIVE: This study sought to compare the value of transvaginal ultrasonography (TVUS) and hysteroscopy in premenopausal and postmenopausal women in the diagnosis of endometrial polyp. METHODS: The records of 694 women with an ultrasonographic diagnosis of suspected endometrial polyp who underwent hysteroscopy were studied. Patients were divided into two groups according to menopausal status, and a comparison was made between two groups. RESULTS: There were 299 postmenopausal and 395 premenopausal women in the study. Hysteroscopy confirmed the ultrasonographic diagnosis of endometrial polyp in 212 (71%) and 212 (53%) patients in the postmenopausal and premenopausal groups, respectively (P = 0.001). In postmenopausal patients, 94% of the polyps observed by hysteroscopy were confirmed by histology, whereas in premenopausal patients, the percentage was 85% (P = 0.004). CONCLUSION: In premenopausal patients, the diagnostic value of TVUS and hysteroscopy is lower than in postmenopausal patients. The appropriate time for TVUS and hysteroscopy should be scheduled in premenopausal women, especially in women with abnormal uterine bleeding.

Endometrial Polyp Size and the Risk of Malignancy in Asymptomatic Postmenopausal Women.

OBJECTIVE: The appropriate management of endometrial polyps in asymptomatic postmenopausal patients remains controversial. The aim of the study was to evaluate the relationship between endometrial polyp size and malignancy risk among asymptomatic postmenopausal women. METHODS: This observational retrospective study investigated 472 postmenopausal asymptomatic women who underwent hysteroscopic polypectomy between 2010 and 2014 (Canadian Task Force Classification II-3). RESULTS: Of the 472 women, premalignant and malignant lesions were found in 11 (2.33%) cases; four (0.84%) had endometrial carcinoma, and seven (1.49%) had atypical endometrial hyperplasia. The incidence of premalignant or malignant lesions among various cut-offs of polyp size (10, 15, 20 mm) was not significantly different. CONCLUSION: In the current series no significant risk factor for malignancy was found among different cut-offs of polyp size.

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.

Is there a survival advantage in diagnosing endometrial cancer in asymptomatic postmenopausal patients? An Israeli Gynecology Oncology Group study.

BACKGROUND: Incidental ultrasonographic findings in asymptomatic postmenopausal women, such as thickened endometrium or polyps, often lead to invasive procedures and to the occasional diagnosis of endometrial cancer. Data supporting a survival advantage of endometrial cancer diagnosed prior to the onset of postmenopausal bleeding are lacking. OBJECTIVE: To compare the survival of asymptomatic and bleeding postmenopausal patients diagnosed with endometrial cancer. STUDY DESIGN: This was an Israeli Gynecology Oncology Group retrospective multicenter study of 1607 postmenopausal patients with endometrial cancer: 233 asymptomatic patients and 1374 presenting with postmenopausal bleeding. Clinical, pathological, and survival measures were compared. RESULTS: There was no significant difference between the asymptomatic and the postmenopausal bleeding groups in the proportion of patients in stage II-IV (23.5% vs 23.8%; P = .9) or in high-grade histology (41.0% vs 38.4%; P = .12). Among patients with stage-I tumors, asymptomatic patients had a greater proportion than postmenopausal bleeding patients of stage IA (82.1% vs 66.2%; P < .01) and a smaller proportion received adjuvant postoperative radiotherapy (30.5% vs 40.6%; P = .02). There was no difference between asymptomatic and postmenopausal bleeding patients in the 5-year recurrence-free survival (79.1% vs 79.4%; P = .85), disease-specific survival (83.2% vs 82.2%; P = .57), or overall survival (79.7% vs 76.8%; P = .37). CONCLUSION: Endometrial cancer diagnosed in asymptomatic postmenopausal women is not associated with higher survival rates. Operative hysteroscopy/curettage procedures in asymptomatic patients with ultrasonographically diagnosed endometrial polyps or thick endometrium are rarely indicated. It is reasonable to reserve these procedures for patients whose ultrasonographic findings demonstrate significant change over time.

[SENTINEL LYMPH NODES DISSECTION IN GYNECOLOGICAL MALIGNANCIES].

INTRODUCTION: During the last decade sentinel lymph nodes biopsy has become an essential part of primary surgical treatment in a number of malignancies including breast cancer, melanoma and head-and-neck malignancies. Dye or radioactive substances are injected at the primary tumor site, followed by pre-operative and intra-operative mapping. During surgery only positive lymph nodes are being dissected instead of a complete dissection of the lymphatic basin. The advantages of sentinel lymph nodes dissection are reducing the side effects of extensive lymph nodes dissection, while maintaining high detection rates and sensitivity in identifying cases with lymphatic tumor spread. In the past years, the use of sentinel lymph nodes biopsy has also been incorporated in the treatment of gynecological malignancies. In vulvar cancer, it has been shown that sentinel lymph nodes biopsy is correlated with the same survival and recurrence rates as full groin lymph nodes dissection, while substantially lowering complications and especially morbid lymphedema. Preliminary experience in cervical cancer and carcinoma of the endometrium also displays the feasibility and liability of this method. Yet, there are still several controversies regarding the optimal detection method, site of injection and its oncological safety. In this article we present a review of the current literature on this evolving field.

Can malignant potential of endometrial polyps be determined by incorporating the endometrial intraepithelial neoplasia (EIN) classification?

OBJECTIVE: The reported frequency of malignant or premalignant changes confined to endometrial polyps (EP) is 0.5-6%. The management of atypical endometrial hyperplasia (AEH) confined to EP is not yet established. Recently, an alternative pathological nomenclature has emerged using the term endometrial intraepithelial neoplasia (EIN) instead of atypia. The objective of this study was to evaluate the safety of conservative hysteroscopic resection of endometrial polyps with AEH or EIN. METHODS: Retrospective cohort study of all cases of hysteroscopic resections of EP was performed at a single center between the years 2000-2011. All patients with a pathologic diagnosis of AEH in EP were included. A post-hoc revision of the pathologic specimens was made according to the EIN classification. RESULTS: Of the 32 patients with AEH in EP, 25 had normal endometrial curetting. Even with AEH confined to EP, 12 cases (48%) showed AEH (11 cases) or carcinoma (1 case) in the hysterectomy specimens. EIN in EP (14 cases) was correlated with 57% of diagnosis of EIN or carcinoma in the uterus; whereas in the absence of EIN in EP only 1 of 9 cases showed EIN in the final pathologic specimen (p=0.002), and none with carcinoma, which yields a PPV of 14% and a NPV of 100%. CONCLUSION: The diagnosis of EIN in EP may be a better predictor than AEH for endometrial involvement with malignant or pre-malignant neoplasms. The safety of conservative hysteroscopic resection of EP with AEH/EIN is questioned.

L1CAM is expressed in triple-negative breast cancers and is inversely correlated with androgen receptor.

BACKGROUND: Breast cancer is a heterogeneous disease displaying distinct molecular features and clinical outcome. The molecular profile of triple-negative breast cancers (TNBCs) overlaps with that of basal-like breast cancers that in turn show similarities with high-grade serous ovarian and endometrial carcinoma. L1CAM is an established biomarker for the latter cancers and we showed before that approximately 18% of primary breast cancers are positive for L1CAM and have a bad prognosis. Here we analysed the expression of L1CAM breast cancer subtypes. METHODS: We analyzed mRNA and protein expression data from different breast cancer cohorts for L1CAM, estrogen receptor, progesterone receptor, Her-2 and Androgen receptor (AR) and correlated the data. We performed Western blot analysis on tumor cell lysates and carried out chromatin-immuno-precipitation (CHIP) after AR overexpression. RESULTS: We find that L1CAM is expressed preferentially though not exclusively in TNBCs. Using the human cancer genome atlas database and two independent breast cancer cohorts we find that L1CAM is inversely correlated with androgen receptor (AR) expression. We found that L1CAM(high)AR(low) primary breast tumors have the worst clinical outcome. Overexpression of AR in MDA-MB436 breast cancer cells decreased L1CAM expression at the protein and mRNA level and CHIP-analysis revealed binding of AR to the L1CAM promoter region. CONCLUSIONS: These results suggest that L1CAM in breast cancer is under AR control. The data also strongly advocate the use of L1CAM assessment in breast cancer diagnosis. We suggest that L1CAM expression could be causally related to the bad prognosis of TNBCs.

The omentum and omentectomy in epithelial ovarian cancer: a reappraisal. Part I--Omental function and history of omentectomy.

OBJECTIVE: This article reviews the literature concerning the function of the omentum and how omentectomy came to be part of the staging and treatment of epithelial ovarian cancer. METHODS: A review of the English language literature based on a MEDLINE (PubMed) database search using the key words: ovary, cancer, carcinoma, omentum, and omentectomy. An additional collection of reports was found by systematically reviewing all references from retrieved papers. RESULTS: Descriptions of the omentum can be found as far back as the time of the ancient Egyptians. An immunologic role of the omentum was confirmed in 1980s when "milky spots" were described. Omentectomy arrived as part of the ovarian cancer guidelines in the 1960s after observing that the omentum was a frequent site of metastasis and that patients with removal of all diseased tissue did better. The exact role of the omentum in immunology and cancer remains incompletely understood. CONCLUSIONS: Historically, occult omental metastases in otherwise early disease have led to the inclusion of omentectomy for the purpose of accurate staging and for a possible therapeutic benefit. Laboratory studies on the role in cancer of the omental fat and milky spots are controversial.

Assessment of labor progress by ultrasound vs manual examination: a randomized controlled trial.

BACKGROUND: Assessment of labor progress via digital examination is considered the standard of care in most delivery rooms. However, this method can be stressful, painful, and imprecise, and multiple examinations increase the risk for chorioamnionitis. Intrapartum ultrasound was found to be an objective, noninvasive tool to monitor labor progression. OBJECTIVE: This study aimed to investigate whether, among nulliparous women, the use of intrapartum ultrasound can reduce the rate of intrapartum fever by reducing the number of digital examinations. STUDY DESIGN: This was a prospective, randomized controlled trial in term nulliparas admitted with prelabor rupture of membranes, induction of labor, or in latent phase of labor with a cervical dilation of <4 cm. Women were randomized into 1 of the following 2 arms: (1) labor progress assessed by ultrasound, avoiding digital examinations as much as possible; and (2) control group in which labor progression was assessed according to the regular protocol. Before the study, all labor ward physicians underwent training in intrapartum ultrasound. RESULTS: A total of 90 women were randomized to the ultrasound group and 92 were randomized to the control group. When compared with the control group, the ultrasound group had significantly lower rates of intrapartum fever (11.1% vs 26.1%; P=.01), clinical chorioamnionitis (3.3% vs 16.5%; P>.01), and histologic chorioamnionitis (2.2% vs 9.8%; P=.03). The median number of digital examinations was significantly lower in the ultrasound group (5; interquartile range, 4-6) than in the control group (8; interquartile range, 6-10; P<.01). The median number of digital examinations per hour in the ultrasound group was significantly lower than in the control group (0.2 vs 0.4; P<.01). The induction rates, time from admission to delivery, mode of delivery, Apgar score at 5 minutes, and neonatal intensive care unit admission rates did not differ significantly between the groups. CONCLUSION: The use of intrapartum ultrasound lessens the total number of digital examinations needed to be performed during labor and, consequently, the incidence of intrapartum fever and chorioamnionitis are reduced. No adverse effects on labor progression and short-term maternal or neonatal outcomes were noted.

Can assessing the angle of progression before labor onset assist to predict vaginal birth after cesarean?: A prospective cohort observational study.

OBJECTIVE: To assess whether pre-labor measurement of the angle of progression (AOP) can assist in predicting a successful vaginal birth after cesarean in women without a previous vaginal birth. METHODS: A prospective observational cohort study performed in a single tertiary center including women at term with a single previous cesarean delivery (CD), without prior vaginal births, who desire a trial of labor. Transperineal ultrasound was used to measure the AOP before the onset of labor. The managing staff in the delivery suite was blinded to the ultrasound measurements. Clinical data and delivery outcome were retrieved from medical records. The study was approved by the institutional ethics committee (KMC 0117-10). RESULTS: Of the 111 women included in the study, 67 (60.4%) had a successful vaginal birth after CD. Women were sonographically assessed at a median of 3 days [interquartile range (IQR) 1-3 days] prior to delivery. The median AOP was significantly narrower in women who eventually underwent a CD than in those who delivered vaginally (88°, IQR 78-96° vs. 99°, IQR 89-107°, respectively; p < .001). An AOP >98° (derived from a receiver operating characteristic curve) was associated with a successful vaginal birth after CD in 87.5% of women. Multivariable regression analysis demonstrated that each additional 1° in the AOP increases the chance for a successful vaginal birth after CD by 6%. CONCLUSIONS: Pre-labor AOP may be a useful sonographic tool for predicting vaginal birth after CD and can assist in consulting primiparous women with a prior CD opting for a trial of labor.

Predictors of uncommon location of sentinel nodes in endometrial and cervical cancers.

OBJECTIVE: Sentinel node mapping is widely used in the treatment of gynecologic cancers. The current study aimed to identify predictors of uncommon sentinel lymph node (SLN) locations. METHODS: The current study included women who were operated for endometrial or cervical cancer with attempted sentinel lymph node mapping during surgical staging. Data were collected from electronic charts. The pelvis and the external ilia and obturator basins were common node locations. Para-aortic, pre-sacral, common iliac, internal iliac, and parametrial nodes were considered uncommon locations. We conducted analyses stratified according to common, uncommon, and very uncommon (para-aortic, pre-sacral, parametrial) node location sites. RESULTS: A total of 304 women were enrolled in the current study; 15.8% had SLN in uncommon locations and 4.3% had very uncommon node locations. Body mass index (BMI) was a negative predictor for uncommon SLN locations (OR 0.88, p = 0.03). The use of either indocyanine green (ICG) or Tc99 & blue dye was an independent predictor for uncommon SLN locations (OR 8.24, p = 0.006). More recent surgeries and the presence of positive nodes were independent predictors for very uncommon node locations (OR 2.13, p = 0.011, and OR 9.3, p = 0.002, respectively). CONCLUSIONS: BMI, tracer type, surgical year, and positive nodes were independent predictors for uncommon SLN locations. These findings suggest that surgical effort, technique and experience may result in better identification of uncommon SLN locations.

Does sentinel lymph node biopsy in endometrial cancer surgery have an impact on the rate of adjuvant post operative pelvic radiation? An Israeli Gynecologic Oncology Group Study.

Objective: To compare the rates of post-operative radiotherapy between two methods of lymph nodes assessment during surgical staging for endometrial cancer (EC). Methods: We conducted a comparative study of all consecutive women with endometrial cancer who underwent sentinel lymph node detection and biopsy using blue dye and isotope scan (SLNB) at Kaplan Medical Center and patients from the IGOG database, who underwent staging lymphadenectomy (PLND). The primary outcome was the rate of adjuvant and therapeutic radiation. The secondary outcome was a comparison of disease-free survival (DFS) and overall survival (OS). Results: There were 138 patients in the SLNB group and 1022 women in the PLND group. The detection rate of SLN was 74% for unilateral detection and 54% for bilateral detection. In the PLND group 57% were high risk patients vs. 47% in SLNB group (p = 0.03). 43% of high-risk patients in the PLND group received adjuvant or therapeutic pelvic radiation vs. 28% of high-risk women in the SLNB arm (p = 0.017). No statistically significant difference in recurrence rates nor in death rates had been observed in the high-risk group patients. The 5-years survival in the high-risk PLND group was 80% and the recurrence rate was 19% vs. 75% 5-year survival and 14% recurrence in high-risk SLNB cohort, log-rank p = 0.82 for survival and long-rank p = 0.25 for recurrence. Conclusion: Endometrial cancer patients undergoing lymph node assessment by sentinel lymph node biopsy, receive less pelvic radiotherapy.

Predicting the rate of adjuvant postoperative chemo/radiation in cervical cancer with tumor size ≥2 cm and <4 cm: An Israeli Gynecologic Oncology Group study.

OBJECTIVE: Women with cervical cancer who undergo radical hysterectomy are often treated postoperatively with chemoradiation. Patient selection that minimizes adjuvant treatment is valuable. We compared two methods for predicting postoperative adjuvant treatment of women with tumor size ≥2 cm and <4 cm. STUDY DESIGN: This multicenter retrospective study included 272 women with tumor size ≥2 cm and <4 cm. A receiver operating characteristic curve (ROC) analysis was used to determine the optimal tumor cutoff size to predict adjuvant treatment. A second analysis compared the rate of adjuvant treatment between women with and without lymph vascular space involvement (LVSI). RESULTS: According to the ROC, the optimal cutoff value of tumor size for predicting adjuvant treatment was 2.95 cm (sensitivity 0.70, specificity 0.67). Tumors were ≥3.0 cm in 166 (61.0%) women. The rate of adjuvant treatment was higher in women with larger tumor diameter (73.8% vs. 47.9%, p < 0.0001). Of the 241 women with a LVSI record, LVSI was present in 81 (34%) women. Among women with LVSI, rates were higher of positive lymph nodes (41.0% vs 14.5%, p < 0.0001) and postoperative adjuvant treatment (83.3% vs. 53.7%, p < 0.001). Among women with tumor size ≥3.0 cm and LVSI, the rate of adjuvant treatment was 90.0%. In the multivariate analysis, both tumor size ≥3.0 cm and the presence of LVSI were independently associated with adjuvant treatment (OR 3.9, 95% CI 2.1-7.1; p < 0.0001 and OR 4.9, 95% CI 2.4-10.0; p < 0.0001, respectively). CONCLUSION: In women with cervical cancer who underwent radical hysterectomy, tumors ≥3 cm were associated with a >70% rate of adjuvant treatment, and LVSI was associated with a >80% rate. These data should be weighed in multidisciplinary consultation with radiation oncologists when deciding treatment strategy.

Minimally invasive approach in endometrial cancer with lower uterine segment involvement in stage ≥ II: A retrospective study.

OBJECTIVE: To compare oncological outcomes in women with lower uterine segment involvement (LUSI) in endometrial carcinoma (EC) stage ≥ II - staged by a minimally invasive surgery (MIS) versus laparotomy. STUDY DESIGN: A retrospective multi-center cohort study. Univariate analysis, Kaplan-Meier survival and Cox proportional hazard analysis were performed to compare between women staged by MIS and those staged by laparotomy. RESULTS: Over a median follow-up period of 3 years (interquartile range, 1.5-6 years) 212 women were included, 68 (32.1%) were surgically staged by MIS. Stages of disease did not vary between MIS and laparotomy and were 32.1%, 51.9%, and 16.0%, in stages II, III and IV - respectively. Adjuvant radiation and chemotherapy rate did not differ between groups. Overall recurrence rate was comparable (p = 0.084). Locoregional recurrence rate was higher in the MIS group odds ratio 2.17, 95% confidence interval 1.19-4.20). Overall and progression free survival were similar in both groups (log rank test p = 0.08 and p = 0.912 respectively). In Cox regression model adjusting for age, comorbidities, tumor grade, stage and adjuvant therapy, route of surgery (MIS vs. laparotomy) was not associated with overall survival (p = 0.169). CONCLUSIONS: In women with advanced EC and LUSI, although MIS is associated with locoregional recurrences, survival is comparable to laparotomy.

Up-regulation of L1CAM is linked to loss of hormone receptors and E-cadherin in aggressive subtypes of endometrial carcinomas.

Endometrial carcinomas (ECs) are classified into type 1 (less aggressive) and type 2 (aggressive) tumours that differ in genetic alterations. So far, reliable immunohistochemical markers that can identify patients with high risk for recurrence are rare. We have defined the expression of L1 cell adhesion molecule (L1CAM), a biomarker previously identified for EC, and compared its expression to oestrogen receptor (ER)/progesterone receptor (PR) and E-cadherin. We found that L1CAM was absent in normal endometrium and the vast majority of endometrioid ECs (type 1) but was strongly expressed in serous and clear-cell ECs, considered as type 2. 78/272 cases were identified as L1CAM-positive endometrioid ECs that were correlated with a poor prognosis. Strikingly, we observed an inverse relationship between L1CAM and ER/PR/E-cadherin expression in all ECs. In mixed ECs, composed of endometrioid (L1CAM(-) ER/PR(+) E-cadherin(+)) and clear-cell/serous (L1CAM(+) ER/PR(-) E-cadherin(-)), both phenotypes were co-expressed. In some of these cases L1CAM was up-regulated at the leading edge of the tumour, where ER/PR and E-cadherin expression were selectively lost. In EC cell lines treated with the epithelial-mesenchymal transition (EMT) inducer TGFbeta1, L1CAM and vimentin were strongly up-regulated, while E-cadherin expression was reduced. The treatment also resulted in an increased expression of the EMT transcription factor Slug and an enhanced cell invasion. Depletion of Slug by siRNA knockdown prevented both L1CAM up-regulation and enhanced cell invasion. According to our analysis, we suggest that L1CAM is a novel marker for EMT in ECs and that L1CAM-typing could identify endometrioid ECs that have type 2-like features and are at high risk for recurrence.

Intrapartum ultrasound at the initiation of the active second stage of labor predicts spontaneous vaginal delivery.

BACKGROUND: Longer duration of active pushing during labor is associated with a higher rate of operative delivery and an increased risk of maternal and neonatal complications. Although immediate pushing at complete dilatation is associated with lower rates of chorioamnionitis and postpartum hemorrhage, it is also associated with a longer duration of pushing. OBJECTIVE: This study aimed to evaluate whether fetal head station and position, as assessed by ultrasound at the beginning of the pushing process, can predict the mode of delivery and duration of pushing in nulliparous women. STUDY DESIGN: This prospective observational study included nulliparous women with neuraxial analgesia and complete cervical dilatation. The following sonographic parameters were assessed just before the beginning of the pushing process, at rest, and while pushing during contraction: head position, angle of progression, head-perineum distance, and head-symphysis distance. The change between rest and pushing was designated as delta angle of progression, delta head-perineum distance, and delta head-symphysis distance. The sonographic measurements and fetal head station assessed by vaginal examination were compared between women who had a spontaneous vaginal delivery to those who underwent an operative delivery, and between those who pushed for more or less than 1 hour. RESULTS: Of the 197 women included in this study, 166 (84.3%) had a spontaneous vaginal delivery, 31 (15.7%) had an operative delivery, 23 (11.6%) had a vacuum delivery, and 8 (4.0%) had a cesarean delivery. Spontaneous vaginal delivery and shorter duration of pushing (less than an hour) were significantly more common with a nonocciput posterior position (10.6% vs 47.3%; P<.005), a wider angle of progression, a shorter head-perineum distance and head-symphysis distance (both during rest and while pushing), and a lower fetal head station as assessed by digital vaginal examination. However, a logistic regression model revealed that only the angle of progression at rest and the delta angle of progression were independently associated with a spontaneous vaginal delivery with an area under the curve of 0.82 (95% confidence interval, 0.76-0.87; P<.0001) and 0.75 (95% confidence interval, 0.67-0.79; P<.0001), respectively. CONCLUSION: Ultrasound performed at the beginning of the active second stage of labor can assist in predicting the mode of delivery and duration of pushing and perform better than the traditional digital examination, with the angle of progression at rest and delta angle of progression being the best predictors.

The diagnosis of endometrial cancer in women with asymptomatic endometrial polyp does not increase survival rates: an israel gynecologic oncology group study.

OBJECTIVE: To compare outcomes of symptomatic and asymptomatic women with endometrial cancer and a preoperative diagnosis of an endometrial polyp. DESIGN: An Israel Gynecologic Oncology Group multi-center retrospective cohort study. METHODS: Of 635 patients with endometrial cancer and a preoperative diagnosis of an endometrial polyp who underwent surgery between 2002 and 2014 in one of 11 centers in Israel were divided into two groups according to the presence of bleeding symptoms. Outcome measures included recurrence-free survival, disease-specific survival and overall survival. Survival data were plotted according to the method of Kaplan and Meier and compared using the log-rank test. RESULTS: There were 513 symptomatic and 122 asymptomatic women with endometrial cancer and a preoperative diagnosis of an endometrial polyp. The median follow-up was 52 months (range 12-120 months). There were no differences between patients who experienced bleeding and those who did not in 5-year recurrence-free survival (85.2 % vs. 85.7 %; p=0.83, respectively), disease-specific survival (88.2 % vs. 89.2 %; p=0.71, respectively), or overall survival (80.2% vs. 78.4 %; p=0.97, respectively). CONCLUSION: The diagnosis of endometrial cancer in patients with asymptomatic endometrial polyps is not associated with improved outcomes as compared with patients with bleeding. In the absence of factors indicating a high risk of endometrial cancer, clinical and sonographic follow-up is the advised management strategy for these patients.