Expression of the miR-200 family in tumor tissue, plasma and urine of epithelial ovarian cancer patients in comparison to benign counterparts.

OBJECTIVE: Plasma, but also urine sample could represent a simple liquid biopsy for ovarian cancer biomarker detection. The miRNA-200 family has been shown to be dysregulated in ovarian cancer. The aim of this study was to isolate three members of miR-200 family from tumor tissue, plasma and urine of high-grade serous ovarian cancer patients in comparison with samples from patients with benign ovarian tumors. This is a methodological pilot study of a prospective ovarian cancer patient cohort investigating the potential of liquid biopsies and the role of miRNAs in ovarian cancer treatment. RESULTS: MiR-200a, miR-200b and miR-200c were isolated from samples of nine ovarian cancer patients and seven patients with benign ovarian tumor. The most significant finding is that all three miRNAs were detectable in all sample types. Tumor tissue and plasma, but not urine analysis was able to discriminate malignant and benign samples. A correlation between the miRNA-200 expression in urine and plasma was observed in malignant samples only. Plasma and urine with respect to miRNA detection show potential according to this study, but larger studies are needed to clarify the usefulness of these liquid biopsies in ovarian cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT02758652, May 2, 2016.

Association of cesarean scar defect with abnormal uterine bleeding: The results of a prospective study.

OBJECTIVE: To evaluate the relationship between cesarean scar defect and abnormal uterine bleeding at one year after cesarean section (CS). STUDY DESIGN: A prospective observational cohort study was conducted in 401 women who delivered by CS between January 2016 and January 2017. Women were screened for isthmocele with sonohysterography six months after CS and followed by electronic questionnaires at 12, 13 and 14 months after CS. The main outcome measure was the prevalence of postmenstrual spotting. Secondary outcome measures were the duration of menstrual bleeding, prevalence of postcoital bleeding, dyspareunia or dysmenorrhea, usage of painkillers, and absence from work or other activities. RESULTS: The response rate was 88 %. In the isthmocele group, the prevalence of postmenstrual spotting was 20.0 % compared to 8.3 % in women without isthmocele (OR 2.75 [95 % CI 1.39-5.44]; P = 0.004). Additionally, women with isthmocele reported more frequently postcoital bleeding (8.3 % vs. 2.4 %; OR 3.73 [95 % CI 1.18-11.83]; P = 0.026). The prevalence of postmenstrual spotting was even higher in the subgroup of large isthmoceles, (25.9 % vs. 9.5 %; (OR 3.34 [95 % CI 1.72-6.49]; P < 0.001). CONCLUSION: The prevalence of postmenstrual spotting among isthmocele patients was 20.0 %. Additionally, postmenstrual spotting was associated with the presence of isthmocele inquired at 1 year after CS.

Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2/ENGOT-ov24): a randomised, phase 2, superiority trial.

BACKGROUND: Platinum-based chemotherapy is the foundation of treatment for platinum-sensitive recurrent ovarian cancer, but has substantial toxicity. Bevacizumab and maintenance poly(ADP-ribose) polymerase (PARP) inhibitors both significantly improve efficacy versus standard therapy, primarily in terms of progression-free survival, and offer the potential for chemotherapy-free treatment. AVANOVA2 compared niraparib and bevacizumab versus niraparib alone as definitive treatment for platinum-sensitive recurrent ovarian cancer. METHODS: This open-label, randomised, phase 2, superiority trial in 15 university hospitals in Denmark, Sweden, Finland, Norway, and the USA enrolled women aged 18 years or older with measurable or evaluable high-grade serous or endometrioid platinum-sensitive recurrent ovarian cancer. Patients had to have an Eastern Cooperative Oncology Group performance status of 0-2, and had to have previously received platinum-containing therapy for primary disease but ≤1 prior non-platinum-containing regimen for recurrent disease. Previous treatment with bevacizumab or first-line maintenance PARP inhibitors was permitted. Eligible patients were randomly assigned 1:1 (by random permuted blocks with block sizes of two and four, no masking), stratified by homologous recombination deficiency status and chemotherapy-free interval, to receive once-daily oral niraparib 300 mg alone or with intravenous bevacizumab 15 mg/kg once every 3 weeks until disease progression. The primary endpoint was progression-free survival, assessed by the investigators in the intention-to-treat population after events in at least 62 patients. Safety was analysed in all patients who received at least one dose of study drug. This ongoing trial is registered with ClinicalTrials.gov, number NCT02354131. FINDINGS: Between May 23, 2016, and March 6, 2017, 97 patients were enrolled and randomly assigned: 48 to niraparib plus bevacizumab and 49 to single-agent niraparib. Median follow-up was 16·9 months (IQR 15·4-20·9). Niraparib plus bevacizumab significantly improved progression-free survival compared with niraparib alone (median progression-free survival 11·9 months [95% CI 8·5-16·7] vs 5·5 months [3·8-6·3], respectively; adjusted hazard ratio [HR] 0·35 [95% CI 0·21-0·57], p<0·0001). Grade 3 or worse adverse events occurred in 31 (65%) of 48 patients who received niraparib plus bevacizumab and 22 (45%) of 49 who received single-agent niraparib. The most common grade 3 or worse adverse events in both groups were anaemia (7 [15%] of 48 vs 9 [18%] of 49) and thrombocytopenia (5 [10%] vs 6 [12%]), and hypertension in the combination group (10 [21%] vs 0). Niraparib plus bevacizumab was associated with increased incidences of any-grade proteinuria (10 [21%] of 48 patients vs 0) and hypertension (27 [56%] of 48 vs 11 [22%] of 49) compared with niraparib alone. No treatment-related deaths occurred. INTERPRETATION: The efficacy observed with this chemotherapy-free combination of approved agents in women with platinum-sensitive recurrent ovarian cancer warrants further evaluation. A randomised phase 3 trial investigating niraparib plus bevacizumab versus chemotherapy plus bevacizumab in platinum-sensitive recurrent ovarian cancer is planned. FUNDING: Nordic Society of Gynaecological Oncology and Tesaro.

Cesarean scar defect: a prospective study on risk factors.

BACKGROUND: Cesarean scar defect (isthmocele) is a known complication after cesarean delivery. It has become more common due to a rising cesarean delivery rate. Isthmocele has been associated with various gynecological and obstetric problems such as uterine rupture, cesarean scar pregnancy, and bleeding disorders. OBJECTIVE: We sought to prospectively investigate factors associated with the risk for isthmocele assessed by sonohysterography. STUDY DESIGN: A prospective observational cohort study was conducted in 401 nonpregnant women who were recruited within 3 days of cesarean delivery. Women were evaluated with sonohysterography 6 months after cesarean delivery to detect a possible isthmocele. The ultrasonographer was blinded to any clinical information. The main outcome measure was the presence of isthmocele. Type of surgery (elective vs emergency), maternal background variables, and factors related to pregnancy, labor, and postoperative recovery were analyzed in relation to isthmocele. A logistic regression model was used to assess independent risk factors from univariate analysis. RESULTS: In all, 371 women were examined with sonohysterography resulting in a follow-up rate of 92.5%. The prevalence of isthmocele was 45.6%. Independent risk factors for isthmocele development were a history of gestational diabetes (odds ratio, 1.73; 95% confidence interval, 1.02-2.92; P = .042), previous cesarean delivery (odds ratio, 3.14; 95% confidence interval, 1.90-5.17; P < .001), and advanced maternal body mass index (odds ratio, 1.06; 95% confidence interval, 1.01-1.11; P = .012). Every additional unit of body mass index increased the risk of isthmocele by 6%. In the subgroup of emergency cesarean delivery, longer duration of active labor increased the risk for isthmocele (odds ratio, 1.06; 95% confidence interval, 1.01-1.11; P = .032). There was no statistically significant difference in prevalence between the groups of elective and emergency cesarean delivery (P = .898). CONCLUSION: Based on sonohysterographic examination, maternal body mass index, gestational diabetes, and previous cesarean deliveries are associated with an increased risk for incomplete healing of the uterine incision.

FAIMS analysis of urine gaseous headspace is capable of differentiating ovarian cancer.

AIM: We hypothesized that field asymmetric waveform ion mobility spectrometry (FAIMS) as a novel artificial olfactory technology could differentiate urine of women with malignant ovarian tumors from controls and women with benign tumors, based on previous findings on the ability of canine olfactory system to "smell" cancer. PATIENTS AND METHODS: Preoperative urine samples from 51 women with ovarian tumors, both benign and malignant, and from 18 women with genital prolapse, as controls, were collected. The samples were analyzed by FAIMS device. Data analysis was processed by quadratic data analysis (QDA) and linear discriminant analysis (LDA), and cross-validated using 10-fold cross-validation. RESULTS: Thirty-three women had malignant ovarian tumors, of which 18 were high-grade cancers. FAIMS distinguished controls from malignancies with the accuracy of 81.3% (sensitivity 91.2% and specificity 63.1%), and benign tumors from malignancies with the accuracy of 77.3% (sensitivity 91.5% and specificity 51.4%). Moreover, low grade tumors were also separated from high grade cancers and benign ovarian tumors with accuracies of 88.7% (sensitivity 87.8% and specificity 89.6%) and 83.9% (sensitivity 73.1% and specificity 92.9%), respectively. CONCLUSIONS: This proof of concept-study indicates that the FAIMS from urine has potential to discriminate malignant ovarian tumors from no tumor-bearing controls and benign tumors.

Comparison of transvaginal ultrasound and saline contrast sonohysterography in evaluation of cesarean scar defect: a prospective cohort study.

INTRODUCTION: The aim of this study was to investigate the prevalence of post-cesarean isthmocele and to measure agreement between transvaginal ultrasonography and saline contrast sonohysterography in assessment of isthmocele. MATERIAL AND METHODS: A prospective observational cohort study was carried out at Tampere University Hospital, Finland. Non-pregnant women delivered by cesarean section (n = 371) were examined with transvaginal ultrasonography (TVUS) and sonohysterography (SHG) six months after cesarean section. The main outcome measure was the prevalence of isthmocele using TVUS and SHG. Secondary outcome measures were characteristics of isthmocele. RESULTS: In all, 371 women were included. The prevalence of isthmocele was 22.4% based on TVUS and 45.6% based on SHG. Sensitivity and specificity for TVUS was 49.1 and 100%, respectively, when compared with SHG. Therefore, half of the defects (50.9%) diagnosed with SHG remained undiagnosed with TVUS. Bland-Altman analysis showed an underestimation of 1.1 mm (range 0.00-7.90) for TVUS compared with SHG, with 95% limits of agreement from -1.9 to 4.1 mm. CONCLUSIONS: This methodological study provides confirmatory data that TVUS and SHG are not in good agreement in the isthmocele diagnostics and the use of only TVUS may lead to an underestimation of the prevalence of isthmocele. Thus, SHG should be considered as a method of choice in diagnostics of isthmocele.

Robotic-Assisted Infrarenal Para-aortic Lymphadenectomy in Gynecological Cancers: Technique and Surgical Outcomes.

OBJECTIVE: Mini-invasive surgery has essentially replaced open laparotomy in surgery for endometrial and cervical carcinoma. Of the procedures needed for a complete staging, especially para-aortic lymphadenectomy (PALND) is challenging to perform. The present study was undertaken to investigate the technical and surgical outcomes of robotic-assisted PALND for gynecological cancers in the setting of a tertiary university hospital in Finland. METHODS: This was a retrospective chart review of 283 robotic-assisted para-aortic lymphadenectomies using the single-docking transperitoneal technique performed at the Department of Obstetrics and Gynecology of Tampere University Hospital, in 2009-2016. The primary outcome measure was the extent of the operation in terms of the height, that is, how often the level cranial to the inferior mesenteric artery (IMA) was achieved. The secondary outcome measures included operation time and surgical outcome. RESULTS: The majority of operations (n = 239 [84.4%]) were performed for endometrial carcinoma. The most common operation type was robotic-assisted hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy and PALND, which took a median of 3:38 hours or 218 minutes (range, 140-341 minutes) to perform. The high PALND (above the level of IMA) succeeded in 235 operations (83%). In the total cohort, the median number of para-aortic lymph nodes removed was 12 (range, 0-38), with a learning curve approximately more than 40 operations. Para-aortic lymph node metastases were found in 43 patients (15.2%). Seven conversions to laparotomy (2.5%) were done. The conversion and intraoperative complication rates were 2.5% and 3.5%, respectively, and postoperative complications was 18%, according to the classification of Clavien-Dindo. The median length of the postoperative hospital stay was 2 days (range, 1-8 days). CONCLUSIONS: Using the transperitoneal technique for PALND, the area between IMA and the renal veins can be reached in more than 80% of the operations, with a very low or 2.5% conversion rate.

Costs of Robotic-Assisted Versus Traditional Laparoscopy in Endometrial Cancer.

OBJECTIVES: The purpose of this study was to compare the costs of traditional laparoscopy and robotic-assisted laparoscopy in the treatment of endometrial cancer. METHODS AND MATERIALS: A total of 101 patients with endometrial cancer were randomized to the study and operated on starting from 2010 until 2013, at the Department of Obstetrics and Gynecology of Tampere University Hospital, Tampere, Finland. Costs were calculated based on internal accounting, hospital database, and purchase prices and were compared using intention-to-treat analysis. Main outcome measures were item costs and total costs related to the operation, including a 6-month postoperative follow-up. RESULTS: The total costs including late complications were 2160 &OV0556; higher in the robotic group (median for traditional 5823 &OV0556;, vs robot median 7983 &OV0556;, P < 0.001). The difference was due to higher costs for instruments and equipment as well as to more expensive operating room and postanesthesia care unit time. Traditional laparoscopy involved higher costs for operation personnel, general costs, medication used in the operation, and surgeon, although these costs were not substantial. There was no significant difference in in-patient stay, laboratory, radiology, blood products, or costs related to complications. CONCLUSIONS: According to this study, robotic-assisted laparoscopy is 37% more expensive than traditional laparoscopy in the treatment of endometrial cancer. The cost difference is mainly explained by amortization of the robot and its instrumentation.

Urinary Polyamines as Biomarkers for Ovarian Cancer.

OBJECTIVES: Elevated concentrations of polyamines have been found in urine of patients with malignant tumors, including ovarian cancer. Previous research has suffered from poorly standardized detection methods. Our liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is capable of simultaneous standardized analysis of most known polyamines. Liquid chromatography-tandem mass spectrometry has not previously been used in the differential diagnostics of ovarian tumors in postmenopausal women. MATERIALS AND METHODS: In this prospective study, postmenopausal women (n = 71) presenting with an adnexal mass and, as controls, women with genital prolapse or urinary incontinence scheduled for surgery (n = 22) were recruited in the study. For analysis of the polyamines, a morning urine sample was obtained before surgery. Preoperative serum CA125 concentrations were determined in the study group. RESULTS: Twenty-three women with benign and 37 with malignant ovarian tumors were eligible. Of all analyzed polyamines, only urinary N,N-diacetylspermine showed statistically significant differences between all groups except controls versus benign tumors. N,N-diacetylspermine was elevated in malignant versus benign tumors (P < 0.001), in high-grade versus low malignant potential tumors (P < 0.001), in stage III to IV versus stage I to II cancers (P < 0.001), and even in early-stage cancer (stage I-II) versus benign tumors (P = 0.017). N,N-diacetylspermine had better sensitivity (86.5%) but lower specificity (65.2%) for distinguishing benign and malignant ovarian tumors than CA125 with a cut-off value of 35 kU/L (sensitivity, 75.7%; specificity, 69.6%). CONCLUSIONS: Urinary N,N-diacetylspermine seems to be able to distinguish benign and malignant ovarian tumors as well as early and advanced stage, and low malignant potential and high-grade ovarian cancers from each other, respectively.

Vulvodynia-Younger Age and Combined Therapies Associate With Significant Reduction in Self-Reported Pain.

OBJECTIVES: Eight percent of women have vulvodynia (VD), a chronic pain disorder with unknown etiology. The aim of our study was to assess the efficacy of given VD treatments measured by numerical rating scale (NRS) for pain and patients' quality of life. MATERIALS AND METHODS: Study material consisted of a retrospective VD patient cohort (N = 70). Data were collected by postal questionnaires and review of the medical records. RESULTS: We report here a statistically significant reduction in NRS only with combination of therapies (median NRS before treatments 8 vs median NRS 4 after treatments, p < .001) but not with any individual therapy alone, i.e., physiotherapy, topical medications, oral pharmaceutical therapy, sexual counseling by a trained nurse, sacral neuromodulation, and laser treatment or surgery. Older age (>30) and frequent (≥6) outpatient clinic visits associated with a significantly minor reduction in NRS (p = .03 and p = .04, respectively). CONCLUSIONS: The results of this retrospective study suggest that an effective, multimodality-based treatment is most beneficial for VD patients and VD at older age may represent a subtype more resistant to therapy.

Comparison of lifestyle, hormonal and medical factors in women with sporadic and Lynch syndrome-associated endometrial cancer: A retrospective case-case study.

Data available on lifestyle-associated hormonal and medical factors among endometrial cancer (EC)-affected women who carry the Lynch Syndrome (LS) mutation is limited. The aim of the present retrospective case study was to compare the reproductive and medical history, as well as lifestyle-associated factors, among patients with LS and sporadic EC. The study population consisted of 50 verified germline mismatch repair (MMR) gene mutation carriers diagnosed with EC, and 110 sporadic EC patients. Data were collected using postal questionnaires. Apart from the mean age at the time of the EC diagnosis (LS, 48.7 years compared with sporadic patients, 55.2 years; P<0.0001), the characteristics of sporadic and LS EC patients were similar with regard to body mass index (BMI) at age 18, 40 or at the time of the survey, and smoking and alcohol consumption. LS women reported a significantly lower rate of spontaneous abortion (P=0.043) and also more frequent use of contraceptives (P=0.004). The prevalence of co-morbidities, including diabetes, atherosclerosis, hypercholesterolemia and hypertension, was similar between the LS and the sporadic groups. A trend for a higher prevalence of endometriosis among mutation carriers was detected (16.0 vs. 8.1%, P=0.137). As anticipated, the prevalence of gastrointestinal tract, urinary tract and ovarian cancer was higher among the LS women (P<0.0001, P=0.006 and P=0.056, respectively). Co-morbidity and lifestyle-associated factors appeared to be comparable among patients with LS and sporadic EC. The reported difference in the use of contraceptives warrants further investigation. Future studies are also required to address the possible association between LS and endometriosis.

Sentinel Node and Ovarian Tumors: A Series of 20 Patients.

OBJECTIVE: Intraoperative detection of ovarian sentinel nodes has been shown to be feasible. We examined the detection rate and locations of sentinel nodes in patients with ovarian tumors. We also aimed to assess the reliability of sentinel node method in predicting regional lymph node metastasis. METHODS: Twenty patients scheduled for laparotomy because of a pelvic mass were recruited to the study. In the beginning of the laparotomy, radioisotope and blue dye were injected under the serosa next to the junction of the ovarian tumor and suspensory ligament. The number and locations of the hot and/or blue nodes/spots were recorded during the operation. If the tumor was malignant according to the frozen section, systematic lymphadenectomies were performed, the sentinel nodes sampled separately, and their status compared with other regional lymph nodes. RESULTS: Eleven patients had a right-sided ovarian tumor, 7 patients a left-sided tumor, and 2 patients had bilateral tumors. A median of 2 sentinel nodes/locations per patient (range, 1-3) were found. Sixty percent of all sentinel nodes were located in the para-aortic region only, compared with 30% in both para-aortic and pelvic areas and 10% in pelvic area only. Both unilateral and bilateral locations were found. In 83% of the cases with more than 1 sentinel node location, they were located in separate anatomical regions. In 3 patients, systematic lymphadenectomies were performed. One of them had nodal metastases in 2 regions and also a metastasis in 1 of her 2 sentinel nodes in 1 of those regions. CONCLUSIONS: In patients with ovarian tumor(s), the detection of sentinel nodes is feasible. They are located in different anatomic areas both ipsilaterally and contralaterally, although most of them are found in the para-aortic region. The reliability of the sentinel node concept should be evaluated in the framework of a multicenter trial.

Robotic-assisted vs traditional laparoscopic surgery for endometrial cancer: a randomized controlled trial.

BACKGROUND: Previous studies comparing robotic-assisted laparoscopic surgery to traditional laparoscopic or open surgery in gynecologic oncology have been retrospective. To our knowledge, no prospective randomized trials have thus far been performed on endometrial cancer. OBJECTIVE: We sought to prospectively compare traditional and robotic-assisted laparoscopic surgery for endometrial cancer. STUDY DESIGN: This was a randomized controlled trial. From December 2010 through October 2013, 101 endometrial cancer patients were randomized to hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy either by robotic-assisted laparoscopic surgery or by traditional laparoscopy. The primary outcome measure was overall operation time. The secondary outcome measures included total time spent in the operating room, and surgical outcome (number of lymph nodes harvested, complications, and recovery). The study was powered to show at least a 25% difference in the operation time using 2-sided significance level of .05. The differences between the traditional laparoscopy and the robotic surgery groups were tested by Pearson χ2 test, Fisher exact test, or Mann-Whitney test. RESULTS: In all, 99 patients were eligible for analysis. The median operation time in the traditional laparoscopy group (n = 49) was 170 (range 126-259) minutes and in the robotic surgery group (n = 50) was 139 (range 86-197) minutes, respectively (P < .001). The total time spent in the operating room was shorter in the robotic surgery group (228 vs 197 minutes, P < .001). In the traditional laparoscopy group, there were 5 conversions to laparotomy vs none in the robotic surgery group (P = .027). There were no differences as to the number of lymph nodes removed, bleeding, or the length of postoperative hospital stay. Four (8%) vs no (0%) patients (P = .056) had intraoperative complications and 5 (10%) vs 11 (22%) (P = .111) had major postoperative complications in the traditional and robotic surgery groups, respectively. CONCLUSION: In patients with endometrial cancer, robotic-assisted laparoscopic surgery was faster to perform than traditional laparoscopy. Also total time spent in the operation room was shorter in the robotic surgery group and all conversions to laparotomy occurred in the traditional laparoscopy group. Otherwise, the surgical outcome was similar between the groups. Robotic surgery offers an effective and safe alternative in the surgical treatment of endometrial cancer.

Implementing robotic surgery to gynecologic oncology: the first 300 operations performed at a tertiary hospital.

OBJECTIVE: To investigate the initial experience with robotic-assisted laparoscopic surgery in gynecologic oncology. DESIGN: A retrospective survey. SETTING: Tertiary referral center. POPULATION: The first 300 patients operated on using robotic assistance at the Department of Obstetrics and Gynecology of Tampere University Hospital, from March 2009 through January 2013. METHODS: Retrospective patient chart review. MAIN OUTCOME MEASURES: The primary outcome measure was the learning curve events, and the complication and conversion rates were secondary outcome measures. RESULTS: The commonest type of operation was hysterectomy, bilateral salpingoophorectomy and pelvic lymphadenectomy (LH + BSO + PLND, n = 89), followed by the same procedure amended by para-aortic lymphadenectomy (PALND, n = 74), type II radical hysterectomy (n = 24), and PLND + PALND ± omentectomy (n = 15). A learning curve was most evident for LH + BSO + PLND: whereas the median operative time of all 89 operations was 167 min (range 403-104), it was 260 (range 403-135) and 153 (range 247-104) min in the case of the first and last 20 operations, respectively. The learning curve was short, or 10 procedures. A learning curve was also seen for the preoperative time in the operation room and for the number of lymph nodes harvested. The median blood loss during all 300 operations was 100 mL (range 5-3200). The median postoperative hospital stay was 1 day. The conversion rate was 4.0%, and the complication rate 19.3% (major in 9%). CONCLUSION: The learning curve of robotic-assisted laparoscopic surgery appears to be short, or 10 operations. Robotic-assisted procedures seem to offer a safe and useful alternative to traditional techniques.

Gynecologic Cancer InterGroup (GCIG) consensus review: uterine and ovarian leiomyosarcomas.

OBJECTIVES: The Gynecologic Cancer InterGroup aimed to provide an overview of uterine and ovarian leiomyosarcoma management. METHODS: Published articles and author experience were used to draft management overview. The draft manuscript was circulated to international members of the Gynecologic Cancer InterGroup for review and comment, and appropriate revisions were made. RESULTS: The approach to management of uterine and ovarian leiomyosarcoma management is reviewed. CONCLUSIONS: Uterine and ovarian leiomyosarcomas are rare and aggressive cancers that require specialized expertise for optimal management.

Endoglin, VEGF, and its receptors in predicting metastases in endometrial carcinoma.

Preoperative evaluation of the risk for metastases in endometrial carcinoma is challenging. The growth of new vessels, angiogenesis, is important for tumor growth and purported to be involved in the metastatic process. The aim of this study was to evaluate the significance of preoperative serum levels and immunohistochemical expression of angiogenic markers in predicting a metastasized disease. Preoperative sera from 98 consecutive women presenting with endometrial carcinoma were collected. Serum concentrations of VEGF, sFLT1, and CD105 were assessed by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to assess the expression of CD105, VEGF, FLT1, and KDR. The results were correlated to the presence of metastases, presence of deep (≥50%) myometrial invasion, and the histological grade of the tumor. Tumors with other than endometrioid histology were excluded. Of the 80 evaluable patients, 11 had a metastasized disease. The serum concentration of VEGF was higher in the group with metastases than in the group without metastases (median [range], 743 pg/mL [546-1,183 pg/mL] vs. 383 pg/mL [31-1,524 pg/mL], p < 0.001, respectively). In the multivariable analysis, the concentration of VEGF was the sole independent, albeit weak predictive factor for the presence of metastases (odds ratio, 1.004, 95% confidence interval, 1.002-1.007; p = 0.001). The immunohistochemical expression of the markers was not associated with any of the clinicopathological features of the tumors. The results of the present study suggest that preoperative serum VEGF concentration correlates with the presence of metastases in endometrioid endometrial carcinoma.

Predictive value of serum human epididymis protein 4 and cancer antigen 125 concentrations in endometrial carcinoma.

OBJECTIVE: The purpose of this study was to evaluate the performance of preoperative serum levels of human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) in the prediction of the presence of metastases in endometrial carcinoma. STUDY DESIGN: Preoperative sera were collected from 98 women with a diagnosis of endometrial carcinoma. The concentrations of HE4 and CA125 were assessed by enzyme-linked immunosorbent assay and correlated with the results of the final histopathologic report. RESULTS: Fourteen patients had metastases (≥stage IIIA, International Federation of Gynecology and Obstetrics 2009 classification). The serum concentrations of HE4 and CA125 were higher in the group with metastases than in the group without metastases (median [interquartile range], 148.6 pmol/L [71.6-219.1 pmol/L] vs 77.2 pmol/L [52.9-99.3 pmol/L]; P = .001; and 20.0 U/mL [10.1-70.8 U/mL] vs 4.3 U/mL [2.9-10.4 U/mL]; P < .001, respectively). By a multivariate analysis, the combination of HE4 and CA125 (a risk score algorithm) was the only predictive factor for the presence of metastases (odds ratio, 21.562; 95% confidence interval, 5.472-84.963; P < .001), and the grade was the predictor for a deep (≥50%) myometrial invasion by the tumor (odds ratio, 2.005; 95% confidence interval, 1.123-3.581; P = .019). The sensitivity, specificity, positive predictive value, and negative predictive value for the combination of the markers to predict the presence of metastases were 71.4%, 89.5%, 55.6%, and 94.4%, respectively. CONCLUSION: A combination of preoperative HE4 and CA125 seems to be a better predictor of metastatic disease than either 1 alone in endometrial carcinoma.

The preoperative assessment of deep myometrial invasion by three-dimensional ultrasound versus MRI in endometrial carcinoma.

OBJECTIVE: To evaluate the usefulness of three-dimensional ultrasound (3D US), magnetic resonance imaging (MRI) and three-dimensional power Doppler angiography (3D-PDA) in the preoperative assessment of myometrial invasion in endometrial carcinoma. DESIGN: A prospective observational study. SETTING: University hospital. POPULATION: Twenty consecutive patients diagnosed with endometrial carcinoma. METHODS: Preoperative 3 T MRI and 3D US examinations were performed, and the depth of myometrial invasion was assessed. The vascularity indices, vascularization index, flow index and vascularization flow index, were calculated by 3D-PDA. MAIN OUTCOME MEASURES: The results were compared with the final histopathology report after a surgical staging. RESULTS: In detecting deep myometrial invasion, the sensitivity of 3D US, MRI and their combination was 50, 91.7 and 100%, respectively. The specificity was 87.5, 50 and 50%, respectively. There were no significant differences in the 3D-PDA vascularity indices between the two groups. CONCLUSIONS: MRI appears to be more sensitive than 3D US in detecting deep invasion, while 3D US has a better specificity.