Health-related quality of life in patients with newly diagnosed advanced ovarian cancer treated with niraparib vs placebo: Results from the phase 3 randomized PRIMA/ENGOT-OV26/GOG-3012 trial.

OBJECTIVE: To assess patient-reported health-related quality of life (HRQoL) in patients with ovarian cancer (OC) who received niraparib as first-line maintenance therapy. METHODS: PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) enrolled patients with newly diagnosed advanced OC who responded to first-line platinum-based chemotherapy. Patients were randomized (2:1) to niraparib or placebo once daily in 28-day cycles until disease progression, intolerable toxicity, or death. HRQoL was assessed as a prespecified secondary end point using patient-reported responses to the European Organisation for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30), the EORTC QLQ Ovarian Cancer Module (EORTC QLQ-OV28), the Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI), and EQ-5D-5L questionnaires. Assessments were collected at baseline and every 8 weeks (±7 days) for 56 weeks, beginning on cycle 1/day 1, then every 12 weeks (±7 days) thereafter while the patient received study treatment. RESULTS: Among trial participants (niraparib, n = 487; placebo, n = 246), PRO adherence exceeded 80% for all instruments across all cycles. Patients reported no decline over time in HRQoL measured via EORTC QLQ-C30 Global Health Status/QoL and FOSI overall scores. Scores for abdominal/gastrointestinal symptoms (EORTC QLQ-OV28) and nausea and vomiting, appetite loss, and constipation (EORTC QLQ-C30) were higher (worse symptoms) in niraparib-treated patients than placebo-treated patients; except for constipation, these differences resolved over time. Patients did not self-report any worsening from baseline of fatigue, headache, insomnia, or abdominal pain on questionnaires. CONCLUSIONS: Despite some early, largely transient increases in gastrointestinal symptoms, patients with OC treated with niraparib first-line maintenance therapy reported no worsening in overall HRQoL.

Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer.

BACKGROUND: Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a BRCA mutation. The effect of combining maintenance olaparib and bevacizumab in patients regardless of BRCA mutation status is unknown. METHODS: We conducted a randomized, double-blind, international phase 3 trial. Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and were having a response after first-line platinum-taxane chemotherapy plus bevacizumab. Patients were eligible regardless of surgical outcome or BRCA mutation status. Patients were randomly assigned in a 2:1 ratio to receive olaparib tablets (300 mg twice daily) or placebo for up to 24 months; all the patients received bevacizumab at a dose of 15 mg per kilogram of body weight every 3 weeks for up to 15 months in total. The primary end point was the time from randomization until investigator-assessed disease progression or death. RESULTS: Of the 806 patients who underwent randomization, 537 were assigned to receive olaparib and 269 to receive placebo. After a median follow-up of 22.9 months, the median progression-free survival was 22.1 months with olaparib plus bevacizumab and 16.6 months with placebo plus bevacizumab (hazard ratio for disease progression or death, 0.59; 95% confidence interval [CI], 0.49 to 0.72; P<0.001). The hazard ratio (olaparib group vs. placebo group) for disease progression or death was 0.33 (95% CI, 0.25 to 0.45) in patients with tumors positive for homologous-recombination deficiency (HRD), including tumors that had BRCA mutations (median progression-free survival, 37.2 vs. 17.7 months), and 0.43 (95% CI, 0.28 to 0.66) in patients with HRD-positive tumors that did not have BRCA mutations (median progression-free survival, 28.1 vs. 16.6 months). Adverse events were consistent with the established safety profiles of olaparib and bevacizumab. CONCLUSIONS: In patients with advanced ovarian cancer receiving first-line standard therapy including bevacizumab, the addition of maintenance olaparib provided a significant progression-free survival benefit, which was substantial in patients with HRD-positive tumors, including those without a BRCA mutation. (Funded by ARCAGY Research and others; PAOLA-1 ClinicalTrials.gov number, NCT02477644.).

Primary HPV screening for cervical cancer: Results after two screening rounds in a regional screening program in Finland.

INTRODUCTION: Since 2012, cervical cancer screening has been conducted with a primary high-risk human papillomavirus (hrHPV) test and conventional cytology triage in the city of Tampere, Finland. The women who were screened with the hrHPV test in 2012 were invited to participate in the second screening round in 2017. The aim of the present report was to compare the number of colposcopy referrals and the number of histological high-grade squamous intraepithelial lesion (HSIL)+ (cervical intraepithelial neoplasia [CIN2+]) lesions between the first and second screening rounds of women of a specific age group who were screened twice with the hrHPV test. MATERIAL AND METHODS: The primary hrHPV test used was the RealTime hrHPV PCR assay by Abbott. Women with a positive hrHPV test and cytology triage equal to or worse than low-grade squamous intraepithelial lesion or atypical glandular cells, favor neoplasia, were directly referred to colposcopy, whereas hrHPV-positive women with a negative or equivocal cytology triage were re-screened after approximately 12-16 months. hrHPV-negative women were scheduled for re-screening after 5 years. The present report focuses on the cohort of women who were screened twice with the hrHPV test, who were 35-55 years old in 2012, and 40-60 years old in 2017. RESULTS: In all, 8076 women were invited for HPV screening in 2012 and 8331 women were invited for the second round 5 years later, with attendance rates of 70% and 71%, respectively. Of the women who were screened in 2012, 4571 (69%) belonged to the 35- to 55-year age cohort. In 2017, 4807 (73%) of the women aged 40-60 years participated in the screening. In this cohort, 185 (4.0%) colposcopies were performed in the first screening round, compared with 139 (2.9%) in the second round, and the colposcopy rate was 29% smaller in the second round (P = .002). The number of histological HSIL+ cases was 38 (0.8%) during the first screening round and 29 (0.6%) during the second round (P = .220). CONCLUSIONS: In the setting of routine organized cervical cancer screening, the initially high colposcopy rate associated with primary HPV screening seems to level off at the second screening round in women who were screened twice with an hrHPV test.

Descriptive study on subjective experience of genetic testing with respect to relationship, family planning and psychosocial wellbeing among women with lynch syndrome.

BACKGROUND: Due to increased risk of endometrial and ovarian cancer, women belonging to known Lynch Syndrome (LS) families are recommended to undergo germline testing. Current practice in Finland is to offer counselling to women with pathogenic variant and advocate risk-reducing surgery (RRS) after completion of childbirth. The present study aimed to clarify the impacts of positive germline testing on family planning and reproductive decisions of these women, which are relatively unknown. METHODS: Seventy-nine carriers of germline MMR gene pathogenic variant (path_MMR) were identified from the Finnish LS Registry as having genetic testing performed before the age of 45 years and not having undergone hysterectomy or oophorectomy. These women were sent a questionnaire concerning family planning, intimate relationships and psychosocial wellbeing. RESULTS: Thirty-five women (44.3%) responded. Parity of path_MMR carriers (2.1) was slightly higher than parity among Finnish women in general (1.8). No significant differences were found between parity, number of induced abortions or sterilizations before and after genetic testing. Only minority of subjects reported any influence on family planning (20%) or negative impact on feminine self and body image (14%). CONCLUSIONS: The positive germline testing does not seem to have a major negative impact on family planning, intimate relationships or feminine self and body image. According to the open comments, counselling, supportive and empathic attitude of the professionals seem to have a significant impact on this. These results are a valuable addition to the counselling of LS women at reproductive age.

Characterization of immunoreactivity with whole-slide imaging and digital analysis in high-grade serous ovarian cancer.

Ovarian cancer is the most lethal of gynecological cancers with 5-year survival rate of ca. 45%. The most common histologic subtype is high-grade serous carcinoma, which typically is presented with advanced stage and development of chemoresistance. Therefore, new treatment options, including immunotherapies, are needed. Understanding the features of the immune cell populations in the tumor microenvironment is essential for developing personalized treatments and finding predictive biomarkers. Digital image analysis may enhance the accuracy and reliability of immune cell infiltration assessment in the tumor microenvironment. The aim of this study was to characterize tumor microenvironment in a retrospective cohort of high-grade serous carcinoma samples with whole-slide imaging and digital image analysis. Formalin-fixed paraffin-embedded high-grade serous carcinoma tumor tissue samples (n = 67) were analyzed for six immunohistochemical stainings: CD4, CD8, FoxP3, granzyme B, CD68, and CD163. The stained sample slides were scanned into a digital format and assessed using QuPath 0.1.2 and ImageJ software. Staining patterns were associated with clinicopathological data. The higher numbers of intraepithelial CD8+, CD163+, and granzyme B+ immune cells were associated with survival benefit when analyzed individually, while high levels of both CD8+ and granzyme B+ tumor-infiltrating lymphocytes were an independent prognostic factor in the Cox multivariate regression analysis (median progression-free survival; hazard ratio = 0.287, p = 0.002). Specimens taken after administration of neoadjuvant chemotherapy presented with lower FoxP3+ tumor-infiltrating lymphocyte density (Fisher's exact test, p = 0.013). However, none of the studied immunomarkers was associated with overall survival or clinical factors. Tumors having high amount of both intraepithelial CD8+ and granzyme B+ tumor-infiltrating lymphocytes showed better progression-free survival, possibly reflecting an activated immune state in the tumor microenvironment. The combined positivity of CD8 and granzyme B warrants further investigation with respect to predicting response to immune therapy. Neoadjuvant chemotherapy may have an effect on the tumor microenvironment and therefore on the response to immuno-oncologic or chemotherapy treatments.

Expectations and preferences of patients with primary and relapsed ovarian cancer to maintenance therapy: A NOGGO/ENGOT-ov22 and GCIG survey (Expression IV).

BACKGROUND: Maintenance therapy induces remission and prolongs disease free interval in primary and recurrent ovarian disease. For the treatment decision making process, aspects of quality of life and patients' preferences are crucial, despite the fact that scientific data are lacking. Therefore, we conducted this European-wide study in patients with ovarian cancer. METHODS: A 25 item questionnaire was provided to ovarian cancer patients via the internet or as a paper version in 10 European countries (Austria, Belgium, France, Germany, Italy, Romania, Slovenia, Finland, Turkey, and Spain). Data recorded were demographics, tumor stage, therapy after firstline and recurrent disease, preferences for administration, and expectations concerning maintenance therapy. RESULTS: Overall, 1954 patients participated from September 2013 to March 2016; 42% had recurrent disease. Most patients (98%) with primary epithelial ovarian cancer underwent surgery followed by chemotherapy (91%). Almost one-third of participants (29%) were receiving maintenance therapy whereas 45% had only heard of it. For 70% of patients with primary epithelial ovarian cancer, they heard about maintenance therapy from their doctor, 10% heard about maintenance therapy from other patients, and 8% from the internet. The main source of information about maintenance therapy in patients with epithelial ovarian cancer relapse was from the treating physician (72%), from other patients (8%), and from the internet (7%). For patients undergoing maintenance therapy, the four most disturbing adverse effects were polyneuropathy (37%), nausea (36%), hair loss (34%), and vomiting (34%). The main objective of maintenance treatment, as perceived by patients, was to increase the chances of cure (73%), improvement in quality of life (47%), and delay in tumor growth (37%). Many patients were willing to undergo maintenance therapy until tumor progression (38%) and 39% would prefer oral administration. No significant differences were detected in the cross country subanalysis regarding expectations of maintenance therapy and patients with primary or relapsed ovarian cancer. CONCLUSION: Patients with ovarian cancer were willing to accept maintenance therapy of prolonged duration and preferred oral administration. There is still a gap between the efficacy of maintenance therapy and patient expectations. Patients need more information on the adverse effects and treatment goals of maintenance therapy to avoid misunderstandings.

In Vitro Vascular Network Modified to Function as Culture Platform and Angiogenic Induction Potential Test for Cancer Cells.

Drug treatments have been designed to inhibit tumor angiogenesis in hope of stopping tumor growth. However, not all tumor types respond to this type of treatment. A screening method which identifies angiogenesis inducing cancer types would help predict the efficacy of angiogenesis-inhibiting drugs for the patients. Our goal is to develop (1) a cell assay to assess the angiogenic induction potential of patient-derived tumor cells, and (2) a protocol for culturing cancer cells on a vascular platform. We optimized the media composition and seeding density of cells (hASC, HUVEC, and cancer cells) to 48-, 96-, and even 384-well plate sizes to allow vascular formation and cancer cell proliferation and subsequent analysis with high throughput. The angiogenic induction potential of patient-derived cancer cells was investigated by quantifying the formation of tubular structures and the drug response of cancer cells grown on a vascular platform was evaluated using gene expression and cell viability (WST-1) assay. Immunocytochemistry was performed with von Willebrand factor, collagen IV, CD44, cytokeratin 19 and ALDH1A1. The angiogenic induction potential test was shown to be responsive to the induction of angiogenesis by cancer cells. The responses of cancer cells were different when grown on a vascular platform or on plastic, seen in gene expression level and viability results. These two protocols are promising novel tools for aiding the selection of efficient cancer drugs for personalized medicine and as an alternative cancer cell culture platform.

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.

Robot-assisted approach to cervical cancer (RACC): an international multi-center, open-label randomized controlled trial.

BACKGROUND: Radical hysterectomy with pelvic lymphadenectomy represents the standard treatment for early-stage cervical cancer. Results from a recent randomized controlled trial demonstrate that minimally invasive surgery is inferior to laparotomy with regards to disease-free and overall survival. PRIMARY OBJECTIVE: To investigate the oncologic safety of robot-assisted surgery for early-stage cervical cancer as compared with standard laparotomy. STUDY HYPOTHESIS: Robot-assisted laparoscopic radical hysterectomy is non-inferior to laparotomy in regards to recurrence-free survival with the advantage of fewer post-operative complications and superior patient-reported outcomes. TRIAL DESIGN: Prospective, multi-institutional, international, open-label randomized clinical trial. Consecutive women with early-stage cervical cancer will be assessed for eligibility and subsequently randomized 1:1 to either robot-assisted laparoscopic surgery or laparotomy. Institutional review board approval will be required from all participating institutions. The trial is coordinated from Karolinska University Hospital, Sweden. MAJOR INCLUSION/EXCLUSION CRITERIA: Women over 18 with cervical cancer FIGO (2018) stages IB1, IB2, and IIA1 squamous, adenocarcinoma, or adenosquamous will be included. Women are not eligible if they have evidence of metastatic disease, serious co-morbidity, or a secondary invasive neoplasm in the past 5 years. PRIMARY ENDPOINT: Recurrence-free survival at 5 years between women who underwent robot-assisted laparoscopic surgery versus laparotomy for early-stage cervical cancer. SAMPLE SIZE: The clinical non-inferiority margin in this study is defined as a 5-year recurrence-free survival not worsened by >7.5%. With an expected recurrence-free survival of 85%, the study needs to observe 127 events with a one-sided level of significance (α) of 5% and a power (1-ß) of 80%. With 5 years of recruitment and 3 years of follow-up, the necessary number of events will be reached if the study can recruit a total of 768 patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Trial launch is estimated to be May 2019 and the trial is estimated to close in May 2027 with presentation of data shortly thereafter. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (NCT03719547).

Implementation of HPV-based cervical cancer screening in an organised regional screening programme: 3 years of experience.

OBJECTIVE: The aim of this study was to evaluate the performance of human papillomavirus (HPV)-based screening in the framework of an organised cervical cancer screening programme. METHODS: A total of 46 708 women aged 35-60 years invited to the regional cervical cancer screening programme from 1 January 2012, to 31 December 2014, were enrolled. Overall, 17 770 women were screened by the Abbot RealTime hrHPV test with cytology triage and 15 605 were screened by conventional (Papanicolaou, Pap) cytology. In both groups, women with at least low-grade squamous intraepithelial lesions were referred directly for colposcopy, whereas HPV-positive women with borderline or normal cytology were invited to intensified screening in the following year. In the Pap group, the indication for intensified follow-up was borderline cytology. RESULTS: The attendance rate was similar in the HPV and Pap groups (72% and 71%, respectively). Overall, 6.0% of women in the HPV group vs 6.4% in the Pap group were referred to intensified follow-up (relative risk 0.94, 95% confidence interval [CI]: 0.87-1.03). At the index screening years, the relative sensitivity of the HPV test with cytology triage vs conventional screening was 1.64 (95% CI: 1.05-2.55) for CIN2+ and 2.06 (95% CI: 1.17-3.41) for CIN3+. The specificity of the hrHPV test with cytology triage for CIN2+ and CIN3+ was equal to that of the Pap screening (99.2% vs 99.2% for CIN2+ and 99.1% vs 99.1% for CIN3+). CONCLUSIONS: Due to its high sensitivity and specificity, primary hrHPV testing with cytology triage seems to be acceptable for cervical cancer screening in an organised setting.

Ovarian tumours of different histologic type and clinical stage induce similar changes in lipid metabolism.

BACKGROUND: Previous results obtained from serum samples of late-stage, high-grade serous ovarian carcinoma patients showed large alterations in lipid metabolism. To validate and extend the results, we studied lipidomic changes in early-stage ovarian tumours. In addition to serous ovarian cancer, we investigated whether these changes occur in mucinous and endometrioid histological subtypes as well. METHODS: Altogether, 354 serum or plasma samples were collected from three centres, one from Germany and two from Finland. We performed lipidomic analysis of samples from patients with malignant (N = 138) or borderline (N = 25) ovarian tumours, and 191 controls with benign pathology. These results were compared to previously published data. RESULTS: We found 39 lipids that showed consistent alteration both in early- and late-stage ovarian cancer patients as well as in pre- and postmenopausal women. Most of these changes were already significant at an early stage and progressed with increasing stage. Furthermore, 23 lipids showed similar alterations in all investigated histological subtypes. CONCLUSIONS: Changes in lipid metabolism due to ovarian cancer occur in early-stage disease but intensify with increasing stage. These changes occur also in other histological subtypes besides high-grade serous carcinoma. Understanding lipid metabolism in ovarian cancer may lead to new therapeutic and diagnostic alternatives.

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.

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.

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.

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.

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.

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.

Endometrial cancer risk factors among Lynch syndrome women: a retrospective cohort study.

BACKGROUND: Lynch syndrome (LS) is associated with a significant lifetime risk of endometrial cancer (EC). There are limited data on factors modifying the EC risk in LS patients. METHODS: The study cohort included 136 LS mutation-positive women. Exposure data were collected by postal questionnaires. Cox regression model was used to estimate the associations between lifestyle, hormonal, reproductive and medical factors and the risk of EC. RESULTS: Increased EC risk was associated with type II diabetes and hypercholesterolaemia in univariable (HR 3.21, (95% CI 1.34-7.78), P=0.009 and HR 2.08, (95% CI 1.11-3.90), P=0.02; respectively) and with diabetes and duration of hormone replacement therapy (HRT) in multivariable analysis (HR 4.18 (95% CI 1.52-11.52), P=0.006 and HR 1.07 (95% CI 1.02-1.13), P=0.010; respectively). CONCLUSIONS: Prevention of diabetes and avoiding long-duration HRT are potential targets for reduction of EC risk in women with LS.