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Background Disordered fetal adrenal steroidogenesis can cause marked clinical effects including virilization of female fetuses. In postnatal life, adrenal disorders can be life-threatening due to the risk of adrenal crisis and must be carefully managed. However, testing explicit adrenal steroidogenic inhibitory effects of therapeutic drugs is challenging due to species-specific characteristics, and particularly the impact of adrenocorticotropic hormone (ACTH) stimulation on drugs targeting steroidogenesis has not previously been examined in human adrenal tissue. Therefore, this study aimed to examine the effects of selected steroidogenic inhibitors on human fetal adrenal (HFA) steroid hormone production under basal and ACTH-stimulated conditions. Methods This study used an established HFA ex vivo culture model to examine treatment effects in 78 adrenals from 50 human fetuses (gestational weeks 8–12). Inhibitors were selected to affect enzymes critical for different steps in classic adrenal steroidogenic pathways, including CYP17A1 (Abiraterone acetate), CYP11B1/2 (Osilodrostat), and a suggested CYP21A2 inhibitor (Efavirenz). Treatment effects were examined under basal and ACTH-stimulated conditions in tissue from the same fetus and determined by quantifying the secretion of adrenal steroids in the culture media using liquid chromatography-tandem mass spectrometry. Statistical analysis was performed on ln-transformed data using one-way ANOVA for repeated measures followed by Tukey’s multiple comparisons test. Results Treatment with Abiraterone acetate and Osilodrostat resulted in potent inhibition of CYP17A1 and CYP11B1/2, respectively, while treatment with Efavirenz reduced testosterone secretion under basal conditions. ACTH-stimulation affected the inhibitory effects of all investigated drugs. Thus, treatment effects of Abiraterone acetate were more pronounced under stimulated conditions, while Efavirenz treatment caused a non-specific inhibition on steroidogenesis. ACTH-stimulation prevented the Osilodrostat-mediated CYP11B1 inhibition observed under basal conditions. Conclusions Our results show that the effects of steroidogenic inhibitors differ under basal and ACTH-stimulated conditions in the HFA ex vivo culture model. This could suggest that in vivo effects of therapeutic drugs targeting steroidogenesis may vary in conditions where patients have suppressed or high ACTH levels, respectively. This study further demonstrates that ex vivo cultured HFAs can be used to evaluate steroidogenic inhibitors and thereby provide novel information about the local effects of existing and emerging drugs that targets steroidogenesis.

Context Disorders affecting adrenal steroidogenesis promote an imbalance in the normally tightly controlled secretion of mineralocorticoids, glucocorticoids, and androgens. This may lead to differences/disorders of sex development in the fetus, as seen in virilized girls with congenital adrenal hyperplasia (CAH). Despite the important endocrine function of human fetal adrenals, neither normal nor dysregulated adrenal steroidogenesis is understood in detail. Objective Due to significant differences in adrenal steroidogenesis between human and model species (except higher primates), we aimed to establish a human fetal adrenal model that enables examination of both de novo and manipulated adrenal steroidogenesis. Design and Setting Human adrenal tissue from 54 1st trimester fetuses were cultured ex vivo as intact tissue fragments for 7 or 14 days. Main Outcome Measures Model validation included examination of postculture tissue morphology, viability, apoptosis, and quantification of steroid hormones secreted to the culture media measured by liquid chromatography-tandem mass spectrometry. Results The culture approach maintained cell viability, preserved cell populations of all fetal adrenal zones, and recapitulated de novo adrenal steroidogenesis based on continued secretion of steroidogenic intermediates, glucocorticoids, and androgens. Adrenocorticotropic hormone and ketoconazole treatment of ex vivo cultured human fetal adrenal tissue resulted in the stimulation of steroidogenesis and inhibition of androgen secretion, respectively, demonstrating a treatment-specific response. Conclusions Together, these data indicate that ex vivo culture of human fetal adrenal tissue constitutes a novel approach to investigate local effects of pharmaceutical exposures or emerging therapeutic options targeting imbalanced steroidogenesis in adrenal disorders, including CAH.

Introduction/Background In 2016 the Danish Multidisciplinary Cancer Group’s (DMCG) national Multidisciplinary Team (MDT) working committee established recommended quality standards in Danish healthcare. This current study investigates the status of implementation of the guideline published in 2016 amongst the clinicians who now manages and carry out the developed guideline at the MDT conference. The aims are to identify challenges and successful initiatives based on individual experiences and to point out areas of development within the MDT conference. Methodology The study is conducted as a social scientific questionnaire using the complexity theoretic model by Ralph Stacey, designed using MSC (Most Significant Change technique) which focusses on development and dynamics in organizations that are constantly and rapidly changing. 618 participants were identified and invited by either their own MDT leader or by a contact person appointed by the chairman of the cancer group. Results Answers were calculated using selective coding resulting in themes leading to the following outcome: The MDT conference is a well-established part of clinical practice, and are perceived as significant, qualified and qualifying; Measures that can further qualify the conference decision include more time for the task; A spinoff effect is identified on the conference participants’ social and professional relationship, which are developed, valued and supported in relation to the meetings Conclusion Multiple opportunities for improvement and future development potentials are presented in this article Disclosures The authors have nothing to disclose. ICMJE forms signed. Funding and Trial registration Funding by the Danish Multidisciplinary Cancer Group (DMCG) and the Danish Cancer Collaboration Center (DCCC)

Background PTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study. Methods Tumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran–Mantel–Haenszel tests. Results Downregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65–0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value p value = 0.019) and associated with higher CD8 counts (p value = 0.0016). Conclusions PTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes.

Ovarian cancer has a high mortality rate, especially in Denmark where mortality rates have been reported higher than in adjacent countries with similar demographics. This study therefore examined recent survival and mortality among Danish ovarian cancer patients over an 18-year study period.This nationwide registry-based observational study used data from the Danish Gynecology Cancer Database, Danish Pathology Registry, and Danish National Patient Registry. All patients with ovarian cancer diagnosed between 1995 and 2012 were included in the study. The data sources were linked via the patients' personal identification number and the analyses included data on cancer stage, age, survival, surgery status and comorbidity. The computed outcome measures were age-adjusted mortality rates and age-adjusted overall and relative survival rates for one and five years.We identified 9972 patients diagnosed with ovarian cancer in the period 1995-2012. The absolute one-year mortality rate decreased from 42.8 (CI 40.3-45.6) in 1995-1999 to 28.3 (CI 25.9-30.9) in 2010-2012, and the five-year mortality rate decreased from 28.2 (CI 27.0-29.5) in 1995-1999 to 23.9 (CI 22.9-25.0) in 2005-2009. After stratification by age, comorbidity and cancer stage, the decrease in one-year mortality was most substantial in the 65-74 year old age group 41.1 (CI 38.8-43.5) to 26.5 (CI 24.4-28.7) and for stage III 39.1 (CI 35.1-43.6) to 22.9 (CI 19.9-26.5) and stage IV 91.3 (CI 80.8-103.2) to 41.9 (CI 35.5-49.5). For overall survival, we showed an increase in one-year survival from 68% (CI 66-69%) in 1995-1999 to 76% (CI 74-78%) in 2010-2012 and an increase in five-year survival from 33% (CI 32-35%) in 1995-1999 to 36% (CI 34-38%) in 2005-2009. Relative survival showed similar increases through the period.Ovarian cancer survival in Denmark has improved substantially from 1995 to 2012, bringing Denmark closer to the standards set by adjacent countries.

Contains fulltext : 170949.pdf (Publisher’s version ) (Closed access) BACKGROUND: Observational studies have reported a positive association between body mass index (BMI) and ovarian cancer risk. However, questions remain as to whether this represents a causal effect, or holds for all histological subtypes. The lack of association observed for serous cancers may, for instance, be due to disease-associated weight loss. Mendelian randomization (MR) uses genetic markers as proxies for risk factors to overcome limitations of observational studies. We used MR to elucidate the relationship between BMI and ovarian cancer, hypothesizing that genetically predicted BMI would be associated with increased risk of non-high grade serous ovarian cancers (non-HGSC) but not HGSC. METHODS: We pooled data from 39 studies (14 047 cases, 23 003 controls) in the Ovarian Cancer Association Consortium. We constructed a weighted genetic risk score (GRS, partial F-statistic = 172), summing alleles at 87 single nucleotide polymorphisms previously associated with BMI, weighting by their published strength of association with BMI. Applying two-stage predictor-substitution MR, we used logistic regression to estimate study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted BMI and risk, and pooled these using random-effects meta-analysis. RESULTS: Higher genetically predicted BMI was associated with increased risk of non-HGSC (pooled OR = 1.29, 95% CI 1.03-1.61 per 5 units BMI) but not HGSC (pooled OR = 1.06, 95% CI 0.88-1.27). Secondary analyses stratified by behaviour/subtype suggested that, consistent with observational data, the association was strongest for low-grade/borderline serous cancers (OR = 1.93, 95% CI 1.33-2.81). CONCLUSIONS: Our data suggest that higher BMI increases risk of non-HGSC, but not the more common and aggressive HGSC subtype, confirming the observational evidence.

ObjectiveProper planning of intervention and care of ovarian cancer surgery is of outmost importance and involves a wide range of personnel at the departments involved. The aim of this study is to evaluate the introduction of an ovarian surgery classification (COVA) system for facilitating multidisciplinary team (MDT) decisions.Materials and MethodsFour hundred eighteen women diagnosed with ovarian cancers (n = 351) or borderline tumors (n = 66) were selected for primary debulking surgery from January 2008 to July 2013. At an MDT meeting, women were allocated into 3 groups named “pre-COVA” 1 to 3 classifying the expected extent of the primary surgery and need for postoperative care. On the basis of the operative procedures performed, women were allocated into 1 of the 3 corresponding COVA 1 to 3 groups. The outcome measure was the predictive value of the pre-COVA score compared with the actual COVA performed.ResultsThe MDT meeting allocated 213 women (51%) to pre-COVA 1, 136 (33%) to pre-COVA 2, and 52 (12%) to pre-COVA 3. At the end of surgery, 168 (40%) were classified as COVA 1, 158 (38%) were classified as COVA 2, and 28 (7%) were classified as COVA 3. Traced individually, 212 (51%) patients were correctly preclassified at the MDT meeting and distributed into 110 (52%) COVA 1, 71 (52%) COVA 2, and 17 (32%) COVA 3. Analyzing the subgroup of patients with cancer, 164 (47%) were correctly preclassified. Regarding the International Federation of Gynecology and Obstetrics (FIGO) stages, the pre-COVA classification predicted the actual COVA group in 79 (49%) FIGO stages I to IIIB and in 85 (45%) FIGO stages IIIC to IV.ConclusionsThe COVA classification system is a simple and useful tool in the MDT setting where specialists make treatment decisions based on advanced technology. The use of pre-COVA classification facilitates well-organized patient care–relevant procedures to be undertaken. Pre-COVA accurately predicts the final COVA in 51% classified women.

Ovarian cancer patients in whom complete tumor removal is impossible with primary debulking surgery (PDS) may benefit from neoadjuvant chemotherapy and interval debulking surgery. However, the task of performing a pre-operative evaluation of the feasibility of PDS is difficult. We aimed to investigate whether the risk of malignancy index (RMI) was a useful marker for this evaluation. RMI and surgical outcome were investigated in 164 patients, 49 of whom had no residual tumor after PDS. The receiver operating characteristic curve showed an area under the curve of 0.72 (confidence interval: 0.64-0.80). The possibility of complete tumor removal decreased with increasing RMI and there was a tendency towards higher RMI in patients with residual tumor after PDS, but no single cut-off value of RMI produced useful clinical predictive values. In conclusion, RMI alone is not an optimal method to determine whether complete tumor removal is possible with PDS.

Background: Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome, we evaluated single-nucleotide polymorphisms (SNP) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes. Methods: Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000-observed person-years and 4,478 deaths. Cox proportional hazards models were used to examine the association between candidate SNPs and ovarian cancer recurrence or survival with and without adjustment for key covariates. Results: We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined. Conclusions: These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies. Impact: These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed. Cancer Epidemiol Biomarkers Prev; 22(5); 987–. ©2013 AACR.

Objective Diagnostic factors are needed to improve the currently used serum CA125 and risk of malignancy index (RMI) in differentiating ovarian cancer (OC) from other pelvic masses, thereby achieving precise and fast referral to a tertiary center and correct selection for further diagnostics. The aim was to evaluate serum Human Epididymis protein 4 (HE4) and the risk of ovarian malignancy algorithm (ROMA) for these purposes. Methods Serum from 1218 patients in the prospective ongoing pelvic mass study was collected prior to diagnosis. The HE4 and CA125 data were registered and evaluated separately and combined in ROMA and compared to RMI. Results 809 benign tumors, 79 borderline ovarian tumors, 252 OC (64 early and 188 late stage), 9 non-epithelial ovarian tumors and 69 non-ovarian cancers were evaluated. Differentiating between OC and benign disease the specificity was 62.2 (CA125), 63.2 (HE4), 76.5 (ROMA) and 81.5 (RMI) at a set sensitivity of 94.4 which corresponds to RMI=200. The areas under the curve (AUC) were 0.854 (CA125), 0.864 (HE4), 0,897 (ROMA) and 0.905 (RMI) for benign vs. early stage OC. For premenopausal benign vs. OC AUC were 0.925 (CA125), 0.905 (HE4), 0.909 (ROMA) and 0.945 (RMI). Conclusion HE4 and ROMA helps differentiating OC from other pelvic masses, even in early stage OC. ROMA performs equally well as the ultrasound depending RMI and might be valuable as a first line biomarker for selecting high risk patients for referral to a tertiary center and further diagnostics. Further improvements of HE4 and ROMA in differentiating pelvic masses are still needed, especially regarding premenopausal women.

ObjectivesThe surgical management of advanced ovarian cancer involves complex surgery. Implementation of a quality management program has a major impact on survival. The goal of this work was to develop a list of quality indicators (QIs) for advanced ovarian cancer surgery that can be used to audit and improve the clinical practice. This task has been carried out under the auspices of the European Society of Gynaecologic Oncology (ESGO).MethodsQuality indicators were based on scientific evidence and/or expert consensus. A 4-step evaluation process included a systematic literature search for the identification of potential QIs and the documentation of scientific evidence, physical meetings of an ad hoc multidisciplinarity International Development Group, an internal validation of the targets and scoring system, and an external review process involving physicians and patients.ResultsTen structural, process, or outcome indicators were selected. Quality indicators 1 to 3 are related to achievement of complete cytoreduction, caseload in the center, training, and experience of the surgeon. Quality indicators 4 to 6 are related to the overall management, including active participation to clinical research, decision-making process within a structured multidisciplinary team, and preoperative workup. Quality indicator 7 addresses the high value of adequate perioperative management. Quality indicators 8 to 10 highlight the need of recording pertinent information relevant to improvement of quality. An ESGO-approved template for the operative report has been designed. Quality indicators were described using a structured format specifying what the indicator is measuring, measurability specifications, and targets. Each QI was associated with a score, and an assessment form was built.ConclusionsThe ESGO quality criteria can be used for self-assessment, for institutional or governmental quality assurance programs, and for the certification of centers. Quality indicators and corresponding targets give practitioners and health administrators a quantitative basis for improving care and organizational processes in the surgical management of advanced ovarian cancer.

The purpose of this study was to develop a novel index for preoperative, non-invasive prediction of complete primary cytoreduction in patients with FIGO stage IIIC-IV epithelial ovarian cancer. Prospectively collected clinical data was registered in the Danish Gynecologic Cancer Database. Blood samples were collected within 14 days of surgery and stored by the Danish CancerBiobank. Serum human epididymis protein 4 (HE4), serum cancer antigen 125 (CA125), age, performance status, and presence/absence of ascites at ultrasonography were evaluated individually and combined to predict complete tumor removal. One hundred fifty patients with advanced epithelial ovarian cancer were treated with primary debulking surgery (PDS). Complete PDS was achieved in 41 cases (27 %). The receiver operating characteristic curves demonstrated an area under the curve of 0.785 for HE4, 0.678 for CA125, and 0.688 for age. The multivariate model (Cancer Ovarii Non-invasive Assessment of Treatment Strategy (CONATS) index), consisting of HE4, age, and performance status, demonstrated an AUC of 0.853. According to the Danish indicator level, macro-radical PDS should be achieved in 60 % of patients admitted to primary surgery (positive predictive value of 60 %), resulting in a negative predictive value of 87.5 %, sensitivity of 68.3 %, specificity of 83.5 %, and cutoff of 0.63 for the CONATS index. Non-invasive prediction of complete PDS is possible with the CONATS index. The CONATS index is meant as a supplement to the standard preoperative evaluation of each patient. Evaluation of the CONATS index combined with radiological and/or laparoscopic findings may improve the assessment of the optimal treatment strategy in patients with advanced epithelial ovarian cancer.

Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, and Consortium of Modifiers of BRCA1 and BRCA2: et al., [Objective]: Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3' UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. [Methods]: Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). [Results]: We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. [Conclusions]: rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers., The COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 — HEALTH-F2-2009-223175). The scientific development and funding for this project were in part supported by the US National Cancer Institute GAME-ON Post-GWAS Initiative (U19-CA148112). Funding for the project was provided by the Wellcome Trust under award 076113. This work was partially supported by Spanish Association against Cancer (AECC08), RTICC 06/0020/1060, FISPI08/1120, Mutua Madrileña Foundation (FMMA) and SAF2010-20493. Was supported by a grant RD12/00369/0006 and 12/00539 from ISCIII (Spain), partially supported by European Regional Development FEDER funds. Contract grant sponsor: Asociación Española Contra el Cáncer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia. Contract grant numbers: ISCIIIRETIC RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/00748, PI13/00285 and 2009SGR290.

ObjectiveTo evaluate the role of 2-deoxy-2-(18F)fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) for selecting patients with extensive ovarian cancer (OC) for neoadjuvant chemotherapy by evaluating predictors of overall survival in patients with stage IIIC/IV OC.Materials and MethodsFrom September 1, 2004, to November 20, 2011, 514 consecutive patients with a pelvic tumor underwent preoperative PET/CT; 179 patients had stage IIIC/IV OC. Patients’ characteristics were collected from 153 patients with stage IIIC/IV OC who underwent primary surgery. In 152 patients with stage IIIC/IV OC, clinical predictors and PET/CT predictors of survival were evaluated.ResultsMedian age was 64 years (range, 38–88 years); 87% (113) of the 153 patients had a performance status of less than 2; 55% (84) of the 153 patients had PET/CT stage III, and 45% (69) of the 153 patients had PET/CT stage IV. Using univariate analysis, incomplete debulking (P = 0.0001), pleural exudates (P = 0.001), postmenopausal state (P = 0.01), WHO performance status greater than 2 (P = 0.01), PET/CT stage IV (P = 0.01), and large bowel mesentery implants (P = 0.02) were statistically significant prognostic variables. Using multivariate Cox regression analysis, incomplete debulking was the only statistically significant independent prognostic variable (P = 0.0001). Median overall survival was significantly longer in the 53 patients with no residual tumor than in the 99 patients with residual tumor (33.3 vs 25.5 months; P = 0.0001)ConclusionSuggested PET/CT criteria for referral of patients with advanced OC to neoadjuvant chemotherapy are PET/CT stage IV, pleural exudates, and PET-positive large bowel mesentery implants. Evaluation of selection criteria for neoadjuvant chemotherapy should be promoted in prospective clinical trials, with survival as the primary end point.

Objective Risk of malignancy index (RMI), based on a serum cancer antigen 125 level, ultrasound findings and menopausal status, is used to discriminate ovarian cancer from benign pelvic mass. In Denmark, patients with pelvic mass and RMI ≥200 are referred to tertiary gynecologic oncology centers according to the national guidelines for ovarian cancer treatment. The guidelines include recalculation of RMI at the tertiary center and, if indicated, positron emission tomography/computed tomography and fast-track surgery by specialists in cancer surgery. The aim of this study was to validate the use of RMI ≥200 as a tool for preoperative identification of ovarian cancer at a tertiary center. Design Prospective observational study. Setting A tertiary center in Copenhagen, Denmark. Population One thousand one hundred and fifty-nine women with pelvic mass. Methods The RMI was calculated after ultrasound examination and blood sampling for serum cancer antigen 125 analysis within two weeks before surgery. Main outcome measures Sensitivity, specificity, positive and negative predictive values were calculated to evaluate the ability of RMI to distinguish between ovarian cancer and benign pelvic mass. Results There were 778 women diagnosed with benign pelvic mass, while 251 had ovarian cancer and 74 had borderline ovarian tumor. Fifty-six women were diagnosed with other forms of cancer. Sensitivity and specificity for ovarian cancer vs. benign pelvic mass for RMI ≥200 were 92 and 82%, respectively. Corresponding positive and negative predictive values were 62 and 97%. Conclusions Risk of malignancy index ≥200 is a reliable tool for identifying patients with ovarian cancer pelvic masses at a tertiary centre to select patients for further preoperative examinations.

Background Previous reports have shown that the proteomic markers apolipoprotein A1, hepcidin, transferrin, inter-alpha trypsin IV internal fragment, transthyretin, connective-tissue activating protein 3 and beta-2 microglobulin may discriminate between a benign pelvic mass and ovarian cancer (OC). The aim was to determine if these serum proteomic biomarkers alone as well as in combination with age and serum CA125, could be helpful in triage of women with a pelvic mass. Methods We included prospectively 144 patients diagnosed with (OC), 40 with a borderline tumor and 469 with a benign tumor. Surface-enhanced laser desorption/ionization time of flight-mass spectrometry was used for analyses. The Danish Index (DK-Index) based on the proteomic data, age and CA125 was developed using logistic regression models. Results Multivariate logistic regression analysis demonstrated that the selected proteomic markers, CA125 and age were independent predictors of OC and the combination of these is proposed as the DK-index. A sensitivity (SN) of 99% had a specificity (SP) of 57% for DK-index and 49% for CA125. At a SN of 95%, the SP increased to 81% for DK-index compared to 68% for CA125 alone. For stage I+II the SP was 58% for DK-index and 49% for CA125. For stage III+IV the corresponding values were 94% and 86% respectively. Conclusions The DK-index warrants further evaluation in independent cohorts.

Objective. Surgical-site infections are serious complications and thorough follow-up is important for accurate surveillance. We aimed to compare the frequency of complications recorded in a clinical quality database with those noted in a randomized clinical trial with follow-up visits. Design. Evaluation study. Setting. Danish Gynecological Cancer Database (DGCD) and the Danish multicenter trial on perioperative oxygen and surgical-site infections (PROXI). Sample. Paired data from 222 patients who participated in the PROXI trial taking place at Copenhagen University Hospital, Rigshospitalet between November 2006 and October 2008 and data from the DGCD. Methods. Outcomes within 30 days from the trial and the database were compared and levels of agreements were calculated with kappa-statistics. Main Outcome Measures. Primary outcome was surgical-site infection. Other outcomes included re-operation, urinary tract infection, pneumonia and sepsis. Results. Surgical-site infection was found in 21 of 222 patients (9.5%) in the PROXI trial versus 6 of 222 patients (2.7%) in the DGCD (p < 0.01, kappa 0.42). Twelve of 15 superficial and three of six deep or organ-space surgical-site infections were registered in the PROXI trial, but not in the DGCD. Agreements between secondary outcomes were very varying (kappa-value 0.77 for re-operation, 0.37 for urinary tract infections, 0.19 for sepsis and 0.18 for pneumonia). Conclusions. The randomized trial reported significantly more surgical-site infections than the clinical database. The DGCD reported only 50% of the deep and organ-space infections, and hence, the low-overall agreement indicates a need for more careful database registration.

Objective To investigate if the use of diagnostic FDG-PET/CT leads to stage migration in patients with advanced ovarian cancer and to evaluate the prognostic significance of FDG-PET/CT. Methods From September 2004 to August 2007, 201 patients with a Risk of Malignancy Index (RMI) >150 based on serum CA-125, ultrasound examinations and menopausal state, underwent PET/CT within 2 weeks prior to standard surgery/debulking of a pelvic tumor. On 15 August, 2009 overall survival and prognostic variables were analysed in 66 ovarian cancer patients (64 stage III and 2 stage IV). Results Median follow-up was 30.2 months; median age was 62.5 years (range 35–85 years); 97% (64/66) had a performance status ≤2; 38% (25/66) underwent complete debulking (no macroscopic residual tumor); 51% (39/66) was diagnosed with PET/CT stage III and 41% (27/66) was diagnosed with PET/CT stage IV. Survival was significantly longer for patients with PET/CT stage III than for patients with PET/CT stage IV ( P =0.03). Using univariate analysis, PET/CT stage III ( P =0.03), complete debulking (no macroscopic residual tumor) ( P =0.002), and GOG performance status ≤2 ( P =0.04) were statistically significant prognostic variables. Using multivariate Cox regression analysis, complete debulking was the only statistically significant independent prognostic variable ( P =0.02). Conclusion In primary advanced ovarian cancer the use of diagnostic FDG-PET/CT leads to stage migration. Adequate staging is the foundation for ovarian cancer treatment and advanced imaging for optimal evaluation of metastases should be promoted in clinical trials. The strongest determinant of patient outcome is residual abdominal tumor after primary surgery.

To examine whether urine can be used to measure specific ovarian cancer proteomic profiles and whether one peak alone or in combination with other peaks or CA125 has the sensitivity and specificity to discriminate between ovarian cancer pelvic mass and benign pelvic mass.A total of 209 women were admitted for surgery for pelvic mass at the Gynaecological Department at Rigshospitalet, Copenhagen. Of the women, 156 had benign gynaecological tumors, 13 had borderline tumors and 40 had malignant epithelial ovarian cancer. The prospectively and preoperatively collected urine samples were aliquotted and frozen at -80 degrees until the time of analysis. The urine was fractionated using equalizer bead technology and then analyzed with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Biomarkers were purified and identified using combinations of chromatographic techniques and tandem mass spectrometry.Benign and malignant ovarian cancer cases were compared; 21 significantly different peaks (p0.001) were visualized using Mann-Whitney analysis, ranging in m/z values from 1,500 to 185,000. The three most significant peaks were purified and identified as fibrinogen alpha fragment (m/z=2570.21), collagen alpha 1 (III) fragment (m/z=2707.32) and fibrinogen beta NT fragment (m/z=4425.09). The area under the receiver operator characteristic curve (ROC AUC) value for these three peaks in combination was 0.88, and their ROC AUC value in combination with CA125 was 0.96.This result supports the feasibility of using urine as a clinical diagnostic medium, and the ROC AUC value for the three most significant peaks in combination with or without CA125 demonstrates the enhanced prediction performance of combined marker analysis.

Udgivelsesdato: 2009-null OBJECTIVE: To determine which treatment should be offered to women with a non-ruptured tubal pregnancy: a single dose of methotrexate (MTX) or laparoscopic surgery. DESIGN: Prospective, randomized, open multicenter study. SETTING: Seven Danish departments of obstetrics and gynecology. SAMPLE: A total of 106 women diagnosed with ectopic pregnancy (EP). METHODS: Between March 1997 and September 2000, 1,265 women were diagnosed with EP, 395 (31%) were eligible, 109 (9%) were randomized of whom 106 had an EP. The study was originally powered to a sample size of 422 patients. The women were randomized to either medical (MTX; 53) or surgical (laparoscopic salpingotomy; 53) treatment. Follow-up by questionnaire and through national patient databases for a maximum of 10 years. MAIN OUTCOME MEASURES: Uneventful decline of plasma-human chorionic gonadotropin to less than 5 IU/L, rates of spontaneous, subsequent intrauterine, and recurrent ectopic pregnancies. RESULTS: The success rates were 74% following MTX treatment and 87% after surgery (n.s.); the subsequent spontaneous intrauterine pregnancy rate was 73% after MTX and 62% after surgery; and the EP rate was 9.6% after MTX and 17.3% following surgery (n.s.). CONCLUSIONS: In women with an EP, who are hemodynamically stable and wishing to preserve their fertility, medical treatment with single dose MTX tends to be equal to treatment with laparoscopic surgery regarding success rate, complications, and subsequent fertility. Although the two treatment modalities seemed to be similar in outcome, it is crucial that the diagnosis is based on a high-quality ultrasonographic evaluation, as two patients had intrauterine pregnancies despite fulfilling the diagnostic algorithm for EP.

To prospectively identify combined PET/CT predictors of incomplete/suboptimal primary cytoreduction in advanced ovarian cancer.From September 2004 to March 2007, 179 patients with a Risk of Malignancy Index (RMI)150 based on serum CA-125, ultrasound examinations and menopausal state, underwent PET/CT within 2 weeks prior to standard surgery/debulking of a pelvic tumor. Ten PET/CT features were identified and evaluated as predictors of cytoreduction in 54 patients with advanced ovarian cancer.Complete cytoreduction (no macroscopic residual disease) was achieved in 35% and optimal cytoreduction (1 cm residual disease) was achieved in 56%. Using univariate analysis, predictors of incomplete cytoreduction were large bowel mesentery implants (LBMI) (P0.003), pleural effusion (P0.009), ascites (P0.009) and peritoneal carcinosis (P0.01). LBMI (P0.03) and ascites (P0.05) were also predictors of suboptimal cytoreduction. Using multivariate analysis, LBMI was the only independent predictor of incomplete cytoreduction (P=0.004) and no predictor of suboptimal cytoreduction was found.PET/CT predictors of cytoreduction were found. But they should not be used to withhold patients form primary cytoreductive surgery. We suggest PET/CT as a supplementary image modality prior to surgery in primary OC patients whenever accurate and comprehensive preoperative evaluation of primary tumor and metastases is desired.

Objective To investigate the clinical value of PET/CT as a supplement to FIGO staging in patients with cervical cancer stage ≥1B. Methods This prospective study included 120 consecutive patients. After staging, a whole-body PET/CT scan was performed and these examinations were divided into two groups: (1) patients suitable for radical hysterectomy including lymph node dissection and (2) patients referred to combined chemo/radiation therapy. The results were compared to histopathological findings and/ or follow-up. Results Twenty-seven patients underwent radical surgery; four of these had PET/CT scans revealing pathological foci in the pelvis. Three (11%) were true positive; one was false positive. Twenty-two patients had true negative PET/CT scans concerning pelvic lymph nodes. One patient had a false negative node. For these patients, we found the positive predictive value (PPV) to be 75%, negative predictive value (NPV) 96%, sensitivity 75%, specificity 96%. Regarding para -aortal nodal disease in the total population of 119 patients, 15 patients had true positive scans. The number of true negatives was 103, resulting in PPV 94%, NPV 100%, sensitivity 100% and specificity 99%. PET/CT scans showed distant metastases in 19 patients, 10 were true positive and nine were false positive. The remaining 100 patients were considered true negative for distant metastases and for these patients, we found PPV 63%, NPV 100%, sensitivity 100% and specificity 94%. Conclusions Whole-body FDG PET/CT scanning for newly diagnosed cervical cancer FIGO stage ≥1B has a high sensitivity and specificity, and can be a valuable supplement to the FIGO staging procedure.

© 2015 Cancer Research UK. All rights reserved. Background: Observational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer. Methods: We used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype. Results: Overall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30-34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99-1.23); BMI: ≥35, pHR: 1.12 (95% CI: 1.01-1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m -2) and endometrioid subtypes (pHR: 1.08 per 5 kg m -2), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m -2) subtype, but only the association with high-grade serous cancers was significant. Conclusions: Higher BMI is associated with adverse survival among the majority of women with ovarian cancer.

In patients undergoing colonic surgery the postoperative hospital stay has been reduced from 8-12 days to 2-4 days with multimodal rehabilitation programs. The aim of this study was to evaluate the postoperative outcome after surgery for ovarian malignancy with conventional care compared to fast-track multimodal rehabilitation.Seventy-two consecutive patients receiving conventional care (group 1) were compared with 69 consecutive patients receiving multimodal, fast-track rehabilitation with a planned care program including continuous epidural analgesia, early oral feeding and mobilization (group 2) in the same department. Outcome was postoperative hospital stay and morbidity during the first postoperative month.Median age was 63 years (group 1) and 62 years (group 2). Median postoperative hospital stay was reduced from 6 days in group 1 (mean 7.3) to 5 days in group 2 (mean 5.4) (p0.05). There was no difference in the overall complication rate, although severe medical complications were reduced in group 2 (14% versus 2%; p0.01). Readmission rate was 10% in group 1 and 3% in group 2 (p0.05).The concept of fast-track multimodal rehabilitation appears to be beneficial in patients operated for ovarian malignancy, as hospital stay and medical morbidity are reduced.

Background. The medical response to adult sexual assault should comprise: the collection of forensic evidence, the treatment of injuries, and follow-up counselling. In the past, victims of sexual assault reporting directly to the police may not have received this total medical care. The Copenhagen Center for Victims of Sexual Assault at Rigshospitalet, Denmark offers a 24-h service. Medical treatment and psychosocial follow up is offered independent of police reporting. The aim of this study was to assess whether adult sexual assault victims who reported to the police differed from those who did not report to the police. Methods. Using clinical records, sociodemographics, characteristics of the assault, and type of preventive medical treatment received were obtained for 156 consecutive women consulting the Copenhagen Center (March 1st to December 31st 2000). Comparisons between characteristics of victims who reported to the police or not were determined. Results. Ninety-four (60.2%) of the women reported ...

To investigate the prognostic significance of dividing epithelial ovarian cancer (EOC) in type I and type II tumors based on pathologic variables.We used the Danish Gynecologic Cancer Database to identify all patients diagnosed with EOC from 2005 to 2012. Information on histologic type and grade were used to classify tumors as either type I or type II. Death, and several prognostic factors were used in the multivariate Cox regression, and Landmark analysis was used to estimate hazard ratios of all-cause mortality.Among 2660 patients diagnosed with EOC, 735 were categorized as type I tumors, and 1925 as type II tumors. Patients with type II EOC were more frequently diagnosed in late FIGO stages (stages III-IV) than patients with type I EOC (78.1% vs. 32.1% respectively; P0.001). Time dependent multivariate Cox analysis, adjusted for known prognostic variables, showed no significant difference in survival within the first two years after diagnosis, however, after 730days of follow-up a significantly increased overall survival for type I tumors was observed (hazard ratio 1.72, 95% confidence interval: 1.28-2.31, P0.001). Similarly the Landmark analysis for survival confirmed the increased overall survival for type I tumors after two years of follow-up (hazard ratio: 1.85, 95% confidence interval: 1.35-2.54, P0.001).Classification of EOC in type I and type II tumors based on pathologic variables was associated with an increased risk of death for type II tumors after two years of follow-up, while no increased risk was seen during the first two years of follow-up.

Background: Invasive ovarian cancer is a significant cause of gynecologic cancer mortality. Methods: We examined whether this mortality was associated with inherited variation in approximately 170 candidate genes/regions [993 single-nucleotide polymorphisms (SNPs)] in a multistage analysis based initially on 312 Mayo Clinic cases (172 deaths). Additional analyses used The Cancer Genome Atlas (TCGA; 127 cases, 62 deaths). For the most compelling gene, we immunostained Mayo Clinic tissue microarrays (TMA, 326 cases) and conducted consortium-based SNP replication analysis (2,560 cases, 1,046 deaths). Results: The strongest initial mortality association was in HGF (hepatocyte growth factor) at rs1800793 (HR = 1.7, 95% CI = 1.3–2.2, P = 2.0 × 10−5) and with overall variation in HGF (gene-level test, P = 3.7 × 10−4). Analysis of TCGA data revealed consistent associations [e.g., rs5745709 (r2 = 0.96 with rs1800793): TCGA HR = 2.4, CI = 1.4–4.1, P = 2.2 × 10−3; Mayo Clinic + TCGA HR = 1.6, CI = 1.3–1.9, P = 7.0 × 10−5] and suggested genotype correlation with reduced HGF mRNA levels (P = 0.01). In Mayo Clinic TMAs, protein levels of HGF, its receptor MET (C-MET), and phospho-MET were not associated with genotype and did not serve as an intermediate phenotype; however, phospho-MET was associated with reduced mortality (P = 0.01) likely due to higher expression in early-stage disease. In eight additional ovarian cancer case series, HGF rs5745709 was not associated with mortality (HR = 1.0, CI = 0.9–1.1, P = 0.87). Conclusions: We conclude that although HGF signaling is critical to migration, invasion, and apoptosis, it is unlikely that HGF genetic variation plays a major role in ovarian cancer mortality. Furthermore, any minor role is not related to genetically-determined expression. Impact: Our study shows the utility of multiple data types and multiple data sets in observational studies. Cancer Epidemiol Biomarkers Prev; 20(8); 1638–48. ©2011 AACR.

Purpose: To determine if the level of apolipoprotein A1, hepcidin, transferrin, inter-α trypsin IV internal fragment, transthyretin (TT), connective-tissue activating protein 3 (CTAP3), serum amyloid A1, β-2 microglobulin (B2M) might have impact on overall and progression-free survival for ovarian cancer (OC) patients. Experimental design: Serum from 150 OC patients was tested using SELDI-TOF-MS. Results: A proteomic prognostic index (xb-pro) was constructed using the regression coefficients based on inter-α trypsin IV internal fragment, B2M and TT. A multivariable Cox survival analysis including the xb-pro index showed that xb-pro (p

In patients with advanced ovarian cancer undergoing preoperative PET/CT, we investigated the prognostic value of SUV in the primary tumor and we evaluated the value of SUV for predicting incomplete primary cytoreduction (macroscopic residual tumor).From September 2004 to August 2007, 201 consecutive patients with a pelvic tumor and a Risk of Malignancy Index (RMI)150 based on serum CA-125, ultrasound examinations and menopausal state, underwent PET/CT within two weeks prior to standard surgery/debulking of a pelvic tumor. At two-year follow-up (August 15, 2009) the association between SUV and overall survival/cytoreductive result were analyzed in 60 ovarian cancer patients (58 stage III and two stage IV).At inclusion median age was 62 years (range 35-85 years); 97% (58/60) had a performance status ≤2; 42% (25/60) underwent complete debulking (no macroscopic residual tumor); median SUV(max) was 13.5 (range 2.5-39.0). Median follow-up was 30.2 months. At follow-up 57% (34/60) were alive and 43% (26/60) had died from ovarian cancer. SUV(max) in patients alive was not statistically different from SUV(max) in dead patients (p=0.69), and SUV(max) was not correlated with the amount of residual tumor after surgery (p=0.19). Using univariate Cox regression analysis, residual tumor was a significant prognostic variable (p=0.001); SUV(max) was not a statistically significant prognostic variable (p=0.86).FDG uptake (SUV(max)) in the primary tumor of patients with advanced ovarian cancer was not a prognostic variable and the FDG uptake did not predict complete cytoreduction after primary surgery. Future prospective clinical trials will need to clarify if other PET tracers can serve as prognostic variables in ovarian cancer.

Udgivelsesdato: 2009-Oct-14 CONTEXT: Use of 80% oxygen during surgery has been suggested to reduce the risk of surgical wound infections, but this effect has not been consistently identified. The effect of 80% oxygen on pulmonary complications has not been well defined. OBJECTIVE: To assess whether use of 80% oxygen reduces the frequency of surgical site infection without increasing the frequency of pulmonary complications in patients undergoing abdominal surgery. DESIGN, SETTING, AND PATIENTS: The PROXI trial, a patient- and observer-blinded randomized clinical trial conducted in 14 Danish hospitals between October 2006 and October 2008 among 1400 patients undergoing acute or elective laparotomy. INTERVENTIONS: Patients were randomly assigned to receive either 80% or 30% oxygen during and for 2 hours after surgery. MAIN OUTCOME MEASURES: Surgical site infection within 14 days, defined according to the Centers for Disease Control and Prevention. Secondary outcomes included atelectasis, pneumonia, respiratory failure, and mortality. RESULTS: Surgical site infection occurred in 131 of 685 patients (19.1%) assigned to receive 80% oxygen vs 141 of 701 (20.1%) assigned to receive 30% oxygen (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.72-1.22; P = .64). Atelectasis occurred in 54 of 685 patients (7.9%) assigned to receive 80% oxygen vs 50 of 701 (7.1%) assigned to receive 30% oxygen (OR, 1.11; 95% CI, 0.75-1.66; P = .60), pneumonia in 41 (6.0%) vs 44 (6.3%) (OR, 0.95; 95% CI, 0.61-1.48; P = .82), respiratory failure in 38 (5.5%) vs 31 (4.4%) (OR, 1.27; 95% CI, 0.78-2.07; P = .34), and mortality within 30 days in 30 (4.4%) vs 20 (2.9%) (OR, 1.56; 95% CI, 0.88-2.77; P = .13). CONCLUSION: Administration of 80% oxygen compared with 30% oxygen did not result in a difference in risk of surgical site infection after abdominal surgery. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00364741.

Vulvodynia is a chronic painful disorder with an estimated prevalence of 9-12%. A rising incidence of the condition constitutes a growing problem. This has lead to an increased focus on etiology and treatment, while the definition also requires attention. Previous assumptions stating that the problem is solely a psychological disorder have been abandoned, because inflammatory mechanisms and genetic factors have been found to be involved in the pathogenesis as well as psychosexual contributors. This article describes the terminology and definition of the condition, theories on patho-physiological mechanisms underlying the disorder, methods of diagnosis and evidence and recommendations on clinical management. A critical examination of the literature regarding vulvodynia reveals numerous strategies and recommendations for treatment, many of which are not evidence-based, and a lack of effective treatment for all patients. Research is being undertaken internationally to find more specific and unequivocal causes of the disorder, as well as to develop evidence-based methods of treatment.

During a 3-4 year period, 324 women with a positive smear were registered consecutively and prospectively and divided into two groups according to the design of the investigation. In one group the smear was taken with an Ayre spatula and in the other group with a cotton swab. The purpose of this investigation has been to make a comparison between the endocervical smear and the smear taken from the surface of the portio and at the same time between the samples taken with a dry wooden Ayre spatula and with a cotton swab. No differences were found. The cytological findings have been registered and correlated both with the histological findings by colposcopically directed punch-biopsies and endocervical curettings and with the final histological diagnosis obtained by punch-biopsy, conization or hysterectomy.

Objectives To prospectively evaluate the diagnostic value of combined PET/CT in detecting a malignant tumor in patients with no previous cancer history, presenting with a pelvic mass. Methods From September 2004 to March 2006, 101 patients (median age=60 years, range=24–85 years) with a Risk of Malignancy Index (RMI)>150 based on serum CA-125, ultrasound examinations (US) and menopausal state, were referred to PET/CT within 2 weeks prior to standard surgery/debulking of a pelvic tumor. Histological specimens from 97 patients were evaluated and the histological diagnoses were compared to the PET/CT results to calculate the diagnostic value of PET/CT in differentiating between malignant and borderline/benign tumors. Four patients refrained from surgery or biopsy. Results The average serum CA-125 in the 97 studied patients was 784 U/ml (range=22–9665 U/ml). PET/CT demonstrated areas of abnormally increased metabolic activity considered highly suspicious for malignant tumor in 60 patients (62%). In 37 patients (38%) the tumors were considered benign on PET/CT. Histopathology showed benign tumors in 40 patients and malignant tumors in 57 patients. The sensitivity and specificity for PET/CT in diagnosing a malignant pelvic tumor were 100% (57/57) and 92.5% (37/40), respectively ( P Conclusion Combined PET/CT demonstrates high diagnostic value in identifying primary ovarian cancer in patients with a pelvic mass of unknown origin and RMI>150. We suggest PET/CT as the image modality of choice when US shows a pelvic tumor and additional information prior to surgery is needed.

Aim The objective was to analyse the impact of secondary cytoreductive surgery in patients with recurrent ovarian carcinoma. Methods Retrospective review of 572 consecutive patients with primary ovarian carcinoma. Thirty-eight patients with intraabdominal/pelvic recurrence consisted the study group. Clinical variables affecting tumour resectability and survival were evaluated. Results Complete tumour resection was obtained in 42% of patients. A solitary tumour recurrence was independently associated with complete tumour resection (p=0.009). Median survival for patients with complete and incomplete tumour resection was 51.8 and 19.9 months. The parameter, residual tumour, was found independently correlated with survival after the relapse surgical procedure (p=0.02). However, including also the parameter, number of relapse tumour sites, in the multivariate analysis, the parameter, residual tumour, was no longer significantly associated with survival. Conclusions Complete tumour resection following secondary cytoreductive surgery is associated with improved survival in selected groups of patients with recurrent ovarian cancer. However, other clinical factors than surgical cytoreduction are of considerable significance in determining the outcome of the salvage treatment.

5061 Background: The frequency and poor prognosis of ovarian cancer (OC) emphasizes the need for better markers usable for both diagnostics and screening. Instead of a single marker could the wante...

Vaginal rupture is a rare complication of hysterectomy. It is, among others, related to age and the incidence is higher in postmenopausal women. The rupture can occur spontaneously or in relation to clinical follow-up. In ovarian cancer the follow-up after surgery includes clinical examination, cancer antigen (CA)-125, and transabdominal and transvaginal ultrasonography. We experienced vaginal rupture in three patients with ovarian cancer. All patients had undergone surgery for ovarian cancer and were receiving chemotherapy. The rupture occurred shortly after transvaginal ultrasonography, performed by separate radiologists specialised in ultrasonography. All patients had acute surgery without any complications. Caution should be taken when performing transvaginal ultrasonography in hysterectomised patients and the complication of vaginal rupture should always be borne in mind.

22060 Background: Pre-operative cancer stage and grade are inadequate predictors of survival in patients with ovarian cancer. Methods: Pre-operative serum samples were collected with IRB approval i...

During a 3 year period, 35 pregnant woman with grade III or IV cytological changes found at pregnancy control were followed during pregnancy and up to 4 years after delivery. These 35 patients constitute 0.35% of all the pregnant women admitted for antepartum consultation. Complete regression of dysplasia was seen in one third of the patients. The patients were followed with colposcopy and sometimes punch biopsy and the decision regarding final treatment was postponed until 8 weeks after delivery. No invasive lesion was found, and no recurrences or invasive lesions were found at follow up. It is concluded that cytology and colposcopy with punch biopsy on suspicion of early invasion is an adequate control procedure during the pregnancy at intervals of 2-3 months.