Publications by authors named "Daniela Fischerova"

49 Publications

ESGO/ISUOG/IOTA/ESGE Consensus Statement on pre-operative diagnosis of ovarian tumors.

Int J Gynecol Cancer 2021 07 10;31(7):961-982. Epub 2021 Jun 10.

Gynaecologic Oncology, Hammersmith Hospital, Imperial College, London, UK.

The European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis (IOTA) group, and the European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence-based statements on the pre-operative diagnosis of ovarian tumors, including imaging techniques, biomarkers, and prediction models. ESGO/ISUOG/IOTA/ESGE nominated a multidisciplinary international group, including expert practising clinicians and researchers who have demonstrated leadership and expertise in the pre-operative diagnosis of ovarian tumors and management of patients with ovarian cancer (19 experts across Europe). A patient representative was also included in the group. To ensure that the statements were evidence-based, the current literature was reviewed and critically appraised. Preliminary statements were drafted based on the review of the relevant literature. During a conference call, the whole group discussed each preliminary statement and a first round of voting was carried out. Statements were removed when a consensus among group members was not obtained. The voters had the opportunity to provide comments/suggestions with their votes. The statements were then revised accordingly. Another round of voting was carried out according to the same rules to allow the whole group to evaluate the revised version of the statements. The group achieved consensus on 18 statements. This Consensus Statement presents these ESGO/ISUOG/IOTA/ESGE statements on the pre-operative diagnosis of ovarian tumors and the assessment of carcinomatosis, together with a summary of the evidence supporting each statement.
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http://dx.doi.org/10.1136/ijgc-2021-002565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273689PMC
July 2021

Are we better off using multiple endometriosis classifications in imaging and surgery than settle for one universal less than perfect protocol? Review of staging systems in ultrasound, magnetic resonance and surgery.

J Obstet Gynaecol 2021 May 19:1-7. Epub 2021 May 19.

Department of Obstetrics and Gynaecology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 2, Czech Republic.

There are multiple classifications in imaging and surgery of endometriosis and in this article, we offer a review of the main evaluation systems. The International Deep Endometriosis Analysis group consensus is the leading document for ultrasound assessment, while magnetic resonance imaging is guided by the European Society for Urogenital Radiology recommendations on technical protocol. In surgery, the revised American Society for Reproductive Medicine classification is the oldest system, ideally combined with newer classifications, such as Enzian or Endometriosis Fertility Index. Recently, The World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project introduced detailed proforma for clinical and intraoperative findings. There is still no universal consensus, so the initial emphasis should be on the uniform reporting of the disease extent until research clarifies more the correlations between extent, symptoms and progression in order to develop a reliable staging system.Impact Statement There have been several reviews of surgical classifications, comparing their scope and practical use, while in the imaging the attempts for literature review has been scarce. This is the first up to date review offering detailed analysis of the main classification systems across the three main areas involved in endometriosis care - ultrasound, MRI and surgery. The mutual awareness of the radiological classifications for surgeons and vice versa is crucial in an efficient multidisciplinary communication and patient care. On these comparisons we were able to demonstrate the lack of consensus in description of the extent of the disease and even further lack of prognostic features (with the exemption of one surgical system). Future attempts of scientific societies should focus on defining uniform nomenclature for extent description. In the second step the staging classification should encompass prognostic value (risk of disease and symptoms recurrence).
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http://dx.doi.org/10.1080/01443615.2021.1887111DOI Listing
May 2021

4D Doppler Ultrasound in High Grade Serous Ovarian Cancer Vascularity Evaluation-Preliminary Study.

Diagnostics (Basel) 2021 Mar 24;11(4). Epub 2021 Mar 24.

Department of Obstetrics and Gynecology, Clínica Universidad de Navarra, University of Navarra, Avenida Pio XII, 36, 31008 Pamplona, Spain.

The aim of the study was to evaluate the usefulness of 4D Power Doppler tissue evaluation to discriminate between normal ovaries and ovarian cancer tumors. This was a prospective observational study. Twenty-three cases of surgically confirmed ovarian High Grade Serous Carcinoma (HGSC) were analyzed. The control group consisted of 23 healthy patients, each matching their study-group counterpart age wise (±3 years) and according to their menopausal status. Transvaginal Doppler 4D ultrasound scans were done on every patient and analyzed with 3D/4D software. Two 4D indices-volumetric Systolic/Diastolic Index (vS/D) and volumetric Pulsatility Index (vPI)-were calculated. To keep results standardized and due to technical limitations, virtual 1cc spherical tissue samples taken from the part with highest vascularization as detected by bi-directional Power Doppler were analyzed for both groups of ovaries. Values of volumetric S/D indices and volumetric PI indices were statistically lower in ovarian malignant tumors compared to normal ovaries: 1.096 vs. 1.794 and 0.092 vs. 0.558, respectively ( < 0.001). The 4D bi-directional Power Doppler vascular indices were statistically different between malignant tumors and normal ovaries. These findings could support the rationale for future studies for assessing this technology to discriminate between malignant and benign tumors.
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http://dx.doi.org/10.3390/diagnostics11040582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064103PMC
March 2021

Tumour-free distance: a novel prognostic marker in patients with early-stage cervical cancer treated by primary surgery.

Br J Cancer 2021 Mar 14;124(6):1121-1129. Epub 2020 Dec 14.

Gynecologic Oncology Center, Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Apolinarska 18, Prague 2, 12800, Czech Republic.

Background: Models predicting recurrence risk (RR) of cervical cancer are used to tailor adjuvant treatment after radical surgery. The goal of our study was to compare available prognostic factors and to develop a prognostic model that would be easy to standardise and use in routine clinical practice.

Methods: All consecutive patients with early-stage cervical cancer treated by primary surgery in a single referral centre (01/2007-12/2016) were eligible if assessed by standardised protocols for pre-operative imaging and pathology. Fifteen prognostic markers were evaluated in 379 patients, out of which 320 lymph node (LN)-negative.

Results: The best predictive model for the whole cohort entailed a combination of tumour-free distance (TFD) ≤ 3.5 mm and LN positivity, which separated two subgroups with a substantially distinct RR 36% and 6.5%, respectively. In LN-negative patients, a combination of TFD ≤ 3.5 mm and adenosquamous tumour type separated a group of nine patients with RR 33% from the rest of the group with 6% RR.

Conclusions: A newly identified prognostic marker, TFD, surpassed all traditional tumour-related markers in the RR assessment. Predictive models combining TFD, which can be easily accessed on pre-operative imaging, with LN status or tumour type can be used in daily practice and can help to identify patients with the highest RR.
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http://dx.doi.org/10.1038/s41416-020-01204-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961006PMC
March 2021

Sentinel lymph node mapping and intraoperative assessment in a prospective, international, multicentre, observational trial of patients with cervical cancer: The SENTIX trial.

Eur J Cancer 2020 09 1;137:69-80. Epub 2020 Aug 1.

Department of Gynaecology, St Olav's Hospital, Trondheim, Norway.

Background: SENTIX (ENGOT-CX2/CEEGOG-CX1) is an international, multicentre, prospective observational trial evaluating sentinel lymph node (SLN) biopsy without pelvic lymph node dissection in patients with early-stage cervical cancer. We report the final preplanned analysis of the secondary end-points: SLN mapping and outcomes of intraoperative SLN pathology.

Methods: Forty-seven sites (18 countries) with experience of SLN biopsy participated in SENTIX. We preregistered patients with stage IA1/lymphovascular space invasion-positive to IB2 (4 cm or smaller or 2 cm or smaller for fertility-sparing treatment) cervical cancer without suspicious lymph nodes on imaging before surgery. SLN frozen section assessment and pathological ultrastaging were mandatory. Patients were registered postoperatively if SLN were bilaterally detected in the pelvis, and frozen sections were negative.

Trial Registration: ClinicalTrials.gov (NCT02494063).

Results: We analysed data for 395 preregistered patients. Bilateral detection was achieved in 91% (355/395), and it was unaffected by tumour size, tumour stage or body mass index, but it was lower in older patients, in patients who underwent open surgery, and in sites with fewer cases. No SLN were found outside the seven anatomical pelvic regions. Most SLN and positive SLN were localised below the common iliac artery bifurcation. Single positive SLN above the iliac bifurcation were found in 2% of cases. Frozen sections failed to detect 54% of positive lymph nodes (pN1), including 28% of cases with macrometastases and 90% with micrometastases.

Interpretation: SLN biopsy can achieve high bilateral SLN detection in patients with tumours of 4 cm or smaller. At experienced centres, all SLN were found in the pelvis, and most were located below the iliac vessel bifurcation. SLN frozen section assessment is an unreliable tool for intraoperative triage because it only detects about half of N1 cases.
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http://dx.doi.org/10.1016/j.ejca.2020.06.034DOI Listing
September 2020

Validation of models to diagnose ovarian cancer in patients managed surgically or conservatively: multicentre cohort study.

BMJ 2020 07 30;370:m2614. Epub 2020 Jul 30.

Department of Development and Regeneration, KU Leuven, Herestraat 49 Box 805, 3000 Leuven, Belgium.

Objective: To evaluate the performance of diagnostic prediction models for ovarian malignancy in all patients with an ovarian mass managed surgically or conservatively.

Design: Multicentre cohort study.

Setting: 36 oncology referral centres (tertiary centres with a specific gynaecological oncology unit) or other types of centre.

Participants: Consecutive adult patients presenting with an adnexal mass between January 2012 and March 2015 and managed by surgery or follow-up.

Main Outcome Measures: Overall and centre specific discrimination, calibration, and clinical utility of six prediction models for ovarian malignancy (risk of malignancy index (RMI), logistic regression model 2 (LR2), simple rules, simple rules risk model (SRRisk), assessment of different neoplasias in the adnexa (ADNEX) with or without CA125). ADNEX allows the risk of malignancy to be subdivided into risks of a borderline, stage I primary, stage II-IV primary, or secondary metastatic malignancy. The outcome was based on histology if patients underwent surgery, or on results of clinical and ultrasound follow-up at 12 (±2) months. Multiple imputation was used when outcome based on follow-up was uncertain.

Results: The primary analysis included 17 centres that met strict quality criteria for surgical and follow-up data (5717 of all 8519 patients). 812 patients (14%) had a mass that was already in follow-up at study recruitment, therefore 4905 patients were included in the statistical analysis. The outcome was benign in 3441 (70%) patients and malignant in 978 (20%). Uncertain outcomes (486, 10%) were most often explained by limited follow-up information. The overall area under the receiver operating characteristic curve was highest for ADNEX with CA125 (0.94, 95% confidence interval 0.92 to 0.96), ADNEX without CA125 (0.94, 0.91 to 0.95) and SRRisk (0.94, 0.91 to 0.95), and lowest for RMI (0.89, 0.85 to 0.92). Calibration varied among centres for all models, however the ADNEX models and SRRisk were the best calibrated. Calibration of the estimated risks for the tumour subtypes was good for ADNEX irrespective of whether or not CA125 was included as a predictor. Overall clinical utility (net benefit) was highest for the ADNEX models and SRRisk, and lowest for RMI. For patients who received at least one follow-up scan (n=1958), overall area under the receiver operating characteristic curve ranged from 0.76 (95% confidence interval 0.66 to 0.84) for RMI to 0.89 (0.81 to 0.94) for ADNEX with CA125.

Conclusions: Our study found the ADNEX models and SRRisk are the best models to distinguish between benign and malignant masses in all patients presenting with an adnexal mass, including those managed conservatively.

Trial Registration: ClinicalTrials.gov NCT01698632.
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http://dx.doi.org/10.1136/bmj.m2614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391073PMC
July 2020

Ovarian mesonephric-like adenocarcinoma arising in serous borderline tumor: a case report with complex morphological and molecular analysis.

Diagn Pathol 2020 Jul 21;15(1):91. Epub 2020 Jul 21.

Gynecologic Oncology Center, Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Apolinarska 18, 12808, Prague 2, Czech Republic.

Background: Mesonephric-like adenocarcinoma (M-LAC) is a rare, recently described tumor occurring in the uterine corpus and ovary, which shares the same morphological and immunohistochemical features with the more common mesonephric adenocarcinoma (MAC), which mostly arises the uterine cervix. Despite the similarities between these tumors, the histogenesis of M-LAC is still disputable.

Case Presentation: Sixty-one-year-old woman presented with an advanced tumor of the left ovary with intraabdominal spread and liver metastases. After receiving 5 cycles of neoadjuvant chemotherapy, she underwent a hysterectomy with bilateral salpingo-oophorectomy, and resection of the liver metastasis, omentum, and appendix. Histologically, the ovarian tumor consisted of two components, whose morphology and immunohistochemical results were typical of either a serous borderline tumor (immunohistochemical positivity for PAX8, WT1, ER and PR) or a mesonephric-like carcinoma (immunohistochemical positivity for PAX8, TTF1 and GATA3). Only the component of the mesonephric-like adenocarcinoma metastasized to the omentum and liver. A molecular analysis with a panel of 271 genes (size 1020 kbp) was performed separately on samples from the borderline tumor, primary ovarian mesonephric-like adenocarcinoma, and liver metastasis. The results showed the clonal origin of all samples, which shared the same KRAS (NM_004985.3:c.34G > T, p.(G12C)) and PIK3CA (NM_006218.2:c.1633G > A, p.(E545K)) somatic mutations. Moreover, in the sample from the primary mesonephric-like carcinoma and its liver metastasis a likely pathogenic somatic MYCN mutation (NM_005378.4:c.131C > T, p.(P44L) was found. In all samples, the deletion of exons 9-10 in the CHEK2 gene was present, which is in concordance with the previously performed genetic testing of the blood specimen which revealed the hereditary CHEK2 mutation in this patient.

Conclusions: Our result support the theory that at least some mesonephric-like ovarian adenocarcinomas are of Müllerian origin. The serous borderline tumor seems to be a precursor of mesonephric-like adenocarcinoma, which has been proven in our case by both tumors sharing the same mutations, and the presence of cumulative molecular aberrations in the mesonephric-like adenocarcinoma.
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http://dx.doi.org/10.1186/s13000-020-01012-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372838PMC
July 2020

Micrometastases in Sentinel Lymph Nodes Represent a Significant Negative Prognostic Factor in Early-Stage Cervical Cancer: A Single-Institutional Retrospective Cohort Study.

Cancers (Basel) 2020 May 31;12(6). Epub 2020 May 31.

Gynecologic Oncology Center, Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, 128 00 Prague, Czech Republic.

The data on the prognostic significance of low volume metastases in lymph nodes (LN) are inconsistent. The aim of this study was to retrospectively analyze the outcome of a large group of patients treated with sentinel lymph node (SLN) biopsy at a single referral center. Patients with cervical cancer, stage T1a-T2b, common tumor types, negative LN on preoperative staging, treated by primary surgery between 01/2007 and 12/2016, with at least unilateral SLN detection were included. Patients with abandoned radical surgery due to intraoperative SLN positivity detected by frozen section were excluded. All SLNs were postoperatively processed by an intensive protocol for pathological ultrastaging. Altogether, 226 patients were analyzed. Positive LN were detected in 38 (17%) cases; macrometastases (MAC), micrometastases (MIC), isolated tumor cells (ITC) in 14, 16, and 8 patients. With the median follow-up of 65 months, 22 recurrences occurred. Disease-free survival (DFS) reached 90% in the whole group, 93% in LN-negative cases, 89% in cases with MAC, 69% with MIC, and 87% with ITC. The presence of MIC in SLN was associated with significantly decreased DFS and OS. Patients with MIC and MAC should be managed similarly, and SLN ultrastaging should become an integral part of the management of patients with early-stage cervical cancer.
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http://dx.doi.org/10.3390/cancers12061438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352782PMC
May 2020

European Society of Gynaecological Oncology quality indicators for surgical treatment of cervical cancer.

Int J Gynecol Cancer 2020 01;30(1):3-14

Clinical Research Unit, Institut Bergonie, Bordeaux, France.

Background: Optimizing and ensuring the quality of surgical care is essential to improve the management and outcome of patients with cervical cancer.To develop a list of quality indicators for surgical treatment of cervical cancer that can be used to audit and improve clinical practice.

Methods: Quality indicators were developed using a four-step evaluation process that included a systematic literature search to identify potential quality indicators, in-person meetings of an ad hoc group of international experts, an internal validation process, and external review by a large panel of European clinicians and patient representatives.

Results: Fifteen structural, process, and outcome indicators were selected. Using a structured format, each quality indicator has a description specifying what the indicator is measuring. Measurability specifications are also detailed to define how the indicator will be measured in practice. Each indicator has a target which gives practitioners and health administrators a quantitative basis for improving care and organizational processes.

Discussion: Implementation of institutional quality assurance programs can improve quality of care, even in high-volume centers. This set of quality indicators from the European Society of Gynaecological Cancer may be a major instrument to improve the quality of surgical treatment of cervical cancer.
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http://dx.doi.org/10.1136/ijgc-2019-000878DOI Listing
January 2020

Ultrasound and Clinical Preoperative Characteristics for Discrimination Between Ovarian Metastatic Colorectal Cancer and Primary Ovarian Cancer: A Case-Control Study.

Diagnostics (Basel) 2019 Dec 1;9(4). Epub 2019 Dec 1.

Gynecologic Oncology Centre, Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University, General University Hospital in Prague, Prague 12851, Czech Republic.

The aim of this study was to describe the clinical and sonographic features of ovarian metastases originating from colorectal cancer (mCRC), and to discriminate mCRC from primary ovarian cancer (OC). We conducted a multi-institutional, retrospective study of consecutive patients with ovarian mCRC who had undergone ultrasound examination using the International Ovarian Tumor Analysis (IOTA) terminology, with the addition of evaluating signs of necrosis and abdominal staging. A control group included patients with primary OC. Clinical and ultrasound data, subjective assessment (SA), and an assessment of different neoplasias in the adnexa (ADNEX) model were evaluated. Fisher's exact and Student's -tests, the area under the receiver-operating characteristic curve (AUC), and classification and regression trees (CART) were used to conduct statistical analyses. In total, 162 patients (81 with OC and 81 with ovarian mCRC) were included. None of the patients with OC had undergone chemotherapy for CRC in the past, compared with 40% of patients with ovarian mCRC ( < 0.001). The ovarian mCRC tumors were significantly larger, a necrosis sign was more frequently present, and tumors had an irregular wall or were fixed less frequently; ascites, omental cake, and carcinomatosis were less common in mCRC than in primary OC. In a subgroup of patients with ovarian mCRC who had not undergone treatment for CRC in anamnesis, tumors were larger, and had fewer papillations and more locules compared with primary OC. The highest AUC for the discrimination of ovarian mCRC from primary OC was for CART (0.768), followed by SA (0.735) and ADNEX calculated with CA-125 (0.680). Ovarian mCRC and primary OC can be distinguished based on patient anamnesis, ultrasound pattern recognition, a proposed decision tree model, and an ADNEX model with CA-125 levels.
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http://dx.doi.org/10.3390/diagnostics9040210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963303PMC
December 2019

What Is the Role of Imaging at Primary Diagnostic Work-Up in Uterine Cervical Cancer?

Curr Oncol Rep 2019 07 29;21(9):77. Epub 2019 Jul 29.

Department of Obstetrics and Gynaecology, Maastricht University Medical Centre, Maastricht, The Netherlands.

Purpose Of Review: For uterine cervical cancer, the recently revised International Federation of Gynecology and Obstetrics (FIGO) staging system (2018) incorporates imaging and pathology assessments in its staging. In this review we summarize the reported staging performances of conventional and novel imaging methods and provide an overview of promising novel imaging methods relevant for cervical cancer patient care.

Recent Findings: Diagnostic imaging during the primary diagnostic work-up is recommended to better assess tumor extent and metastatic disease and is now reflected in the 2018 FIGO stages 3C1 and 3C2 (positive pelvic and/or paraaortic lymph nodes). For pretreatment local staging, imaging by transvaginal or transrectal ultrasound (TVS, TRS) and/or magnetic resonance imaging (MRI) is instrumental to define pelvic tumor extent, including a more accurate assessment of tumor size, stromal invasion depth, and parametrial invasion. In locally advanced cervical cancer, positron emission tomography-computed tomography (PET-CT) or computed tomography (CT) is recommended, since the identification of metastatic lymph nodes and distant metastases has therapeutic consequences. Furthermore, novel imaging techniques offer visualization of microstructural and functional tumor characteristics, reportedly linked to clinical phenotype, thus with a potential for further improving risk stratification and individualization of treatment. Diagnostic imaging by MRI/TVS/TRS and PET-CT/CT is instrumental for pretreatment staging in uterine cervical cancer and guides optimal treatment strategy. Novel imaging techniques may also provide functional biomarkers with potential relevance for developing more targeted treatment strategies in cervical cancer.
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http://dx.doi.org/10.1007/s11912-019-0824-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663927PMC
July 2019

Ultrasound characteristics of a symptomatic and asymptomatic lymphocele after pelvic and/or paraaortic lymphadenectomy.

Taiwan J Obstet Gynecol 2019 Mar;58(2):266-272

Gynecological Oncology Center, Department of Obstetrics and Gynecology, Charles University - First Faculty of Medicine and General University Hospital, Apolinarska 18, 128 00 Prague, Czech Republic; Department of Obstetrics and Gynecology, Charles University - First Faculty of Medicine and Na Bulovce Hospital, Budinova 67/2, 181 00 Prague, Czech Republic. Electronic address:

Objective: To describe the sonographic characteristics of a lymphocele after pelvic and/or paraaortic lymphadenectomy for gynecological malignancy, analyze and identify ultrasound characteristics related to the symptomatic and asymptomatic lymphoceles.

Materials And Methods: This is a retrospective analysis of ultrasound examination data collected consecutively in patients after pelvic and/or paraaortic lymphadenectomy in one institution. We recorded the number of lymphoceles, localization, size; ultrasound morphology following International Ovarian Tumor Analysis group classification and symptoms.

Results: We described and analyzed 227 lymphoceles (150 asymptomatic and 77 symptomatic) in 161 patients. The asymptomatic lymphocele is typically a thick-walled cystic lesion without vascularization, round and unilocular with anechoic or ground-glass content. The symptomatic lymphocele is typically an oval, or ovoid, unilocular lesion with low-level or anechoic content (ground glass content is unlikely to be present, p < 0.001) and the presence of debris and septations. The lymphocele size (p = 0.001), number of lymphoceles (>1) (p = 0.005), septa (p = 0.002), and debris (p < 0.001) were independent ultrasound features correlating to symptoms development. More than one lymphocele (p = 0.047), septations (p = 0.007) and presence of debris (p < 0.001) were independent ultrasound features correlated to infection.

Conclusion: Ultrasound features of symptomatic and asymptomatic lymphocele differ. The clues for lymphocele differential diagnosis are the history of lymphadenectomy and the finding cystic lesion with typically ultrasound features of lymphocele, adjacent to great pelvic vessels. Unique ultrasound features of lymphocele may help to distinguish from tumor relapse, hematoma, abscess, seroma or urinoma.
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http://dx.doi.org/10.1016/j.tjog.2019.01.018DOI Listing
March 2019

Clinical and Ultrasound Characteristics of the Microcystic Elongated and Fragmented (MELF) Pattern in Endometrial Cancer According to the International Endometrial Tumor Analysis (IETA) criteria.

Int J Gynecol Cancer 2019 01;29(1):119-125

Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.

Objectives: To describe sonographic features of the microcystic elongated and fragmented (MELF) pattern of myometrial invasion (MI) using the International Endometrial Tumor Analysis (IETA) criteria; to assess the effect of the MELF pattern on preoperative ultrasound evaluation of MI; and to determine the relationship of the MELF pattern to more advanced stage (≥ IB) and lymph node metastases in women with endometrioid endometrial cancer.

Methods/materials: We included 850 women with endometrioid endometrial cancer from the prospective IETA 4 study. Ultrasound experts performed all ultrasound examinations, according to the IETA protocol. Reference pathologists assessed the presence or absence of the MELF pattern. Sonographic features and accuracy of ultrasound assessment of MI were compared in cases with the presence and the absence of the MELF pattern. The MELF pattern was correlated to more advanced stage (≥IB) and lymph node metastases.

Results: The MELF pattern was present in 197 (23.2%) women. On preoperative ultrasound imaging the endometrium was thicker (p = 0.031), more richly vascularized (p = 0.003) with the multiple multifocal vessel pattern (p < 0.001) and the assessment of adenomyosis was more often uncertain (p < 0.001). The presence or the absence of the MELF pattern did not affect the accuracy of the assessment of MI. The MELF pattern was associated with deep myometrial invasion (≥ 50%) (p < 0.001), cervical stromal invasion (p = 0.037), more advanced stage (≥ IB) (p < 0.001) and lymph node metastases (p = 0.011).

Conclusions: Tumors with the MELF pattern were slightly larger, more richly vascularized with multiple multifocal vessels and assessment of adenomyosis was more uncertain on ultrasound imaging. The MELF pattern did not increase the risk of underestimating MI in preoperative ultrasound staging. Tumors with the MELF pattern were more than twice as likely to have more advanced stage (≥ IB) and lymph node metastases.
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http://dx.doi.org/10.1136/ijgc-2018-000045DOI Listing
January 2019

Surgical treatment of "intermediate risk" lymph node negative cervical cancer patients without adjuvant radiotherapy-A retrospective cohort study and review of the literature.

Gynecol Oncol 2018 12 20;151(3):438-443. Epub 2018 Oct 20.

Department of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, and Department of Obstetrics and Gynaecology, Melbourne University, Melbourne, Australia.

Objectives: The role of adjuvant radiotherapy for lymph node-negative stage IB patients with tumor-related negative prognostic factors is not uniformly accepted. It is advocated based on the GOG 92 trial, which was initiated in 1989. The aim of the current study is to report the oncological outcome of "intermediate risk" patients treated by tailored surgery without adjuvant radiotherapy. Data from two institutions that refer these patients for adjuvant radiotherapy served as a control group.

Methods: Included were patients with stage IB cervical cancer treated with radical hysterectomy and pelvic lymphadenectomy, who had negative pelvic lymph nodes but a combination of negative prognostic factors adopted from the GOG 92 trial. Data were obtained from prospectively collected databases of three institutions. Radical surgery was a single-treatment modality in one of them and in the remaining two institutes it was followed by adjuvant chemoradiation.

Results: In 127 patients who received only radical surgery, with a median follow-up of 6.1 years, the local recurrence rate was 1.6% (2 cases), and total recurrence was 6.3% (8 cases). Disease-specific survival at 5 years was 95.7% (91.9%; 99.4%) and 91% (83.7%; 98.3%) at 10 years. The only significant factor for disease-specific survival was tumor size ≥4 cm (P = 0.032). The recurrence rate, local control or overall survival did not differ from the control group. Adjuvant radiotherapy was not a significant prognostic factor within the whole cohort.

Conclusions: An excellent oncological outcome, especially local control, can be achieved by both radical surgery or combined treatment in stage IB lymph node-negative cervical cancer patients with negative prognostic factors. The substantially better outcome than in the GOG 92 trial can be attributed to more accurate pre-operative and pathological staging and an improvement in surgical techniques.
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http://dx.doi.org/10.1016/j.ygyno.2018.10.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615487PMC
December 2018

Correction to: Correction to: The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology Guidelines for the Management of Patients with Cervical Cancer.

Virchows Arch 2018 07 25:391. Epub 2018 Jul 25.

University Hospital, Careggi, Florence, Italy.

Regrettably, the author metadata used for the previous correction (doi: https://doi.org/10.1007/s00428-018-2380-7 ) contained an error in the tagging of W. Glenn McCluggage's name; this has been corrected. No further adjustments have been made to the Correction, or the original Guideline paper (doi: https://doi.org/10.1007/s00428-018-2362-9 ).
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http://dx.doi.org/10.1007/s00428-018-2419-9DOI Listing
July 2018

The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology guidelines for the management of patients with cervical cancer.

Radiother Oncol 2018 Jun 1;127(3):404-416. Epub 2018 May 1.

University Hospital, Careggi, Florence, Italy.

Background: Despite significant advances in the screening, detection, and treatment of preinvasive cervical lesions, invasive cervical cancer is the fifth most common cancer in European women. There are large disparities in Europe and worldwide in the incidence, management, and mortality of cervical cancer.

Objective: The European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly develop clinically relevant and evidence-based guidelines in order to improve the quality of care for women with cervical cancer across Europe and worldwide.

Methods: The ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of cervical cancer (23 experts across Europe). To ensure that the guidelines are evidence based, the current literature identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 159 international reviewers, selected through ESGO/ESTRO/ESP and including patient representatives.

Results: The guidelines cover comprehensively staging, management, and follow-up for patients with cervical cancer. Management includes fertility sparing treatment; stage T1a, T1b1/T2a1, clinically occult cervical cancer diagnosed after simple hysterectomy; early and locally advanced cervical cancer; primary distant metastatic disease; cervical cancer in pregnancy; and recurrent disease. Principles of radiotherapy and pathological evaluation are defined.
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http://dx.doi.org/10.1016/j.radonc.2018.03.003DOI Listing
June 2018

The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology Guidelines for the Management of Patients with Cervical Cancer.

Virchows Arch 2018 Jun 4;472(6):919-936. Epub 2018 May 4.

University Hospital, Careggi, Florence, Italy.

Background: Despite significant advances in the screening, detection, and treatment of preinvasive cervical lesions, invasive cervical cancer is the fifth most common cancer in European women. There are large disparities in Europe and worldwide in the incidence, management, and mortality of cervical cancer.

Objective: The European Society of Gynecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly develop clinically relevant and evidence-based guidelines in order to improve the quality of care for women with cervical cancer across Europe and worldwide.

Methods: The ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of cervical cancer (23 experts across Europe). To ensure that the guidelines are evidence based, the current literature identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 159 international reviewers, selected through ESGO/ESTRO/ESP and including patient representatives.

Results: The guidelines cover comprehensively staging, management, and follow-up for patients with cervical cancer. Management includes fertility sparing treatment; stage T1a, T1b1/T2a1, clinically occult cervical cancer diagnosed after simple hysterectomy; early and locally advanced cervical cancer; primary distant metastatic disease; cervical cancer in pregnancy; and recurrent disease. Principles of radiotherapy and pathological evaluation are defined.
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http://dx.doi.org/10.1007/s00428-018-2362-9DOI Listing
June 2018

The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology Guidelines for the Management of Patients With Cervical Cancer.

Int J Gynecol Cancer 2018 05;28(4):641-655

Background: Despite significant advances in the screening, detection, and treatment of preinvasive cervical lesions, invasive cervical cancer is the fifth most common cancer in European women. There are large disparities in Europe and worldwide in the incidence, management, and mortality of cervical cancer.

Objective: The European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly develop clinically relevant and evidence-based guidelines in order to improve the quality of care for women with cervical cancer across Europe and worldwide.

Methods: The ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of cervical cancer (23 experts across Europe). To ensure that the guidelines are evidence based, the current literature identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 159 international reviewers, selected through ESGO/ESTRO/ESP and including patient representatives.

Results: The guidelines cover comprehensively staging, management, and follow-up for patients with cervical cancer. Management includes fertility sparing treatment; stage T1a, T1b1/T2a1, clinically occult cervical cancer diagnosed after simple hysterectomy; early and locally advanced cervical cancer; primary distant metastatic disease; cervical cancer in pregnancy; and recurrent disease. Principles of radiotherapy and pathological evaluation are defined.
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http://dx.doi.org/10.1097/IGC.0000000000001216DOI Listing
May 2018

The Diagnostic Accuracy of Ultrasound in Assessment of Myometrial Invasion in Endometrial Cancer: Subjective Assessment versus Objective Techniques.

Biomed Res Int 2017 24;2017:1318203. Epub 2017 Jul 24.

Gynecologic Oncology Centre, Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University, General University Hospital, Prague, Czech Republic.

The aim of this study was to assess the diagnostic accuracy of subjective ultrasound evaluation of myometrial invasion of endometrial cancer and to compare its accuracy to objective methods. All consecutive patients with histologically proven endometrial cancer, who underwent ultrasound evaluation followed by surgical staging between January 2009 and December 2011, were prospectively enrolled. Myometrial invasion was evaluated by subjective assessment using ultrasound (<50% or ≥50%) and calculated as deepest invasion/normal myometrium ratio (Gordon's ratio) and as tumor/uterine anteroposterior diameter ratio (Karlsson's ratio). Histological assessment from hysterectomy was considered the gold standard. Altogether 210 patients were prospectively included. Subjective assessment and two objective ratios were found to be statistically significant predictors of the myometrial invasion (AUC = 0.65, value < 0.001). Subjective assessment was confirmed as the most reliable method to assess myometrial invasion (79.3% sensitivity, 73.2% specificity, and 75.7% overall accuracy). Deepest invasion/normal myometrium (Gordon's) ratio (cut-off 0.5) reached 69.6% sensitivity, 65.9% specificity, and 67.3% overall accuracy. Tumor/uterine anteroposterior diameter (Karlsson's) ratio with the same cut-off reached 56.3% sensitivity, 76.4% specificity, and 68.1% overall accuracy. The subjective ultrasound evaluation of myometrial invasion performed better than objective methods in nearly all measures but showed statistically significantly better outcomes only in case of sensitivity.
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http://dx.doi.org/10.1155/2017/1318203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546069PMC
April 2018

Validation of the Performance of International Ovarian Tumor Analysis (IOTA) Methods in the Diagnosis of Early Stage Ovarian Cancer in a Non-Screening Population.

Diagnostics (Basel) 2017 Jun 2;7(2). Epub 2017 Jun 2.

Department of Development and Regeneration, KU Leuven, Leuven post code3000, Belgium.

Background: The aim of this study was to assess and compare the performance of different ultrasound-based International Ovarian Tumor Analysis (IOTA) strategies and subjective assessment for the diagnosis of early stage ovarian malignancy.

Methods: This is a secondary analysis of a prospective multicenter cross-sectional diagnostic accuracy study that included 1653 patients recruited at 18 centers from 2009 to 2012. All patients underwent standardized transvaginal ultrasonography by experienced ultrasound investigators. We assessed test performance of the IOTA Simple Rules (SRs), Simple Rules Risk (SRR), the Assessment of Different NEoplasias in the adneXa (ADNEX) model and subjective assessment to discriminate between stage I-II ovarian cancer and benign disease. Reference standard was histology after surgery.

Results: 230 (13.9%) patients proved to have stage I-II primary invasive ovarian malignancy, and 1423 (86.1%) had benign disease. Sensitivity and specificity with respect to malignancy (95% confidence intervals) of the original SRs (classifying all inconclusive cases as malignant) were 94.3% (90.6% to 96.7%) and 73.4% (71.0% to 75.6%). Subjective assessment had a sensitivity and specificity of 90.0% (85.4% to 93.2%) and 86.7% (84.9% to 88.4%), respectively. The areas under the receiver operator characteristic curves of SRR and ADNEX were 0.917 (0.902 to 0.933) and 0.905 (0.920 to 0.934), respectively. At a 1% risk cut-off, sensitivity and specificity for SRR were 100% (98.4% to 100%) and 38.0% (35.5% to 40.6%), and for ADNEX were 100% (98.4% to 100%) and 19.4% (17.4% to 21.5%). At a 30% risk cut-off, sensitivity and specificity for SRR were 88.3% (83.5% to 91.8%) and 81.1% (79% to 83%), and for ADNEX were 84.5% (80.5% to 89.6%) and 84.5% (82.6% to 86.3%).

Conclusion: This study shows that all three IOTA strategies have good ability to discriminate between stage I-II ovarian malignancy and benign disease.
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http://dx.doi.org/10.3390/diagnostics7020032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489952PMC
June 2017

Clinical Utility of Risk Models to Refer Patients with Adnexal Masses to Specialized Oncology Care: Multicenter External Validation Using Decision Curve Analysis.

Clin Cancer Res 2017 Sep 16;23(17):5082-5090. Epub 2017 May 16.

Department of Development and Regeneration, KU Leuven, Leuven, Belgium.

To evaluate the utility of preoperative diagnostic models for ovarian cancer based on ultrasound and/or biomarkers for referring patients to specialized oncology care. The investigated models were RMI, ROMA, and 3 models from the International Ovarian Tumor Analysis (IOTA) group [LR2, ADNEX, and the Simple Rules risk score (SRRisk)]. A secondary analysis of prospectively collected data from 2 cross-sectional cohort studies was performed to externally validate diagnostic models. A total of 2,763 patients (2,403 in dataset 1 and 360 in dataset 2) from 18 centers (11 oncology centers and 7 nononcology hospitals) in 6 countries participated. Excised tissue was histologically classified as benign or malignant. The clinical utility of the preoperative diagnostic models was assessed with net benefit (NB) at a range of risk thresholds (5%-50% risk of malignancy) to refer patients to specialized oncology care. We visualized results with decision curves and generated bootstrap confidence intervals. The prevalence of malignancy was 41% in dataset 1 and 40% in dataset 2. For thresholds up to 10% to 15%, RMI and ROMA had a lower NB than referring all patients. SRRisks and ADNEX demonstrated the highest NB. At a threshold of 20%, the NBs of ADNEX, SRrisks, and RMI were 0.348, 0.350, and 0.270, respectively. Results by menopausal status and type of center (oncology vs. nononcology) were similar. All tested IOTA methods, especially ADNEX and SRRisks, are clinically more useful than RMI and ROMA to select patients with adnexal masses for specialized oncology care. .
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http://dx.doi.org/10.1158/1078-0432.CCR-16-3248DOI Listing
September 2017

The association of enchondromatosis with malignant transformed chondrosarcoma and ovarian juvenile granulosa cell tumor (Ollier disease).

Taiwan J Obstet Gynecol 2017 Apr;56(2):253-257

Gynecologic Oncology Center, Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic. Electronic address:

Objective: Ovarian juvenile granulosa cell tumor has an interesting association with multiple enchondromatosis (Ollier disease and Maffucci syndrome) and should be considered a leading diagnosis when an ovarian mass is found in young patients with these conditions. Besides the association with nonskeletal malignancies, there is a high risk of malignant transformation of enchondroma in chondrosarcoma as was also the case in this instance.

Case Report: The report uses multiple images to document the representative and characteristic markers of multiple enchondromas in a 22-year-old patient with Ollier disease complicated by malignant transformation of chondrosarcoma and in whom the disease is associated with ovarian juvenile granulosa cell tumor of the right ovary.

Conclusion: It is important to recognize that when the female patient presents with enchondromatosis and a large unilateral multilocular-solid ovarian mass, the specific diagnosis of granulosa cell tumor can be made with high accuracy.
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http://dx.doi.org/10.1016/j.tjog.2017.02.002DOI Listing
April 2017

Anastomosing Hemangioma of the Ovary: A Clinicopathological Study of Six Cases with Stromal Luteinization.

Pathol Oncol Res 2017 Oct 3;23(4):717-722. Epub 2017 Jan 3.

Gynecologic Oncology Center, Department of Obstetrics and Gynecology, First Faculty of Medicine Charles University and General University Hospital in Prague, Prague, Czech Republic.

We report six cases of anastomosing hemangioma of the ovary. All lesions were unilateral and arose in 43 to 81 year old females. In all but one patient, the tumor was asymptomatic and represented incidental finding. The exception was a tumor associated with massive ascites and elevated CA 125. The tumors were, on cut section, spongy and dark violet in color. The size of tumors ranged from 0.5 to 3.5 cm. All lesions showed the same histological features and consisted of capillary sized anastomosing vessels with sinusoid-like pattern intermingled with sporadic medium sized vessels. Interestingly, in all cases there were areas of luteinized cells at the tumor periphery, which ranged from rare small nests to multiple and commonly confluent areas. In one tumor, components of mature adipose tissue were present. Immunohistochemically, all tumors were CD31 and CD34 positive. Other markers examined were negative, including; estrogen receptor, progesterone receptor, androgen receptor, and D2-40. Proliferative activity (Ki-67 index) was very low in all cases. Anastomosing hemangioma is a rare entity, only 8 lesions occurring in ovary has been described from its initial description in 2009. We report six additional cases with their clinicopathological correlation.
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http://dx.doi.org/10.1007/s12253-016-0186-yDOI Listing
October 2017

Sensitivity of Follow-Up Methods in Patients After Fertility-Sparing Surgery for Cervical Cancers.

Int J Gynecol Cancer 2017 01;27(1):147-153

*1st Faculty of Medicine, Department of Gynecology and Obstetrics, Gynecologic Oncology Centre, Charles University and General University Hospital in Prague; and †Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic.

Objective: The aim of our study was to compare the sensitivity of various methods and their combinations in the follow-up of patients with cervical cancer after fertility-sparing surgery (FSS).

Methods: Included were women with cervical cancer in stages IA2 to IB2 who underwent FSS, which includes pelvic lymphadenectomy, sentinel lymph node biopsy, abdominal radical trachelectomy, vaginal trachelectomy, or needle conization. Follow-up visits were scheduled at 3-month intervals and included symptom-oriented discussion, gynecological and physical examination, colposcopy, Papanicolaou test, human papillomavirus (HPV) DNA test, and ultrasound examination. All cases with a recurrent disease were thoroughly analyzed, and the results of individual examinations were compared.

Results: In total, 43 women (IA2, 8; IB1, 33; IB2, 2) were enrolled. The mean patient age was 31 years; most patients were nulliparous (68.4%, 26/38) with squamous cell cancers (26/38). Abdominal radical trachelectomy was performed in 10 women, simple vaginal trachelectomy was performed in 11 women, and conization was performed in 22 women, according to the tumor characteristics and topography. The median duration of the follow-up reached 37 months. Invasive cancer and high- and low-grade squamous intraepithelial lesions were detected in 8, 1, and 1 patients, respectively. All except 1 event were central, detected within the first year after FSS. Only 2 cases were symptomatic. Colposcopy detected 7 of 10 recurrences; 5 of them were HPV positive, and, in 2 cases, a Papanicolaou test revealed abnormalities. Papanicolaou tests were false positive in 27.7%, especially after trachelectomies.

Conclusions: Most patients in whom cancer recurred after FSS reveal central or pelvic lesions, which can be successfully treated with salvage surgery or radiotherapy. The early detection of recurrence is an essential condition for a favorable oncological outcome. Colposcopy alone and in combination with HPV positivity showed the highest sensitivity for the detection of recurrent diseases, whereas other methods had limited reliability.
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http://dx.doi.org/10.1097/IGC.0000000000000835DOI Listing
January 2017

Results of less radical fertility-sparing procedures with omitted parametrectomy for cervical cancer: 5years of experience.

Gynecol Oncol 2016 09 7;142(3):401-4. Epub 2016 Jul 7.

Department of Gynecology and Obstetrics, 1(st) Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic.

Objective: The aim of our study was to describe oncological and obstetrical outcomes in patients who underwent less radical fertility-sparing surgical (FSS) procedures with omitted parametrectomy for cervical cancer.

Methods: Included were women with cervical cancer stages IA2-IB2 who were under the age of 40 and desired future pregnancy. Patients underwent pelvic lymphadenectomy and sentinel lymph node biopsy. Node-negative cases underwent subsequent cervical surgery and were further analyzed. Neoadjuvant chemotherapy (NAC) was administered in patients with tumors >2cm and/or involving >2/3 of cervical stroma. Simple vaginal trachelectomy or needle conization were performed according to tumor extent and topography. The follow-up period started once free surgical margins were reached.

Results: Out of 44 women enrolled, 32 women (IA2=7, IB1=23, IB2=2) successfully completed FSS. NAC was administered in 9 (28.1%) cases. A simple trachelectomy was performed in 11 patients and needle conization in 21 patients. During the follow-up, 6 out of 32 women became pregnant. Of these, 1 miscarried and 5 successfully delivered. Disease recurred in 6 patients; 5 recurrences were central and 1 recurrence presented as an ovarian mass. Invasive cervical carcinoma, high-grade squamous intraepithelial (HSIL), and low-grade squamous intraepithelial (LSIL) lesions were detected in 4, 1 and 1 patients, respectively. Three of them received NAC. All events were detected within 16months after surgery.

Conclusions: Nearly 27% of patients cannot complete FSS due to node positivity, progression during NAC, or involved margins. The total recurrence rate reached 18.8%, with the majority of invasive recurrences detected in patients after NAC followed by FSS. These patients represent cases at a higher risk of recurrence even if adequate free margins are reached by surgery. Nearly half of the cohort did not consider pregnancy in the near future because of personal reasons.
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http://dx.doi.org/10.1016/j.ygyno.2016.07.008DOI Listing
September 2016

Prospective Evaluation of Ultrasound Accuracy in the Detection of Pelvic Carcinomatosis in Patients with Ovarian Cancer.

Ultrasound Med Biol 2016 09 28;42(9):2196-202. Epub 2016 Jun 28.

Gynecologic Oncology Center, Department of Gynecology and Obstetrics, First Faculty of Medicine and General University Hospital, Charles University in Prague, Prague, Czech Republic. Electronic address:

We analyzed the accuracy of transvaginal sonography in detection of pelvic carcinomatosis in ovarian cancer patients and factors (age, body mass index, performance status, ascites, stage, histotype, tumor grade) influencing the performance of ultrasound. In this prospective study, all 191 consecutively included patients underwent a pre-operative ultrasound staging examination according to institutional protocol. Peritoneal spread was assessed on the basis of peri-operative findings or histology. The area under the receiver operating characteristic curve for the detection of carcinomatosis was 0.90 (0.84-0.93); the sensitivity was 84% (95% confidence interval [CI]: 75%-%90), specificity 96% (95% CI: 89%-99%), positive predictive value 96% (95% CI: 89%-99%), negative predictive value 83% (95% CI: 74%-90%) and overall accuracy 89% (95% CI: 84%-93%). We report that transvaginal sonography is clinically useful in the detection of pelvic carcinomatosis.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2016.05.014DOI Listing
September 2016

Age-related differences in the sonographic characteristics of endometriomas.

Hum Reprod 2016 08 9;31(8):1723-31. Epub 2016 Jun 9.

Department of Obstetrics and Gynecology, KU Leuven, Leuven, Belgium.

Study Question: Do sonographic characteristics of ovarian endometriomas vary with age in premenopausal women?

Summary Answer: With increasing age, multilocular cysts and cysts with papillations and other solid components become more common whereas ground glass echogenicity of cyst fluid becomes less common.

What Is Known Already: Expectant or medical management of women with endometriomas is now accepted. Therefore, the accuracy of non-invasive diagnosis of these cysts is pivotal. A clinically relevant question is whether the sonographic characteristics of ovarian endometriomas are the same irrespective of the age of the woman.

Study Design, Size, Duration: This is a secondary analysis of cross-sectional data in the International Ovarian Tumor Analysis (IOTA) database. The database contains clinical and ultrasound information collected pre-operatively between 1999 and 2012 from 5914 patients with adnexal masses in 24 ultrasound centres in 10 countries.

Participants/materials, Setting, Methods: There were 1005 histologically confirmed endometriomas in adult premenopausal patients found in the database and these were used in our analysis. The following ultrasound variables (defined using IOTA terminology) were used to describe the ultrasound appearance of the endometriomas: tender mass at ultrasound, largest diameter of lesion, tumour type (unilocular, unilocular-solid, multilocular, multilocular-solid, solid), echogenicity of cyst content, presence of papillations, number of papillations, height (mm) of largest papillation, presence and proportion of solid tissue and number of cyst locules, as well as vascularity in papillations and colour content of the tumour scan (colour score) on colour or power Doppler ultrasounds. Results are reported as median difference or odds ratio (OR) per 10 years increase in age.

Main Results And The Role Of Chance: Maximal lesion diameter did not vary substantially with age (+1.3 mm difference per 10 years increase in age, 95% confidence interval (CI) -1.4 to 4.0). Tender mass at scan was less common in the older the woman (OR 0.75, 95% CI 0.63-0.89), as were unilocular cysts relative to multilocular cysts (OR 0.70, 95% CI 0.57-0.85) and to lesions with solid components (OR 0.61, 95% CI 0.48-0.77), and ground glass echogenicity relative to homogeneous low-level echogenicity (OR 0.74, 95% CI 0.58-0.94) and other types of echogenicity of cyst contents (OR 0.64, 95% CI 0.50-0.81). Papillations were more common the older the woman (OR 1.65, 95% CI 1.24-2.21), but their height and vascularization showed no clear relation to age.

Limitations, Reasons For Caution: It is a limitation that we have little clinical information on the women included, e.g. previous surgery or medical treatment for endometriosis. It is important to emphasize that we do not know the age of the endometrioma itself and that our study is not longitudinal and so does not describe changes in endometriomas over time. The differences in the ultrasound appearance of endometriomas between women of different ages might be explained by previous surgery or medical treatment and might not be an effect of age per se.

Wider Implications Of The Findings: Awareness of physicians that the ultrasound appearance of endometriomas differs between women of different ages may facilitate a correct diagnosis of endometrioma.

Study Funding/competing Interests: This study was supported in part by the Regione Autonoma della Sardegna (project code CPR-24750). B.V.C., A.C. and D.T. are supported by the Fund for Scientific Research Flanders, Belgium (FWO). The authors declare that there is no conflict of interest.
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http://dx.doi.org/10.1093/humrep/dew113DOI Listing
August 2016

Predicting the risk of malignancy in adnexal masses based on the Simple Rules from the International Ovarian Tumor Analysis group.

Am J Obstet Gynecol 2016 Apr 19;214(4):424-437. Epub 2016 Jan 19.

Skåne University Hospital Malmö, Lund University, Malmö, Sweden.

Background: Accurate methods to preoperatively characterize adnexal tumors are pivotal for optimal patient management. A recent metaanalysis concluded that the International Ovarian Tumor Analysis algorithms such as the Simple Rules are the best approaches to preoperatively classify adnexal masses as benign or malignant.

Objective: We sought to develop and validate a model to predict the risk of malignancy in adnexal masses using the ultrasound features in the Simple Rules.

Study Design: This was an international cross-sectional cohort study involving 22 oncology centers, referral centers for ultrasonography, and general hospitals. We included consecutive patients with an adnexal tumor who underwent a standardized transvaginal ultrasound examination and were selected for surgery. Data on 5020 patients were recorded in 3 phases from 2002 through 2012. The 5 Simple Rules features indicative of a benign tumor (B-features) and the 5 features indicative of malignancy (M-features) are based on the presence of ascites, tumor morphology, and degree of vascularity at ultrasonography. Gold standard was the histopathologic diagnosis of the adnexal mass (pathologist blinded to ultrasound findings). Logistic regression analysis was used to estimate the risk of malignancy based on the 10 ultrasound features and type of center. The diagnostic performance was evaluated by area under the receiver operating characteristic curve, sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), positive predictive value (PPV), negative predictive value (NPV), and calibration curves.

Results: Data on 4848 patients were analyzed. The malignancy rate was 43% (1402/3263) in oncology centers and 17% (263/1585) in other centers. The area under the receiver operating characteristic curve on validation data was very similar in oncology centers (0.917; 95% confidence interval, 0.901-0.931) and other centers (0.916; 95% confidence interval, 0.873-0.945). Risk estimates showed good calibration. In all, 23% of patients in the validation data set had a very low estimated risk (<1%) and 48% had a high estimated risk (≥30%). For the 1% risk cutoff, sensitivity was 99.7%, specificity 33.7%, LR+ 1.5, LR- 0.010, PPV 44.8%, and NPV 98.9%. For the 30% risk cutoff, sensitivity was 89.0%, specificity 84.7%, LR+ 5.8, LR- 0.13, PPV 75.4%, and NPV 93.9%.

Conclusion: Quantification of the risk of malignancy based on the Simple Rules has good diagnostic performance both in oncology centers and other centers. A simple classification based on these risk estimates may form the basis of a clinical management system. Patients with a high risk may benefit from surgery by a gynecological oncologist, while patients with a lower risk may be managed locally.
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http://dx.doi.org/10.1016/j.ajog.2016.01.007DOI Listing
April 2016

Ultrasound in gynecological cancer: is it time for re-evaluation of its uses?

Curr Oncol Rep 2015 Jun;17(6):28

Gynecologic Oncology Centre, Department of Obstetrics and Gynecology, First Faculty of Medicine and General University Hospital, Charles University in Prague, Apolinarska 18, 120 00, Prague, Czech Republic,

Ultrasound is the primary imaging modality in gynecological oncology. Over the last decade, there has been a massive technology development which led to a dramatic improvement in the quality ultrasound imaging. If performed by an experienced sonographer, ultrasound has an invaluable role in the primary diagnosis of gynecological cancer, in the assessment of tumor extent in the pelvis and abdominal cavity, in the evaluation of the treatment response, and in follow-up. Ultrasound is also a valuable procedure for monitoring patients treated with fertility-sparing surgery. Furthermore, it is an ideal technique to guide tru-cut biopsy for the collection of material for histology. Taking into consideration that besides its accuracy, the ultrasound is a commonly available, non-invasive, and inexpensive imaging method that can be carried out without any risk or discomfort to the patient; it is time to reconsider its role in gynecologic oncology and to allocate resources for a specialized education of future experts in ultrasound imaging in gynecology.
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http://dx.doi.org/10.1007/s11912-015-0449-xDOI Listing
June 2015
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