Publications by authors named "Michal Zikan"

64 Publications

Molecular testing in endometrial carcinoma (Joint recommendation of Czech Oncological Society, Oncogynecological Section of the Czech Gynecological and Obstetrical Society, Society of Radiation Oncology, Biology and Physics, and the Society of Czech Pathologists).

Cesk Patol 2021 ;57(3):181-187

Molecular classification of endometrial carcinoma is becoming an important part of the diagnostic process with direct therapeutic implications. Recent international guidelines, including the joint ESGO-ESTRO-ESP recommendation, include the molecular classification into standard diagnostic algorithms. Molecular testing of endometrial carcinomas is also recommended in the latest (5th) edition of the WHO classification of Female Genital Tumors. Due to the need to implement these recommendations in practice, representatives of four professional societies of Czech Medical Association of J. E. Purkyně (Czech Oncological Society, Oncogynecological Section of the Czech Gynecological and Obstetrical Society, Society of Radiation Oncology, Biology and Physics, and the Society of Czech Pathologists) organized a meeting focused on this topic. The result of this meeting is a joint recommendation for molecular testing of endometrial carcinoma in routine diagnostic practice in the Czech Republic.
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September 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

Germline mutations in RAD51C and RAD51D and hereditary predisposition to ovarian cancer.

Klin Onkol 2021 ;34(1):26-32

Ovarian cancer is one of the most common gynecologic cancers with the highest mortality rate over a long period. Genetic predisposition to ovarian cancer is unusually high. In the Czech Republic, causal mutation in any ovarian cancer predisposition gene is identified in approximately 30% of the ovarian cancer patients. Therefore, according to the current guidelines, all ovarian cancer patients should be provided with genetic testing. The BRCA1 and BRCA2 are the two major ovarian cancer predisposition genes. Nevertheless, mutations in other predisposition genes, including RAD51C and RAD51D, are associated with high ovarian cancer risk. Mutations in RAD51C and RAD51D are found in 1% of ovarian cancer patients in each respective gene. Currently, identification of germline mutation in RAD51C and RAD51D is primarily of preventive importance but it potentially could make a prognostic difference. The aim of this review is to summarize the recent RAD51C and RAD51D knowledge, including the biological function, cancer risks associated with germline mutations, and recommendations for mutation carriers.
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http://dx.doi.org/10.48095/ccko202126DOI Listing
January 2021

DNA methylation signatures to predict the cervicovaginal microbiome status.

Clin Epigenetics 2020 11 23;12(1):180. Epub 2020 Nov 23.

Department of Women's Cancer, EGA Institute for Women's Health, University College London, London, UK.

Background: The composition of the microbiome plays an important role in human health and disease. Whether there is a direct association between the cervicovaginal microbiome and the host's epigenome is largely unexplored.

Results: Here we analyzed a total of 448 cervicovaginal smear samples and studied both the DNA methylome of the host and the microbiome using the Illumina EPIC array and next-generation sequencing, respectively. We found that those CpGs that are hypo-methylated in samples with non-lactobacilli (O-type) dominating communities are strongly associated with gastrointestinal differentiation and that a signature consisting of 819 CpGs was able to discriminate lactobacilli-dominating (L-type) from O-type samples with an area under the receiver operator characteristic curve (AUC) of 0.84 (95% CI = 0.77-0.90) in an independent validation set. The performance found in samples with more than 50% epithelial cells was further improved (AUC 0.87) and in women younger than 50 years of age was even higher (AUC 0.91). In a subset of 96 women, the buccal but not the blood cell DNA showed the same trend as the cervicovaginal samples in discriminating women with L- from O-type cervicovaginal communities.

Conclusions: These findings strongly support the view that the epithelial epigenome plays an essential role in hosting specific microbial communities.
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http://dx.doi.org/10.1186/s13148-020-00966-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686703PMC
November 2020

Diagnostic Reliability, Accuracy and Safety of Ultrasound-guided Biopsy and Ascites Puncture in Primarily Inoperable Ovarian Tumours.

Anticancer Res 2020 Jun;40(6):3527-3534

Department of Gynecology and Obstetrics, University Hospital Pilsen, Charles University, Faculty of Medicine in Pilsen, Pilsen, Czech Republic

Background/aim: To compare the diagnostic reliability, accuracy and safety of ultrasound-guided biopsy (Tru-Cut biopsy) and ascites puncture in patients with a primarily inoperable malignant ovarian tumor.

Patients And Methods: This is a retrospective analysis of the studied methods in consecutively examined patients and a prospective validation of these methods. 79 women with a suspected primarily inoperable ovarian tumor underwent Tru-Cut biopsies and were included in the ultrasound-guided biopsy group. In addition, 55 patients after ascites puncture were enrolled in the comparison group. Both procedures were performed in 48 patients for the prospective validation.

Results: Significant differences in favour of ultrasound-guided biopsy were found in all studied variables (malignancy confirmation 72.9% vs. 95.8%, tumor origin 52.1% vs. 89.6%, histologic subtype 43.8% vs. 85.4% and accuracy, i.e. agreement of preoperative and definitive diagnosis 43.7% vs. 95.4%).

Conclusion: Ultrasound-guided biopsy is an accurate, reliable, safe and minimally invasive method. Owing to the high reliability and accuracy, it has the capacity to replace ascites puncture with cytologic examination or a more invasive method (laparoscopy, laparotomy) for adequate tumor sampling.
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http://dx.doi.org/10.21873/anticanres.14341DOI Listing
June 2020

The role of a pathologist in surgical staging for carcinoma of the cervix uteri.

Cesk Patol 2020 ;56(1):38-44

The incidence of cervical cancer is high in the Czech Republic. Altogether 822 new cases were found in this country during 2016 which means the incidence 15,3 new diseases / 100,000 women. FIGO (Fédération Internationale de Gynécologie et d´Obstétrique) staging of carcinoma for the cervix was changed as follows. Lateral extension measurement is removed in the stage IA, the only criterion is the measured deepest invasion.
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August 2020

Multigene Panel Germline Testing of 1333 Czech Patients with Ovarian Cancer.

Cancers (Basel) 2020 Apr 13;12(4). Epub 2020 Apr 13.

Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, 128 53 Prague, Czech Republic.

Ovarian cancer (OC) is the deadliest gynecologic malignancy with a substantial proportion of hereditary cases and a frequent association with breast cancer (BC). Genetic testing facilitates treatment and preventive strategies reducing OC mortality in mutation carriers. However, the prevalence of germline mutations varies among populations and many rarely mutated OC predisposition genes remain to be identified. We aimed to analyze 219 genes in 1333 Czech OC patients and 2278 population-matched controls using next-generation sequencing. We revealed germline mutations in 18 OC/BC predisposition genes in 32.0% of patients and in 2.5% of controls. Mutations in , , , and mismatch repair genes conferred high OC risk (OR > 5). Mutations in and were associated with moderate risk (both OR = 3.5). mutations dominated in almost all clinicopathological subgroups including sporadic borderline tumors of ovary (BTO). Analysis of remaining 201 genes revealed somatic mosaics in and germline mutations in and associating with a high/moderate OC risk significantly; however, further studies are warranted to delineate their contribution to OC development in other populations. Our findings demonstrate the high proportion of patients with hereditary OC in Slavic population justifying genetic testing in all patients with OC, including BTO.
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http://dx.doi.org/10.3390/cancers12040956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226062PMC
April 2020

The association among cervical, anal, and oral HPV infections in high-risk and low-risk women.

Eur J Obstet Gynecol Reprod Biol X 2019 Oct 19;4:100061. Epub 2019 Jun 19.

First Faculty of Medicine, Charles University and General University Hospital, Gynaecologic Oncology Centre, Apolinarska 18, Praha 2, 128 51, Prague, Czech Republic.

Objective: The human papillomavirus (HPV) can cause premalignant and malignant tumors in the anogenital and oropharyngeal regions. The aim of this study was to describe the association in the prevalence of cervical, anal, and oral HPV infections in high-risk patients with biopsy-confirmed high-grade cervical lesion compared to low-risk women.

Study Design: A total of 718 immunocompetent women were enrolled in the study. The high-risk (HR) group consisted of 473 patients with biopsy-confirmed high-grade cervical lesion while the low-risk (LR) group consisted of other 245 women. All participants completed an anonymous self-administered questionnaire and were subjected to cervical, anal, and oral HPV genotyping using the Linear array HPV test.

Results: A total of 81.4% women were infected in the cervix, 43.3% in the anus, and 2.7% in the oral cavity in the HR group in comparison with only 26.9%, 24.5%, and 1.4% in the low-risk LR group, respectively. The cervical and anal HPV infections were much more frequent in the HR patients (p < 0.001); the difference in the oral HPV prevalence was not significant (p = 0.511) between groups. Concurrent cervical-anal infection was observed in 39.3% of HR women and in 8.3% of the LR patients (p < 0.001) and it significantly increased with the grade of cervical lesion (p<0.001). The higher prevalence of concurrent cervical-oral, anal-oral, and cervical-anal-oral infections in HR women was statistically not significant according to the generally small oral HPV prevalence.

Conclusions: All HPV infections occurred more often in HR than in LR women but not all results were statistically significant. The genotype HPV 16 was found in approximately half of all infections at all sites.
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http://dx.doi.org/10.1016/j.eurox.2019.100061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728742PMC
October 2019

Contribution of Massive Parallel Sequencing to Diagnosis of Hereditary Ovarian Cancer in the Czech Republic.

Klin Onkol 2019 ;32(Supplementum2):72-78

Background: Ovarian cancer is a disease with high mortality. Approximately 1,000 women are diagnosed with ovarian cancer in the Czech Republic annually. Women harboring a mutation in cancer-predisposing genes face an increased risk of tumor development. Mutations in BRCA1, BRCA2, BRIP1, and Lynch syndrome genes (RAD51C, RAD51D, and STK11) are associated with a high risk of ovarian cancer, and mutations in ATM, CHEK2, NBN, PALB2, and BARD1 appear to increase the risk. Our aim was to examine the frequency of mutations in cancer-predisposing genes in the Czech Republic.

Materials And Methods: We analyzed 1,057 individuals including ovarian cancer patients and 617 non-cancer controls using CZECANCA panel next-generation sequencing on the Illumina platform. Pathogenic mutations in high-risk genes, including CNVs, were detected in 30.6% of patients. The mutation frequency reached 25.0% and 18.2% in subgroups of unselected ovarian cancer patients and patients with a negative family cancer history, respectively. The most frequently mutated genes were BRCA1 and BRCA2. The overall frequency of mutations in non-BRCA genes was comparable to that in BRCA2. The mutation frequency in ovarian cancer patients aged >70 years was three times higher than that in patients diagnosed before the age of 30.

Conclusion: Ovarian cancer is a heterogeneous disease with a high proportion of hereditary cases. The lack of efficient screening for early diagnosis emphasizes the importance of identifying carriers of mutations in ovarian cancer-predisposing genes; this is because proper follow-up and prevention strategies can reduce overall ovarian cancer-related mortality. This work was supported by grants AZV 15-27695A, SVV2019/260367, PROGRES Q28/LF1. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 7. 3. 2019 Accepted: 24. 4. 2019.
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http://dx.doi.org/10.14735/amko2019S72DOI Listing
January 2020

Association between the cervicovaginal microbiome, BRCA1 mutation status, and risk of ovarian cancer: a case-control study.

Lancet Oncol 2019 08 9;20(8):1171-1182. Epub 2019 Jul 9.

Department of Women's Cancer, EGA Institute for Women's Health, Faculty of Population Health Sciences, University College London, London, UK. Electronic address:

Background: Various factors-including age, family history, inflammation, reproductive factors, and tubal ligation-modulate the risk of ovarian cancer. In this study, our aim was to establish whether women with, or at risk of developing, ovarian cancer have an imbalanced cervicovaginal microbiome.

Methods: We did a case-control study in two sets of women aged 18-87 years in the Czech Republic, Germany, Italy, Norway, and the UK. The ovarian cancer set comprised women with epithelial ovarian cancer and controls (both healthy controls and those diagnosed with benign gynaecological conditions). The BRCA set comprised women with a BRCA1 mutation but without ovarian cancer and controls who were wild type for BRCA1 and BRCA2 (both healthy controls and those with benign gynaecological conditions). Cervicovaginal samples were gathered from all participants with the ThinPrep system and then underwent 16S rRNA gene sequencing. For each sample, we calculated the proportion of lactobacilli species (ie, Lactobacillus crispatus, Lactobacillus iners, Lactobacillus gasseri, and Lactobacillus jensenii), which are essential for the generation of a protective low vaginal pH, in the cervicovaginal microbiota. We grouped samples into those in which lactobacilli accounted for at least 50% of the species present (community type L) and those in which lactobacilli accounted for less than 50% of the species present (community type O). We assessed the adjusted association between BRCA1 status and ovarian cancer status and cervicovaginal microbiota community type, using a logistic regression model with a bias reduction method.

Findings: Participants were recruited between Jan 2, 2016, and July 21, 2018. The ovarian cancer set (n=360) comprised 176 women with epithelial ovarian cancer, 115 healthy controls and 69 controls with benign gynaecological conditions. The BRCA set (n=220) included 109 women with BRCA1 mutations, 97 healthy controls wild type for BRCA1 and BRCA2 and 14 controls with a benign gynaecological condition wild type for BRCA1 and BRCA2. On the basis of two-dimensional density plots, receiver-operating characteristic curve analysis, and age thresholds used previously, we divided the cohort into those younger than 50 years and those aged 50 years or older. In the ovarian cancer set, women aged 50 years or older had a higher prevalence of community type O microbiota (81 [61%] of 133 ovarian cancer cases and 84 [59%] of 142 healthy controls) than those younger than 50 years (23 [53%] of 43 cases and 12 [29%] of 42 controls). In the ovarian cancer set, women younger than 50 years with ovarian cancer had a significantly higher prevalence of community type O microbiota than did age-matched controls under a logistic regression model with bias correction (odds ratio [OR] 2·80 [95% CI 1·17-6·94]; p=0·020). In the BRCA set, women with BRCA1 mutations younger than 50 years were also more likely to have community type O microbiota than age-matched controls (OR 2·79 [95% CI 1·25-6·68]; p=0·012), after adjustment for pregnancy (ever). This risk was increased further if more than one first-degree family member was affected by any cancer (OR 5·26 [95% CI 1·83-15·30]; p=0·0022). In both sets, we noted that the younger the participants, the stronger the association between community type O microbiota and ovarian cancer or BRCA1 mutation status (eg, OR for community type O for cases aged <40 years in the ovarian cancer set 7·00 [95% CI 1·27-51·44], p=0·025; OR for community type O for BRCA1 mutation carriers aged <35 years in the BRCA set 4·40 [1·14-24·36], p=0·031).

Interpretation: The presence of ovarian cancer, or factors known to affect risk for the disease (ie, age and BRCA1 germline mutations), were significantly associated with having a community type O cervicovaginal microbiota. Whether re-instatement of a community type L microbiome by using, for example, vaginal suppositories containing live lactobacilli, would alter the microbiomial composition higher up in the female genital tract and in the fallopian tubes (the site of origin of high-grade serous ovarian cancer), and whether such changes could translate into a reduced incidence of ovarian cancer, needs to be investigated.

Funding: EU Horizon 2020 Research and Innovation Programme, EU Horizon 2020 European Research Council Programme, and The Eve Appeal.
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http://dx.doi.org/10.1016/S1470-2045(19)30340-7DOI Listing
August 2019

A Novel Approach to Preoperative Risk Stratification in Endometrial Cancer: The Added Value of Immunohistochemical Markers.

Front Oncol 2019 12;9:265. Epub 2019 Apr 12.

Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czechia.

The current model used to preoperatively stratify endometrial cancer (EC) patients into low- and high-risk groups is based on histotype, grade, and imaging method and is not optimal. Our study aims to prove whether a new model incorporating immunohistochemical markers, L1CAM, ER, PR, p53, obtained from preoperative biopsy could help refine stratification and thus the choice of adequate surgical extent and appropriate adjuvant treatment. The following data were prospectively collected from patients operated for EC from January 2016 through August 2018: age, pre- and post-operative histology, grade, lymphovascular space invasion, L1CAM, ER, PR, p53, imaging parameters obtained from ultrasound, CT chest/abdomen, final FIGO stage, and current decision model (based on histology, grade, imaging method). In total, 132 patients were enrolled. The current model revealed 48% sensitivity and 89% specificity for high-risk group determination. In myometrial invasion >50%, lower levels of ER ( = 0.024), PR (0.048), and higher levels of L1CAM ( = 0.001) were observed; in cervical involvement a higher expression of L1CAM ( = 0.001), lower PR ( = 0.014); in tumors with positive LVSI, higher L1CAM ( = 0.014); in cases with positive LN, lower expression of ER/PR ( < 0.001), higher L1CAM ( = 0.002) and frequent mutation of p53 ( = 0.008). Cut-offs for determination of high-risk tumors were established: ER <78% ( = 0.001), PR <88% ( = 0.008), and L1CAM ≥4% ( < 0.001). The positive predictive values (PPV) for ER, PR, and L1CAM were 87% (60.8-96.5%), 63% (52.1-72.8%), 83% (70.5-90.8%); the negative predictive values (NPV) for each marker were as follows: 59% (54.5-63.4%), 65% (55.6-74.0%), and 77% (67.3-84.2%). Mutation of p53 revealed PPV 94% (67.4-99.1%) and NPV 61% (56.1-66.3%). When immunohistochemical markers were included into the current diagnostic model, sensitivity improved (48.4 vs. 75.8%, < 0.001). PPV was similar for both methods, while NPV (i.e., the probability of extremely low risk in negative test cases) was improved (66 vs. 78.9%, < 0.001). We proved superiority of new proposed model using immunohistochemical markers over standard clinical practice and that new proposed model increases accuracy of prognosis prediction. We propose wider implementation and validation of the proposed model.
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http://dx.doi.org/10.3389/fonc.2019.00265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6473394PMC
April 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

Synchronous endometrioid endometrial and ovarian carcinomas are biologically related: A clinico-pathological and molecular (next generation sequencing) study of 22 cases.

Oncol Lett 2019 Feb 20;17(2):2207-2214. Epub 2018 Dec 20.

Institute of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12800 Prague, Czech Republic.

The criteria for distinction between independent primary tumors and metastasis from one site to the other in synchronous endometrioid endometrial and ovarian carcinoma (SEO) has been a matter of dispute for a long time. In our study we performed a comprehensive clinico-pathological and molecular analysis of 22 cases of SEO. Based on conventional clinico-pathological criteria the cases were classified as independent primary tumors (10 cases) and metastasis from one location to the other (12 cases). All tumors were analyzed by NGS with a panel of 73 genes (219 kbp). Clonal origin was confirmed in all cases by at least one shared mutation in and . Two patients carried germline pathogenic mutation in cancer-predisposing genes or . Microsatellite instable phenotype was detected in 5/22 (22.7%) SEO, but in one case only in the endometrial tumor. In conclusion, our results showed that all 22 SEOs were clonally related, irrespectively of their clinico-pathological features. Even low grade and low stage tumors classified as independent primaries, according to the conventional morphological criteria, have a clonal origin. From the practical point of view, only the conventional morphological criteria should be used for the classification (staging) of these tumors. However, molecular profiling of these tumors may have prognostic and predictive meaning.
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http://dx.doi.org/10.3892/ol.2018.9855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341770PMC
February 2019

Struma ovarii - ultrasound features of a rare tumor mimicking ovarian cancer.

Med Ultrason 2018 Aug;20(3):355-361

Department of Gynecology and Obstetrics Charles University in Prague-First Faculty of Medicine and Hospital Na Bulovce, Czech Republic.

Aims: To describe the ultrasound features of benign struma ovarii that often mimic ovarian cancer in the background of complex clinical and histopathological pictures.

Material And Methods: We retrospectively identified patients with histologically confirmed benign struma ovarii, treated in our institution between 2003-2016 with complete imaging, clinical, nd histopathological data available. Ultrasound findings were drawn from images, and reports using terms and definitions of the International Ovarian Tumor Analysis group and pattern recognition description was applied.

Results: In all, 19 patients were identified; 10 with pure and 9 with impure struma. Median age was 47 (range 24-69); 10 (53%) were premenopausal. Only four (21%) patients presented with pain, others were asymptomatic. Using pattern recognition, 74% strumas (14/19) were uni-/multilocular solid or solid tumors. The solid components were roundish with smooth contours. Six struma pearls were detected. The subjective color score was moderate or abundant in the majority of solid components. Only 5 (26%) tumors were purely cystic.

Conclusions: The ultrasound characteristics differ widely from typical mature ovarian teratoma. Features such as, solid roundish components with smooth contours, struma pearls, acoustic shadowing and occasionally signs of dermoid are clues and may help preoperatively to differentiate benign struma from malignant adnexal lesions.
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http://dx.doi.org/10.11152/mu-1526DOI Listing
August 2018

Brenner tumor of the ovary - ultrasound features and clinical management of a rare ovarian tumor mimicking ovarian cancer.

Ginekol Pol 2018 ;89(7):357-363

University Hospital Brno, Department of Obstetrics and Gynecology, Medical Faculty, Masaryk University, Jihlavska 20, 62500 Brno, Czech Republic.

Objectives: To describe the ultrasound features of benign Brenner tumor in the background of complex clinical and histopathological pictures.

Material And Methods: We retrospectively identified patients with histologically confirmed benign Brenner tumor of the ovary who were treated in our institution in 2003-2016, and for whom complete imaging, clinical, perioperative and histopathological data were available in the database. Ultrasound findings were drawn from images and reports using terms and definitions of the International Ovarian Tumor Analysis group and pattern recognition description was applied.

Results: Twenty-three patients were identified, most postmenopausal and asymptomatic. On ultrasound, 19/23 tumors were found unilaterally, 4/23 bilaterally, and 82% of tumors were detected in the left ovary. Most Brenner tumors (16/23) contained solid components and revealed no or minimal blood flow by subjective color score upon Doppler examination (19/23, 83%). Calcifications with shadowing were observed in 57% of all Brenner tumors and in 81% of tumors containing solid components. The complex appearance of the tumor misled the sonographers to describe the mass as malignant in 9 cases (39%), and frozen section was performed perioperatively. Surgery was performed via laparoscopy in 11 (48%) and via laparotomy in 12 (52%) cases.

Conclusions: The complexity of the ultrasound picture, consisting of features like calcifications with acoustic shadowing, a poorly vascularized solid mass, and a left-sided localization could be signs of a benign Brenner tumor and could preop-eratively help to differentiate between benign and malignant tumor.
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http://dx.doi.org/10.5603/GP.a2018.0061DOI Listing
October 2018

[Anogenital HPV Infection as the Potential Risk Factor for Oropharyngeal Carcinoma].

Klin Onkol Spring 2018;31(2):103-109

Background: Human papillomavirus (HPV) can cause cervical, other genital, anal, head, and neck cancers. The incidence of oropharyngeal squamous cell carcinoma (OSCC), the head and neck cancer most commonly caused by HPV infection, is increasing. The prevalence of oral HPV infections is considerably lower than that of genital HPV infections; however, infection of both sites is strongly associated with sexual behavior. Although the natural histories of cervical and oral HPV infections do not markedly differ, the virus seems to rarely infect oral and genital sites simultaneously. On the other hand, the standardized incidence ratio of OSCC is higher in cervical cancer patients than in other populations. Furthermore, women with OSCC have a significantly increased risk of developing HPV-related genital cancers. Administration of the HPV vaccine to both genders will undoubtedly dramatically change the epidemiology of HPV-related cancers.

Aim: This work provides an overview of the literature and estimates the risk of OSCC in women with anogenital HPV infections.

Conclusion: The biological relationship between different HPV-infected sites might be complex; however, the increased prevalence of HPV in oral samples of women positive for anogenital HPV indicates that such infections are unlikely to be independent of one another. Sexual activity likely affects the risk of concurrent anogenital and oral coinfections. However, it is also possible that one infection site provides a reservoir that can increase the risk of autoinoculation at anatomically distant locations or that coinfections develop as a result of other factors, such as immunodeficiency. Nevertheless, women with HPV-associated malignancy undoubtedly have a higher risk of developing OSCC.Key words: human papillomavirus - HPV - genital HPV infection - oral HPV infection - oropharyngeal squamous cell carcinoma - standardized incidence ratio - head and neck cancer This article was supported by by the project UNCE 204065 of Charles University. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 26. 8. 2017Accepted: 4. 1. 2018.
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http://dx.doi.org/10.14735/amko2018103DOI Listing
September 2019

Epigenome-based cancer risk prediction: rationale, opportunities and challenges.

Nat Rev Clin Oncol 2018 05 27;15(5):292-309. Epub 2018 Feb 27.

Department of Applied Health Research, Institute of Epidemiology and Healthcare, University College London, UK.

The incidence of cancer is continuing to rise and risk-tailored early diagnostic and/or primary prevention strategies are urgently required. The ideal risk-predictive test should: integrate the effects of both genetic and nongenetic factors and aim to capture these effects using an approach that is both biologically stable and technically reproducible; derive a score from easily accessible biological samples that acts as a surrogate for the organ in question; and enable the effectiveness of risk-reducing measures to be monitored. Substantial evidence has accumulated suggesting that the epigenome and, in particular, DNA methylation-based tests meet all of these requirements. However, the development and implementation of DNA methylation-based risk-prediction tests poses considerable challenges. In particular, the cell type specificity of DNA methylation and the extensive cellular heterogeneity of the easily accessible surrogate cells that might contain information relevant to less accessible tissues necessitates the use of novel methods in order to account for these confounding issues. Furthermore, the engagement of the scientific community with health-care professionals, policymakers and the public is required in order to identify and address the organizational, ethical, legal, social and economic challenges associated with the routine use of epigenetic testing.
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http://dx.doi.org/10.1038/nrclinonc.2018.30DOI Listing
May 2018

A collagen-fibrin patch for the prevention of symptomatic lymphoceles after pelvic lymphadenectomy in women with gynecologic malignancies: A randomized clinical trial.

Gynecol Oncol 2018 04 12;149(1):140-145. Epub 2018 Feb 12.

Department of Obstetrics and Gynecology, Ruhr University Bochum, Bochum, Germany. Electronic address:

Objective: To evaluate the efficacy of a collagen-fibrin patch for the prevention of symptomatic lymphoceles after pelvic lymphadenectomy in women with gynecologic malignancies.

Methods: In a multicenter, randomized, clinical trial, 164 women with pelvic lymphadenectomy were allocated either to bilateral pelvic application of two collagen-fibrin patches or no intervention. Main outcome was efficacy, defined as reduction of symptomatic lymphocele rate diagnosed within four weeks after surgery. Secondary outcomes were asymptomatic lymphoceles and subsequent interventions. Sample size was based on the assumption that application of a collagen-fibrin patch reduces the prevalence of symptomatic lymphoceles by at least 66%. The study was single-blinded, i.e., patients and primary outcome assessors, but not surgeons, were blinded to the treatment allocation.

Results: A total of 75 women were randomized to the intervention and 89 to the control group. All women received the allocated intervention. In total, 42 (27.4%) lymphoceles and 8 (5.2%) symptomatic lymphoceles were observed. Symptomatic lymphoceles were observed in 5/68 (7.4%) women in the intervention group and 3/85 (3.5%) women in the control group (p = 0.47). Asymptomatic lymphoceles were observed in 16 (23.5%) women in the intervention group compared to 18 (21.2%) in the control group (p = 0.85). In a multivariate logistic regression model, no independent risk factor for the development of a symptomatic lymphocele was ascertained.

Discussion: Intraoperative application of collagen-fibrin patches to the pelvic side walls does not reduce the incidence of symptomatic lymphoceles in women with gynecologic malignancies undergoing pelvic lymphadenectomy.
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http://dx.doi.org/10.1016/j.ygyno.2018.01.012DOI Listing
April 2018

Genome profiling is an efficient tool to avoid the STUMP classification of uterine smooth muscle lesions: a comprehensive array-genomic hybridization analysis of 77 tumors.

Mod Pathol 2018 05 12;31(5):816-828. Epub 2018 Jan 12.

Department of Biopathology, Institut Bergonié, Comprehensive Cancer Centre, Bordeaux, France.

The diagnosis of a uterine smooth muscle lesion is, in the majority of cases, straightforward. However, in a small number of cases, the morphological criteria used in such lesions cannot differentiate with certainty a benign from a malignant lesion and a diagnosis of smooth muscle tumor with uncertain malignant potential (STUMP) is made. Uterine leiomyosarcomas are often easy to diagnose but it is difficult or even impossible to identify a prognostic factor at the moment of the diagnosis with the exception of the stage. We hypothesize, for uterine smooth muscle lesions, that there is a gradient of genomic complexity that correlates to outcome. We first tested this hypothesis on STUMP lesions in a previous study and demonstrated that this 'gray category' could be split according to genomic index into two groups. A benign group, with a low to moderate alteration rate without recurrence and a malignant group, with a highly rearranged profile akin to uterine leiomyosarcomas. Here, we analyzed a large series of 77 uterine smooth muscle lesions (from 76 patients) morphologically classified as 19 leiomyomas, 14 STUMP and 44 leiomyosarcomas with clinicopathological and genomic correlations. We confirmed that genomic index with a cut-off=10 is a predictor of recurrence (P<0.0001) and with a cut-off=35 is a marker for poor overall survival (P=0.035). For the tumors confined to the uterus, stage as a prognostic factor was not useful in survival prediction. At stage I, among the tumors reclassified as molecular leiomyosarcomas (ie, genomic index ≥10), the poor prognostic markers were: 5p gain (overall survival P=0.0008), genomic index at cut-off=35 (overall survival P=0.0193), 13p loss including RB1 (overall survival P=0.0096) and 17p gain including MYOCD gain (overall survival P=0.0425). Based on these findings (and the feasibility of genomic profiling by array-comparative genomic hybridization), genomic index, 5p and 17p gains prognostic value could be evaluated in future prospective chemotherapy trials.
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http://dx.doi.org/10.1038/modpathol.2017.185DOI Listing
May 2018

The potential of circulating tumor DNA methylation analysis for the early detection and management of ovarian cancer.

Genome Med 2017 12 22;9(1):116. Epub 2017 Dec 22.

Genedata AG, Margarethenstrasse 38, 4053, Basel, Switzerland.

Background: Despite a myriad of attempts in the last three decades to diagnose ovarian cancer (OC) earlier, this clinical aim still remains a significant challenge. Aberrant methylation patterns of linked CpGs analyzed in DNA fragments shed by cancers into the bloodstream (i.e. cell-free DNA) can provide highly specific signals indicating cancer presence.

Methods: We analyzed 699 cancerous and non-cancerous tissues using a methylation array or reduced representation bisulfite sequencing to discover the most specific OC methylation patterns. A three-DNA-methylation-serum-marker panel was developed using targeted ultra-high coverage bisulfite sequencing in 151 women and validated in 250 women with various conditions, particularly in those associated with high CA125 levels (endometriosis and other benign pelvic masses), serial samples from 25 patients undergoing neoadjuvant chemotherapy, and a nested case control study of 172 UKCTOCS control arm participants which included serum samples up to two years before OC diagnosis.

Results: The cell-free DNA amount and average fragment size in the serum samples was up to ten times higher than average published values (based on samples that were immediately processed) due to leakage of DNA from white blood cells owing to delayed time to serum separation. Despite this, the marker panel discriminated high grade serous OC patients from healthy women or patients with a benign pelvic mass with specificity/sensitivity of 90.7% (95% confidence interval [CI] = 84.3-94.8%) and 41.4% (95% CI = 24.1-60.9%), respectively. Levels of all three markers plummeted after exposure to chemotherapy and correctly identified 78% and 86% responders and non-responders (Fisher's exact test, p = 0.04), respectively, which was superior to a CA125 cut-off of 35 IU/mL (20% and 75%). 57.9% (95% CI 34.0-78.9%) of women who developed OC within two years of sample collection were identified with a specificity of 88.1% (95% CI = 77.3-94.3%). Sensitivity and specificity improved further when specifically analyzing CA125 negative samples only (63.6% and 87.5%, respectively).

Conclusions: Our data suggest that DNA methylation patterns in cell-free DNA have the potential to detect a proportion of OCs up to two years in advance of diagnosis and may potentially guide personalized treatment. The prospective use of novel collection vials, which stabilize blood cells and reduce background DNA contamination in serum/plasma samples, will facilitate clinical implementation of liquid biopsy analyses.
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http://dx.doi.org/10.1186/s13073-017-0500-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5740748PMC
December 2017

Methylation patterns in serum DNA for early identification of disseminated breast cancer.

Genome Med 2017 12 22;9(1):115. Epub 2017 Dec 22.

Genedata AG, Margarethenstrasse 38, 4053, Basel, Switzerland.

Background: Monitoring treatment and early detection of fatal breast cancer (BC) remains a major unmet need. Aberrant circulating DNA methylation (DNAme) patterns are likely to provide a highly specific cancer signal. We hypothesized that cell-free DNAme markers could indicate disseminated breast cancer, even in the presence of substantial quantities of background DNA.

Methods: We used reduced representation bisulfite sequencing (RRBS) of 31 tissues and established serum assays based on ultra-high coverage bisulfite sequencing in two independent prospective serum sets (n = 110). The clinical use of one specific region, EFC#93, was validated in 419 patients (in both pre- and post-adjuvant chemotherapy samples) from SUCCESS (Simultaneous Study of Gemcitabine-Docetaxel Combination adjuvant treatment, as well as Extended Bisphosphonate and Surveillance-Trial) and 925 women (pre-diagnosis) from the UKCTOCS (UK Collaborative Trial of Ovarian Cancer Screening) population cohort, with overall survival and occurrence of incident breast cancer (which will or will not lead to death), respectively, as primary endpoints.

Results: A total of 18 BC specific DNAme patterns were discovered in tissue, of which the top six were further tested in serum. The best candidate, EFC#93, was validated for clinical use. EFC#93 was an independent poor prognostic marker in pre-chemotherapy samples (hazard ratio [HR] for death = 7.689) and superior to circulating tumor cells (CTCs) (HR for death = 5.681). More than 70% of patients with both CTCs and EFC#93 serum DNAme positivity in their pre-chemotherapy samples relapsed within five years. EFC#93-positive disseminated disease in post-chemotherapy samples seems to respond to anti-hormonal treatment. The presence of EFC#93 serum DNAme identified 42.9% and 25% of women who were diagnosed with a fatal BC within 3-6 and 6-12 months of sample donation, respectively, with a specificity of 88%. The sensitivity with respect to detecting fatal BC was ~ 4-fold higher compared to non-fatal BC.

Conclusions: Detection of EFC#93 serum DNAme patterns offers a new tool for early diagnosis and management of disseminated breast cancers. Clinical trials are required to assess whether EFC#93-positive women in the absence of radiological detectable breast cancers will benefit from anti-hormonal treatment before the breast lesions become clinically apparent.
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http://dx.doi.org/10.1186/s13073-017-0499-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5740791PMC
December 2017

Integrated genome analysis of uterine leiomyosarcoma to identify novel driver genes and targetable pathways.

Int J Cancer 2018 03 7;142(6):1230-1243. Epub 2017 Nov 7.

Department of Oncology, Gynecologic Oncology, KU Leuven (University of Leuven), Leuven, 3000, Belgium.

Uterine leiomyosarcomas (uLMS) are rare, aggressive malignancies for which limited treatment options are available. To gain novel molecular insights into uLMS and identify potential novel therapeutic targets, we characterized 84 uLMS samples for genome-wide somatic copy number alterations, mutations, gene fusions and gene expression and performed a data integration analysis. We found that alterations affecting TP53, RB1, PTEN, MED12, YWHAE and VIPR2 were present in the majority of uLMS. Pathway analyses additionally revealed that the PI3K/AKT/mTOR, estrogen-mediated S-phase entry and DNA damage response signaling pathways, for which inhibitors have already been developed and approved, frequently harbored genetic changes. Furthermore, a significant proportion of uLMS was characterized by amplifications and overexpression of known oncogenes (CCNE1, TDO2), as well as deletions and reduced expression of tumor suppressor genes (PTEN, PRDM16). Overall, it emerged that the most frequently affected gene in our uLMS samples was VIPR2 (96%). Interestingly, VIPR2 deletion also correlated with unfavorable survival in uLMS patients (multivariate analysis; HR = 4.5, CI = 1.4-14.3, p = 1.2E-02), while VIPR2 protein expression was reduced in uLMS vs. normal myometrium. Moreover, stimulation of VIPR2 with its natural agonist VIP decreased SK-UT-1 uLMS cell proliferation in a dose-dependent manner. These data suggest that VIPR2, which is a negative regulator of smooth muscle cell proliferation, might be a novel tumor suppressor gene in uLMS. Our work further highlights the importance of integrative molecular analyses, through which we were able to uncover the genes and pathways most frequently affected by somatic alterations in uLMS.
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http://dx.doi.org/10.1002/ijc.31129DOI Listing
March 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

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

Potential Targets' Analysis Reveals Dual PI3K/mTOR Pathway Inhibition as a Promising Therapeutic Strategy for Uterine Leiomyosarcomas-an ENITEC Group Initiative.

Clin Cancer Res 2017 Mar;23(5):1274-1285

Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.

Uterine sarcomas are rare and heterogeneous tumors characterized by an aggressive clinical behavior. Their high rates of recurrence and mortality point to the urgent need for novel targeted therapies and alternative treatment strategies. However, no molecular prognostic or predictive biomarkers are available so far to guide choice and modality of treatment. We investigated the expression of several druggable targets (phospho-S6 ribosomal protein, PTEN, PDGFR-α, ERBB2, and EGFR) in a large cohort of human uterine sarcoma samples (288), including leiomyosarcomas, low-grade and high-grade endometrial stromal sarcomas, undifferentiated uterine sarcomas, and adenosarcomas, together with 15 smooth muscle tumors of uncertain malignant potential (STUMP), 52 benign uterine stromal tumors, and 41 normal uterine tissues. The potential therapeutic value of the most promising target, p-S6, was tested in patient-derived xenograft (PDX) leiomyosarcoma models. In uterine sarcomas and STUMPs, S6 phosphorylation (reflecting mTOR pathway activation) was associated with higher grade ( = 0.001) and recurrence ( = 0.019), as shown by logistic regression. In addition, p-S6 correlated with shorter progression-free survival ( = 0.034). Treatment with a dual PI3K/mTOR inhibitor significantly reduced tumor growth in 4 of 5 leiomyosarcoma PDX models (with tumor shrinkage in 2 models). Remarkably, the 4 responding models showed basal p-S6 expression, whereas the nonresponding model was scored as negative, suggesting a role for p-S6 in response prediction to PI3K/mTOR inhibition. Dual PI3K/mTOR inhibition represents an effective therapeutic strategy in uterine leiomyosarcoma, and p-S6 expression is a potential predictive biomarker for response to treatment. .
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http://dx.doi.org/10.1158/1078-0432.CCR-16-2149DOI Listing
March 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

Serous tubal intraepithelial carcinoma (STIC) - clinical impact and management.

Expert Rev Anticancer Ther 2016 Dec 22;16(12):1311-1321. Epub 2016 Oct 22.

c Gynecological Oncology Center, Department of Obstetrics and Gynecology , Charles University in Prague - First Faculty of Medicine , Prague 2 , Czech Republic.

Introduction: Serous tubal intraepithelial carcinoma (STIC) is most likely precursor lesion of the most part of high-grade serous pelvis carcinomas, carcinosarcoma and undifferentiated carcinoma with incidence of 0.6% to 7% in BRCA carriers or women with strong family history of breast or ovarian carcinoma. STIC is a pathomorphologically and immunohistochemically detectable lesion which biological significance and clinical relevance is unknown. Areas covered: We investigate methods of STIC diagnostics and we present an overview of recent studies and available knowledge on surgical management, adjuvant chemotherapy and subsequent follow-up procedure in women with an isolated STIC. Expert commentary: Patients found to have an incidental STIC lesion should be referred for screening of BRCA1/2 mutation. In absence of an invasive disease, follow-up of patient remains a reasonable choice. A rational scheme should include check-ups every 6 months consisting of gynecological examinations, CA 125 and/or HE4 and pelvic ultrasound examination by an expert sonographer.
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http://dx.doi.org/10.1080/14737140.2016.1247699DOI Listing
December 2016

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

[Recommendation for genetic testing in patients suffering from gynecological malignancy].

Authors:
Michal Zikán

Ceska Gynekol 2015 Mar;80(2):97-103

Objective: To present an overview of indications and recommendations for genetic testing in patients with hereditary susceptibility to develop malignant gynecological tumors.

Subject: Review.

Setting: Gynecological Oncology Center, Department of Obstetrics and Gynecology, Charles University, First Faculty of Medicine and General Faculty Hospital, Prague.

Subject And Method: Literature review and recommendations for practice based on evidence and clinical experience.

Conclusion: Women with hereditary susceptibility to malignant gynecological tumors represent only a relatively small part of the population. However, it is a well-defined risk factor and set of preventive and prophylactic measures can minimize the risk of cancer development (or risk of death from tumor). Knowledge of the indications for genetic testing is one of the basic knowledge of every gynecologist.
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March 2015
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