Predikce odpovědi na chemoterapii jako důležitou složku léčby nebyla dosud u ovariálního karcinomu možná. Některé skupiny nádorů jsou však zřejmě definovány molekulárním, expresním, nebo jiným funkčním vzorcem a vykazují podobné a jedinečné vlastnosti. Kombinace detekovatelných funkčních změn (výpadků nebo nadprodukce některých proteinových produktů) v nádorových buňkách, některých morfologických znaků, somatických mutací nebo větších genových přestaveb a epigenetických změn může definovat vzorec typický pro nádory s různým biologickým chováním, tedy i s odlišnou odpovědí na systémovou léčbu (chemoterapie +/- cílená léčba). Nádory s hereditární mutací genů BRCA1 a BRCA2 představují právě takovou skupinu se specifickým biologickým chováním, kterou nelze odlišit pouze morfologicky. Mapování morfologických, expresních, genetických a epigenetických změn ve skupnách nádorů definovaných přítomností, nebo nepřítomností defektů genů BRCA1 a BRCA2 může vést k identifikaci podtypů nádorů s různou odpovědí na systémovou léčbu.; Valid prediction of response to chemotherapy in ovarian cancer patients as an important part of treatment has not been possible so far. However, it appears that some tumor subgroups, defined by molecular, expressional or other functional patterns, have similar and unique features and biological behavior. Combination of detectable functional changes (loss or overexpression of proteins) i ntumor cells, some morphological characteristics, somatic gene mutations or rearrangements and epigenetic changes may define such a pattern typical for a subgroup with specific biological behavior, i.e. with different response to systemic treatment (chemotherapy +/- targeted treatment). Tumors with hereditary inactivation of the BRCA1 or BRCA2 genes represent a group with specific biological features and behavior, which cannot be distinguished morphologically only. Mapping of morphology, protein expression, genetic and epigenetic changes in specific groups of BRCA1/2 positive tumors may lead to identification of tumor subtypes with different response to systemic treatment.

• MeSH
• geny BRCA1 MeSH
• geny BRCA2 MeSH
• imunohistochemie MeSH
• kritéria léčebné odpovědi MeSH
• lidé MeSH
• nádorové biomarkery analýza   MeSH
• nádory cystické, mucinózní a serózní farmakoterapie   genetika   MeSH
• nádory vaječníků farmakoterapie   genetika   MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• gynekologie a porodnictví
• onkologie
• genetika, lékařská genetika
• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

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 BRCA1/BRCA2, RAD51C/RAD51D, BARD1, and mismatch repair genes conferred high OC risk (OR > 5). Mutations in BRIP1 and NBN were associated with moderate risk (both OR = 3.5). BRCA1/2 mutations dominated in almost all clinicopathological subgroups including sporadic borderline tumors of ovary (BTO). Analysis of remaining 201 genes revealed somatic mosaics in PPM1D and germline mutations in SHPRH and NAT1 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.

• Publikační typ
• časopisecké články MeSH

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.

• MeSH
• asymptomatické nemoci MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• lymfadenektomie statistika a číselné údaje   MeSH
• lymfokela diagnostické zobrazování   patologie   MeSH
• nádory ženských pohlavních orgánů chirurgie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• ultrasonografie * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

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 (ptrend<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.

• Publikační typ
• časopisecké články MeSH

Background: 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. Materials and Methods: 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). Results: 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 (p = 0.024), PR (0.048), and higher levels of L1CAM (p = 0.001) were observed; in cervical involvement a higher expression of L1CAM (p = 0.001), lower PR (p = 0.014); in tumors with positive LVSI, higher L1CAM (p = 0.014); in cases with positive LN, lower expression of ER/PR (p < 0.001), higher L1CAM (p = 0.002) and frequent mutation of p53 (p = 0.008). Cut-offs for determination of high-risk tumors were established: ER <78% (p = 0.001), PR <88% (p = 0.008), and L1CAM ≥4% (p < 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%, p < 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%, p < 0.001). Conclusion: 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.

• Publikační typ
• časopisecké články MeSH

• MeSH
• genetické testování MeSH
• geny BRCA1 MeSH
• geny BRCA2 MeSH
• lidé MeSH
• nádory vaječníků * etiologie   genetika   prevence a kontrola   MeSH
• profylaktické chirurgické výkony MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

• MeSH
• lidé MeSH
• nádory vaječníků * farmakoterapie   MeSH
• PARP inhibitory aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• protinádorové látky terapeutické užití   MeSH
• protokoly protinádorové léčby MeSH
• randomizované kontrolované studie jako téma MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

• MeSH
• genetické testování MeSH
• gynekologické chirurgické výkony MeSH
• lidé MeSH
• nádory vaječníků * diagnóza   genetika   terapie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

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.

• MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• hodnocení rizik MeSH
• invazivní růst nádoru patologie   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádory vaječníků diagnostické zobrazování   patologie   chirurgie   MeSH
• ovarektomie metody   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• staging nádorů MeSH
• struma ovarii diagnostické zobrazování   patologie   chirurgie   MeSH
• ultrasonografie dopplerovská barevná metody   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

• MeSH
• antigen CA-125 analýza   krev   MeSH
• intervenční ultrasonografie metody   MeSH
• lidé MeSH
• nádorové biomarkery krev   MeSH
• nádory vaječníků * diagnostické zobrazování   epidemiologie   krev   MeSH
• senzitivita a specificita MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH