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1.
Int J Cancer ; 154(4): 679-691, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-37861205

RESUMO

Analysis of cell-free DNA methylation (cfDNAme), alone or combined with CA125, could help to detect ovarian cancers earlier and may reduce mortality. We assessed cfDNAme in regions of ZNF154, C2CD4D and WNT6 via targeted bisulfite sequencing in diagnostic and early detection (preceding diagnosis) settings. Diagnostic samples were obtained via prospective blood collection in cell-free DNA tubes in a convenience series of patients with a pelvic mass. Early detection samples were matched case-control samples derived from the UK Familial Ovarian Cancer Screening Study (UKFOCSS). In the diagnostic set (ncases = 27, ncontrols = 41), the specificity of cfDNAme was 97.6% (95% CI: 87.1%-99.9%). High-risk cancers were detected with a sensitivity of 80% (56.3%-94.3%). Combination of cfDNAme and CA125 resulted in a sensitivity of 94.4% (72.7%-99.9%) for high-risk cancers. Despite technical issues in the early detection set (ncases = 29, ncontrols = 29), the specificity of cfDNAme was 100% (88.1%-100.0%). We detected 27.3% (6.0%-61.0%) of high-risk cases with relatively lower genomic DNA (gDNA) contamination. The sensitivity rose to 33.3% (7.5%-70.1%) in samples taken <1 year before diagnosis. We detected ovarian cancer in several patients up to 1 year before diagnosis despite technical limitations associated with archival samples (UKFOCSS). Combined cfDNAme and CA125 assessment may improve ovarian cancer screening in high-risk populations, but future large-scale prospective studies will be required to validate current findings.


Assuntos
Metilação de DNA , Neoplasias Ovarianas , Humanos , Feminino , Estudos de Casos e Controles , Estudos Prospectivos , Detecção Precoce de Câncer/métodos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Biomarcadores Tumorais/genética , Antígeno Ca-125 , Fatores de Transcrição Kruppel-Like/genética
2.
Int J Gynecol Cancer ; 34(7): 985-992, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950926

RESUMO

OBJECTIVES: To assess the diagnostic performance of ultrasonography in pre-operative assessment of lymph nodes in patients with cervical cancer, to compare the outcomes for pelvic and para-aortic regions, and to detect macrometastases and micrometastases separately. METHODS: Patients were retrospectively included if they met the following inclusion criteria: pathologically verified cervical cancer; ultrasonography performed by one of four experienced sonographers; surgical lymph node staging, at least in the pelvic region-sentinel lymph node biopsy or systematic pelvic lymphadenectomy or debulking. The final pathological examination was the reference standard. RESULTS: 390 patients met the inclusion criteria between 2009 and 2019. Pelvic node macrometastases (≥2 mm) were confirmed in 54 patients (13.8%), and micrometastases (≥0.2 mm and <2 mm) in another 21 patients (5.4%). Ultrasonography had sensitivity 72.2%, specificity 94.0%, and area under the curve (AUC) 0.831 to detect pelvic macrometastases, while sensitivity 53.3%, specificity 94.0%, and AUC 0.737 to detect both pelvic macrometastases and micrometastases (pN1). Ultrasonography failed to detect pelvic micrometastases, with sensitivity 19.2%, specificity 85.2%, and AUC 0.522. There was no significant impact of body mass index on diagnostic accuracy. Metastases in para-aortic nodes (macrometastases only) were confirmed in 16 of 71 patients who underwent para-aortic lymphadenectomy. Ultrasonography yielded sensitivity 56.3%, specificity 98.2%, and AUC 0.772 to identify para-aortic node macrometastases. CONCLUSION: Ultrasonography performed by an experienced sonographer can be considered a sufficient diagnostic tool for pre-operative assessment of lymph nodes in patients with cervical cancer, showing similar diagnostic accuracy in detection of pelvic macrometastases as reported for other imaging methods (18F-fluorodeoxyglucose positron emission tomography/CT or diffusion-weighted imaging/MRI). It had low sensitivity for detection of small-volume macrometastases (largest diameter <5 mm) and micrometastases. The accuracy of para-aortic assessment was comparable to that for pelvic lymph nodes, and assessment of the para-aortic region should be an inseparable part of the examination protocol.


Assuntos
Linfonodos , Metástase Linfática , Ultrassonografia , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Pessoa de Meia-Idade , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfonodos/cirurgia , Estudos Retrospectivos , Ultrassonografia/métodos , Adulto , Metástase Linfática/diagnóstico por imagem , Idoso , Sensibilidade e Especificidade , Excisão de Linfonodo , Cuidados Pré-Operatórios/métodos , Micrometástase de Neoplasia/diagnóstico por imagem
3.
Int J Mol Sci ; 25(5)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38474119

RESUMO

There is extensive coverage in the existing literature on implant-associated lymphomas like anaplastic large-cell lymphoma, but breast implant-associated squamous cell carcinoma (BIA-SCC) has received limited scholarly attention since its first case in 1992. Thus, this study aims to conduct a qualitative synthesis focused on the underexplored association between breast implants and BIA-SCC. A systematic review was conducted utilizing the PubMed, Web of Science, and Cochrane databases to identify all currently reported cases of BIA-SCC. Additionally, a literature review was performed to identify potential biochemical mechanisms that could lead to BIA-SCC. Studies were vetted for quality using the NIH quality assessment tool. From an initial pool of 246 papers, 11 met the quality criteria for inclusion, examining a total of 14 patients aged between 40 and 81 years. BIA-SCC was found in a diverse range of implants, including those with smooth and textured surfaces, as well as those filled with saline and silicone. The condition notably manifested a proclivity for aggressive clinical progression, as evidenced by a mortality rate approximating 21.4% within a post-diagnostic interval of six months. Our literature review reveals that chronic inflammation, driven by various external factors such as pathogens and implants, can initiate carcinogenesis through epigenetic modifications and immune system alterations. This includes effects from exosomes and macrophage polarization, showcasing potential pathways for the pathogenesis of BIA-SCC. The study highlights the pressing need for further investigation into BIA-SCC, a subject hitherto inadequately addressed in the academic sphere. This necessitates the urgency for early screening and intervention to improve postoperative outcomes. While the review is confined by its reliance on case reports and series, it serves as a valuable reference for future research endeavors.


Assuntos
Implante Mamário , Implantes de Mama , Neoplasias da Mama , Linfoma Anaplásico de Células Grandes , Mamoplastia , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Implantes de Mama/efeitos adversos , Implante Mamário/efeitos adversos , Mamoplastia/efeitos adversos , Neoplasias da Mama/patologia , Linfoma Anaplásico de Células Grandes/patologia
4.
Bratisl Lek Listy ; 125(2): 92-95, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38219061

RESUMO

BACKGROUND: Toxoplasma gondii infection in pregnant women could lead to significant changes during the pregnancy, affect the outcomes of pregnancy and the timing of labour. Small­for­gestational­age (SGA) newborns are defined by birthweight below the 10th percentile for gestational age. We tested an association between latent toxoplasmosis in pregnant women and deliveries of SGA babies. MATERIAL AND METHODS: For testing, we included 1,647 women who gave birth to a singleton baby at ≥ 37 weeks of gestation. The complement-fixation test (CFT) and enzyme-linked immunosorbent assay (ELISA) tests for IgG and IgM were used. The latent form of toxoplasmosis was defined as a CFT titre of 1:8 or higher, together with index positivity IgG ELISA > 1.1 and negative IgM. RESULTS: There were 406 (24.7 %) women positive, and 1,241 (75.3 %) women negative for latent toxoplasmosis. Of all deliveries. 190 were SGA­positive and 1,457 were SGA­negative. Our study found a statistically significant association between latent toxoplasmosis and SGA foetuses born at term. The Pearson chi-square model was statistically significant (χ2(1) = 7.365, p = .007). The odds ratio was 1.567. CONCLUSION: Pregnant women with latent toxoplasmosis giving birth at ≥ 37 weeks of gestation have a 1.567 times higher risk of delivering an SGA baby (Tab. 2, Fig. 1, Ref. 30).


Assuntos
Toxoplasma , Toxoplasmose , Gravidez , Feminino , Recém-Nascido , Humanos , Masculino , Toxoplasmose/epidemiologia , Peso ao Nascer , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G , Imunoglobulina M
5.
Int J Cancer ; 152(6): 1269-1274, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36056582

RESUMO

The majority of endometrial and cervical cancers present with abnormal vaginal bleeding but only a small proportion of women suffering from vaginal bleeding actually have such a cancer. A simple, operator-independent and accurate test to correctly identify women presenting with abnormal bleeding as a consequence of endometrial or cervical cancer is urgently required. We have recently developed and validated the WID-qEC test, which assesses DNA methylation of ZSCAN12 and GYPC via real-time PCR, to triage women with symptoms suggestive of endometrial cancer using ThinPrep-based liquid cytology samples. Here, we investigated whether the WID-qEC test can additionally identify women with cervical cancer. Moreover, we evaluate the test's applicability in a SurePath-based hospital-cohort by comparing its ability to detect endometrial and cervical cancer to cytology. In a set of 23 cervical cancer cases and 28 matched controls the receiver operating characteristic (ROC) area under the curve (AUC) is 0.99 (95% confidence interval [CI]: 0.97-1.00) with a sensitivity and specificity of 100% and 92.9%, respectively. Amongst the hospital-cohort (n = 330), the ROC AUC is 0.99 (95% CI: 0.98-1) with a sensitivity and specificity of 100% and 82.5% for the WID-qEC test, respectively, and 33.3% and 96.9% for cytology (considering PAP IV/V as positive). Our data suggest that the WID-qEC test detects both endometrial and cervical cancer with high accuracy.


Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Estudos de Viabilidade , Endométrio/patologia , Citodiagnóstico , Sensibilidade e Especificidade , Hemorragia Uterina/diagnóstico , Hemorragia Uterina/patologia , Displasia do Colo do Útero/diagnóstico , Esfregaço Vaginal , Infecções por Papillomavirus/diagnóstico
6.
Int J Cancer ; 152(9): 1977-1988, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36533702

RESUMO

The incidence of endometrial cancer is rising. Measures to identify women at risk and to detect endometrial cancer earlier are required to reduce the morbidity triggered by the aggressive treatment required for advanced endometrial cancer. We developed the WID-EC (Women's cancer risk IDentification-Endometrial Cancer) test, which is based on DNA methylation at 500 CpG sites, in a discovery set of cervical liquid-based cytology samples from 1086 women with and without an endometrial cancer (217 cancer cases and 869 healthy controls) with a worse prognosis (grade 3 or ≥stage IB). We validated the WID-EC test in an independent external validation set of 64 endometrial cancer cases and 225 controls. We further validated the test in 150 healthy women (prospective set) who provided a cervical sample as part of the routine Swedish cervical screening programme, 54 of whom developed endometrial cancer within 3 years of sample collection. The WID-EC test identified women with endometrial cancer with a receiver operator characteristic area under the curve (AUC) of 0.92 (95% CI: 0.88-0.97) in the external set and of 0.82 (95% CI: 0.74-0.89) in the prospective validation set. Using an optimal cutoff, cancer cases were detected with a sensitivity of 86% and a specificity of 90% in the external validation set, and a sensitivity and specificity of 52% and 98% respectively in the prospective validation set. The WID-EC test can identify women with or at risk of endometrial cancer.


Assuntos
Neoplasias do Endométrio , Neoplasias do Colo do Útero , Feminino , Humanos , Detecção Precoce de Câncer , Estudos de Casos e Controles , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Sensibilidade e Especificidade
7.
Ceska Gynekol ; 88(2): 126-130, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37130739

RESUMO

Anti-Müllerian hormone (AMH) is a protein produced already in human fetus. It has an essential role in the differentiation of the reproductive tract, regulation of the ovaries and testes. The determination of serum AMH levels is used in clinical practice. Today, especially in reproductive medicine in the assessment of ovarian reserve and in the prediction of the response to ovarian stimulation. However, in young cancer patients, it can also predict the risk of ovarian failure after anticancer treatment. It finds further use in pediatric endocrinology in the diagnosis of sexual differentiation disorders. In oncology, it is used as a tumor marker for monitoring patients with granulosa tumors. In the future, however, it is also promising to use the knowledge of AMH function for the treatment of gynecological as well as other solid malignancies expressing a tissue-specific receptor for AMH.


Assuntos
Hormônio Antimülleriano , Doenças Ovarianas , Feminino , Humanos , Folículo Ovariano , Indução da Ovulação
8.
Ceska Gynekol ; 88(2): 100-105, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37130734

RESUMO

OBJECTIVE: To describe the multidisciplinary approach that led to the successful management of severe hepatic rupture in HELLP syndrome at 35 weeks of gestation. CASE REPORT: The clinical course and management procedure of a 34-year-old female patient with ruptured liver due to HELLP syndrome, who was admitted with symptoms lasting about 4 hours (pain in the right hypochondrium, nausea, vomiting, flashes before the eyes) are described in the form of a case report. An acute caesarean section was performed, during which a rupture of the subcapsular hematoma of the liver was dia-gnosed. Subsequently, the patient developed hemorrhagic shock and coagulopathy with the need for repeated surgical revisions of bleeding from the rupture of the liver. CONCLUSION: Subcapsular hematoma rupture is a rare but serious complication of HELLP syndrome. This case shows the importance of early dia-gnosis and prompt termination of pregnancy in the shortest possible time in pregnancy after 34 weeks. The most fundamental factor that influenced the patient's outcome and morbidity was the management of multidisciplinary cooperation and the correct timing of individual steps.


Assuntos
Síndrome HELLP , Hepatopatias , Gravidez , Humanos , Feminino , Adulto , Síndrome HELLP/diagnóstico , Cesárea/efeitos adversos , Ruptura Espontânea/etiologia , Ruptura Espontânea/cirurgia , Hepatopatias/diagnóstico , Hepatopatias/etiologia , Hepatopatias/cirurgia , Hematoma/etiologia
9.
Ceska Gynekol ; 88(5): 347-352, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37932051

RESUMO

OBJECTIVE: To describe the implementation process and evaluate the success of compliance with the recommended ERAS protocol in the Czech healthcare system. METHODS: The study included 163 patients from March to September 2022, a total of 7 months. Patients were divided into three groups according to the type of surgery. Clinical protocol: Oncogynecology, hysterectomy and laparoscopy. The implementation was realized in three phases (preparation, implementation of the protocol itself and evaluation). RESULTS AND CONCLUSIONS: The cumulative adherence rate was 90% or more in all three groups. Based on the pilot results at our department, we evaluated the ERAS concept as a well-implemented tool for gynaecological departments in the Czech healthcare system.


Assuntos
Ginecologia , Laparoscopia , Feminino , Humanos , Protocolos Clínicos , Projetos Piloto , Complicações Pós-Operatórias , Fidelidade a Diretrizes
10.
Ceska Gynekol ; 86(2): 124-127, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34020560

RESUMO

OBJECTIVE: To present current possibilities of the prevention and therapy of ovarian hyperstimulation syndrome (OHSS). METHODS: Literature and guidelines were researched. RESULTS: From the view of safety and prevention of OHSS, antagonistic protocol is suitable. Patients with syndrome of polycystic ovaries benefit from the use of metformin or letrozole that can be sufficient to induce ovulation. As a treatment of imminent OHSS, it is recommended to administer 0.5 mg of cabergoline per os daily as well as low molecular weight heparin subcutaneously in prophylactic dose and to maintain sufficient fluid intake. Diuretics are strongly discouraged to use. To maintain intravascular volume, drained ascites can be reintroduced. CONCLUSION: We present a review of current literature and recommendations.


Assuntos
Síndrome de Hiperestimulação Ovariana , Síndrome do Ovário Policístico , Cabergolina , Feminino , Fertilização in vitro , Humanos , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Indução da Ovulação/efeitos adversos , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/terapia
11.
Ceska Gynekol ; 86(5): 304-310, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34736327

RESUMO

OBJECTIVE: The aim of this study was to compare the relation between the quality of life, level of depression and some other psychological characteristics of women and the method (pharmacological or instrumental) they chose to terminate their pregnancy up to 49 days of amenorrhoea. METHODS: From Jan 1st, 2019 to Aug 31st, 2020 we prospectively analyzed data obtained by evaluating questionnaires from 106 women with a choice of pharmacological (faUUT) and 105 women with a choice of surgical (iUUT) termination of pregnancy. The questionnaires focused on their quality of life and other characteristics. RESULTS: Women undergoing faUUT have a statistically significantly higher quality of life (P = 0.001), they are physically (P = 0.003) and mentally (P = 0.027) healthier, they have a higher socioeconomic status, and they are more satisfied with their environment (P = 0.022). CONCLUSION: Women with a differently chosen method of termination of pregnancy had a statistically significantly different quality of life as a whole. This difference is statistically significant in the sub-areas of the quality of life: feeling of physical health and mental well-being, satisfaction with the environment, and subjective perception of the quality of life. The result doesnt confirm a statistically significant difference between both groups on the level of depression and their cohabitation.


Assuntos
Aborto Induzido , Qualidade de Vida , Feminino , Humanos , Gravidez , Inquéritos e Questionários
12.
Ceska Gynekol ; 86(4): 264-272, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34493052

RESUMO

Molecular classification of endometrial carcinoma is becoming an important part of the dia-gnostic process with direct therapeutic implications. Recent international guidelines, including the joint recommendation of the European Society of Gynaecological Oncology, the European Society for Radiotherapy and Oncology and the European Society of Pathology include the molecular classification into standard dia-gnostic algorithms. Molecular testing of endometrial carcinomas is also recommended in the latest (5th edition) of the World Health Organization classification of female genital tumors. Due to the need to implement these recommendations in practice, representatives of four professional societies of the Czech Medical Association of J. E. Purkyně (the Czech Oncological Society, the Oncogynecological Section of the Czech Gynecological and Obstetrical Society, the Society of Radiation Oncology, Biology and Physics, and the Society of Czech Pathologists) organized a meeting focused on this topic. Recommendation for molecular testing of endometrial carcinoma in routine dia-gnostic practice in the Czech Republic.


Assuntos
Neoplasias do Endométrio , Radioterapia (Especialidade) , Biologia , República Tcheca , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Feminino , Humanos , Técnicas de Diagnóstico Molecular , Patologistas , Física
13.
Cesk Patol ; 57(3): 181-187, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34551568

RESUMO

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.


Assuntos
Neoplasias do Endométrio , Radioterapia (Especialidade) , Biologia , República Tcheca , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Feminino , Humanos , Técnicas de Diagnóstico Molecular , Patologistas , Física
14.
Cesk Patol ; 56(1): 38-44, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32393045

RESUMO

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.


Assuntos
Estadiamento de Neoplasias , Patologistas , Neoplasias do Colo do Útero , República Tcheca , Feminino , Humanos , Papel Profissional , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia
15.
Lancet Oncol ; 20(8): 1171-1182, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31300207

RESUMO

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.


Assuntos
Carcinoma Epitelial do Ovário/microbiologia , Colo do Útero/microbiologia , Neoplasias Ovarianas/microbiologia , Vagina/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína BRCA1/genética , Carcinoma Epitelial do Ovário/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Microbiota , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , Fatores de Risco , Adulto Jovem
16.
Int J Cancer ; 142(6): 1230-1243, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29063609

RESUMO

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.


Assuntos
Carcinogênese/genética , Leiomiossarcoma/genética , Receptores Tipo II de Peptídeo Intestinal Vasoativo/genética , Transdução de Sinais/genética , Neoplasias Uterinas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Genes Supressores de Tumor , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Estimativa de Kaplan-Meier , Leiomiossarcoma/mortalidade , Leiomiossarcoma/patologia , Leiomiossarcoma/terapia , Pessoa de Meia-Idade , Miométrio/patologia , Oncogenes/genética , Análise de Sequência de RNA/métodos , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/patologia , Neoplasias Uterinas/terapia , Sequenciamento Completo do Genoma/métodos
17.
Mod Pathol ; 31(5): 816-828, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29327710

RESUMO

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.


Assuntos
Perfilação da Expressão Gênica , Análise de Sequência com Séries de Oligonucleotídeos , Tumor de Músculo Liso/diagnóstico , Tumor de Músculo Liso/genética , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 5/genética , Feminino , Humanos , Leiomioma/diagnóstico , Leiomioma/genética , Leiomioma/patologia , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/genética , Leiomiossarcoma/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Tumor de Músculo Liso/patologia , Análise de Sobrevida , Neoplasias Uterinas/patologia
18.
Gynecol Oncol ; 149(1): 140-145, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29395308

RESUMO

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.


Assuntos
Neoplasias dos Genitais Femininos/cirurgia , Excisão de Linfonodo/métodos , Linfocele/prevenção & controle , Feminino , Humanos , Excisão de Linfonodo/efeitos adversos , Linfocele/etiologia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Método Simples-Cego
19.
Ginekol Pol ; 89(7): 357-363, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30091444

RESUMO

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.


Assuntos
Tumor de Brenner/diagnóstico por imagem , Tumor de Brenner/terapia , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/terapia , Adulto , Tumor de Brenner/patologia , Gerenciamento Clínico , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Ultrassonografia Doppler em Cores/métodos
20.
Klin Onkol ; 31(2): 103-109, 2018.
Artigo em Tcheco | MEDLINE | ID: mdl-29708352

RESUMO

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.


Assuntos
Doenças do Ânus/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Doenças dos Genitais Femininos/epidemiologia , Neoplasias Orofaríngeas/epidemiologia , Infecções por Papillomavirus/epidemiologia , Feminino , Humanos , Fatores de Risco
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