Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 41
Filtrar
Mais filtros

Bases de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Am J Obstet Gynecol ; 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39181495

RESUMO

BACKGROUND: Robotic-assisted laparoscopy has become a widely and increasingly used modality of minimally invasive surgery in the treatment of endometrial cancer. Due to its technical advantages, robotic-assisted laparoscopic surgery offers benefits, such as a lower rate of conversions compared to conventional laparoscopy. Yet, data on long-term oncological outcomes after robotic-assisted laparoscopy is scarce and based on retrospective cohort studies only. OBJECTIVE: This study aimed to assess overall survival, progression-free survival, and long-term surgical complications in patients with endometrial cancer randomly assigned to robotic-assisted or conventional laparoscopy. STUDY DESIGN: This randomized controlled trial was conducted at the Department of Gynecology and Obstetrics of Tampere University Hospital, Finland. Between 2010 and 2013, 101 patients with low-grade endometrial cancer scheduled for minimally invasive surgery were randomized preoperatively 1:1 either to robotic-assisted or conventional laparoscopy. All patients underwent laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy. A total of 97 patients (49 in the robotic-assisted laparoscopy group and 48 in the conventional laparoscopy group) were followed up for a minimum of 10 years. Survival was analyzed using Kaplan-Meier curves, log-rank test, and Cox proportional hazard models. Binary logistic regression analysis was used to analyze risk factors for trocar site hernia. RESULTS: In the multivariable regression analysis, overall survival was favorable in the robotic-assisted group (hazard ratio 0.39; 95% confidence interval [CI], 0.15-0.99, P=.047) compared to the conventional laparoscopy group. There was no difference in progression-free survival (log-rank test, P=.598). The 3-, 5-, and 10-year overall survival were 98.0% (95% CI, 94.0-100) vs 97.9% (93.8-100), 91.8% (84.2-99.4) vs 93.7% (86.8-100), and 75.5% (64.5-87.5) vs 85.4% (75.4-95.4) for the conventional laparoscopy and the robotic-assisted groups, respectively. Trocar site hernia developed more often for the robotic-assisted group compared to the conventional laparoscopy group 18.2% vs 4.1% (odds ratio 5.42, 95% CI, 1.11-26.59, P=.028). The incidence of lymphocele, lymphedema, or other long-term complications did not differ between the groups. CONCLUSION: The results of this randomized controlled trial suggest a minor overall survival benefit in endometrial cancer after robotic-assisted laparoscopy compared to conventional laparoscopy. Hence, the use of robotic-assisted technique in the treatment of endometrial cancer seems safe, though larger randomized controlled trials are needed to confirm any potential survival benefit. No alarming safety signals were detected in the robotic-assisted group since the rate of long-term complications differed only in the incidence of trocar site hernia.

2.
Int J Gynecol Cancer ; 33(11): 1807-1811, 2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37813479

RESUMO

BACKGROUND: Endometrial carcinomas can be classified into four molecular subgroups - mismatch repair deficient (MMRd), p53 abnormal (p53abn), polymerase-ϵ (POLE) ultramutated, and 'no specific molecular profile' (NSMP). Retrospective data imply that the response to adjuvant therapies may depend on the molecular subgroup. These findings emphasize the need for adjuvant therapy trials where patients are randomized to treatment arms separately within each molecular subgroup. PRIMARY OBJECTIVE: The PErsonalized TReatment for Endometrial Carcinoma (PETREC) trial clarifies the value of molecular classification in the determination of adjuvant therapies of high-intermediate risk and early-stage high-risk endometrial carcinoma. STUDY HYPOTHESIS: Compared with vaginal brachytherapy, the utilization of whole pelvic radiotherapy may result in improved outcomes for either MMRd or NSMP high-intermediate risk carcinomas. Early-stage high-risk p53abn and nonendometrioid carcinomas are postulated to gain benefits from chemoradiotherapy, as opposed to chemotherapy alone. POLE ultramutated carcinomas harboring high-intermediate or high-risk clinicopathologic features are speculated to have favorable prognosis without any adjuvant therapy. TRIAL DESIGN: This prospective, multicenter, phase 3 trial compares the efficacy of vaginal brachytherapy vs whole pelvic radiotherapy in high-intermediate risk MMRd and NSMP molecular subgroups, and chemotherapy vs chemoradiotherapy in early-stage high-risk p53abn subtype and nonendometrioid carcinomas. Eligible women who consent to participation in the trial are randomly allocated (1:1) to treatment arms. MAJOR INCLUSION/EXCLUSION CRITERIA: Women with stages I-II molecular integrated high-intermediate risk or high-risk endometrial carcinoma will be included. PRIMARY ENDPOINT: The primary endpoint is the 5 year cumulative incidence of disease recurrence. SAMPLE SIZE: A total sample size of 294 patients (49 subjects in each treatment arm of the three subgroups intended for randomization) was estimated to be sufficient. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Patient recruitment will be completed in 2025, and follow-up will be completed in 2030. TRIAL REGISTRATION: NCT05655260.


Assuntos
Carcinoma , Neoplasias do Endométrio , Humanos , Feminino , Finlândia , Estudos Retrospectivos , Medicina de Precisão , Estudos Prospectivos , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/patologia , Neoplasias do Endométrio/patologia , Carcinoma/patologia
3.
Gynecol Oncol ; 165(3): 478-485, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35397919

RESUMO

OBJECTIVE: To compare survival rates of surgically treated advanced epithelial ovarian cancer patients before and after a programmatic change in surgical approach from standard surgery towards ultra-radical surgery. METHODS: 247 patients with FIGO stage IIIB-IV ovarian, tubal, and primary peritoneal carcinoma were operated during 2013-2019 either by primary or interval cytoreduction in Tampere University Hospital, Finland. Group 1 (n = 122) patients were operated during 2013 and February 2016. Group 2 patients (n = 125) were operated between March 2016 and March 2019, when a systematic change in surgical approach towards more extensive surgery was implemented. RESULTS: The complete resection (R0) rate increased significantly from 17.2% (21/122) to 52.0% (65/125) within the study period (p < 0.001). The median progression-free survival (PFS) was 15.6 months vs 19.3 months (p = 0.037), and the median overall survival (OS) was 33.5 months vs 54.5 months in Groups 1 and 2, respectively (p = 0.028). Median OS for stage III patients in Group 1 was 36.1 months (95% CI 27.4-44.8) but could not be reached in Group 2 (p = 0.009). In Stage IV patients, OS was 32.0 months (16.4-47.7) and 39.3 months (24.8-53.8) in Group 1 and 2, respectively (p = 0.691). Multivariable Cox regression analysis revealed that OS was independently affected by the amount of residual tumor and complication grade. CONCLUSIONS: The change of surgical approach towards maximal surgical effort improved both progression-free and overall survival. The survival benefit was unquestionable for stage III patients but did not reach statistical significance in stage IV patients.


Assuntos
Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/patologia , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Centros de Atenção Terciária
4.
Hered Cancer Clin Pract ; 19(1): 38, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521458

RESUMO

BACKGROUND: Due to increased risk of endometrial and ovarian cancer, women belonging to known Lynch Syndrome (LS) families are recommended to undergo germline testing. Current practice in Finland is to offer counselling to women with pathogenic variant and advocate risk-reducing surgery (RRS) after completion of childbirth. The present study aimed to clarify the impacts of positive germline testing on family planning and reproductive decisions of these women, which are relatively unknown. METHODS: Seventy-nine carriers of germline MMR gene pathogenic variant (path_MMR) were identified from the Finnish LS Registry as having genetic testing performed before the age of 45 years and not having undergone hysterectomy or oophorectomy. These women were sent a questionnaire concerning family planning, intimate relationships and psychosocial wellbeing. RESULTS: Thirty-five women (44.3%) responded. Parity of path_MMR carriers (2.1) was slightly higher than parity among Finnish women in general (1.8). No significant differences were found between parity, number of induced abortions or sterilizations before and after genetic testing. Only minority of subjects reported any influence on family planning (20%) or negative impact on feminine self and body image (14%). CONCLUSIONS: The positive germline testing does not seem to have a major negative impact on family planning, intimate relationships or feminine self and body image. According to the open comments, counselling, supportive and empathic attitude of the professionals seem to have a significant impact on this. These results are a valuable addition to the counselling of LS women at reproductive age.

5.
Tumour Biol ; 42(11): 1010428320971404, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33169632

RESUMO

Ovarian cancer is the most lethal of gynecological cancers with 5-year survival rate of ca. 45%. The most common histologic subtype is high-grade serous carcinoma, which typically is presented with advanced stage and development of chemoresistance. Therefore, new treatment options, including immunotherapies, are needed. Understanding the features of the immune cell populations in the tumor microenvironment is essential for developing personalized treatments and finding predictive biomarkers. Digital image analysis may enhance the accuracy and reliability of immune cell infiltration assessment in the tumor microenvironment. The aim of this study was to characterize tumor microenvironment in a retrospective cohort of high-grade serous carcinoma samples with whole-slide imaging and digital image analysis. Formalin-fixed paraffin-embedded high-grade serous carcinoma tumor tissue samples (n = 67) were analyzed for six immunohistochemical stainings: CD4, CD8, FoxP3, granzyme B, CD68, and CD163. The stained sample slides were scanned into a digital format and assessed using QuPath 0.1.2 and ImageJ software. Staining patterns were associated with clinicopathological data. The higher numbers of intraepithelial CD8+, CD163+, and granzyme B+ immune cells were associated with survival benefit when analyzed individually, while high levels of both CD8+ and granzyme B+ tumor-infiltrating lymphocytes were an independent prognostic factor in the Cox multivariate regression analysis (median progression-free survival; hazard ratio = 0.287, p = 0.002). Specimens taken after administration of neoadjuvant chemotherapy presented with lower FoxP3+ tumor-infiltrating lymphocyte density (Fisher's exact test, p = 0.013). However, none of the studied immunomarkers was associated with overall survival or clinical factors. Tumors having high amount of both intraepithelial CD8+ and granzyme B+ tumor-infiltrating lymphocytes showed better progression-free survival, possibly reflecting an activated immune state in the tumor microenvironment. The combined positivity of CD8 and granzyme B warrants further investigation with respect to predicting response to immune therapy. Neoadjuvant chemotherapy may have an effect on the tumor microenvironment and therefore on the response to immuno-oncologic or chemotherapy treatments.


Assuntos
Antígenos CD8/sangue , Carcinoma Epitelial do Ovário/sangue , Granzimas/sangue , Linfócitos do Interstício Tumoral/metabolismo , Adulto , Idoso , Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Antígenos CD4/sangue , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/epidemiologia , Carcinoma Epitelial do Ovário/patologia , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Fatores de Transcrição Forkhead/sangue , Humanos , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/patologia , Pessoa de Meia-Idade , Receptores de Superfície Celular/sangue , Microambiente Tumoral/efeitos dos fármacos
6.
Int J Mol Sci ; 21(5)2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32155897

RESUMO

Drug treatments have been designed to inhibit tumor angiogenesis in hope of stopping tumor growth. However, not all tumor types respond to this type of treatment. A screening method which identifies angiogenesis inducing cancer types would help predict the efficacy of angiogenesis-inhibiting drugs for the patients. Our goal is to develop (1) a cell assay to assess the angiogenic induction potential of patient-derived tumor cells, and (2) a protocol for culturing cancer cells on a vascular platform. We optimized the media composition and seeding density of cells (hASC, HUVEC, and cancer cells) to 48-, 96-, and even 384-well plate sizes to allow vascular formation and cancer cell proliferation and subsequent analysis with high throughput. The angiogenic induction potential of patient-derived cancer cells was investigated by quantifying the formation of tubular structures and the drug response of cancer cells grown on a vascular platform was evaluated using gene expression and cell viability (WST-1) assay. Immunocytochemistry was performed with von Willebrand factor, collagen IV, CD44, cytokeratin 19 and ALDH1A1. The angiogenic induction potential test was shown to be responsive to the induction of angiogenesis by cancer cells. The responses of cancer cells were different when grown on a vascular platform or on plastic, seen in gene expression level and viability results. These two protocols are promising novel tools for aiding the selection of efficient cancer drugs for personalized medicine and as an alternative cancer cell culture platform.


Assuntos
Movimento Celular , Proliferação de Células , Células Endoteliais da Veia Umbilical Humana/citologia , Células-Tronco Mesenquimais/citologia , Neoplasias/irrigação sanguínea , Neovascularização Patológica , Neovascularização Fisiológica , Bioensaio , Células Cultivadas , Técnicas de Cocultura , Humanos , Técnicas In Vitro , Neoplasias/patologia
7.
Lancet Oncol ; 20(10): 1409-1419, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31474354

RESUMO

BACKGROUND: Platinum-based chemotherapy is the foundation of treatment for platinum-sensitive recurrent ovarian cancer, but has substantial toxicity. Bevacizumab and maintenance poly(ADP-ribose) polymerase (PARP) inhibitors both significantly improve efficacy versus standard therapy, primarily in terms of progression-free survival, and offer the potential for chemotherapy-free treatment. AVANOVA2 compared niraparib and bevacizumab versus niraparib alone as definitive treatment for platinum-sensitive recurrent ovarian cancer. METHODS: This open-label, randomised, phase 2, superiority trial in 15 university hospitals in Denmark, Sweden, Finland, Norway, and the USA enrolled women aged 18 years or older with measurable or evaluable high-grade serous or endometrioid platinum-sensitive recurrent ovarian cancer. Patients had to have an Eastern Cooperative Oncology Group performance status of 0-2, and had to have previously received platinum-containing therapy for primary disease but ≤1 prior non-platinum-containing regimen for recurrent disease. Previous treatment with bevacizumab or first-line maintenance PARP inhibitors was permitted. Eligible patients were randomly assigned 1:1 (by random permuted blocks with block sizes of two and four, no masking), stratified by homologous recombination deficiency status and chemotherapy-free interval, to receive once-daily oral niraparib 300 mg alone or with intravenous bevacizumab 15 mg/kg once every 3 weeks until disease progression. The primary endpoint was progression-free survival, assessed by the investigators in the intention-to-treat population after events in at least 62 patients. Safety was analysed in all patients who received at least one dose of study drug. This ongoing trial is registered with ClinicalTrials.gov, number NCT02354131. FINDINGS: Between May 23, 2016, and March 6, 2017, 97 patients were enrolled and randomly assigned: 48 to niraparib plus bevacizumab and 49 to single-agent niraparib. Median follow-up was 16·9 months (IQR 15·4-20·9). Niraparib plus bevacizumab significantly improved progression-free survival compared with niraparib alone (median progression-free survival 11·9 months [95% CI 8·5-16·7] vs 5·5 months [3·8-6·3], respectively; adjusted hazard ratio [HR] 0·35 [95% CI 0·21-0·57], p<0·0001). Grade 3 or worse adverse events occurred in 31 (65%) of 48 patients who received niraparib plus bevacizumab and 22 (45%) of 49 who received single-agent niraparib. The most common grade 3 or worse adverse events in both groups were anaemia (7 [15%] of 48 vs 9 [18%] of 49) and thrombocytopenia (5 [10%] vs 6 [12%]), and hypertension in the combination group (10 [21%] vs 0). Niraparib plus bevacizumab was associated with increased incidences of any-grade proteinuria (10 [21%] of 48 patients vs 0) and hypertension (27 [56%] of 48 vs 11 [22%] of 49) compared with niraparib alone. No treatment-related deaths occurred. INTERPRETATION: The efficacy observed with this chemotherapy-free combination of approved agents in women with platinum-sensitive recurrent ovarian cancer warrants further evaluation. A randomised phase 3 trial investigating niraparib plus bevacizumab versus chemotherapy plus bevacizumab in platinum-sensitive recurrent ovarian cancer is planned. FUNDING: Nordic Society of Gynaecological Oncology and Tesaro.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Endometrioide/tratamento farmacológico , Indazóis/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Piperidinas/uso terapêutico , Idoso , Anemia Aplástica/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Carcinoma Endometrioide/patologia , Progressão da Doença , Feminino , Humanos , Hipertensão/induzido quimicamente , Indazóis/administração & dosagem , Indazóis/efeitos adversos , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Ovarianas/patologia , Piperidinas/administração & dosagem , Piperidinas/efeitos adversos , Intervalo Livre de Progressão , Proteinúria/induzido quimicamente , Trombocitopenia/induzido quimicamente
8.
BMC Gastroenterol ; 19(1): 189, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730447

RESUMO

BACKGROUND: There is an unmet need for novel treatments, such as drugs or vaccines, adjunctive to or replacing a burdensome life-long gluten-free diet for coeliac disease. The gold standard for successful treatment is a healed small intestinal mucosa, and therefore, the outcome measures in proof-of-concept studies should be based on evaluation of small intestine biopsies. We here evaluated morphometric, immunohistochemical and messenger RNA (mRNA) expression changes in coeliac disease patients challenged with gluten using PAXgene fixed paraffin-embedded biopsies. METHODS: Fifteen coeliac disease patients were challenged with 4 g of gluten per day for 10 weeks and 24 non-coeliac patients served as disease controls. A wide array of histological and immunohistochemical staining and mRNA-based gene expression tests (RT-qPCR and RNAseq) were carried out. RESULTS: Digital quantitative villous height: crypt depth ratio (VH: CrD) measurements revealed significant duodenal mucosal deterioration in all coeliac disease patients on gluten challenge. In contrast, the Marsh-Oberhuber class worsened in only 80% of coeliac patients. Measuring the intraepithelial CD3+ T-lymphocyte and lamina propria CD138+ plasma cell densities simultaneously proved to be a meaningful new measure of inflammation. Stainings for γδ T cells and IgA deposits, where previously frozen samples have been needed, were successful in PAXgene fixed paraffin-embedded samples. Messenger RNA extraction from the same paraffin-embedded biopsy block was successful and allowed large-scale qRT-PCR and RNAseq analyses for gene expression. Molecular morphometry, using the mRNA expression ratio of villous epithelium-specific gene APOA4 to crypt proliferation gene Ki67, showed a similar significant distinction between paired baseline and post-gluten challenge biopsies as quantitative histomorphometry. CONCLUSION: Rigorous digitally measured histologic and molecular markers suitable for gluten challenge studies can be obtained from a single paraffin-embedded biopsy specimen. Molecular morphometry seems to be a promising new tool that can be used in situations where assessing duodenal mucosal health is of paramount importance. In addition, the diagnostically valuable IgA deposits were now stained in paraffin-embedded specimens making them more accessible in routine clinics.


Assuntos
Biópsia/métodos , Doença Celíaca/genética , Doença Celíaca/patologia , Duodeno/patologia , Expressão Gênica , Mucosa Intestinal/patologia , RNA Mensageiro/genética , Adulto , Doença Celíaca/dietoterapia , Doença Celíaca/imunologia , Duodeno/imunologia , Fixadores , Imunofluorescência , Formaldeído , Glutens/imunologia , Humanos , Mucosa Intestinal/imunologia , Inclusão em Parafina , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de RNA , Linfócitos T/patologia
9.
BMC Cancer ; 18(1): 1045, 2018 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-30367623

RESUMO

BACKGROUND: Human epidermal growth factor receptor HER3 (ErbB3), especially in association with its relative HER2 (ErbB2), is known as a key oncogene in breast tumour biology. Nonetheless, the prognostic relevance of HER3 remains controversial. NEDD4-1 and NRDP1 are signalling molecules closely related to the degradation of HER3 via ubiquitination. NEDD4-1 and NRDP1 have been reported to contribute to HER3-mediated signalling by regulating its localization and cell membrane retention. We studied correlations between HER3, NEDD4-1, and NRDP1 protein expression and their association with tumour histopathological characteristics and clinical outcomes. METHODS: The prevalence of immunohistochemically detectable expression profiles of HER3 (n = 177), NEDD4-1 (n = 145), and NRDP1 (n = 145) proteins was studied in primary breast carcinomas on archival formalin-fixed paraffin-embedded (FFPE) samples. Clinicopathological correlations were determined statistically using Pearson's Chi-Square test. The Kaplan-Meier method, log-rank test (Mantel-Cox), and Cox regression analysis were utilized for survival analysis. RESULTS: HER3 protein was expressed in breast carcinomas without association with HER2 gene amplification status. Absence or low HER3 expression correlated with clinically aggressive features, such as triple-negative breast cancer (TNBC) phenotype, basal cell origin (cytokeratin 5/14 expression combined with ER negativity), large tumour size, and positive lymph node status. Low total HER3 expression was prognostic for shorter recurrence-free survival time in HER2-amplified breast cancer (p = 0.004, p = 0.020 in univariate and multivariate analyses, respectively). The majority (82.8%) of breast cancers demonstrated NEDD4-1 protein expression - while only a minor proportion (8.3%) of carcinomas expressed NRDP1. NEDD4-1 and NRDP1 expression were not associated with clinical outcomes in HER2-amplified breast cancer, irrespective of adjuvant trastuzumab therapy. CONCLUSIONS: Low HER3 expression is suggested to be a valuable prognostic biomarker to predict recurrence in HER2-amplified breast cancer. Neither NEDD4-1 nor NRDP1 demonstrated relevance in prognostics or in the subclassification of HER2-amplified breast carcinomas.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Regulação Neoplásica da Expressão Gênica , Ubiquitina-Proteína Ligases Nedd4/metabolismo , Receptor ErbB-3/genética , Ubiquitina-Proteína Ligases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptor ErbB-3/metabolismo
10.
Am J Obstet Gynecol ; 219(5): 458.e1-458.e8, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30240650

RESUMO

BACKGROUND: Cesarean scar defect (isthmocele) is a known complication after cesarean delivery. It has become more common due to a rising cesarean delivery rate. Isthmocele has been associated with various gynecological and obstetric problems such as uterine rupture, cesarean scar pregnancy, and bleeding disorders. OBJECTIVE: We sought to prospectively investigate factors associated with the risk for isthmocele assessed by sonohysterography. STUDY DESIGN: A prospective observational cohort study was conducted in 401 nonpregnant women who were recruited within 3 days of cesarean delivery. Women were evaluated with sonohysterography 6 months after cesarean delivery to detect a possible isthmocele. The ultrasonographer was blinded to any clinical information. The main outcome measure was the presence of isthmocele. Type of surgery (elective vs emergency), maternal background variables, and factors related to pregnancy, labor, and postoperative recovery were analyzed in relation to isthmocele. A logistic regression model was used to assess independent risk factors from univariate analysis. RESULTS: In all, 371 women were examined with sonohysterography resulting in a follow-up rate of 92.5%. The prevalence of isthmocele was 45.6%. Independent risk factors for isthmocele development were a history of gestational diabetes (odds ratio, 1.73; 95% confidence interval, 1.02-2.92; P = .042), previous cesarean delivery (odds ratio, 3.14; 95% confidence interval, 1.90-5.17; P < .001), and advanced maternal body mass index (odds ratio, 1.06; 95% confidence interval, 1.01-1.11; P = .012). Every additional unit of body mass index increased the risk of isthmocele by 6%. In the subgroup of emergency cesarean delivery, longer duration of active labor increased the risk for isthmocele (odds ratio, 1.06; 95% confidence interval, 1.01-1.11; P = .032). There was no statistically significant difference in prevalence between the groups of elective and emergency cesarean delivery (P = .898). CONCLUSION: Based on sonohysterographic examination, maternal body mass index, gestational diabetes, and previous cesarean deliveries are associated with an increased risk for incomplete healing of the uterine incision.


Assuntos
Cesárea/efeitos adversos , Cicatriz/etiologia , Adulto , Índice de Massa Corporal , Cicatriz/diagnóstico por imagem , Cicatriz/epidemiologia , Estudos de Coortes , Diabetes Gestacional , Tratamento de Emergência , Feminino , Idade Gestacional , Humanos , Gravidez , Estudos Prospectivos , Fatores de Risco , Ultrassonografia
11.
Acta Obstet Gynecol Scand ; 97(9): 1130-1136, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29754409

RESUMO

INTRODUCTION: The aim of this study was to investigate the prevalence of post-cesarean isthmocele and to measure agreement between transvaginal ultrasonography and saline contrast sonohysterography in assessment of isthmocele. MATERIAL AND METHODS: A prospective observational cohort study was carried out at Tampere University Hospital, Finland. Non-pregnant women delivered by cesarean section (n = 371) were examined with transvaginal ultrasonography (TVUS) and sonohysterography (SHG) six months after cesarean section. The main outcome measure was the prevalence of isthmocele using TVUS and SHG. Secondary outcome measures were characteristics of isthmocele. RESULTS: In all, 371 women were included. The prevalence of isthmocele was 22.4% based on TVUS and 45.6% based on SHG. Sensitivity and specificity for TVUS was 49.1 and 100%, respectively, when compared with SHG. Therefore, half of the defects (50.9%) diagnosed with SHG remained undiagnosed with TVUS. Bland-Altman analysis showed an underestimation of 1.1 mm (range 0.00-7.90) for TVUS compared with SHG, with 95% limits of agreement from -1.9 to 4.1 mm. CONCLUSIONS: This methodological study provides confirmatory data that TVUS and SHG are not in good agreement in the isthmocele diagnostics and the use of only TVUS may lead to an underestimation of the prevalence of isthmocele. Thus, SHG should be considered as a method of choice in diagnostics of isthmocele.


Assuntos
Cesárea , Cicatriz/diagnóstico por imagem , Ultrassonografia/métodos , Útero/diagnóstico por imagem , Adulto , Cicatriz/patologia , Meios de Contraste , Feminino , Finlândia , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Cloreto de Sódio , Útero/patologia
12.
J Low Genit Tract Dis ; 21(3): 209-214, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28644192

RESUMO

OBJECTIVES: Eight percent of women have vulvodynia (VD), a chronic pain disorder with unknown etiology. The aim of our study was to assess the efficacy of given VD treatments measured by numerical rating scale (NRS) for pain and patients' quality of life. MATERIALS AND METHODS: Study material consisted of a retrospective VD patient cohort (N = 70). Data were collected by postal questionnaires and review of the medical records. RESULTS: We report here a statistically significant reduction in NRS only with combination of therapies (median NRS before treatments 8 vs median NRS 4 after treatments, p < .001) but not with any individual therapy alone, i.e., physiotherapy, topical medications, oral pharmaceutical therapy, sexual counseling by a trained nurse, sacral neuromodulation, and laser treatment or surgery. Older age (>30) and frequent (≥6) outpatient clinic visits associated with a significantly minor reduction in NRS (p = .03 and p = .04, respectively). CONCLUSIONS: The results of this retrospective study suggest that an effective, multimodality-based treatment is most beneficial for VD patients and VD at older age may represent a subtype more resistant to therapy.


Assuntos
Terapia Combinada/métodos , Vulvodinia/epidemiologia , Vulvodinia/terapia , Adulto , Fatores Etários , Feminino , Humanos , Qualidade de Vida , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do Tratamento , Vulvodinia/psicologia
13.
Br J Cancer ; 115(3): 375-81, 2016 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-27336600

RESUMO

BACKGROUND: Lynch syndrome (LS) is associated with a significant lifetime risk of endometrial cancer (EC). There are limited data on factors modifying the EC risk in LS patients. METHODS: The study cohort included 136 LS mutation-positive women. Exposure data were collected by postal questionnaires. Cox regression model was used to estimate the associations between lifestyle, hormonal, reproductive and medical factors and the risk of EC. RESULTS: Increased EC risk was associated with type II diabetes and hypercholesterolaemia in univariable (HR 3.21, (95% CI 1.34-7.78), P=0.009 and HR 2.08, (95% CI 1.11-3.90), P=0.02; respectively) and with diabetes and duration of hormone replacement therapy (HRT) in multivariable analysis (HR 4.18 (95% CI 1.52-11.52), P=0.006 and HR 1.07 (95% CI 1.02-1.13), P=0.010; respectively). CONCLUSIONS: Prevention of diabetes and avoiding long-duration HRT are potential targets for reduction of EC risk in women with LS.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias do Endométrio/epidemiologia , Adulto , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias do Endométrio/complicações , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
14.
Tumour Biol ; 37(7): 9813-23, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26810187

RESUMO

Cyclin E is a well-characterized cell cycle regulator and an amplified oncogene in breast cancer. Over-expression of cyclin E has generally been associated with poor survival. Recent studies have shown an interaction between HER-2 (ERBB2) and cyclin E, but the exact mechanism is unknown. Interestingly, cyclin E over-expression has been associated with trastuzumab resistance. We studied cyclin E over-expression, CCNE1 amplification, and relapse-free survival in HER-2-positive primary breast cancers treated with and without trastuzumab therapy. Formalin-fixed paraffin-embedded tissue samples from 202 HER-2-positive breast carcinomas were studied. Expression levels of cyclin E and proliferation marker Ki-67 were determined using immunohistochemistry. Chromogenic in situ hybridization (CISH) with a gene-specific bacterial artificial chromosome (BAC) probe was used to analyze presence of CCNE1 amplification. Majority of HER-2-positive breast carcinomas exhibited nuclear staining for cyclin E protein. Cyclin E was highly expressed (≥50 % cells) in 37 % of cases. Incidence of CCNE1 amplification (≥6 gene copies/cell or clusters) was 8 %. Cyclin E amplification and over-expression were strongly associated with each other, grade, hormone receptors, and Ki-67. Neither high cyclin E expression nor CCNE1 amplification was associated with relapse-free survival (RFS) irrespective of short-term (9-week regimen) adjuvant trastuzumab therapy. These results confirm cyclin E and HER-2 gene co-amplification in a fraction of HER-2-positive breast cancers. Cyclin E is frequently over-expressed but appears to have limited value as a prognostic or predictive factor in HER-2-positive breast cancer regardless of trastuzumab therapy.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Carcinoma Intraductal não Infiltrante/mortalidade , Carcinoma Lobular/mortalidade , Ciclina E/metabolismo , Recidiva Local de Neoplasia/mortalidade , Proteínas Oncogênicas/metabolismo , Receptor ErbB-2/metabolismo , Animais , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/secundário , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/secundário , Carcinoma Lobular/genética , Carcinoma Lobular/metabolismo , Carcinoma Lobular/secundário , Ciclina E/genética , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Hibridização In Situ , Camundongos Nus , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Metástase Neoplásica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Proteínas Oncogênicas/genética , Prognóstico , Receptor ErbB-2/genética , Estudos Retrospectivos , Taxa de Sobrevida
15.
Int J Gynecol Cancer ; 26(8): 1465-71, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27648714

RESUMO

OBJECTIVE: The aim was to study the association of L1 cell adhesion molecule (L1CAM) expression with the outcome of patients with endometrial cancer, especially with regard to conventional risk variables, and to compare the patterns of relapse in L1CAM-positive and -negative cancers. METHODS: This was a retrospective study of 805 women. The Kaplan-Meier method and univariate and multivariate Cox regression models were applied for survival analyses. Missing data were replaced using multiple imputation. The median follow-up time was 51 months (range, 1-98). RESULTS: One hundred twenty-one (15.0%) cases were L1CAM positive. L1CAM positivity was associated with high stage (I vs II-IV) (odds ratio [OR], 2.3), lymph node involvement (OR, 2.9), poor differentiation (OR, 6.1), non-endometrioid histology (OR, 9.9), lymphovascular space invasion (OR, 2.8), cervical stromal invasion (OR, 1.8), positive peritoneal cytology (OR, 4.1), and age older than 65 years (OR, 2.8). The frequencies of deep myometrial invasion (50% or deeper), tumor size 2 cm or greater, and body mass index 30 kg/m or greater were not significantly different between L1CAM-positive and -negative cases. L1CAM predicted poor disease-specific survival in endometrioid (P < 0.0001) but not in non-endometrioid carcinomas (P = 0.934). The negative impact of L1CAM on outcome was confirmed in a Cox multivariate disease-specific survival analysis. Univariate survival analyses in the different ESMO-ESGO-ESTRO endometrial cancer risk groups showed an association between L1CAM positivity and poor outcome in intermediate (hazard ratio, 12) and high-risk advanced metastatic (hazard ratio, 2.0) groups. Extra-abdominal relapses were more frequent in L1CAM-positive (13.2%) than L1CAM-negative (1.9%) stage I endometrioid carcinomas (P < 0.0001), whereas other site-specific relapses in local cancers were L1CAM independent. CONCLUSIONS: L1CAM is associated with the occurrence of poor prognostic variables and predicts advanced disease in endometrial cancer. L1CAM predicts extra-abdominal relapses and poor survival in endometrioid endometrial cancer, but seems not to be a prognostic factor in non-endometrioid carcinomas.


Assuntos
Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/mortalidade , Molécula L1 de Adesão de Célula Nervosa/biossíntese , Idoso , Análise de Variância , Biomarcadores Tumorais/biossíntese , Carcinoma Endometrioide/metabolismo , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/terapia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Fatores de Risco , Análise Serial de Tecidos
16.
Genes Chromosomes Cancer ; 54(5): 276-87, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25706666

RESUMO

Mutations in the BRCA1 and BRCA2 genes confer an increased lifetime risk for breast and ovarian cancer. Ovarian cancer risk can be decreased by risk-reducing salpingo-oophorectomy (RRSO). Studies on RRSO material have altered the paradigm of serous ovarian cancer pathogenesis. The purpose of this study was to identify candidate genes possibly involved in the pathogenesis of serous ovarian cancer by carrying out a microarray analysis of differentially expressed genes in BRCA1/2- mutation positive ovarian and fallopian tube epithelium derived from RRSO surgery. Freshly frozen ovarian and fallopian tube samples from nine BRCA1/2 mutation carriers scheduled for RRSO were prospectively collected together with five mutation-negative control patients undergoing salpingo-oophorectomy for benign indications. Microarray analysis of genome-wide gene expression was performed on ovarian and fallopian tube samples from the BRCA1/2 and control patients. The validation of microarray data was performed by quantitative real-time polymerase chain reaction (qRT-PCR) in selected cases of RRSO samples and also in high grade serous carcinoma samples collected from patients with a BRCA phenotype. From 22,733 genes, 454 transcripts were identified that were differentially expressed in BRCA1/2 mutation carriers when compared with controls, pooling all ovarian and fallopian tube samples together. Of these, 299 genes were statistically significantly downregulated and 155 genes upregulated. Differentially expressed genes in BRCA1/2 samples reported here might be involved in serous ovarian carcinogenesis and provide interesting targets for further studies.


Assuntos
Biomarcadores Tumorais/genética , Tubas Uterinas/metabolismo , Expressão Gênica , Neoplasias Ovarianas/genética , Ovário/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Epitélio/metabolismo , Feminino , Humanos , Análise em Microsséries , Pessoa de Meia-Idade , Ovariectomia
17.
Tumour Biol ; 35(5): 4651-7, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24420153

RESUMO

Preoperative evaluation of the risk for metastases in endometrial carcinoma is challenging. The growth of new vessels, angiogenesis, is important for tumor growth and purported to be involved in the metastatic process. The aim of this study was to evaluate the significance of preoperative serum levels and immunohistochemical expression of angiogenic markers in predicting a metastasized disease. Preoperative sera from 98 consecutive women presenting with endometrial carcinoma were collected. Serum concentrations of VEGF, sFLT1, and CD105 were assessed by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to assess the expression of CD105, VEGF, FLT1, and KDR. The results were correlated to the presence of metastases, presence of deep (≥50%) myometrial invasion, and the histological grade of the tumor. Tumors with other than endometrioid histology were excluded. Of the 80 evaluable patients, 11 had a metastasized disease. The serum concentration of VEGF was higher in the group with metastases than in the group without metastases (median [range], 743 pg/mL [546-1,183 pg/mL] vs. 383 pg/mL [31-1,524 pg/mL], p < 0.001, respectively). In the multivariable analysis, the concentration of VEGF was the sole independent, albeit weak predictive factor for the presence of metastases (odds ratio, 1.004, 95% confidence interval, 1.002-1.007; p = 0.001). The immunohistochemical expression of the markers was not associated with any of the clinicopathological features of the tumors. The results of the present study suggest that preoperative serum VEGF concentration correlates with the presence of metastases in endometrioid endometrial carcinoma.


Assuntos
Antígenos CD/sangue , Neoplasias do Endométrio/patologia , Receptores de Superfície Celular/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Endoglina , Neoplasias do Endométrio/sangue , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Metástase Neoplásica
18.
Int J Gynecol Pathol ; 33(3): 309-16, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24681744

RESUMO

Mutations in BRCA1 and BRCA2 genes confer an increased lifetime risk for breast and ovarian cancer. Increased lifetime ovarian cancer risk among BRCA1/BRCA2 mutation carriers can be substantially decreased by risk-reducing salpingo-oophorectomy (RRSO), which also provides material for molecular research on early pathogenesis of serous ovarian cancer. RRSO studies have suggested fallopian tube as a primary site of serous high-grade ovarian cancer. In this study, the nuclear expression levels of γ-H2AX and p53 using immunohistochemical (IHC) study was quantitatively assessed in ovarian and fallopian tube epithelium derived from RRSOs in 29 BRCA1 and BRCA2 mutation carriers and in 1 patient with a strong family history of breast and ovarian cancer but showing an unknown BRCA status. Both p53 and γ-H2AX nuclear staining levels were significantly higher in BRCA1/2 mutation-positive fallopian tube epithelium compared with the control fallopian tube epithelium (P<0.006 and P=0.011, respectively). Nuclear expression levels of p53 and γ-H2AX were similar between the BRCA1/2 mutation-positive ovarian epithelium and controls. Both γ-H2AX and p53 showed significantly higher nuclear expression levels in BRCA1/2 mutation-positive fallopian tube epithelium compared with BRCA1/2 mutation-positive ovarian epithelium (P<0.0001 and P<0.0001, respectively). BRCA1/2 mutation-positive fallopian tube epithelium showed a positive correlation between the γ-H2AX and p53 nuclear expression levels (Pearson r=0.508, P=0.003). Our results of quantitative nuclear p53 and γ-H2AX expression levels in ovarian and fallopian tube epithelium derived from RRSO in high-risk patients support the previously suggested role of fallopian tube epithelium serving as a possible site of initial serous ovarian carcinogenesis.


Assuntos
Cistadenocarcinoma Seroso/genética , Neoplasias das Tubas Uterinas/genética , Tubas Uterinas/patologia , Histonas/metabolismo , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Ovário/patologia , Proteína Supressora de Tumor p53/metabolismo , Adulto , Idoso , Proteína BRCA1/genética , Proteína BRCA2/genética , Carcinoma Epitelial do Ovário , Núcleo Celular/metabolismo , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/prevenção & controle , Cistadenocarcinoma Seroso/cirurgia , Epitélio/patologia , Neoplasias das Tubas Uterinas/patologia , Neoplasias das Tubas Uterinas/prevenção & controle , Neoplasias das Tubas Uterinas/cirurgia , Feminino , Predisposição Genética para Doença , Heterozigoto , Humanos , Pessoa de Meia-Idade , Mutação , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/prevenção & controle , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/prevenção & controle , Neoplasias Ovarianas/cirurgia , Ovariectomia
19.
Life Sci Alliance ; 7(6)2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38580393

RESUMO

Epithelial ovarian cancer (EOC) is one of the leading causes of cancer-related death in women worldwide, and is characterized by a high rate of recurrence after surgery and chemotherapy. We sought to implement a circulating tumor DNA (ctDNA)-based blood test for more accurate post-operative surveillance of this disease. We analyzed 264 plasma samples collected between June 2016 and September 2021 from 63 EOC patients using tumor-guided plasma cell-free DNA analysis to detect residual disease after treatment. Assay specificity was verified using cross-patient analysis of 1,195 control samples. ctDNA was detected in 51 of 55 (93%) samples at diagnosis, and 18 of 18 (100%) samples at progression. Positive ctDNA in the last on-treatment sample was associated with rapid progression (median 1.02 versus 3.38 yr, HR = 5.63, P < 0.001) and reduced overall survival (median 2.31 versus NR yr, HR = 8.22, P < 0.001) in patients with high-grade serous cancer. In the case of 12 patients, ctDNA assays detected progression earlier than standard surveillance, with a median lead time of 5.9 mo. To approach the physical limits of ctDNA detection, five patients were analyzed using ultra-sensitive assays interrogating 479-1,856 tumor mutations, capable of tracking ctDNA fractions down to 0.0004%. Our results demonstrate that ctDNA assays achieve high sensitivity and specificity in detecting post-operative residual disease in EOC.


Assuntos
DNA Tumoral Circulante , Neoplasias Ovarianas , Humanos , Feminino , DNA Tumoral Circulante/genética , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/genética , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética
20.
Cell Death Discov ; 9(1): 222, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37400436

RESUMO

Wnt pathway dysregulation through genetic and non-genetic alterations occurs in multiple cancers, including ovarian cancer (OC). The aberrant expression of the non-canonical Wnt signaling receptor ROR1 is thought to contribute to OC progression and drug resistance. However, the key molecular events mediated by ROR1 that are involved in OC tumorigenesis are not fully understood. Here, we show that ROR1 expression is enhanced by neoadjuvant chemotherapy, and Wnt5a binding to ROR1 can induce oncogenic signaling via AKT/ERK/STAT3 activation in OC cells. Proteomics analysis of isogenic ROR1-knockdown OC cells identified STAT3 as a downstream effector of ROR1 signaling. Transcriptomics analysis of clinical samples (n = 125) revealed that ROR1 and STAT3 are expressed at higher levels in stromal cells than in epithelial cancer cells of OC tumors, and these findings were corroborated by multiplex immunohistochemistry (mIHC) analysis of an independent OC cohort (n = 11). Our results show that ROR1 and its downstream STAT3 are co-expressed in epithelial as well as stromal cells of OC tumors, including cancer-associated fibroblasts or CAFs. Our data provides the framework to expand the clinical utility of ROR1 as a therapeutic target to overcome OC progression.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA