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1.
Pol J Pathol ; 72(1): 84-86, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34060291

RESUMO

Gastrointestinal type of endometrial carcinoma is a newly described entity for which clearly defined diagnostic criteria have only recently been published. Among morphologic criteria, gastrointestinal mucinous adenocarcinoma of endometrium must not show a typical endometrioid component. We present a case with morphologic diversity, with areas showing gastric and intestinal differentiation as well as an endometrioid-like component. However, the endometrioid-like component not only did not show classic squamous metaplasia, but was also MUC6-positive, while the positivity for ER/PR was only focal. The recognition of gastric/gastrointestinal differentiation in endometrial carcinomas is best accomplished using both morphology and immunohistochemistry rather than either alone.


Assuntos
Adenocarcinoma Mucinoso , Neoplasias do Endométrio , Neoplasias Uterinas , Diferenciação Celular , Feminino , Humanos , Imuno-Histoquímica
2.
J Int Med Res ; 49(6): 3000605211018592, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34082605

RESUMO

OBJECTIVE: To explore the neddylation pathway, found to be highly activated in various cancers, as a potential therapeutic target in endometrial carcinoma, one of the three most frequent malignant tumours in the female reproductive system. METHODS: Data from The Cancer Genome Atlas were analysed using online servers. Expression levels of key neddylation genes were validated by reverse-transcription polymerase chain reaction and western blots of tumour and adjacent tissues. Underlying mechanisms and the effects on cell activities of the neddylation pathway-specific inhibitor, MLN4924, were investigated in endometrial cancer cell lines. RESULTS: Key neddylation enzymes, ubiquitin conjugating enzyme E2 M (UBC12), ubiquitin conjugating enzyme E2 F (UBE2F), ring-box 1 (RBX1) and ring finger protein 7 (RBX2), were significantly overexpressed in endometrial carcinoma tissues versus normal tissues, but only UBE2F and RBX2 positively correlated with patient survival. MLN4924 significantly suppressed proliferation and colony formation in EC cells by inducing DNA re-replication, cell cycle arrest and apoptosis. Mechanism study revealed that MLN4924 induced the accumulation of cullin-RING ligase substrates in vitro. CONCLUSIONS: The neddylation pathway was identified to play an important role in endometrial cancer. The neddylation specific inhibitor, MLN4924, may be a potential therapeutic drug for endometrial carcinoma.


Assuntos
Neoplasias do Endométrio , Ubiquitinas , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Ciclopentanos/farmacologia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Feminino , Humanos , Proteína NEDD8/genética , Pirimidinas , Ubiquitinas/genética
3.
JSLS ; 25(2)2021.
Artigo em Inglês | MEDLINE | ID: mdl-33981135

RESUMO

Background and Objectives: The aim of this study was to define new techniques for performing vaginal closure with endo-staplers to prevent tumor spillage during laparoscopic surgeries for endometrial cancer and early stage cervical cancer. Methods: Thirteen patients were retrospectively studied for the use of endo-staplers for vaginal closure before colpotomy during laparoscopic surgeries for endometrial cancer and early stage cervical cancer to prevent tumor spillage. Results: There were no short-term or any long-term complication related to the use of the endo-staplers for colpotomy in the surgeries included in this study. Conclusion: Use of the endo-staplers to close the vagina before colpotomy according to the technique described is safe and feasible, with prevention of gross spillage of any malignant cells in the peritoneal cavity or vagina, which will further have a favorable oncologic outcome.


Assuntos
Colpotomia , Neoplasias do Endométrio/cirurgia , Neoplasias do Colo do Útero/cirurgia , Vagina/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colpotomia/métodos , Feminino , Humanos , Laparoscopia/métodos , Pessoa de Meia-Idade , Cavidade Peritoneal/patologia , Estudos Retrospectivos , Instrumentos Cirúrgicos
4.
Medicine (Baltimore) ; 100(21): e26170, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032778

RESUMO

ABSTRACT: To identify prognostic tumor-infiltrating immune cells of endometrial adenocarcinoma.The gene expression profiles of endometrial adenocarcinoma were downloaded from the Cancer Genome Atlas (TCGA). The abundance of tumor-infiltrating immune cells in endometrial adenocarcinoma samples was calculated by CIBERSORT algorithm. Kaplan-Meier analysis was used to identify prognostic tumor-infiltrating immune cells.This study identified 22 kinds of tumor-infiltrating immune cells. Macrophages M0 and CD8 T cells were prognostic factors of endometrial adenocarcinoma. The abundance of macrophages M0 (P = .038) was significantly correlated with better prognosis of endometrial adenocarcinoma. In contrast, the abundance of CD8 T cells (P = .049) was associated with poor prognosis of endometrial adenocarcinoma.Tumor-infiltrati macrophages M0 and CD8 T cells were prognostic factors of endometrial adenocarcinoma.


Assuntos
Adenocarcinoma/imunologia , Linfócitos T CD8-Positivos/imunologia , Neoplasias do Endométrio/imunologia , Linfócitos do Interstício Tumoral/imunologia , Macrófagos/imunologia , Algoritmos , Feminino , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Microambiente Tumoral
5.
BMJ Case Rep ; 14(5)2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34011660

RESUMO

Herlyn-Werner-Wunderlich syndrome, a rare Mullerian duct anomaly, includes a triad of uterine didelphys, obstructed haemivagina and ipsilateral renal agenesis. A 58-year-old woman with Herlyn-Werner-Wunderlich syndrome, reported of recurrent genital bleeding for 9 years, was finally diagnosed with endometrial cancer. She had a history of vaginal septum resection and nephrectomy of atrophic right kidney. MRI demonstrated uterine didelphys, a tumour filling the left uterus and a cyst on the right lateral side of the uterus. Robot-assisted hysterectomy, including bilateral salpingo-oophorectomy and pelvic lymphadenectomy, was performed. As the cyst communicated with the right cervix, but not with the urinary tract, a Gartner duct cyst was diagnosed. Uncertain diagnosis and delay of treatment in endometrial cancer may occur in patients with Herlyn-Werner-Wunderlich syndrome. We should preoperatively fully evaluate the anatomy of the uterus and surrounding tissues and plan surgical procedures, especially in patients with urogenital malformations.


Assuntos
Neoplasias do Endométrio , Laparoscopia , Robótica , Anormalidades Urogenitais , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia , Rim/diagnóstico por imagem , Rim/cirurgia , Pessoa de Meia-Idade , Anormalidades Urogenitais/complicações , Anormalidades Urogenitais/cirurgia , Útero/diagnóstico por imagem , Útero/cirurgia , Vagina/cirurgia
6.
Stud Health Technol Inform ; 281: 769-773, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34042682

RESUMO

The main challenge in the pathway analysis of cancer treatments is the complexity of the process. Process mining is one of the approaches that can be used to visualize and analyze these complex pathways. In this study, our purpose was to use process mining to explore variations in the treatment pathways of endometrial cancer. We extracted patient data from a hospital information system, created the process model, and analyzed the variations of the 62-day pathway from a General Practitioner referral to the first treatment in the hospital. We also analyzed the variations based on three different criteria: the type of the first treatment, the age at diagnosis, and the year of diagnosis. This approach should be of interest to others dealing with complex medical and healthcare processes.


Assuntos
Neoplasias do Endométrio , Clínicos Gerais , Sistemas de Informação Hospitalar , Assistência à Saúde , Neoplasias do Endométrio/terapia , Feminino , Humanos , Encaminhamento e Consulta
7.
Eur J Radiol ; 140: 109745, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33962254

RESUMO

PURPOSE: To assess the value of volumetric ADC histogram metrics in evaluating the histological subtype and grade of endometrial cancer. METHOD: Preoperative MRI datasets of 317 patients with endometrial cancer were used to obtain volumetric ADC histogram metrics (tumour volume; minADC, maxADC and meanADC; 10th, 25th, 50th, 75th and 90th percentiles of ADC; skewness; and kurtosis). The Mann-Whitney test or Student's t-test was used to compare the difference in ADC histogram metrics between endometrioid adenocarcinomas (EACs) and serous endometrial cancers (SECs) and between different tumour grades (G1, G2, G3). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to evaluate the performance of ADC histogram metrics or combined models in predicting the tumour subtype and grade. RESULTS: SECs showed a significantly larger tumour volume (P < 0.001) and lower meanADC, 50th, 75th and 90th percentiles of ADC than EACs (all P < 0.05). MinADC, maxADC, meanADC, 10th, 25th, 50th, 75th, 90th percentiles of ADC were significantly higher in G1 than in G2 and G3 EACs (all P < 0.05), while were not significantly different between G2 and G3 EACs (all P > 0.05). A tumour volume ≥ 7.752 cm3 allowed for the prediction of SECs, with an AUC of 0.765 (0.714-0.810). A meanADC ≥ 0.892 × 10-3  mm2/s enabled to discriminate G1 from G2 and G3 EACs, with an AUC of 0.818 (0.769-0.861). CONCLUSION: Volumetric ADC histogram analysis is helpful for non-invasive preoperatively predicting the subtype of endometrial cancer and differentiating G1 from G2 and G3 EACs.


Assuntos
Neoplasias do Endométrio , Interpretação de Imagem Assistida por Computador , Imagem de Difusão por Ressonância Magnética , Neoplasias do Endométrio/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética , Curva ROC , Estudos Retrospectivos
8.
BMJ Open ; 11(5): e045888, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33986058

RESUMO

OBJECTIVES: The benefits of minimally invasive surgery (MIS) for endometrial carcinoma (EC) are well established although the financial impact of robotic-assisted hysterectomy (RH) compared with laparoscopic hysterectomy (LH) is disputed. DESIGN: Retrospective cohort study. SETTING: English National Health Service hospitals 2011-2017/2018. PARTICIPANTS: 35 304 women having a hysterectomy for EC identified from Hospital Episode Statistics. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the association between route of surgery on cost at intervention, 30, 90 and 365 days for women undergoing an open hysterectomy (OH) or MIS (LH/RH) for EC in England. The average marginal effect was calculated to compare RH versus OH and RH versus LH which adjusted for any differences in the characteristics of the surgical approaches. Secondary outcomes were to analyse costing data for each surgical approach by age, Charlson Comorbidity Index (CCI) and hospital MIS rate classification. RESULTS: A total of 35 304 procedures were performed, 20 405 (57.8%) were MIS (LH: 18 604 and RH: 1801), 14 291 (40.5%) OH. Mean cost for LH was significantly less than RH, whereas RH was significantly less than OH at intervention, 30, 90 and 365 days (p<0.001). Over time, patients who underwent RH had increasing CCI scores and by the 2015/2016 year had a higher average CCI than LH. Comparing the cost of LH and RH against CCI score identified that the costs closely reflected the patients' CCI. Increasing disparity was also seen between the MIS and OH costs with rising age. When exploring the association between provider volume, MIS rate and surgical costs, there was an association with the higher the MIS rate the lower the average cost. CONCLUSIONS: Further research is needed to investigate costs in matched patient cohorts to determine the optimum surgical modality in different populations.


Assuntos
Neoplasias do Endométrio , Laparoscopia , Análise Custo-Benefício , Neoplasias do Endométrio/cirurgia , Inglaterra , Feminino , Humanos , Histerectomia , Procedimentos Cirúrgicos Minimamente Invasivos , Estudos Retrospectivos , Medicina Estatal
9.
J Med Case Rep ; 15(1): 262, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33947445

RESUMO

BACKGROUND: Low-grade endometrial stromal sarcoma is a rare neoplastic growth in the uterine cavity, representing less than 1% of uterine tumors. Such tumors usually affect premenopausal and perimenopausal women, with a mean age of 46 years. Treatment generally starts with surgical resection of the tumor, followed by chemotherapy, radiotherapy, or hormonal therapy. CASE PRESENTATION: In the current report, we again present a case of low-grade endometrial stromal sarcoma in a 51-year-old Mediterranean woman presenting with abdominopelvic pain. Computed tomography scan revealed a primary uterine tumor measuring 17 × 9 × 9 cm metastasizing to the lungs, bladder, and ureteral orifice, along with lymphovascular involvement. The patient underwent total abdominal hysterectomy, omentectomy, and lymph node dissection. Estrogen deprivation was accomplished by bilateral salpingo-oophorectomy. Lifelong hormonal therapy consisting of letrozole 2.5 mg per day was prescribed, which demonstrated remarkable efficacy, resulting in a partial remission of lung metastasis within 8 months after surgery. Full remission was observed after 18 months of hormonal therapy, with no recurrence. Another scan was performed after 2.5 years, revealing complete remission with no recurrence. CONCLUSION: We again report a case of complete remission of low-grade endometrial stromal sarcoma after surgical removal of the tumor along with first-line hormonal therapy without the use of chemotherapy or radiotherapy, emphasizing the role of hormonal therapy in the treatment of such tumors.


Assuntos
Neoplasias do Endométrio , Sarcoma do Estroma Endometrial , Inibidores da Aromatase/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Feminino , Humanos , Letrozol/uso terapêutico , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Sarcoma do Estroma Endometrial/tratamento farmacológico
10.
BMJ Case Rep ; 14(5)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-33986013

RESUMO

A 52-year-old long-term user of the levonorgestrel-releasing intrauterine system (LNG-IUS) presented with vaginal bleeding. Endometrial biopsy was performed and revealed endometrioid adenocarcinoma. The patient had a laparoscopic hysterectomy and bilateral salpingo-oophorectomy. Endometrial cancer is rare in women with LNG-IUS as only seven cases have been published in the literature. Although scientific evidence shows LNG-IUS has a protective effect on the endometrium from developing cancer, our report highlights the importance of clinicians to be vigilant in cases of women with LNG-IUS who develop intermittent vaginal bleeding.


Assuntos
Anticoncepcionais Femininos , Neoplasias do Endométrio , Dispositivos Intrauterinos Medicados , Anticoncepcionais Femininos/efeitos adversos , Endométrio , Feminino , Humanos , Dispositivos Intrauterinos Medicados/efeitos adversos , Levanogestrel/efeitos adversos , Pessoa de Meia-Idade , Hemorragia Uterina/induzido quimicamente
11.
Pan Afr Med J ; 38: 200, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995806

RESUMO

Introduction: endometrial carcinoma (EC) is the seventh most common cancer in females in Malaysia, of which the majority is composed of lower grade type I EC. Although less prevalent, type II EC which is of higher grade has poorer outcome and prognosis. Human epidermal growth factor receptor 2 (HER2) is one of the possible prognostic molecular markers which can be a target for immunotherapy. This study aimed to assess the expression of HER2 in common type of EC in the local population and to determine its correlation with the clinicopathological features. Methods: a total of 53 cases of endometrioid type of EC were selected within a six-year period comprising of 22 cases of grade 1, 25 cases of grade 2 and six cases of grade 3 carcinoma. The selected whole tumour tissue sections were immune-stained with HER2 antibody. The scoring was semi-quantitatively analyzed based on 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAPs) guidelines for the scoring of HER2 in breast cancer. Results: all cases regardless of grades of endometrioid carcinoma showed negative expression of HER2 (score 0). Conclusion: there was no significant HER2 expression in endometrioid carcinoma. However, a follow-up study with a larger number of samples from different type of endometrial carcinoma is needed. Testing of several tumour tissue blocks to assess possible tumour heterogeneity, as well as correlation with HER2 gene amplification status by in-situ-hybridisation, are also recommended.


Assuntos
Neoplasias do Endométrio/genética , Receptor ErbB-2/genética , Adulto , Idoso , Neoplasias do Endométrio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico
12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(3): 489-496, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34018370

RESUMO

Objective: To probe for factors that can be used effectively to predict the prognostic survival of patients with endometrial cancer recurrence. Methods: The clinicopathological data of 473 patients with stage Ⅰ to Ⅲ endometrial cancer who underwent standard surgical treatment from October 2013 to May 2019 were retrospectively collected, and post-operative recurrence of the patients were followed up. Overall recurrence includes local recurrence and poor prognosis recurrence. The endpoint indicators of this study are the recurrence-free survival (RFS) and overall survival (OS) of patients with overall recurrence, local recurrence, and poor prognosis recurrence (PPR). The Kaplan-Meier survival curve was used to evaluate the OS and RFS of patients. Cox proportional-hazards model was used to identify factors affecting the prognostic survival of patients with endometrial cancer recurrence. Results: Among the 473 patients, 406 did not experience recurrence. A total of 67 patients, accounting for 14.2%, had recurrence. Among them, 27 had local recurrence, accounting for 5.7%, while 40 had poor prognosis recurrence, accounting for 8.5%. The median follow-up time of patients with recurrence was 38 months. The survival curve showed that the RFS and OS of the patients in the recurrence-free group remained unchanged, while the patients in the recurrence group, regardless of whether they had overall recurrence, local recurrence or PPR, experienced a decrease in RFS and OS( P<0.001). The overall 3-year OS rate of patients with recurrence was 44.8%, the median survival time was 29 months, and the median recurrence time was 17 months. The 3-year OS rate of patients in the recurrence-free group was 98.8%, and the median survival time was 40 months; the 3-year OS rate of patients with local recurrence was 59.3%, the median survival time was 27 months, and the median recurrence time was 15 months. The 3-year OS rate of patients with PPR was only 35.0%, the median survival time was 22 months, and the median recurrence time was 10 months. The results of multivariate Cox regression analysis showed that, for overall recurrence patients, FIGO stage Ⅲ (hazard ratio ( HR)=3.432, P=0.005), increased expression of K-i67 ( HR=1.015, P=0.025), and decreased expression of estrogen receptor (ER) ( HR=0.985, P=0.005) are independent factors for the decline in RFS, FIGO stage Ⅲ ( HR=4.918, P=0.005) and the decreased expression of progesterone receptor (PR) ( HR=0.977, P=0.003) are independent factors for the decrease in OS. For patients with local recurrence, special pathological types ( HR=2.545, P=0.049) and increased expression of Ki-67 ( HR=1.024, P=0.033) are independent factors influencing the decrease in RFS, while decreased expression of PR ( HR=0.973, P=0.009) is an independent risk factor for decreased OS. For patients with PPR, FIGO stage Ⅲ ( HR=5.977, P=0.002) and decreased ER expression ( HR=0.984, P=0.023) are independent risk factors for the decline in RFS, while FIGO stage Ⅲ ( HR=10.098, P=0.001) is an independent factor influencing the decline of OS. Conclusion: FIGO stage Ⅲ, increased Ki-67 expression, and decreased ER expression can increase patients' risk of postoperative recurrence, and FIGO stage Ⅲ and decreased expression of PR can increase the risk of death in patients with recurrence.


Assuntos
Neoplasias do Endométrio , Recidiva Local de Neoplasia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
13.
Adv Ther ; 38(5): 2717-2731, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33830463

RESUMO

INTRODUCTION: Endometrial cancer is the fifth most common cancer in women and atypical endometrial hyperplasia is a precancerous lesion. Obesity is an important risk factor for endometrioid endometrial adenocarcinoma and endometrial hyperplasia. Progesterone is recommended as first-line treatment in endometrial cancer or atypical endometrial hyperplasia in women who wish to preserve fertility, but optimal treatment schedules have not been defined. Metformin or bariatric surgery may also be useful in these women. The effectiveness and safety of fertility-preserving treatments being used for women with atypical endometrial hyperplasia and stage IA grade 1 endometrial cancer is unclear. Therefore, the systematic review aims to determine this point. METHODS: We will search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, trial registers, conference proceedings, abstracts, cooperative trial groups and reference lists. We will include randomised controlled trials (RCTs) that compare fertility-preserving therapy including orally administered progesterone versus a levonorgestrel-releasing intrauterine system (IUS), metformin, other pharmacological interventions or bariatric surgery, and any of these interventions with womb-removing surgery. Quasi-randomised trials, non-randomised trials and cohort studies will be included. Two review authors will independently assess study eligibility and risk of bias and extract data. The primary outcomes are complete pathologic response and live birth rate. Secondary outcomes include overall survival, progression-free survival, pregnancy rate, need for hysterectomy, adverse events, psychological symptoms and quality of life. PLANNED OUTCOMES: This review aims to clarify the effectiveness and risks of fertility-preserving treatments, including complete pathologic response rate, live birth rates, need for surgical treatment, adverse events, psychological symptoms and quality of life. The broad scope of the review includes the use of progesterone, metformin to reverse insulin resistance, and bariatric surgery or operative hysteroscopy. RESULTS: The results may help to determine the optimal fertility-sparing treatment in endometrial cancer and atypical endometrial hyperplasia. SYSTEMATIC REVIEW REGISTRATION: Prospero 2019 number CRD42019145991.


Assuntos
Hiperplasia Endometrial , Neoplasias do Endométrio , Dispositivos Intrauterinos Medicados , Hiperplasia Endometrial/tratamento farmacológico , Hiperplasia Endometrial/cirurgia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia , Levanogestrel , Literatura de Revisão como Assunto , Revisões Sistemáticas como Assunto
14.
J Cancer Res Clin Oncol ; 147(7): 2035-2045, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33885953

RESUMO

PURPOSE: BRCA mutation carriers have an increased risk of developing breast or ovarian cancer. Risk-reducing bilateral salpingo-oophorectomy (RRBSO) is associated with a decrease in risk for tubal and ovarian cancer. Hormone replacement therapy (HRT) may increase breast, ovarian, and endometrial cancer risk in the general population. This review analyses the published data on HRT and risk of cancer in BRCA mutation carriers with and without RRBSO. METHODS: We included all relevant articles published in English from 1995 to October 2020. Sources were identified through a search on PubMed and Cochrane Library. RESULTS: We included one case-control and one retrospective cohort study on ovarian and one case-control study on endometrial cancer risk and HRT in BRCA mutation carriers. Regarding breast cancer risk, one case-control study on BRCA mutation carriers with and without RRBSO and one case-control study, one Markov chain decision model, two prospective cohort studies, and one metaanalysis on carriers after RRBSO were included. For ovarian cancer, results were ambiguous. For breast cancer, most studies did not find an adverse effect associated with HRT. However, some of the studies found a risk modification associated with different formulations and duration of use. CONCLUSION: Although data are limited, HRT does not seem to have a relevant effect on cancer risk in BRCA mutation carriers. RRBSO should not be postponed to avoid subsequent HRT in this population. Adequate HRT after RRBSO should be offered to avoid chronic diseases resulting from low estrogen levels. However, further data on the safety of different formulations are needed.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/etiologia , Neoplasias do Endométrio/etiologia , Terapia de Reposição Hormonal/efeitos adversos , Mutação , Neoplasias Ovarianas/etiologia , Neoplasias da Mama/patologia , Neoplasias do Endométrio/patologia , Feminino , Predisposição Genética para Doença , Heterozigoto , Humanos , Neoplasias Ovarianas/patologia
15.
Int J Mol Sci ; 22(8)2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33917029

RESUMO

Endometrial cancer (EC) is associated with increased estrogen actions. Locally, estrogens can be formed from estrone-sulphate (E1-S) after cellular uptake by organic anion-transporting polypeptides (OATP) or organic anion transporters (OAT). Efflux of E1-S is enabled by ATP Binding Cassette transporters (ABC) and organic solute transporter (OST)αß. Currently, 19 E1-S transporters are known but their roles in EC are not yet understood. Here, we analysed levels of E1-S transporters in Ishikawa (premenopausal EC), HEC-1-A (postmenopausal EC), HIEEC (control) cell lines, in EC tissue, examined metabolism of steroid precursor E1-S, studied effects of OATPs' inhibition and gene-silencing on E1-S uptake, and assessed associations between transporters and histopathological data. Results revealed enhanced E1-S metabolism in HEC-1-A versus Ishikawa which could be explained by higher levels of OATPs in HEC-1-A versus Ishikawa, especially 6.3-fold up-regulation of OATP1B3 (SLCO1B3), as also confirmed by immunocytochemical staining and gene silencing studies, lower ABCG2 expression and higher levels of sulfatase (STS). In EC versus adjacent control tissue the highest differences were seen for ABCG2 and SLC51B (OSTß) which were 3.0-fold and 2.1-fold down-regulated, respectively. Immunohistochemistry confirmed lower levels of these two transporters in EC versus adjacent control tissue. Further analysis of histopathological data indicated that SLCO1B3 might be important for uptake of E1-S in tumours without lymphovascular invasion where it was 15.6-fold up-regulated as compared to adjacent control tissue. Our results clearly indicate the importance of E1-S transporters in EC pathophysiology and provide a base for further studies towards development of targeted treatment.


Assuntos
Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Estrona/análogos & derivados , Transportadores de Ânions Orgânicos/genética , Transportadores de Ânions Orgânicos/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Fatores Etários , Transporte Biológico , Linhagem Celular Tumoral , Neoplasias do Endométrio/patologia , Estrona/metabolismo , Feminino , Imunofluorescência , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Família Multigênica , Gradação de Tumores , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Estadiamento de Neoplasias , Pós-Menopausa , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/genética , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/metabolismo
16.
Crit Rev Oncol Hematol ; 161: 103306, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33839243

RESUMO

The incidence of endometrial cancer (EC) is increasing worldwide. The prognosis for patients diagnosed with early-stage remains good, whereas for patients with recurrent or metastatic disease, the prognosis is poor and treatment options, until recently, were limited. In 2017, pembrolizumab was approved by the US Food and Drug Administration (FDA) for those patients with mistmach repair deficiency (MMRd) or high microsatellite instability (MSI-H) tumors. However, only 20-30 % of EC have MSI, and just over half of these patients benefit from treatment. In 2019, the FDA granted breakthrough therapy designation to lenvatinib in combination with pembrolizumab for the potential treatment of patients with advanced microsatellite stable EC that has progressed after treatment with at least one previous systemic therapy. It appears clear that immune check-point inhibitors will have a definite place in the management of EC, both as single agent or in combination with other targeted agents. In this review, we summarize the current evidence of immune check point blockade and the identification of potential biomarkers, beyond MSI-H or MMRd, that could help to predict response to this agents in correlation with the genomic EC subtypes.


Assuntos
Neoplasias do Endométrio , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Feminino , Humanos , Instabilidade de Microssatélites , Prognóstico
17.
Eur J Obstet Gynecol Reprod Biol ; 261: 59-64, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33892210

RESUMO

OBJECTIVE: The aim of this study was to describe our latest results using dual cervical and fundal indocyanine green injection for detection of sentinel lymph node (SLN) in endometrial cancer. METHODS: A prospective observational study was conducted between 26 June 2014 and 31 December 2019 with 278 patients that underwent laparoscopic surgery for endometrial cancer at our institution. In all cases, we performed SLN biopsy with dual cervical and fundal indocyanine green injection. All SLNs were processed with an ultrastaging technique. A total of 128 patients also underwent total pelvic and paraaortic lymphadenectomy. RESULTS: The detection rates were as follows: 93.5 % (260/278) overall for SLNs; 90.7 % (252/278) overall for pelvic SLNs; 68.0 % (189/278) for bilateral SLNs; 66.9 % (186/278) for paraaortic SLNs, and 2.9 % (8/278) for isolated paraaortic SLNs. We found macroscopic lymph node metastasis in 26 patients (10.0 %) and microdisease in lymph nodes in another 48 patients, raising the overall rate of lymph node involvement to 16.2 %. There was one false negative (negative SLN biopsy but positive lymphadenectomy). Applying the SLN algorithm, the sensitivity of detection was 97.9 % (95 % CI 89.1-99.6), specificity 100 % (95 % CI 98.2-100), negative predictive value 99.5 % (95 % CI 97.4-99.9), and positive predictive value 100 % (95 % CI 92.4-100). CONCLUSIONS: Dual sentinel node injection is a feasible technique that achieves adequate detection rates. Additionally, this technique allows a high rate of aortic detection, identifying a non-negligible percentage of isolated aortic metastases. Aortic metastases in endometrial cancer are possible and we should not give up actively looking for them.


Assuntos
Neoplasias do Endométrio , Linfonodo Sentinela , Neoplasias do Endométrio/patologia , Feminino , Humanos , Verde de Indocianina , Excisão de Linfonodo , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Estadiamento de Neoplasias , Estudos Prospectivos , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela
18.
Eur J Obstet Gynecol Reprod Biol ; 261: 72-77, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33894621

RESUMO

OBJECTIVE: This study evaluated diagnostic accuracy of intraoperative sentinel lymph node (SLN) frozen section examination and scrape cytology as a possible solution for management of SLN positive patients. STUDY DESIGN: Clinically early-stage endometrial cancer patients who underwent SLN algorithm and intraoperative SLN examination were analyzed. Findings were compared with final pathology results and diagnostic accuracy of frozen section and scrape cytology were evaluated. RESULTS: Of the 208 eligible patients, 100 patients (48 %) had frozen section examination and 108 (52 %) had scrape cytology of the SLN. Intraoperative examination and final pathology were negative for metastasis in 187/208 (90 %) cases. The rest 21 cases had metastatic SLNs according to final pathology. 12 of 21 (57 %) metastases were classified as macrometastasis. Intraoperative examination of SLNs correctly identified 13 cases (true positive) and missed 8 cases (false negative). Five of 8 false negative cases had micrometastasis or isolated tumor cells. Considering identification of macrometastasis, sensitivity and negative predictive value were 85.71 % and 98.94 %, respectively, for the frozen section and 60.00 % and 98.15 %, respectively, for the scrape cytology. CONCLUSION: Frozen section examination of SLN has higher sensitivity in detecting macrometastasis compared to scrape cytology and it could help the surgeon in decision for further lymphadenectomy intraoperatively.


Assuntos
Neoplasias da Mama , Neoplasias do Endométrio , Linfonodo Sentinela , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/cirurgia , Feminino , Secções Congeladas , Humanos , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela
19.
BMJ Case Rep ; 14(4)2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33846186

RESUMO

Benign metastasising leiomyoma (BML) is a rare disease in which histologically benign uterine fibroids spread throughout the body. It is thought to originate from the hematogenous metastasis of myoma cells following myomectomy. To date, BML has been noted in patients with respiratory symptoms, even during regular checkups. There are few case reports of co-occurrence with gynaecological cancer. We report the case of a suspected stage IVb carcinoma based on preoperative examination for endometrial cancer, that indicated lung metastasis. However, postoperative pathology revealed a grade 1, pT1a pN0 tumour. We suspected BML based on the discrepant findings and history of myomectomy, and this was confirmed by lung biopsy. In metastatic lesions of a carcinoma patient with a history of myomectomy, the co-occurrence of BML should be considered when there is discrepancy between the preoperative suspected stage and postoperative pathology.


Assuntos
Neoplasias do Endométrio , Leiomioma , Neoplasias Pulmonares , Neoplasias Uterinas , Diagnóstico Diferencial , Neoplasias do Endométrio/diagnóstico , Feminino , Humanos , Leiomioma/diagnóstico , Leiomioma/cirurgia , Neoplasias Pulmonares/diagnóstico , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/cirurgia
20.
Cancer Imaging ; 21(1): 34, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849649

RESUMO

BACKGROUND: The extent of peritoneal carcinomatosis is difficult to estimate preoperatively, but a valid measure would be important in identifying operable patients. The present study set out to validate the usefulness of integrated 18F-FDG PET/MRI, in comparison with diffusion-weighted MRI (DW-MRI), for estimation of the extent of peritoneal carcinomatosis in patients with gynaecological cancer. METHODS: Whole-body PET/MRI was performed on 34 patients with presumed carcinomatosis of gynaecological origin, all scheduled for surgery. Two radiologists evaluated the peritoneal cancer index (PCI) on PET/MRI and DW-MRI scans in consensus. The surgeon estimated PCI intraoperatively, which was used as the gold standard. RESULTS: Median total PCI for PET/MRI (21.5) was closer to surgical PCI (24.5) (p = 0.6), than DW-MRI (median PCI 20.0, p = 0.007). However, both methods were highly correlated with the surgical PCI (PET/MRI: ß = 0.94 p < 0.01, DW-MRI: ß = 0.86, p < 0.01). PET/MRI was more accurate (p = 0.3) than DW-MRI (p = 0.001) when evaluating patients at primary diagnosis but no difference was noted in patients treated with chemotherapy. PET/MRI was superior in evaluating high tumour burden in inoperable patients. In the small bowel regions, there was a tendency of higher sensitivity but lower specificity in PET/MRI compared to DW-MRI. CONCLUSIONS: Our results suggest that FDG PET/MRI is superior to DW-MRI in estimating total spread of carcinomatosis in gynaecological cancer. Further, the greatest advantage of PET/MRI seems to be in patients at primary diagnosis and with high tumour burden, which suggest that it could be a useful tool when deciding about operability in gynaecological cancer.


Assuntos
Carcinoma/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias do Endométrio/diagnóstico por imagem , Fluordesoxiglucose F18/metabolismo , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Peritoneais/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/patologia , Projetos Piloto , Reprodutibilidade dos Testes , Análise de Sobrevida
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