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1.
PLoS One ; 19(6): e0305360, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38935680

RESUMO

OBJECTIVES: Fertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates between preoperative assessment and postoperative pathology in low-risk EC patients are not high enough. We aimed to predict the postoperative pathology depending on preoperative myometrial invasion (MI) and grade in low-risk EC patients to help extend the current criteria for FST. METHODS/MATERIALS: This ancillary study (KGOG 2015S) of Korean Gynecologic Oncology Group 2015, a prospective, multicenter study included patients with no MI or MI <1/2 on preoperative MRI and endometrioid adenocarcinoma and grade 1 or 2 on endometrial biopsy. Among the eligible patients, Groups 1-4 were defined with no MI and grade 1, no MI and grade 2, MI <1/2 and grade 1, and MI <1/2 and grade 2, respectively. New prediction models using machine learning were developed. RESULTS: Among 251 eligible patients, Groups 1-4 included 106, 41, 74, and 30 patients, respectively. The new prediction models showed superior prediction values to those from conventional analysis. In the new prediction models, the best NPV, sensitivity, and AUC of preoperative each group to predict postoperative each group were as follows: 87.2%, 71.6%, and 0.732 (Group 1); 97.6%, 78.6%, and 0.656 (Group 2); 71.3%, 78.6% and 0.588 (Group 3); 91.8%, 64.9%, and 0.676% (Group 4). CONCLUSIONS: In low-risk EC patients, the prediction of postoperative pathology was ineffective, but the new prediction models provided a better prediction.


Assuntos
Neoplasias do Endométrio , Miométrio , Gradação de Tumores , Invasividade Neoplásica , Humanos , Feminino , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Miométrio/patologia , Miométrio/cirurgia , Pessoa de Meia-Idade , Adulto , República da Coreia/epidemiologia , Estudos Prospectivos , Idoso , Período Pré-Operatório , Imageamento por Ressonância Magnética , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/cirurgia
2.
Int J Gynecol Cancer ; 34(8): 1189-1195, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38754967

RESUMO

OBJECTIVE: To evaluate whether the maximum standardized uptake value (SUVmax) from initial 18F-FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) scans could be a predictor of complete response and recurrence in patients with endometrial cancer who are undergoing fertility sparing management. METHODS: We conducted a retrospective review of patients who were diagnosed with endometrial cancer through biopsy and chose to undergo fertility sparing management using progestin at the Asan Medical Center, from January 2011 to December 2020. Of these, 113 patients who had an 18-FDG-PET/CT scan before starting treatment were included in our study. We measured SUVmax and examined its correlation with complete response and time to progression after achieving complete response to progestin therapy. RESULTS: Of 113 patients, 73 (64.6%) achieved a complete response through fertility sparing management. The receiver operating characteristic curve analysis revealed that the optimal cut-off value of SUVmax for predicting complete response was 6.2 (sensitivity 79.5%, specificity 57.5%, p=0.006). After analyzing recurrence in the 73 patients who achieved complete response, we found that patients with an SUVmax value >6.2 had a significantly shorter time to progression compared with those with a value <6.2. (p=0.04). CONCLUSIONS: SUVmax values of PET-CT, along with other clinicopathological parameters, could be used to predict treatment response and recurrence risk in patients with stage I endometrial cancer undergoing fertility sparing management.


Assuntos
Neoplasias do Endométrio , Preservação da Fertilidade , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Humanos , Feminino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18/administração & dosagem , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/terapia , Estudos Retrospectivos , Adulto , Preservação da Fertilidade/métodos , Compostos Radiofarmacêuticos/administração & dosagem , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Resultado do Tratamento , Recidiva Local de Neoplasia/diagnóstico por imagem
3.
Micromachines (Basel) ; 15(3)2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38542567

RESUMO

This research focuses on the manufacturing of a glass interposer that has gone through glass via (TGV) connection holes. Glass has unique properties that make it suitable for 3D integrated circuit (IC) interposers, which include low permittivity, high transparency, and adjustable thermal expansion coefficient. To date, various studies have suggested numerous techniques to generate holes in glass. In this study, we adopt the selective laser etching (SLE) technique. SLE consists of two processes: local modification via an ultrashort pulsed laser and chemical etching. In our previous study, we found that the process speed can be enhanced by changing the local modification method. For further enhancement in the process speed, in this study, we focus on the chemical etching process. In particular, we try to find a proper etchant for TGV formation. Here, four different etchants (HF, KOH, NaOH, and NH4F) are compared in order to improve the etching speed. For a quantitative comparison, we adopt the concept of selectivity. The results show that NH4F has the highest selectivity; therefore, we can tentatively claim that it is a promising candidate etchant for generating TGV. In addition, we also observe a taper angle variation according to the etchant used. The results show that the taper angle of the hole is dependent on the concentration of the etchant as well as the etchant itself. These results may be applicable to various industrial fields that aim to adjust the taper angle of holes.

4.
Gynecol Oncol ; 179: 106-114, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37976756

RESUMO

OBJECTIVE: The addition of immune checkpoint inhibitors (ICIs), pembrolizumab or dostarlimab, to paclitaxel and carboplatin (TC) has shown better response rates and survival outcomes for patients with primary advanced mismatch repair-deficient (MMRd) endometrial cancer (EC) in NRG-GY018 and RUBY, respectively. Nonetheless, the high cost of ICIs remains a major concern when implementing this strategy in the real world. This study aimed to determine the cost-effectiveness of pembrolizumab and dostarlimab with chemotherapy compared to TC for primary advanced MMRd EC. METHODS: We developed a Markov model including 6600 patients with primary advanced MMRd EC to simulate treatment outcomes. The initial decision points in the model were treatment with pembrolizumab with TC (PEM-TC), dostarlimab with TC (DOS-TC), and TC. Model probabilities, costs, and health utility values were derived with assumptions from published literature. Effectiveness was determined as average quality-adjusted life years (QALYs) gained. The primary outcome was the incremental cost-effectiveness ratio (ICER). RESULTS: TC was the least costly strategy, whereas PEM-TC was the most effective strategy for primary advanced MMRd EC. TC was cost-effective based on a willingness-to-pay (WTP) threshold of $100,000/QALY compared with PEM-TC (ICER, $377,718/QALY), and DOS-TC exhibited absolute dominance (ICER, $401,859/QALY). PEM-TC was cost-effective when the cost of pembrolizumab 200 mg was reduced to $4361 (61% reduction). PEM-TC was selected in 16.5% with a WTP threshold of $300,000/QALY, but in <1% with a WTP threshold range of $100,000-200,000/QALY. CONCLUSION: PEM-TC can become cost-effective for primary advanced MMRd EC when the cost of pembrolizumab substantially decreases.


Assuntos
Neoplasias do Endométrio , Inibidores de Checkpoint Imunológico , Humanos , Feminino , Inibidores de Checkpoint Imunológico/uso terapêutico , Análise de Custo-Efetividade , Reparo de Erro de Pareamento de DNA , Análise Custo-Benefício , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Anos de Vida Ajustados por Qualidade de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
5.
J Nat Prod ; 86(11): 2554-2561, 2023 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-37935005

RESUMO

Nuclear magnetic resonance (NMR) data are rarely deposited in open databases, leading to loss of critical scientific knowledge. Existing data reporting methods (images, tables, lists of values) contain less information than raw data and are poorly standardized. Together, these issues limit FAIR (findable, accessible, interoperable, reusable) access to these data, which in turn creates barriers for compound dereplication and the development of new data-driven discovery tools. Existing NMR databases either are not designed for natural products data or employ complex deposition interfaces that disincentivize deposition. Journals, including the Journal of Natural Products (JNP), are now requiring data submission as part of the publication process, creating the need for a streamlined, user-friendly mechanism to deposit and distribute NMR data.


Assuntos
Produtos Biológicos , Bases de Dados Factuais , Espectroscopia de Ressonância Magnética
6.
Micromachines (Basel) ; 14(9)2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37763929

RESUMO

Selective laser etching is a promising candidate for the mass production of glass interposers. It comprises two steps: local modification by an ultrashort-pulsed laser and chemical etching of the modified volume. According to previous studies, when an ultrashort-pulsed laser beam is irradiated on the sample, electron excitation occurs, followed by phonon vibration. In general, the electron excitation occurs for less than a few tens of picoseconds and phonon vibration occurs for more than 100 picoseconds. Thus, in order to compare the electric absorption and thermal absorption of photons in the commercial glass, we attempt to implement an additional laser pulse of 213 ps and 10 ns after the first pulse. The modified glass sample is etched with 8 mol/L KOH solution with 110 °C to verify the effect. Here, we found that the electric absorption of photons is more effective than the thermal absorption of them. We can claim that this result helps to enhance the process speed of TGV generation.

7.
Nucl Med Commun ; 44(11): 1005-1010, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37578339

RESUMO

OBJECTIVE: High-grade neuroendocrine cervical cancer (HGNECC) is a rare and aggressive cervical cancer subtype. In this study, we aimed to evaluate the prognostic value of fluorodeoxyglucose-PET/computed tomography (CT) parameters for HGNECC. MATERIALS AND METHODS: This single-center retrospective study included 29 patients with HGNECC who underwent fluorodeoxyglucose-PET/CT scan followed by surgery between 2006 and 2016. RESULTS: The median follow-up period was 40 (range, 4-184) months. After surgery, the resection margins were tumor-negative in 28 patients (96.6%), 8 (27.6%) patients had parametrial tumor invasion, and 7 patients (24.1%) tested positive for lymph node metastasis. The tumor recurred in 20 patients (69%) and 18 patients (62.1%) died during the observation period. In the univariate analyses, age and total lesion glycolysis (TLG) were associated with worse disease-free survival (DFS) (age, hazard ratio 1.056, 95% CI 1.014-1.100, P  = 0.009; TLG2.5, hazard ratio 1.003, 95% CI 1-1.006, P  = 0.033; and TLG3.0, hazard ratio 1.003, 95% CI 1-1.006, P  = 0.034). In the multivariate analyses, older age and higher TLG3.0 were identified as independent poor prognostic factors for DFS (age, hazard ratio 1.058, 95% CI 1.014-1.104, P  = 0.009; TLG3.0, hazard ratio 1.004, 95% CI 1-1.007, P  = 0.033), while resection margin involvement was identified as an independent factor to predict poor overall survival (hazard ratio 20.717, 95% CI 1.289-332.964, P  = 0.032). CONCLUSION: Among the preoperative fluorodeoxyglucose-PET/CT parameters, TLG3.0 may be useful for predicting DFS in patients with HGNECC.

8.
Int J Gynecol Cancer ; 33(11): 1743-1749, 2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37541685

RESUMO

OBJECTIVE: Our study aimed to evaluate the incidence of pathological findings in asymptomatic Korean patients with BRCA1/2 pathogenic variants who underwent risk-reducing salpingo-oophorectomy and to assess their long-term prognosis. METHODS: We retrospectively analyzed the medical records of patients with a germinal BRCA1/2 pathologic variant who had undergone risk-reducing salpingo-oophorectomy at Asan Medical Center (Seoul, Korea) between January 2013 and December 2020. All pathologic reports were made based on the sectioning and extensively examining the fimbriated end of the fallopian tube (SEE/FIM) protocol. RESULTS: Out of 243 patients who underwent risk-reducing salpingo-oophorectomy, 121 (49.8%) had a BRCA1 mutation, 119 (48.9%) had a BRCA2 mutation, and three (1.2%) had both mutations. During the procedure, four (3.3%) patients with a BRCA1 mutation were diagnosed with serous tubal intraepithelial carcinoma (STIC) or serous tubal intraepithelial lesion (STIL), and another four patients (3.3%) were diagnosed with occult cancer despite no evidence of malignancy on preoperative ultrasound. In the BRCA2 mutation group, we found one (0.8%) case of STIC, but no cases of STIL or occult cancer. During the median follow-up period of 98 months (range, 44-104) for STIC and 54 months (range, 52-56) for STIL, none of the patients diagnosed with these precursor lesions developed primary peritoneal carcinomatosis. CONCLUSIONS: Risk-reducing salpingo-oophorectomy, in asymptomatic Korean patients with BRCA1/2 pathogenic variants, detected ovarian cancer and precursor lesions, including STIC or STIL. Furthermore, our follow-up period did not reveal any instances of primary peritoneal carcinomatosis, suggesting a limited body of evidence supporting the imperative need for adjuvant treatment in patients diagnosed with these precursor lesions during risk-reducing salpingo-oophorectomy.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias das Tubas Uterinas , Neoplasias Ovarianas , Neoplasias Peritoneais , Feminino , Humanos , Salpingo-Ooforectomia , Proteína BRCA1/genética , Ovariectomia , Neoplasias Peritoneais/epidemiologia , Estudos Retrospectivos , Proteína BRCA2/genética , Neoplasias das Tubas Uterinas/patologia , Neoplasias Ovarianas/patologia , Mutação , Prognóstico , Cistadenocarcinoma Seroso/patologia , República da Coreia
9.
J Gynecol Oncol ; 34(6): e76, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37477099

RESUMO

OBJECTIVE: Extramammary Paget's disease (EMPD) of the vulva is a rare disease which predominantly presents in postmenopausal Caucasian women. As yet, no studies on Asian female patients with EMPD have been performed. This study aimed to identify the clinical features of patients with vulvar EMPD in Korea, and to evaluate the risk factors of recurrence and postoperative complications in surgically treated EMPD. METHODS: We retrospectively reviewed 47 patients with vulvar EMPD who underwent wide local excision or radical vulvectomy. The clinical data and surgical and oncological outcomes following surgery were extracted from medical records and analyzed. Univariate and multivariate analyses for predicting recurrence and postoperative complications were performed. RESULTS: 21.3% of patients had complications after surgery, and wound dehiscence was the most common. 14.9% of patients experienced recurrence, and the median interval to recurrence from initial treatment was 69 (range 33-169) months. Vulvar lesions larger than 40 mm was the independent risk factor of postoperative complications (odds ratio [OR]=7.259; 95% confidence interval [CI]=1.545-34.100; p=0.012). Surgical margin status was not associated with recurrence in surgically treated vulvar EMPD patients (OR=0.83; 95% CI=0.16-4.19; p=1.000). CONCLUSION: Positive surgical margin is a frequent finding in the patients with vulvar EMPD, but disease recurrence is not related with surgical margin status. Since EMPD is a slow growing tumor, a surveillance period longer than 5 years is required.


Assuntos
Doença de Paget Extramamária , Neoplasias Vulvares , Humanos , Feminino , Doença de Paget Extramamária/cirurgia , Doença de Paget Extramamária/patologia , Prognóstico , Estudos Retrospectivos , Margens de Excisão , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Vulva/cirurgia , Vulva/patologia , Neoplasias Vulvares/cirurgia , Neoplasias Vulvares/patologia , Complicações Pós-Operatórias/epidemiologia
10.
J Nutr ; 153(3): 691-702, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36931749

RESUMO

BACKGROUND: Adipocyte dysregulation of lipid droplet (LD) metabolism caused by altered expression of LD proteins contributes to obesity-related metabolic diseases. OBJECTIVES: We aimed to investigate whether expression levels of PLIN1, CIDEA, and CIDEC were altered in adipose tissues of women with obesity and type 2 diabetes and whether their alterations were associated with metabolic risk factors. METHODS: Normal-weight (NW; 18.5 kg/m2 < BMI ≤ 25 kg/m2; n = 43), nondiabetic obese (OB; BMI > 30 kg/m2; n = 38), and diabetic obese (OB/DM; BMI > 30 kg/m2, fasting glucose ≥ 126 mg/dL, HbA1c ≥ 6.5%; n = 22) women were recruited. Metabolic parameters were measured, and expressions of PLIN1, CIDEA, CIDEC, and obesity-related genes were quantified in abdominal subcutaneous (SAT) and visceral adipose tissues (VAT). Effects of proinflammatory cytokines, endoplasmic reticulum (ER) stress inducers, and metabolic improvement agents on LD protein gene expressions were investigated in human adipocytes. RESULTS: PLIN1, CIDEA, and CIDEC expressions were lower in SAT and higher in VAT in OB subjects relative to NW subjects; however, they were suppressed in both fat depots in OB/DM subjects relative to OB (P < 0.05). Across the entire cohort, whereas VAT PLIN1 (r = 0.349) and CIDEC expressions (r = 0.282) were positively associated with BMI (P < 0.05), SAT PLIN1 (r = -0.390) and CIDEA expressions (r = -0.565) were inversely associated. After adjustment for BMI, some or all of the adipose LD protein gene expressions were negatively associated with fasting glucose (r = -0.259 or higher) and triglyceride levels (r = -0.284 or higher) and positively associated with UCP1 expression (r = 0.353 or higher) (P < 0.05). In adipocytes, LD protein gene expressions were 55-70% downregulated by increased proinflammatory cytokines and ER stress but 2-4-fold upregulated by the metabolic improvement agents exendin-4 and dapagliflozin (P < 0.05). CONCLUSIONS: The findings suggest that reduction of adipose LD protein expression is involved in the pathogenesis of metabolic disorders in women with obesity and type 2 diabetes and that increasing LD protein expression in adipocytes could control development of metabolic disorders.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Feminino , Adulto , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Gotículas Lipídicas/metabolismo , Gotículas Lipídicas/patologia , Obesidade/metabolismo , Fatores de Risco , Citocinas/metabolismo , Glucose/metabolismo , Proteínas Associadas a Gotículas Lipídicas/metabolismo , Gordura Intra-Abdominal/metabolismo
11.
Korean J Gastroenterol ; 80(1): 38-42, 2022 07 25.
Artigo em Coreano | MEDLINE | ID: mdl-35879062

RESUMO

Portal biliopathy refers to the changes in the bile duct caused by portal vein thrombosis or obstruction. It is assumed to be caused by cavernous transformation due to the development of the venous system surrounding the bile duct, but the exact pathology is still unknown. Biliary morphologic abnormalities of portal biliopathy are discovered incidentally on radiographic images, but it is sometimes difficult to differentiate them from cholangiocarcinoma. Given the poor prognosis of cholangiocarcinoma, a surgical approach can be considered when the diagnosis is uncertain. Herein, we report a case of portal biliopathy with bile ductal wall thickening, which was diagnosed after surgical resection was performed due to the presumed diagnosis of cholangiocarcinoma.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/patologia , Erros de Diagnóstico , Humanos , Tumor de Klatskin/diagnóstico , Tumor de Klatskin/patologia , Veia Porta/diagnóstico por imagem
12.
Obesity (Silver Spring) ; 30(7): 1430-1441, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35722819

RESUMO

OBJECTIVE: Leukocyte cell-derived chemotaxin 2 (LECT2) is an obesity-upregulated hepatokine inducing skeletal muscle insulin resistance. The study's aim was to explore whether LECT2 is expressed in human adipose tissue and whether the expression is dysregulated during obesity and associated with obesity-related metabolic disorders. METHODS: This study measured metabolic parameters, serum LECT2, and expression of LECT2 and CD209, a gene encoding a putative receptor for LECT2, in abdominal subcutaneous and visceral adipose tissues in women with obesity (with or without type 2 diabetes) and women with normal weight. The expression/secretion of LECT2 and its putative effects were assessed in human adipocytes. RESULTS: Adipose tissue LECT2 mRNA and serum LECT2 were higher in women with obesity and were significantly correlated with parameters related to insulin resistance. LECT2 was mainly expressed by adipocytes. Both LECT2 and CD209 expression was higher in adipocytes from women with obesity. Incubating adipocytes with substances mimicking the microenvironment of obesity adipose tissue increased LECT2 expression/secretion. LECT2 treatment of adipocytes suppressed insulin-stimulated Akt phosphorylation; it reduced adiponectin (ADIPOQ) and increased leptin (LEP) expression in a CD209-dependent manner. CONCLUSIONS: This study demonstrates that LECT2 expression in adipose tissue is high in patients with obesity and associated with insulin resistance and suggests that adipocyte-derived LECT2 may contribute to adipose tissue dysfunction.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Tecido Adiposo/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Resistência à Insulina/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Obesidade/genética , Obesidade/metabolismo , República da Coreia/epidemiologia
13.
J Clin Endocrinol Metab ; 107(3): e1057-e1073, 2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-34718616

RESUMO

CONTEXT: The upregulation of TRIB3 (Tribbles homolog 3), a stress-inducible gene encoding a pseudokinase, has been implicated in the development of insulin resistance in the skeletal muscle and liver of patients with obesity and type 2 diabetes. However, there is little information regarding TRIB3 expression in human adipose tissue. OBJECTIVE: To investigate whether TRIB3 expression is dysregulated in human adipose tissue in the context of obesity and type 2 diabetes and whether TRIB3 expression in adipose tissues is associated with insulin resistance. METHODS: We measured metabolic parameters and TRIB3 expression in abdominal subcutaneous and visceral adipose tissue in obese (with or without type 2 diabetes) and normal-weight women. Regulation of TRIB3 expression was studied in human adipocytes. RESULTS: TRIB3 expression in both fat depots was higher in patients with obesity and/or type 2 diabetes; in addition, the expression level was significantly associated with insulin resistance. Incubating adipocytes under conditions mimicking the microenvironment of obese adipose tissue, including increased endoplasmic reticulum (ER) stress, induced TRIB3 expression. In human adipocytes, the overexpression of TRIB3 impaired insulin-stimulated protein kinase B (AKT) phosphorylation and caused dysregulation of the transcription of genes encoding bioactive molecules released from adipocytes, such as proinflammatory cytokines, adiponectin, and leptin. Pioglitazone, an insulin-sensitizing agent, reduced both these effects of TRIB3 and the ER stressor-induced expression of TRB3. CONCLUSION: Our data indicate that TRIB3 expression in adipose tissue is enhanced in patients with obesity and suggest that increased TRIB3 dysregulates adipocyte function, which may contribute to the development of insulin resistance.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Gordura Intra-Abdominal/metabolismo , Obesidade/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Repressoras/metabolismo , Gordura Subcutânea Abdominal/metabolismo , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adulto , Proteínas de Ciclo Celular/análise , Células Cultivadas , Técnicas de Cocultura , Estresse do Retículo Endoplasmático , Feminino , Humanos , Resistência à Insulina , Gordura Intra-Abdominal/citologia , Macrófagos , Pessoa de Meia-Idade , Pioglitazona/farmacologia , Cultura Primária de Células , Proteínas Serina-Treonina Quinases/análise , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Repressoras/análise , Gordura Subcutânea Abdominal/citologia , Regulação para Cima/efeitos dos fármacos
14.
Cancer Invest ; 39(10): 885-892, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34279158

RESUMO

The aim of this study is to analyze the correlation between clinically significant histologic results and HPV in women with AGC in pap test. Of the 311 women confirmed as AGC, 111 women (35.7%) was identified as positive for HPV. In the AGC analysis, cervical lesions were significantly more common in HPV positive group compared to HPV negative group (61.2 vs. 10.5%, p < 0.001). In contrast, endometrial lesions were not associated with HPV infection (8.1 vs. 4.5%, p = 0.12). The HPV-DNA testing in women with AGC may be a useful tool for predicting clinically significant cervical lesions.


Assuntos
Colo do Útero/patologia , DNA Viral/análise , Teste de Papanicolaou , Papillomaviridae/isolamento & purificação , Lesões Pré-Cancerosas/virologia , Neoplasias do Colo do Útero/virologia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Adulto Jovem
15.
Arch Gynecol Obstet ; 304(4): 1055-1063, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33871703

RESUMO

PURPOSE: The primary objective of our study was to investigate the effectiveness and safety of olaparib maintenance therapy in patients with BRCA-mutated recurrent ovarian cancer in daily practice. The secondary objective of this study was to identify prognostic factors associated with prolonged progression-free survival (PFS) in such patients. METHODS: We conducted a retrospective analysis of 40 patients who received olaparib maintenance treatment. Data on clinicopathological factors, oncological outcomes, and adverse events were obtained from medical records and analyzed. RESULTS: All patients had high-grade serous recurrent ovarian cancer with BRCA mutation and achieved complete or partial response to the most recent platinum-based chemotherapy. After a median follow-up of 14.3 months, the median PFS was 23.7 months (95% confidence interval, 14.1-33.4); however, the median overall survival was not reached. In the log-rank test, the PFS was significantly longer for patients with most recent platinum-free interval (PFI) ≥ 12 months, complete response to the last platinum-based chemotherapy, and less than three lines of previous chemotherapy (p = 0.005, p = 0.016, and p = 0.023, respectively). Most hematologic and non-hematologic adverse events were of grade 1 or 2, and the common adverse events were mostly related to myelosuppression. CONCLUSION: Olaparib maintenance treatment in BRCA-mutated recurrent ovarian cancer is effective and safe in clinical practice. Most recent PFI, response to the last platinum-based chemotherapy, and the number of previous chemotherapy lines were associated with PFS in patients with BRCA-mutated recurrent ovarian cancer.


Assuntos
Neoplasias Ovarianas , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Ftalazinas/efeitos adversos , Piperazinas , Estudos Retrospectivos
16.
J Obstet Gynaecol ; 41(4): 605-611, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32815448

RESUMO

The lymph node status is the most important prognostic factor for endometrial cancer. This study aimed to assess whether sentinel lymph node mapping (SLNM) is applicable in endometrial cancer. A retrospective review of patients with endometrial cancer who were diagnosed and treated in Asan Medical Centre from September 2015 to December 2017 was conducted. One hundred patients underwent robotic (da Vinci®) or laparoscopic surgical treatment, including SLNM with indocyanine green (ICG) fluorescence detection using the Firefly® and NIR/ICG systems. At least one lymph node area was observed in 100% of SLNM cases. Sentinel node detection and frozen biopsy were performed in all cases, and all patients with metastasis were found on SLNM. The sensitivity and negative predictive value were both 100% in the patient-by-patient and station-by-station analyses. SLNM appears to be a feasible method to reduce the morbidity and increase the detection rate in early-stage endometrial carcinoma.What is already known on this subject? There are studies that it is safe to diagnose the possibility of lymph node metastasis through sentinel lymph node mapping in endometrial cancer.What do the results of this study add? In this study, it is shown that the accuracy of sentinel lymph node mapping is 100% accurate.What are the implications of these findings for clinical practise and/or further research? Therefore, total lymphadenectomy will not be necessary for the future.


Assuntos
Corantes , Neoplasias do Endométrio/diagnóstico por imagem , Verde de Indocianina , Metástase Linfática/diagnóstico por imagem , Imagem Óptica/estatística & dados numéricos , Linfonodo Sentinela/diagnóstico por imagem , Adulto , Idoso , Neoplasias do Endométrio/patologia , Feminino , Humanos , Excisão de Linfonodo , Pessoa de Meia-Idade , Imagem Óptica/métodos , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Biópsia de Linfonodo Sentinela
17.
Br J Cancer ; 124(2): 375-382, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32994466

RESUMO

BACKGROUND: This Phase 2b study compared the efficacy and toxicity of belotecan and topotecan in recurrent ovarian cancer. METHODS: Patients with platinum-sensitive recurrent or platinum-resistant recurrent ovarian cancer (PRROC) were randomised 1:1 to receive belotecan 0.5 mg/m2 or topotecan 1.5 mg/m2 for five consecutive days every 3 weeks. The primary endpoint was overall response rate (ORR); secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: A total of 140 (belotecan, n = 71; topotecan, n = 69) and 130 patients (belotecan, n = 66; topotecan, n = 64) were included in the intention-to-treat (ITT) and per-protocol (PP) populations. ORR did not differ significantly between the belotecan and topotecan groups (ITT, 29.6% versus 26.1%; PP, 30.3% versus 25%). Although PFS did not differ between the groups, belotecan was associated with improved OS compared with topotecan in the PP population (39.7 versus 26.6 months; P = 0.034). In particular, belotecan showed longer OS in PRROC and non-high-grade serous carcinoma (non-HGSC; PP, adjusted hazard ratios, 0.499 and 0.187; 95% confidence intervals 0.255-0.977 and 0.039-0.895). Furthermore, there were no differences in toxicities between the two groups. CONCLUSIONS: Belotecan was not inferior to topotecan in terms of overall response for recurrent ovarian cancer. CLINICAL TRIAL REGISTRATION: NCT01630018.


Assuntos
Antineoplásicos/uso terapêutico , Camptotecina/análogos & derivados , Carcinoma Epitelial do Ovário/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Topotecan/uso terapêutico , Adulto , Idoso , Camptotecina/uso terapêutico , Carcinoma Epitelial do Ovário/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Intervalo Livre de Progressão
18.
Gynecol Oncol ; 160(2): 413-417, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33246662

RESUMO

OBJECTIVE: We aimed to investigate the effectiveness of continuing medical therapy in patients who did not achieve complete response (CR) despite 9 months of progestin treatment. We also sought to determine the prognostic factors associated with achieving CR among these patients. METHODS: We retrospectively analyzed 51 patients with presumed stage IA, grade 1 or 2 endometrioid adenocarcinoma who had persistent disease on biopsy performed at 9-12 months after at least 9 months of progestin-based therapy. Data on clinicopathological factors and oncological and obstetrical outcomes following continuous hormonal treatment were extracted from the patients' medical records and analyzed. Univariate and multivariate analyses for predicting CR were performed. RESULTS: Thirty-seven (72.5%) of 51 patients achieved CR after prolonged fertility-sparing treatment. Median time to CR from starting initial progestin was 17.3 months (range, 12.1-91.7 months). On univariate analysis, history of polycystic ovarian syndrome, histologic grade 2, and not achieving partial response (PR) until 12 months were significantly associated with failure to CR (odds ratio [OR], 6.188, 95% confidence interval [CI], 1.405-27.244, p = 0.018; OR, 9.722, 95% CI, 1.614-58.581, p = 0.013; and OR, 21.750, 95% CI, 4.016-117.783, p < 0.001, respectively). Multivariate analysis revealed that not achieving PR until 12 months was an independent prognostic factor predicting failure to CR after prolonged progestin therapy (OR, 21.803, 95% CI, 3.601-132.025, p = 0.001). CONCLUSIONS: Continued medical treatment is effective for persistent early endometrial carcinoma after at least 9 months of progestin therapy in young women who want to preserve their fertility.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Carcinoma Endometrioide/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Preservação da Fertilidade/métodos , Recidiva Local de Neoplasia/epidemiologia , Administração Oral , Biópsia , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/patologia , Intervalo Livre de Doença , Esquema de Medicação , Hiperplasia Endometrial/diagnóstico , Hiperplasia Endometrial/tratamento farmacológico , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Endométrio/diagnóstico por imagem , Endométrio/efeitos dos fármacos , Endométrio/patologia , Feminino , Seguimentos , Humanos , Dispositivos Intrauterinos , Levanogestrel/administração & dosagem , Imageamento por Ressonância Magnética , Acetato de Medroxiprogesterona/administração & dosagem , Acetato de Megestrol/administração & dosagem , Miométrio/diagnóstico por imagem , Miométrio/efeitos dos fármacos , Miométrio/patologia , Gradação de Tumores , Invasividade Neoplásica/diagnóstico por imagem , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Neoplasia Residual , Prognóstico , Estudos Retrospectivos , Fatores de Tempo , Falha de Tratamento , Resultado do Tratamento , Ultrassonografia
19.
Int J Gynecol Cancer ; 30(11): 1780-1783, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32928923

RESUMO

OBJECTIVES: Staging procedure in borderline ovarian tumors is a topic of controversy. Upstaging in non-serous borderline ovarian tumors that are confined to the ovary is rare. The aim of this study was to assess the impact of surgical staging on clinical outcomes in mucinous borderline ovarian tumors. METHODS: This was a retrospective study conducted at the Asan Medical Center, Seoul, Korea between January 1990 and December 2015, that included 432 patients with mucinous borderline ovarian tumors and at least 6 months follow-up. These patients were divided into a 'staging group' and 'unstaged group'. The staging group referred to patients who, in addition to hysterectomy and/or adnexal surgery, underwent at least one of the following: cytology, omental biopsy/omentectomy, peritoneal biopsy, lymph node biopsy/lymphadenectomy, or appendectomy. The unstaged group referred to patients who did not undergo any staging procedure but underwent adnexal surgery (cystectomy or oophorectomy). RESULTS: Median patient age was 40 (range 9-87) years. A total of 367 patients (85%) underwent a staging procedure (staging group) and 65 (15.0%) patients did not (unstaged group). Among the staging group, 258, 4, 100, and 5 patients were FIGO stage IA, IB, IC, or II-III, respectively. Overall recurrence was confirmed in 15 patients and median time to recurrence was 13.4 (range 0.4-127.3) months. One patient was in the unstaged group and had borderline recurrence. Fourteen were in the staging group, and 11 of them had borderline and three had invasive recurrence. Extraovarian disease was found at recurrence only in two patients. There was no significant difference in recurrence-free survival (p=0.39) and in overall survival between the staging group and the unstaged group (p=0.40). In total, 16 (4.4%) of 367 patients who underwent a staging procedure were upstaged. CONCLUSION: Staging in mucinous borderline ovarian tumors may be omitted if there is no obvious evidence of gross extraovarian disease.


Assuntos
Estadiamento de Neoplasias/normas , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/normas , Criança , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
20.
J Minim Invasive Gynecol ; 27(7): 1558-1565, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32084588

RESUMO

STUDY OBJECTIVE: To investigate the prognostic factors and impact of minimally invasive surgery (MIS) in surgically treated early-stage high-grade (HG) neuroendocrine cervical carcinoma (NECC). DESIGN: Retrospective cohort study. SETTING: Asan Medical Center, Seoul, Korea. PATIENTS: Patients with International Federation of Obstetrics and Gynecology (2009) stages IB1 to IIA HG NECC. INTERVENTIONS: All patients underwent radical hysterectomy (RH) with a laparotomy or an MIS approach. MEASUREMENTS AND MAIN RESULTS: Between 1993 and 2017, 47 patients with International Federation of Obstetrics and Gynecology stages IB1 to IIA1 HG NECC were initially treated with RH. Clinicopathologic variables of patients were retrospectively reviewed from electronic medical records. The median follow-up period was 28.2 months (interquartile range, 17.1-42). Stage IB1 disease was the most common (70.2%). Twenty-nine patients (61.7%) underwent RH by MIS. The overall survival (OS) and disease-free survival (DFS) rates were 63.8% and 38.3%, respectively. Lymph node metastasis and resection margin involvement were significant risk factors for DFS (hazard ratio [HR], 2.227; 95% confidence interval [CI], 1.018-4.871; p =.045 and HR, 6.494; 95% CI, 1.415-29.809; p =.016, respectively) and OS (HR, 3.236; 95% CI, 1.188-8.815; p =.022 and HR, 12.710; 95% CI, 1.128-143.152; p =.040, respectively). The Kaplan-Meier survival curves revealed no significant differences in OS and DFS between the laparotomy and MIS groups (50% vs 72.4% log-rank p =.196, 38.9% vs 37.9% p =.975). CONCLUSION: Lymph node metastasis and resection margin involvement were poor prognostic factors of survival outcomes in initially surgically treated early-stage HG NECC. No difference was observed in the survival outcomes between the MIS and laparotomy approaches.


Assuntos
Carcinoma Neuroendócrino/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/patologia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Histerectomia , Metástase Linfática , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Estadiamento de Neoplasias , Prognóstico , República da Coreia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos , Resultado do Tratamento , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Adulto Jovem
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