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1.
Breast Cancer Res Treat ; 176(2): 419-427, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31020470

RESUMO

PURPOSE: Alongside the modern trend of delaying childbirth, the high incidence of breast cancer among young women is causing significant pregnancy-related problems in Korea. We estimated the incidence of childbirth for young Korean breast cancer survivors compared with women who did not have breast cancer using a nationally representative dataset. METHODS: Using a database from the National Health Insurance Service in South Korea, we analyzed 109,680 women who were between 20 and 40 years old between 2007 and 2013. They were prospectively followed, and childbirth events were recorded until December 31, 2015. We compared childbirth rates and characteristics between the breast cancer survivors and the noncancer controls. RESULTS: Compared to 10,164 childbirths among 91,400 women without breast cancer (incidence rate: 22.3/1000), 855 childbirths occurred among 18,280 breast cancer survivors (incidence rate: 9.4/1000); the adjusted hazard ratio (HR) for childbirth was 0.41 (95% CI 0.38-0.44). Chemotherapy, endocrine therapy, and target therapy were associated with the decreasing childbirths among survivors, with corresponding adjusted HRs of 0.61 (0.53-0.70), 0.44 (0.38-0.51), and 0.62 (0.45-0.86), respectively. Breast cancer survivors had a lower probability of full-term delivery and a higher frequency of preterm labor than controls, with corresponding adjusted ORs of 0.78 (0.68-0.90) and 1.33 (1.06-1.65), respectively. CONCLUSIONS: We showed that a history of breast cancer has a negative effect on childbirth among young premenopausal women in Korea. Breast cancer survivors should be aware that they have a higher risk for preterm labor and are less likely to have a full-term delivery than women without a history of breast cancer.


Assuntos
Neoplasias da Mama/epidemiologia , Parto , Nascimento Prematuro/epidemiologia , Adulto , Neoplasias da Mama/complicações , Sobreviventes de Câncer , Estudos de Casos e Controles , Bases de Dados Factuais , Feminino , Humanos , Incidência , Gravidez , Estudos Prospectivos , República da Coreia/epidemiologia , Nascimento a Termo , Adulto Jovem
2.
World J Urol ; 37(6): 1205-1210, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30283996

RESUMO

PURPOSE: To investigate the factors associated with hospital readmission (HR) after retrograde intrarenal surgery (RIRS) among renal stone patients. METHODS: The study included patients who underwent RIRS from June 2011 to December 2017. Patients who were readmitted due to surgery-related complications were evaluated retrospectively. Patient demographics including age, medical comorbidity, body mass indices, ASA score, perioperative parameters and stone factors were compared with total cohorts. HR was defined as visits to the Emergency Room or unplanned admission within 30 days after discharge. The factors affecting HR rates were analyzed using uni- and multi-variate analyses. RESULTS: A total of 572 patients were enrolled into the study. The mean age was 57.6 ± 14.1 years and the mean stone diameter was 13.4 ± 6.2 mm. The mean complication rate was 6.1% and the median hospitalization time was 2.1 ± 3.4 days. HR occurred in 20 patients (3.5%). Compared to non-admission patients, readmitted patients had a higher rate of bilateral RIRS (20.0% vs 12.2%, p = 0.035), number of stones (4.65 vs 2.2, p = 0.041) and higher stone complexity score (4.15 vs 2.11, p = 0.003). Multivariate analysis showed bilateral RIRS (OR 1.091, p = 0.031) and stone complexity (OR 1.405, p = 0.003) were significant factors to predict re-admission after RIRS. CONCLUSION: Patients with complex renal stones or those who underwent bilateral RIRS were more likely to have a higher rate of re-admission. Proper perioperative management to prevent complications should be planned based on these predictive factors.


Assuntos
Cálculos Renais/cirurgia , Readmissão do Paciente/estatística & dados numéricos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Procedimentos Cirúrgicos Urológicos/métodos
3.
Invest New Drugs ; 36(4): 545-560, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29349597

RESUMO

Cancer associated fibroblasts (CAFs) are the most abundant components of cancer-microenvironment. They play important roles in cancer initiation, progression, and metastasis. In addition, CAFs can confer drug-resistance to cancer cells. Considering their pro-tumorigenic roles, it is recommended to remove CAFs to prevent cancer recurrence after chemotherapy. Despite their clinical significance, few anti-CAF drugs have been developed. The objective of this study was to find a drug that could suppress the viability of patient-derived CAFs through repurposed screening of 51 drugs that were in clinical trials or received FDA approval. As a result, bortezomib (BTZ), carfilzomib (CFZ), and panobinostat (PST) were identified as anti-CAF drug candidates. It was confirmed that BTZ and PST could decrease the viability of various patients derived CAFs through inducing of caspase-3 mediated apoptosis. Interestingly, combination therapy with BTZ and PST showed better efficacy of inhibiting CAFs than single treatment. The synergistic effect between BTZ and PST on viability of CAFs was observed both in vitro CAF culture and in vivo mouse model. Furthermore, combination therapy with BTZ/PST and conventional anticancer compound docetaxel strongly inhibited tumor growth in xenografts of mouse breast cancer cells with mouse CAFs. In conclusion, our present study revealed that BTZ and PST could significantly reduce the viability of CAFs. Therefore, a combination therapy with BTZ/PST and anticancer drugs might be considered as a new rational for the development of anticancer therapy.


Assuntos
Apoptose/efeitos dos fármacos , Bortezomib/farmacologia , Fibroblastos Associados a Câncer/efeitos dos fármacos , Panobinostat/farmacologia , Animais , Linhagem Celular , Linhagem Celular Tumoral , Reposicionamento de Medicamentos/métodos , Sinergismo Farmacológico , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Recidiva Local de Neoplasia/tratamento farmacológico , Oligopeptídeos/farmacologia
4.
Cytokine ; 76(2): 131-137, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26082022

RESUMO

While Active Hexose Correlated Compound (AHCC) and CpG oligodeoxynucleotide (ODN) are separately known to modulate oxidative stress and immune responses in cancer patients, the combined effect of these two compounds is unknown. To clarify this, we investigated whether AHCC plus KSK-CpG ODN would be therapeutic in B16 melanoma mouse model, if so, and how in reduction-oxidation (redox) balance and cytokines network. We found that treatment groups (AHCC only, KSK-CpG ODN only and AHCC/KSK-CpG ODN) markedly reduced (p<0.001) tumor size when compared to the positive control (PC) group. The total white blood cell (WBC) of AHCC only and KSK-CpG ODN only-treated groups showed significant lower counts than that of PC group. Next, the production of nitric oxide (NO) was significantly increased (p<0.01) in AHCC/KSK-CpG ODN group compared to the PC group. Further, the redox balance was improved in AHCC/KSK-CpG ODN group through significantly low (p<0.001) reactive oxygen species (ROS) production and significantly high (p<0.05) glutathione peroxidase (GPx) activity compared to the PC group. Finally, AHCC/KSK-CpG ODN (p<0.01) and KSK-CpG ODN (p<0.001)-treated groups augmented tumor immune surveillance as shown by significantly increased level of anti-inflammatory cytokine (IL-10) and significantly decreased (p<0.05) level of pro-tumorigenic IL-6 of AHCC/KSK-CpG ODN treated group as compared to the PC group. Collectively, our study indicates therapeutic effect of Active Hexose-Correlated Compound (AHCC) combined with KSK-CpG ODN in B16 melanoma murine model via balancing redox and cytokines network.


Assuntos
Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/imunologia , Oligodesoxirribonucleotídeos/uso terapêutico , Polissacarídeos/uso terapêutico , Animais , Linhagem Celular Tumoral , Citocinas/sangue , Citocinas/química , Citocinas/imunologia , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Glutationa Peroxidase/sangue , Interleucina-10/sangue , Interleucina-12/sangue , Interleucina-6/sangue , Células Matadoras Naturais/imunologia , Melanoma Experimental/metabolismo , Camundongos Endogâmicos C57BL , Óxido Nítrico/sangue , Oxirredução , Estresse Oxidativo , Distribuição Aleatória , Espécies Reativas de Oxigênio/sangue
5.
Int J Urol ; 22(12): 1112-7, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26290403

RESUMO

OBJECTIVE: To determine the association between diabetes mellitus and oncological outcomes in urothelial bladder cancer patients undergoing radical cystectomy. METHODS: From January 2004 to December 2014, 200 non-metastatic urothelial bladder cancer patients who underwent radical cystectomy were divided into two groups according to diabetes mellitus status at the time of surgery. Kaplan-Meier and Cox regression analysis were used to assess the association between diabetes mellitus and urothelial bladder cancer recurrence-free, cancer-specific and overall mortality. RESULTS: Of the 200 patients, 28 (14%) had diabetes mellitus and presented similar preoperative factors and pathological findings after radical cystectomy, including pathological stage, grade, lymph node invasion and positive surgical margin compared with non-diabetes mellitus patients (n = 172). The 5-year cancer-specific survivals were 92.3% and 62.1% in the non-diabetes mellitus and diabetes mellitus groups, respectively (P = 0.022). Multivariate Cox regression analysis showed that diabetes mellitus was a significant predictor for cancer-specific mortality (hazard ratio 1.785, P = 0.038). The 5-year overall survival rate was 92.1% and 59.4% in the non-diabetes mellitus and diabetes mellitus groups, respectively (P = 0.014), and diabetes mellitus was a significant factor for overall mortality by multivariate Cox regression analysis (hazard ratio 1.281, P = 0.042). CONCLUSIONS: Among bladder cancer patients who underwent radical cystectomy, the diabetes mellitus patients had worse cancer-specific mortality and overall mortality outcomes than the non-diabetes mellitus patients. The mechanism of association between diabetes mellitus and urothelial bladder cancer should be investigated to validate the present results in a future prospective study.


Assuntos
Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/terapia , Diabetes Mellitus Tipo 2/complicações , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/terapia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/complicações , Quimioterapia Adjuvante , Cistectomia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/complicações
6.
Breast Cancer Res ; 16(6): 502, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25551703

RESUMO

INTRODUCTION: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) can reveal the metabolic activity of malignant tumors. Recent advances gained from molecular studies suggest that tumor biology can be a good predictor of prognosis in breast cancer. We compared the ability of maximum standardized uptake values (SUVmax) derived by FDG-PET with tumor burden in predicting tumor recurrence for patients with breast cancer. METHODS: 496 patients with breast cancer who underwent preoperative FDG-PET between April 2004 and May 2009 were retrospectively identified. SUVmax was obtained by FDG-PET, and the cutoff point was defined using a time-dependent receiver operating characteristic curve for recurrence-free survival (RFS). The primary endpoint was RFS. RESULTS: In multivariate analysis for RFS, SUVmax carried independent prognostic significance (hazard ratio, 2.39; 95% confidence interval, 1.20 to 4.76; P = 0.012). When the patients were classified into four groups according to the combined factors of tumor size (≤2 cm versus >2 cm) and SUVmax (<4 versus ≥4), RFS differed significantly (P < 0.001). Similarly, SUVmax had prognostic value in combination with nodal status (negative versus positive) or stage (I versus II and III) (P < 0.001 and P = 0.001, respectively). In hormone receptor-positive disease, SUVmax remained a significant prognostic factor for RFS based on multivariate analysis. CONCLUSIONS: Our results highlight the prognostic value of FDG-PET in prediction of tumor relapse for patients with breast cancer. Particularly in patients with hormone receptor-positive disease, the tumor metabolic information provided by FDG-PET is more significantly correlated with prognosis than tumor burden.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Lobular/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Carga Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Carcinoma/diagnóstico por imagem , Carcinoma/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Estudos de Coortes , Técnicas de Apoio para a Decisão , Feminino , Fluordesoxiglucose F18 , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Tomografia por Emissão de Pósitrons , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos
7.
Breast Cancer Res Treat ; 141(1): 89-99, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23933800

RESUMO

Lysyl oxidase-like 2 (LOXL2) is associated with invasiveness and metastasis in breast cancer. We analyzed the prognostic impact of LOXL2 for breast cancer patients and investigated the role of LOXL2 in breast cancer cell lines. Immunohistochemical study of LOXL2 expression was done in samples from 309 patients. Survival analysis was performed using log-rank test and Cox regression hazard model. After identification of LOXL2 expression in breast cancer cell lines, we performed matrigel invasion and wound-healing assays with LOXL2-silenced cell lines. In the human study, LOXL2 was expressed in 16.2 % of patients. Comparing the LOXL2-positive versus negative groups, there was a significantly higher proportion of estrogen receptor-negative patients (54.0 vs. 37.0 %, respectively; p = 0.029) and triple-negative patients (34.0 vs. 18.0 %; p = 0.022) in the positive group. In multivariate analysis for overall survival and metastasis-free survival, positive LOXL2 was demonstrated as a poor prognostic factor (HR 2.27 and 2.10, respectively). In vitro study indicated that LOXL2 silencing induces a mesenchymal-epithelial transition-like process in basal cell lines (MDA-MB-231 and BT549) associated with decreased invasive and migratory properties. These clinical and preclinical data confirm that higher LOXL2 expression is associated with invasiveness of basal-like breast cancer cells and lower survival of breast cancer patients. Our results suggest the clinical value of LOXL2 as a therapeutic target in breast cancer.


Assuntos
Aminoácido Oxirredutases/análise , Neoplasias da Mama/química , Carcinoma/química , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/análise , Adulto , Aminoácido Oxirredutases/biossíntese , Aminoácido Oxirredutases/genética , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma/genética , Carcinoma/mortalidade , Carcinoma/patologia , Carcinoma in Situ/química , Carcinoma in Situ/genética , Carcinoma in Situ/mortalidade , Carcinoma in Situ/patologia , Linhagem Celular Tumoral , Movimento Celular , Colágeno , Intervalo Livre de Doença , Combinação de Medicamentos , Transição Epitelial-Mesenquimal , Feminino , Humanos , Hibridização In Situ , Estimativa de Kaplan-Meier , Laminina , Pessoa de Meia-Idade , Terapia Neoadjuvante , Invasividade Neoplásica , Metástase Neoplásica , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Neoplasias Primárias Múltiplas/química , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/mortalidade , Neoplasias Primárias Múltiplas/patologia , Tumor Filoide/química , Tumor Filoide/genética , Tumor Filoide/mortalidade , Tumor Filoide/patologia , Prognóstico , Modelos de Riscos Proporcionais , Proteoglicanas , Interferência de RNA , RNA Interferente Pequeno/farmacologia , Análise de Sobrevida , Análise Serial de Tecidos , Neoplasias de Mama Triplo Negativas/química , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia
8.
Oncology ; 85(4): 228-34, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24081024

RESUMO

BACKGROUND: We performed this analysis to investigate the clinical presentation of trastuzumab-associated cardiac toxicity in Korean women. METHOD: 124 patients treated in a single institute from January 2006 to November 2011 with adjuvant trastuzumab therapy following primary surgery were identified from a database. We evaluated the cumulative incidence of cardiac toxicity, associated risk factors, and changes in cardiac function during trastuzumab treatment. RESULTS: The median age of patients was 50 years (range 27-73). After 12 months of follow-up, the cumulative incidence of cardiac toxicity was 12.1% (grade I: 8.1%, grade II: 0.8%, grade III: 3.2%). In total, 4% of patients discontinued treatment due to cardiac dysfunction. The left ventricular ejection fraction (LVEF) recovered in all patients who discontinued or delayed treatment due to cardiac dysfunction following treatment discontinuation. The degree of the decrease in LVEF was large at 6 months after the initiation of treatment. A lower LVEF at baseline (<65%) was associated with cardiac toxicity. CONCLUSIONS: The low incidence of cardiac toxicity and the reversibility of cardiac dysfunction may validate the safety of trastuzumab treatment in Korean women with an acceptable baseline LVEF.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Cardiopatias/induzido quimicamente , Coração/efeitos dos fármacos , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Quimioterapia Adjuvante/efeitos adversos , Feminino , Seguimentos , Cardiopatias/epidemiologia , Humanos , Incidência , Pessoa de Meia-Idade , Estudos Prospectivos , República da Coreia , Fatores de Risco , Volume Sistólico , Trastuzumab , Função Ventricular Esquerda/fisiologia
9.
Int J Mol Sci ; 14(12): 23685-99, 2013 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-24304542

RESUMO

The Oncotype DX® recurrence score (RS) predictor has been clinically utilized to appropriately select adjuvant chemotherapy for patients with estrogen receptor (ER)-positive early breast cancer. However, the selection of chemotherapy for patients with intermediate RSs remains controversial. We assessed the prognostic value of a 70-gene signature (70GS) among patients with ER-positive breast cancer and intermediate RSs. In addition, we sought to identify genes associated with poor 70GS scores based on gene expression profiling (GEP). GEP was performed using gene expression data from 186 patients with ER-positive breast cancer. The RS and 70GS score were calculated on the basis of GEP. Among 186 patients, 82 ER-positive patients with intermediate RSs were identified. These patients were stratified by 70GS, overall survival (OS) significantly differed according to 70GS (p=0.013). In a supervised hierarchical analysis according to 70GS, the expression of several representative genes for cell proliferation was significantly higher in the poor 70GS cluster than in the good 70GS cluster. Furthermore, among these patients, FOXM1, AURKA, AURKB, and BIRC5 displayed prognostic significance for OS. In conclusion, 70GS can help to discriminate survival differences among ER-positive patients with intermediate RSs. FOXM1, AURKA, AURKB, and BIRC5, are associated with poor 70GS scores.


Assuntos
Neoplasias da Mama/diagnóstico , Perfilação da Expressão Gênica , Recidiva Local de Neoplasia , Receptores de Estrogênio/metabolismo , Adulto , Idoso , Aurora Quinases/genética , Aurora Quinases/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante , Análise por Conglomerados , Feminino , Proteína Forkhead Box M1 , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Humanos , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Receptores de Estrogênio/genética , Survivina , Adulto Jovem
10.
Prostate ; 72(11): 1187-92, 2012 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-22161951

RESUMO

BACKGROUND: We investigated the association of 5α-reductase inhibitor (5-ARI) treatment with pathologic and biochemical outcome among the contemporary prostate cancer (PCa) patients undergoing radical prostatectomy. METHODS: We reviewed records of 1,204 men who underwent radical prostatectomy from 2003 to 2010. We estimated association of 5-ARI use with high (≥7) pathologic Gleason score and pathologically nonorgan-confined disease (≥pT3) via logistic regression, and biochemical outcome via Cox proportional hazards regression. RESULTS: Of 1,204 patients, 50 (4.2%) reported having history 5-ARI treatment before radical prostatectomy. Median duration of 5-ARI treatment among the 50 patients was 23.0 months. When adjusted for various factors including age, body mass index, prostate-specific antigen, clinical stage, biopsy Gleason, and prostate volume, history of 5-ARI treatment was revealed to be significantly associated with high (≥7) pathologic Gleason score (P = 0.015). Also, 5-ARI use was observed to significantly associated with higher rates of extraprostatic extension of tumor (P = 0.005) and seminal vesicle invasion (P = 0.003), respectively, when adjusted for same variables. However, 5-ARI use was not demonstrated to be a significant preoperative predictor of biochemical recurrence-free survival in multivariate analysis (P = 0.528). CONCLUSIONS: Our results showed 5-ARI treatment may be associated with more aggressive PCa demonstrating higher pathologic Gleason score and advanced pathologic tumor stage in men undergoing radical prostatectomy. However, further investigations via larger-scale, prospective studies would be needed on the actual effect of 5-ARI treatment on PCa-specific morbidity and mortality.


Assuntos
Inibidores de 5-alfa Redutase/efeitos adversos , Próstata/efeitos dos fármacos , Hiperplasia Prostática/tratamento farmacológico , Neoplasias da Próstata/patologia , Inibidores de 5-alfa Redutase/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Modelos de Riscos Proporcionais , Prostatectomia , Neoplasias da Próstata/cirurgia , Resultado do Tratamento
11.
Breast Cancer Res Treat ; 130(3): 863-70, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21861101

RESUMO

The age distribution of breast cancer patients in Korea, where most are less than 60 years of age and have recently entered menopause, differs from that in the West. The aim of this study was to evaluate bone mineral density (BMD) changes in Korean breast cancer patients treated with an aromatase inhibitor (AI) either alone or in combination with zoledronic acid (ZA). Changes in BMD of the lumbar spine and hip were evaluated in 107 patients receiving AI treatment, of which 59 were treated in combination with ZA. The mean age of the patients was 54.9 years, and the median follow-up period was 38.2 months. With AI treatment alone, BMD loss was significant (all P < 0.0001) in the lumbar spine and hip 12 months (4.18 and 3.95%, respectively), 24 months (6.28 and 5.44%), and 36 months (8.17 and 6.82%) after treatment. In contrast, the combination treatment resulted in increased BMD in the lumbar spine and hip 12 months (2.45 and 0.89%, respectively), 24 months (3.51 and 1.03%), and 36 months (3.85 and 1.80%) after treatment. BMD loss in the lumbar spine was significantly greater in AI alone-treated women who had entered menopause within the past year compared with those who had entered menopause more than 1 year ago, when measured 12 and 24 months after treatment (P = 0.017 and 0.021, respectively). Importantly, ZA effectively inhibited AI-associated bone loss, independent of the postmenopausal interval. Because the proportion of patients in this study who had recently entered menopause was high, bone loss in Korean breast cancer patients treated with AI alone was higher than data reported from the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial. In conclusion, we have shown that ZA is very effective in preventing AI-induced bone loss in Korean postmenopausal breast cancer patients.


Assuntos
Inibidores da Aromatase/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Pós-Menopausa , Adulto , Idoso , Inibidores da Aromatase/efeitos adversos , Quimioterapia Adjuvante , Feminino , Seguimentos , Humanos , Coreia (Geográfico) , Pessoa de Meia-Idade , Osteoporose/induzido quimicamente , Osteoporose/prevenção & controle , Ácido Zoledrônico
12.
Asian J Androl ; 21(5): 486-492, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30829291

RESUMO

We aimed to develop and validate a clinical nomogram predicting bladder outlet obstruction (BOO) solely using routine clinical parameters in men with refractory nonneurogenic lower urinary tract symptoms (LUTS). A total of 750 eligible patients ≥50 years of age who had previously not responded (International Prostate Symptom Score [IPSS] improvement <4 points) to at least three different kinds of LUTS medications (including a-blocker) for the last 6 months were evaluated as subcohorts for nomogram development (n = 570) and for split-sample validation (n = 180). BOO was defined as Abrams-Griffiths number ≥40, or 20-39.9 with a slope of linear passive urethral resistance ratio >2 cmH2O ml-1 s-1. A stepwise multivariable logistic regression analysis was conducted to determine the predictors of BOO, and b-coefficients of the final model were selected to create a clinical nomogram. The final multivariable logistic regression model showed that age, IPSS, maximum urinary flow rate, postvoid residual volume, total prostate volume, and transitional zone index were significant for predicting BOO; these candidates were used to develop the final nomogram. The discrimination performance of the nomogram was 88.3% (95% CI: 82.7%-93.0%, P < 0.001), and the nomogram was reasonably well-fitted to the ideal line of the calibration plot. Independent split-sample validation revealed 80.9% (95% CI: 75.5%-84.4%, P < 0.001) accuracy. The proposed BOO nomogram based solely on routine clinical parameters was accurate and validated properly. This nomogram may be useful in determining further treatment, primarily focused on prostatic surgery for BOO, without impeding the detection of possible BOO in men with LUTS that is refractory to empirical medications.


Assuntos
Sintomas do Trato Urinário Inferior/complicações , Sintomas do Trato Urinário Inferior/diagnóstico , Nomogramas , Obstrução do Colo da Bexiga Urinária/diagnóstico , Adulto , Idoso , Estudos de Coortes , Humanos , Sintomas do Trato Urinário Inferior/fisiopatologia , Masculino , Pessoa de Meia-Idade , Próstata/patologia , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Obstrução do Colo da Bexiga Urinária/fisiopatologia , Urodinâmica
13.
J Breast Cancer ; 21(2): 190-196, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29963115

RESUMO

PURPOSE: There is still a clinical need to easily evaluate the metastatic status of lymph nodes during breast cancer surgery. We hypothesized that ex vivo shear-wave elastography (SWE) would predict precisely the presence of metastasis in the excised lymph nodes. METHODS: A total of 63 patients who underwent breast cancer surgery were prospectively enrolled in this study from May 2014 to April 2015. The excised axillary lymph nodes were examined using ex vivo SWE. Metastatic status was confirmed based on the final histopathological diagnosis of the permanent section. Lymph node characteristics and elasticity values measured by ex vivo SWE were assessed for possible association with nodal metastasis. RESULTS: A total of 274 lymph nodes, harvested from 63 patients, were examined using ex vivo SWE. The data obtained from 228 of these nodes from 55 patients were included in the analysis. Results showed that 187 lymph nodes (82.0%) were nonmetastatic and 41 lymph nodes (18.0%) were metastatic. There was significant difference between metastatic and nonmetastatic nodes with respect to the mean (45.4 kPa and 17.7 kPa, p<0.001) and maximum (55.3 kPa and 23.2 kPa, p<0.001) stiffness. The elasticity ratio was higher in the metastatic nodes (4.36 and 1.57, p<0.001). Metastatic nodes were significantly larger than nonmetastatic nodes (mean size, 10.5 mm and 7.5 mm, p<0.001). The size of metastatic nodes and nodal stiffness were correlated (correlation coefficient of mean stiffness, r=0.553). The area under curve of mean stiffness, maximum stiffness, and elasticity ratio were 0.794, 0.802, and 0.831, respectively. CONCLUSION: Ex vivo SWE may be a feasible method to predict axillary lymph node metastasis intraoperatively in patients undergoing breast cancer surgery.

14.
Asian J Androl ; 2018 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-30178776

RESUMO

We evaluated whether the prostate-specific antigen (PSA) mass or free PSA (fPSA) mass (i.e., absolute amount of total circulating PSA or fPSA protein, respectively), versus serum PSA or fPSA concentration, improves the accuracy of predicting the total prostate volume (TPV) in relation to obesity. Among men whose multicore (≥12) transrectal prostate biopsy was negative, 586 who had a PSA of ≤10 ng ml-1 and underwent the fPSA test prior to biopsy were enrolled. The PSA mass or fPSA mass (µ g) was calculated by multiplying the serum level by plasma volume. At each TPV cut-off point (30 ml, 40 ml, and 50 ml), the areas under the receiver operating characteristics curve (AUCs) of each variable were compared in obesity-based subgroups. AUCs of fPSA and fPSA mass for predicting TPV were significantly larger than those for PSA and PSA mass by 8.7%-12.1% at all cut-off points. Subgroup analyses based on obesity showed that, although PSA mass and fPSA mass enhanced accuracy by 4% (P = 0.031) and 1.8% (P = 0.003), respectively, for determining TPVs of ≥30 ml and ≥50 ml in obese and overweight men, they did not improve the accuracy in most other combinations of the degrees of obesity with TPV cut-off points. Thus, compared with serum PSA or fPSA, the absolute amount of PSA or fPSA protein mass improved the accuracy of predicting TPV in obese men very minimally and only for certain TPV cut-off points. Hence, these indicators may not provide clinically meaningful improvement in predicting TPV in obese men.

15.
Cancer Res Treat ; 50(3): 625-633, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28759990

RESUMO

PURPOSE: Although sentinel lymph node biopsy (SLNB) can accurately represent the axillary lymph node (ALN) status, the false-negative rate (FNR) of SLNB is the main concern in the patients who receive SLNB alone instead of ALN dissection (ALND). MATERIALS AND METHODS: We analyzed 1,886 patientswho underwent ALND after negative results of SLNB,retrospectively. A logistic regression analysis was used to identify risk factors associated with a falsenegative (FN) result. Cox regression model was used to estimate the hazard ratio of factors affecting disease-free survival (DFS). RESULTS: Tumor located in the upper outer portion of the breast, lymphovascular invasion, suspicious node in imaging assessment and less than three sentinel lymph nodes (SLNs) were significant independent risk factors for FN in SLNB conferring an adjusted odds ratio of 2.10 (95% confidence interval [CI], 1.30 to 3.39), 2.69 (95% CI, 1.47 to 4.91), 2.59 (95% CI, 1.62 to 4.14), and 2.39 (95% CI, 1.45 to 3.95), respectively. The prognostic factors affecting DFS were tumor size larger than 2 cm (hazard ratio [HR], 1.86; 95% CI, 1.17 to 2.96) and FN of SLNB (HR, 2.51; 95% CI, 1.42 to 4.42) in SLN-negative group (FN and true-negative), but in ALN-positive group (FN and true-positive), FN of SLNB (HR, 0.64; 95% CI, 0.33 to 1.25) did not affect DFS. CONCLUSION: In patients with risk factors for a FN such as suspicious node in imaging assessment, upper outer breast cancer, less than three harvested nodes, we need attention to find another metastatic focus in non-SLNs during the operation. It may contribute to provide an exact prognosis and optimizing adjuvant treatments.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Biópsia de Linfonodo Sentinela/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Reações Falso-Negativas , Feminino , Humanos , Modelos Logísticos , Excisão de Linfonodo/métodos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Adulto Jovem
16.
PLoS One ; 11(2): e0148690, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26848747

RESUMO

BACKGROUND: Our hypothesis is that the location of the seminal vesicles near the base of the prostate, the more positive cores are detected in the base, the greater the risk of seminal vesicle invasion. Therefore we investigate the clinical outcomes of base dominant prostate cancer (BDPC) in transrectal ultrasound (TRUS) -guided biopsies compared with anteromiddle dominant prostate cancer (AMPC). METHODS: From November 2003 to June 2014, a total of 990 intermediate and high risk prostate cancer (PCa) patients who underwent radical prostatectomy (RP) were enrolled and stratified into two groups according to proportion of positive cores-BDPC group had ≥ 33.3% ratio of positive cores from the prostate base among all positive cores and AMPC group < 33.3% in systemic biopsy. Between two groups, we compared the rate of pathologic outcomes and biochemical recurrence (BCR). We performed multivariate logistic regression model to confirm the significance of BDPC to seminal vesicle invasion (SVI) and Cox proportional hazard analysis to BCR. RESULTS: Among these 990 PCa patients, the 487 patients in BDPC group had more advanced clinical stage (p<0.001), a higher biopsy GS (p = 0.002), and a higher rate of extracapsular extension (ECE), SVI and BCR (all p<0.001) than AMPC group. The patients in BDPC group had poor BCR free survival rate via Kaplan-meier analysis (p<0.001). The ratio of the base positive cores was a significant predictor to SVI in multivariate analysis (p < 0.001) and significant predictor of BCR in multivariate Cox proportional analysis (hazard ratio: 1.466, p = 0.004). CONCLUSIONS: BDPC in TRUS-guided prostate biopsies was significantly associated with SVI and BCR after adjusting for other clinical factors. Therefore, BDPC should be considered to be a more aggressive tumor despite an otherwise similar cancer profile.


Assuntos
Invasividade Neoplásica , Neoplasias da Próstata/patologia , Glândulas Seminais/patologia , Idoso , Biópsia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/metabolismo , Prostatectomia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos
17.
PLoS One ; 11(1): e0145807, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26731558

RESUMO

BACKGROUND: Tenascin-C, an adhesion modulatory extracellular matrix molecule, is highly expressed in numerous human malignancies; thus, it may contribute to carcinogenesis and tumor progression. We explored the clinicopathological significance of Tenascin-C as a prognostic determinant of esophageal squamous cell carcinoma (ESCC). METHODS: In ESCC patient tissues and cell lines, the presence of isoforms were examined using western blotting. We then investigated Tenascin-C immunohistochemical expression in 136 ESCC tissue samples. The clinical relevance of Tenascin-C expression and the correlation between Tenascin-C expression and expression of other factors related to cancer-associated fibroblasts (CAFs) were also determined. RESULTS: Both 250 and 350 kDa sized isoforms of Tenascin-C were expressed only in esophageal cancer tissue not in normal tissue. Furthermore, both isoforms were also identified in all of four CAFs derived from esophageal cancer tissues. Tenascin-C expression was remarkably higher in ESCC than in adjacent non-tumor esophageal epithelium (p < 0.001). Tenascin-C expression in ESCC stromal fibroblasts was associated with patient's age, tumor (pT) stage, lymph node metastasis, clinical stage, and cancer recurrence. Tenascin-C expression in cancer cells was correlated with an increase in tumor-associated macrophage (TAM) population, cancer recurrence, and hypoxia inducible factor1α (HIF1α) expression. Moreover, Tenascin-C overexpression in cancer cells and stromal fibroblasts was an independent poor prognostic factor for overall survival (OS) and disease-free survival (DFS). In the Cox proportional hazard regression model, Tenascin-C overexpression in cancer cells and stromal fibroblasts was a significant independent hazard factor for OS and DFS in ESCC patients in both univariate and multivariate analyses. Furthermore, Tenascin-C expression in stromal fibroblasts of the ESCC patients was positively correlated with platelet-derived growth factor α (PDGFRα), PDGFRß, and smooth muscle actin (SMA) expression. The 5-year OS and DFS rates were remarkably lower in patients with positive expressions of both Tenascin-C and PDGFRα (p < 0.001), Tenascin-C and PDGFRß (p < 0.001), Tenascin-C and SMA (p < 0.001), Tenascin-C and fibroblast activation protein (FAP) (p < 0.001), and Tenascin-C and fibroblast-stimulating protein-1 (FSP1) (p < 0.001) in ESCC stromal fibroblasts than in patients with negative expressions of both Tenascin-C and one of the abovementioned CAF markers. CONCLUSION: Our results show that Tenascin-C is a reliable and significant prognostic factor in ESCC. Tenascin-C may thus be a potent ESCC therapeutic target.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/diagnóstico , Esôfago/patologia , Fibroblastos/patologia , Tenascina/análise , Idoso , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Intervalo Livre de Doença , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Células Tumorais Cultivadas
18.
J Nucl Med ; 57(8): 1183-8, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27033896

RESUMO

UNLABELLED: SUV, which is an indicator of the degree of glucose uptake in (18)F-FDG PET, can be applied as a prognostic factor in various malignant tumors. We investigated the prognostic impact of early changes in (18)F-FDG PET uptake in patients with locally advanced breast cancer who received neoadjuvant chemotherapy. METHODS: We retrospectively identified 87 patients who were treated with neoadjuvant chemotherapy followed by surgery for locally advanced breast cancer. All patients underwent (18)F-FDG PET at baseline and after 3 cycles of neoadjuvant chemotherapy, and the SUVmax of the primary tumor was assessed in each scan. Pathologic slides were retrospectively reviewed, and the residual cancer burden (RCB) index was calculated to estimate pathologic response. RCB-0 indicates no residual disease; patients with residual disease were categorized as RCB-1 (minimal residual disease), RCB-2 (moderate residual disease), or RCB-3 (extensive residual disease). RESULTS: There was a negative correlation between reduction in SUVmax and RCB index (r = -0.408; P < 0.001). On multivariate analysis, ΔSUVmax was a significant independent prognostic factor for recurrence-free and overall survival, and the respective adjusted hazard ratios were 0.97 (95% confidence interval, 0.95-0.99; P = 0.001) and 0.97 (95% confidence interval, 0.95-0.99; P = 0.015). When patients were categorized into groups according to pathologic response (RCB index ≤ 1 vs. ≥ 2) and metabolic response (ΔSUVmax ≤ 66.4% vs. > 66.4%), metabolic responders had significantly better recurrence-free and overall survival than metabolic nonresponders among poor-pathologic-response patients. In contrast, among metabolic responders, there was no survival difference according to pathologic response. CONCLUSION: The early change in (18)F-FDG PET SUVmax after third-cycle neoadjuvant chemotherapy is an independent and good prognostic marker beyond pathologic response in patients with locally advanced breast cancer. We suggest that in these patients, the use of ΔSUVmax should be considered not only for the assessment of tumor response but for the prediction of posttreatment outcome.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Monitoramento de Medicamentos/estatística & dados numéricos , Fluordesoxiglucose F18 , Recidiva Local de Neoplasia/prevenção & controle , Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante , Monitoramento de Medicamentos/métodos , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/mortalidade , Neoplasia Residual , Tomografia por Emissão de Pósitrons/métodos , Prevalência , Prognóstico , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Taxa de Sobrevida , Resultado do Tratamento
19.
Cancer Res Treat ; 47(1): 26-33, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25327493

RESUMO

PURPOSE: Tumor response to neoadjuvant chemotherapy (NAC) may adversely affect the identification and accuracy rate of sentinel lymph node biopsy (SLNB). This study was conducted to evaluate the feasibility of SLNB in node-positive breast cancer patients with negative axillary conversion after NAC. MATERIALS AND METHODS: Ninety-six patients with positive nodes at presentation were prospectively enrolled. (18)Fluorodeoxyglucose-positron emission tomography ((18)F-FDG PET) and ultrasonography were performed before and after NAC. A metastatic axillary lymph node was defined as positive if it was positive upon both (18)F-FDG PET and ultrasonography, while it was considered negative if it was negative upon both (18)F-FDG PET and ultrasonography. RESULTS: After NAC, 55 cases (57.3%) became clinically node-negative, while 41 cases (42.7%) remained node-positive. In the entire cohort, the sentinel lymph node (SLN) identification and false-negative rates were 84.3% (81/96) and 18.4% (9/49), respectively. In the negative axillary conversion group, the results of SLNB showed an 85.7% (48/55) identification rate and 16.7% (4/24) false-negative rate. CONCLUSION: For breast cancer patients with clinically positive nodes at presentation, it is difficult to conclude whether the SLN accurately represents the metastatic status of all axillary lymph nodes, even after clinically negative node conversion following NAC.

20.
J Breast Cancer ; 18(4): 371-7, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26770244

RESUMO

PURPOSE: We investigated the relationships between metastasis-free interval (MFI) and tumor characteristics, and assessed the prognostic value of MFI for survival after metastasis in patients with metastatic breast cancer. Furthermore, we compared MFI among the subtypes. METHODS: We identified 335 patients with postoperative tumor recurrence at distant site(s). All patients underwent curative resection and had a MFI of at least 6 months. MFI was categorized as short (<2 years), intermediate (≥2 years and <5 years), or long (≥5 years). Overall survival after metastasis (OSM) was estimated. RESULTS: Patients with a shorter MFI were younger, more likely to have initial metastasis to visceral organs, and had a larger tumor with a higher stage and grade as well as a higher rate of nodal involvement at initial diagnosis. Among 136 patients with known disease subtypes, shorter MFI was associated with the triple-negative subtype while longer MFI was associated with the hormone receptor-positive/human epidermal growth factor receptor 2 negative subtype. Mortality after metastasis declined sharply with increasing MFI up to approximately 2 years, and continued gradually declining between 2 and 5 years. An MFI longer than 5 years did not add any survival benefit. MFI was a significant prognostic factor for OSM independent of nodal status, stage, metastatic site, and hormone receptor status of the metastasized cancer. CONCLUSION: MFI is closely related to biological characteristics of both primary tumors and their metastases, and has a prognostic value for survival after metastasis. We therefore suggest investigation into treatments targeting improvement of MFI as a potential novel strategy.

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