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1.
Oncol Res Treat ; 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39033747

RESUMO

INTRODUCTION: This multicenter, phase II randomized, non-inferiority study reports from the first prospective two-armed randomized control trial that compared the efficacy, safety and quality-of-life of pegylated liposomal doxorubicin (PLD)-based and epirubicin-based as adjuvant chemotherapy for stage I-II Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer. METHODS: Patients with stage I/II HER2-negative breast cancer received PLD (37.5mg/m2, Q3W, 5 cycles, LC arm) plus cyclophosphamide (600mg/m2) or epirubicin (90mg/m2, Q3W, 4 cycles, EC arm) plus cyclophosphamide (600mg/m2). Randomization was stratified by lymph node, ER and PR status. The primary endpoint was disease-free survival (DFS), and secondary endpoints were overall survival (OS), safety profiles, and quality of life (QoL). QoL was assessed using the EORTC QLQ-C30 and QLQ-BR23 questionnaires. RESULTS: A total of 256 patients were assigned to LC (n=148) and EC (n=108). There was no difference in 5-year DFS and OS rate between two groups. LC-based adjuvant regimens had significantly less alopecia, less grade 3-4 hematologic adverse events (AEs). Significantly improved QoL was observed in the LC arm during and after treatment for symptoms including fatigue, nausea and vomiting, and systemic therapy side effects. CONCLUSION: Comparable efficacy and safety between adjuvant PLD and epirubicin for stage I-II HER2-negative breast cancer was observed. There was no difference in 5-year DFS and OS rate between the two treatment arms. However, less grade 3-4 AEs and a trend of favorable QoL symptom scales were observed in the LC arm, suggesting that PLD-containing regimen could become a new standard treatment for early stage HER2-negative breast cancer patients.

2.
J Pers Med ; 12(2)2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35207791

RESUMO

BACKGROUND: Vacuum-assisted breast biopsy (VABB) for benign breast tumor excision is a developing trend in breast surgery. The most common complication of VABB is hematoma. We assessed the efficiency of the thrombin-gelatin matrix (TGM) for hemostasis after VABB. METHODS: From December 2013 to June 2017, 147 patients with breast tumors > 2 cm in size were treated with a 7-gauge ultrasound-guided EnCor EnSpire® breast biopsy system. After VABB, the TGM was applied using an iron-tube device. After injection, brief external compression for 15 min and postoperative bandage compression for approximately 12 h were applied. The medical records were reviewed and analyzed for hematoma and acute bleeding at 1 and 3 months after VABB. RESULTS: A total of 72 patients received hemostasis via TGM, and 75 patients received hemostasis by compression. The rates of postoperative acute bleeding in the TGM group were significantly lower than those in the non-TGM group (5.5% vs. 22.7%, p = 0.003). Among patients with hematoma, there was no statistically significant difference between the two groups (25% vs. 26.7%, p = 0.85). CONCLUSIONS: This is the first cohort study to apply the TGM hemostatic matrix for post-VABB hemostasis. The TGM hemostatic matrix could be an option for patients with large breast tumors.

3.
In Vivo ; 32(6): 1635-1641, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30348727

RESUMO

BACKGROUND: Patients with liver metastasis from breast cancer (LMBC) are usually offered systemic therapy. However, for those with progressive liver disease and limited extra-hepatic conditions, local liver management becomes an option. Herein we present our experience with hepatic arterial infusion chemotherapy (HAIC). PATIENTS AND METHODS: From 1999 to 2018, 42 patients with LMBC, who had progressive liver metastasis after systemic therapy, were treated with HAIC. A catheter was placed angiographically into the hepatic artery and remained there for 5 consecutive days. One cycle of chemotherapy consisted of mitoxantrone, 5-fluorouracil, folinic acid, and cisplatin. This treatment was repeated at monthly intervals. The medical records were reviewed and analyzed for hepatic tumor response, progression-free survival, overall survival and adverse effects. RESULTS: Complete response was observed in two patients (5%), partial response in 18 patients (43%) and stable disease in eight patients (19%). Fourteen patients (33%) had progressive disease after HAIC. The median progression-free survival and overall survival were 8.4 and 19.3 months, respectively. There was no death related to HAIC. The patients with response to the treatment had a significant survival benefit (p<0.005). CONCLUSION: HAIC can be an option for those with progressive liver disease who are heavily pretreated while their extra-hepatic conditions are minimal or stable.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Cisplatino/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Adulto , Idoso , Neoplasias da Mama/patologia , Feminino , Artéria Hepática/efeitos dos fármacos , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Neoplasias Hepáticas/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , Resultado do Tratamento
4.
Breast Cancer Res Treat ; 170(3): 583-591, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29623575

RESUMO

PURPOSE: The aim of this study was to confirm the therapeutic role of eribulin on Taiwanese women with metastatic breast cancer. METHODS: This retrospective study examined 449 females who received eribulin between March 2014 and June 2017 at 14 hospitals in Taiwan for treatment of locally advanced or metastatic breast cancer. RESULTS: The survival rate at 24 months was 57.2% (95% CI 51.0-62.9%) and the median time to treatment failure (TTF) was 3.91 months (95% CI 3.45-3.94). A total of 175 patients (40.1%) received eribulin for fewer than 90 days and the others received it for 90 days or more. Eight patients (1.83%) had complete remission, 82 (18.8%) had partial remission, 202 (46.3%) had stable disease, and 144 (33.0%) had progressive disease (PD). Patients' tumors with the luminal A subtype had a significantly better objective response rate. Kaplan-Meier analysis indicated that hormone receptor positivity, luminal A subtype, receipt of eribulin as the 1st to 3rd line therapy, and metastasis to fewer than 4 organs were significantly associated with longer TTF. Stepwise multivariate analysis showed that only receipt of eribulin as the 1st to 3rd line therapy was significantly associated with TTF (HR 1.49, p < 0.001). All toxicities were manageable and only 18 patients (4.1%) discontinued treatment due to adverse events. CONCLUSIONS: Eribulin appears to have better efficacy and cause fewer adverse events, especially neutropenia, in Taiwanese women than Western women.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Furanos/uso terapêutico , Cetonas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Biomarcadores Tumorais , Neoplasias da Mama/metabolismo , Esquema de Medicação , Feminino , Furanos/administração & dosagem , Furanos/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Cetonas/administração & dosagem , Cetonas/efeitos adversos , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taiwan , Resultado do Tratamento , Adulto Jovem
5.
Oncotarget ; 8(61): 104571-104581, 2017 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-29262662

RESUMO

There is controversy concerning whether radiofrequency ablation (RFA) or surgical resection (SR) is a better treatment option for recurrent HCC after resection. In Kaohsiung Veteran General Hospital, from January 2002 to September 2014, a total of 100 consecutive patients who developed recurrent HCCs with a tumor size ≦ 3 cm and tumor numbers ≦ 3 after surgical resection were enrolled. Among these patients, 57 patients received RFA and 43 patients underwent repeated SR. Baseline characteristics at the time of recurrence after hepatic resection and clinical outcomes following treatment of recurrent HCC were compared between the two groups. The baseline data of initial HCC and the first recurrence of HCC were comparable in both groups. The 1-, 3-, 5-year overall survival rates following treatment of the first recurrence of HCC were 97.6%, 82.7%, 56.4% in the repeated SR group and 98.2%, 77.2%, 52.6% in the RFA group (p = 0.69). The 1-, 3-, 5-year disease-free survival rates were 57.0%, 32.1%, 28.6% in the repeated SR group and 60.8%, 26.6%, 16.6% in the RFA group ((p = 0.89). There was a trend whereby patients who underwent repeated SR had more procedure-related morbidity than patients who underwent RFA (16% vs. 7%, p = 0.14). The median total hospital days were longer in the repeated SR group than that in the RFA group (13 vs. 5 days, p < 0.05). In the small recurrent HCCs after SR, RFA achieved similar overall survival and disease-free survival than those with repeated SR as well as having a shorter hospital stay.

6.
Int J Surg ; 45: 35-41, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28728985

RESUMO

BACKGROUND: Recurrence rate after curative surgical resection of Hepatocellular carcinoma (HCC) remains high. Postoperative hepatic arterial infusion chemotherapy (HAIC) has been suggested to improve survival. This study is to investigate the efficacy of HAIC in the patients with poor tumor factors such as vascular invasion or multiplicity. METHODS: From 2006 to 2014, 221 patients with HCC undergoing hepatectomy and pathologically staged as ≧ T2 (American Joint Committee on Cancer TNM staging system, 7th edition) were included. 61 patients received adjuvant HAIC with 5-fluorouracil, cisplatin, and epirubicin. 160 patients received surgery alone. The overall survival time (OST) and disease free survival time (DFST) were compared between the two groups. RESULTS: In all patients, the multivariate analysis of survival data showed that resection margin less than 10 mm was the independent poor prognostic factors. The median OST and DFST between the HAIC and surgery alone groups were 56.4 vs. 56.9 months (p = 0.76), and 50.6 vs. 54.5 months (p = 0.905), respectively. There was no significant difference. For patients with multiple tumors and concomitantly microvascular invasion, the OST was better in the HAIC group (69.7 vs. 54.6 months, p < 0.05). Based on the image and operative finding, we classified multiple HCC's into two types. Type A: multiple small nodules were close to each other or a huge tumor with several satellite nodules. Type B: two or more tumors scattering in separate segments. Our study showed that type A group benefits from adjuvant HAIC much more than type B. (the median OST in type A versus type B were 85.06 vs. 41.53 months, p = 0.0036). CONCLUSION: The surgical outcome for the patients with multiple HCC's and vascular invasion was poor. Our study showed adjuvant HAIC was beneficial in these patients and formed the basis for further randomized controlled trials.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Hepatectomia , Neoplasias Hepáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/cirurgia , Quimioterapia Adjuvante/métodos , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Seleção de Pacientes , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
7.
Clin Oncol (R Coll Radiol) ; 29(6): 362-369, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28139380

RESUMO

AIMS: Despite the huge and growing global burden of patients who require breast cancer surgery, high-quality population-based studies of breast cancer trends and outcomes are scarce. The purpose of this study was to explore the incidence of breast cancer and predictors of hospital resource utilisation, mortality and recurrence in a nationwide population of patients who have received surgery. MATERIALS AND METHODS: This retrospective study analysed trends and outcomes in a Taiwan population of 77 971 patients after breast cancer surgery during 1996-2010. The Cox proportional hazards model was used for multivariate assessment of both mortality and recurrence predictors. RESULTS: The data analysis indicated that, during this period, the estimated mean hospital treatment cost and mean length of stay increased by 16.3% and 53.4%, respectively. The estimated mean overall survival time was 138.9 months (standard deviation 0.3 months) and the overall 1, 3, 5 and 10 year survival rates were 97.3, 89.2, 82.2 and 70.1%, respectively. The estimated mean overall recurrence time was 10.8 months (standard deviation 0.2 months) and the overall 1, 3, 5 and 10 year recurrence rates were 0.1, 18.8, 26.6 and 36.0%, respectively. Outcomes were significantly associated with age, Deyo-Charlson comorbidity index score, surgeon seniority, hospital volume, surgeon volume, surgery type, hospital level and baseline comorbidities (P<0.001). CONCLUSIONS: Analyses of these population-based data revealed simultaneous increases in the standard incidence of breast cancer surgery and its associated medical resource utilisation. Notably, healthcare providers and patients should recognise that both patient attributes and hospital attributes may affect breast cancer surgery outcomes.


Assuntos
Neoplasias da Mama/epidemiologia , Custos Hospitalares/tendências , Hospitais/estatística & dados numéricos , Tempo de Internação/tendências , Recidiva Local de Neoplasia/epidemiologia , Adulto , Fatores Etários , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Comorbidade , Feminino , Preços Hospitalares , Hospitais/classificação , Humanos , Incidência , Estudos Longitudinais , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Taiwan/epidemiologia , Resultado do Tratamento
8.
World J Surg Oncol ; 11(1): 194, 2013 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-23945398

RESUMO

BACKGROUND: The aim of this study was to evaluate the recurrence pattern after skin-sparing mastectomy (SSM) and immediate breast reconstruction (IBR) using transverse rectus abdominis musculocutaneous (TRAM) flap in patients with invasive breast cancer. METHODS: From 1995 to 2010, patients with invasive breast cancer who underwent SSM followed by IBR using TRAM flap were retrospectively reviewed. The pattern of the first recurrence event was recorded. RESULTS: We identified 249 consecutive patients with invasive breast cancer, two-thirds of whom (67.1%) were diagnosed with stage II or stage III disease. During a median follow-up period of 53 months, three (1.2%) local, 13 (5.2%) regional, 34 (13.7%) distant, and five (2.0%) concurrent locoregional and distant recurrences were observed. The median time to recurrences was 26 months (range, 2 to 70 months) for all recurrences, 23 months (range, 2 to 64 months) for locoregional recurrences, and 26 months (range, 8 to 70 months) for distant recurrences. All local recurrent lesions were detectable by careful physical examination, and detection of local recurrence suggested the presence of distant metastasis (60.0%). In contrast to distant metastasis, the risk of locoregional recurrence did not increase significantly with an increase in disease stage. The 5-year overall, locoregional relapse-free, and distant relapse-free survival rates were 89.7%, 90.8%, and 81.6%, respectively. CONCLUSIONS: SSM followed by immediate reconstruction using TRAM flap is an oncologically safe procedure even in patients with advanced-stage disease. Detection of local recurrence is crucial and can be aided by a thorough physical examination.


Assuntos
Neoplasias da Mama/cirurgia , Mamoplastia , Mastectomia/efeitos adversos , Recidiva Local de Neoplasia/etiologia , Complicações Pós-Operatórias , Reto do Abdome/transplante , Retalhos Cirúrgicos , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Adulto , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/mortalidade , Carcinoma Lobular/patologia , Carcinoma Lobular/cirurgia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
9.
J Chin Med Assoc ; 76(8): 425-31, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23796652

RESUMO

BACKGROUND: To evaluate hyperthermic intraperitoneal chemotherapy (HIPEC) as an adjuvant chemotherapy in advanced gastric cancer (AGC) patients with serosal invasion. METHODS: Patients who received radical surgery and palliative surgery between January 2002 and December 2010 were retrospectively examined. Patients were divided into two groups, namely, one group that underwent surgery and another group that underwent surgery with HIPEC. All patients who received HIPEC had suspected serosal invasion on an abdominal computed tomography or by the surgeon's assessment during the operation. RESULTS: The prophylactic groups included 83 patients who underwent gastrectomy alone. A total of 29 patients underwent gastrectomy with HIPEC. The 5-year survival rates were 10.7% and 43.9%, respectively. The 5-year mean survival times were 22.66 (17.55-25.78) and 34.81 (24.97-44.66) months (p = 0.029), respectively. There were 52 patients who had a recurrence of carcinomatosis among 133 patients who had resections (52/133, 39.1%). The 3-year disease-free survival rate for carcinomatosis was 28.87% in the group that received surgery alone, whereas it was 66.03% in the group that received HIPEC. There was no significant difference in the rate of complication between the two groups in the prophylactic group (p = 0.542). Thus, curative surgery with HIPEC had a better prognosis for AGC with serosal invasion. The carcinomatosis recurrence time was longer in patients who underwent gastrectomy with HIPEC and received R0 resection. CONCLUSION: The survival benefit of HIPEC as an adjuvant therapy for gastric cancer patients with serosal invasion should be validated in a large cohort.


Assuntos
Antineoplásicos/administração & dosagem , Hipertermia Induzida/métodos , Neoplasias Gástricas/terapia , Adulto , Idoso , Quimioterapia Adjuvante , Feminino , Humanos , Injeções Intraperitoneais , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
10.
J Chin Med Assoc ; 75(11): 573-80, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23158035

RESUMO

BACKGROUND: The significance of lymph node involvement regarding the prognosis of primary duodenal adenocarcinoma remains controversial. This study aims to evaluate the prognostic accuracy of nodal metastasis using the seventh edition American Joint Committee on Cancer staging system in patients with primary duodenal adenocarcinoma. METHODS: Between 1993 and 2010, 36 patients who had undergone surgical resection for primary duodenal adenocarcinoma at the Kaohsiung Veterans General Hospital were retrospectively reviewed. RESULTS: The median disease-free survival for all patients was 19 months and the median overall survival was 21 months. Lymph node metastases were found in 26 (72%) of the patients, and 14 patients (39%) patients had in excess of three positive lymph nodes (N2). Patients with N2 disease had significantly reduced overall survival, as compared to patients with three or fewer positive lymph nodes (N1; p = 0.036). In univariate analysis, factors including age >75 years, body weight loss, tumor size ≤ 4 cm, N2 disease and lymph node ratio >0.4 predicted shorter overall survival. Multivariate analysis demonstrated that N2 and lymph node ratio >0.4 are significant risk factors associated with overall survival (p = 0.026 and p = 0.042 respectively). N2 is also the only independent predictive factor for disease-free survival (p = 0.023). CONCLUSION: Subdivision of metastatic lymph nodes into N1 and N2 improves predictive ability. The seventh edition American Joint Committee on Cancer staging system is applicable in the present study with regard to the prediction of the prognosis for primary duodenal adenocarcinoma.


Assuntos
Adenocarcinoma/mortalidade , Neoplasias Duodenais/mortalidade , Linfonodos/patologia , Metástase Linfática/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
11.
Toxicol In Vitro ; 25(3): 636-43, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21232596

RESUMO

The effect of diallyl disulfide (DADS) on cytosolic Ca(2+) concentrations ([Ca(2+)](i)) and viability in PC3 human prostate cancer cells is unclear. This study explored whether DADS changed [Ca(2+)](i) in PC3 cells by using fura-2. DADS at 50-1000 µM increased [Ca(2+)](i) in a concentration-dependent manner. The signal was reduced by removing Ca(2+). DADS-induced Ca(2+) influx was not inhibited by nifedipine, econazole, SK&F96365, and protein kinase C modulators; but was inhibited by aristolochic acid. In Ca(2+)-free medium, pretreatment with the endoplasmic reticulum Ca(2+) pump inhibitors thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) nearly abolished DADS-induced [Ca(2+)](i) rise. Incubation with DADS inhibited thapsigargin or BHQ-induced [Ca(2+)](i) rise. Inhibition of phospholipase C with U73122 did not alter DADS-induced [Ca(2+)](i) rise. At 500-1000 µM, DADS killed cells in a concentration-dependent manner. The cytotoxic effect of DADS was partly reversed by prechelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Propidium iodide staining suggests that DADS (500 µM) induced apoptosis in a Ca(2+)-independent manner. Annexin V/PI staining further shows that 10 µM and 500 µM DADS both evoked apoptosis. DADS also increased reactive oxygen species (ROS) production. Collectively, in PC3 cells, DADS induced [Ca(2+)](i) rise probably by causing phospholipase C-independent Ca(2+) release from the endoplasmic reticulum and Ca(2+) influx via phospholipase A(2)-sensitive channels. DADS induced Ca(2+)-dependent cell death, ROS production, and Ca(2+)-independent apoptosis.


Assuntos
Compostos Alílicos/farmacologia , Antineoplásicos/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Dissulfetos/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Apoptose/efeitos dos fármacos , Cálcio/química , Cálcio/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citosol/efeitos dos fármacos , Citosol/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Fura-2/química , Humanos , Masculino , Neoplasias da Próstata/patologia , Espécies Reativas de Oxigênio/metabolismo
12.
J Am Coll Surg ; 211(5): 580-6, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20851644

RESUMO

BACKGROUND: Genotype B and C are the predominant hepatitis B virus (HBV) strains in Taiwan. We aimed to investigate the role of genotype in HBV-related hepatocellular carcinoma (HCC) after resection. STUDY DESIGN: From October 2005 to November 2008, 64 patients who underwent liver resection for HBV-related HCC were enrolled. HBV genotypes were determined by molecular method. Patient characteristics, biochemical, tumor, and viral factors were evaluated for their prognostic significance. RESULTS: During a mean follow-up of 26.6 ± 13.2 months, patients infected with genotype C had higher HBV viral load (p = 0.007) and worse disease-free survival rate (p = 0.028) than patients with genotype B. By univariate analysis, genotype C, alanine transaminase >50 U/L, tumor size ≥5 cm, and microvascular invasion were associated with tumor recurrence. Further multivariate analysis demonstrated genotype C remained a significant risk factor (p = 0.034). CONCLUSIONS: Genotype C is a strong risk factor for HCC recurrence after resection. More intensive monitoring for recurrence should be considered in patients with genotype C.


Assuntos
Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , Vírus da Hepatite B/genética , Hepatite B/epidemiologia , Hepatite B/virologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Recidiva Local de Neoplasia/epidemiologia , Carcinoma Hepatocelular/epidemiologia , Causalidade , Causas de Morte , Comorbidade , DNA Viral/isolamento & purificação , Intervalo Livre de Doença , Feminino , Seguimentos , Genótipo , Hepacivirus/imunologia , Humanos , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Peliose Hepática , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Carga Viral
13.
Clin Exp Pharmacol Physiol ; 36(3): 297-303, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18986328

RESUMO

1. It has been shown that the antidepressant desipramine is able to induce increases in [Ca(2+)](i) and cell death in MG63 human osteosacroma cells, but whether apoptosis is involved is unclear. In the present study, the effect of desipramine on apoptosis and the underlying mechanisms were explored. It was demonstrated that desipramine induced cell death in a concentration- and time-dependent manner. 2. Cells treated with 100-800 mmol/L desipramine showed typical apoptotic features, including an increase in sub-diploid nuclei and activation of caspase 3, indicating that these cells underwent apoptosis. Immunoblotting revealed that 100 mmol/L desipramine activated extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). Although pretreatment of cells with 20 mmol/L PD98059 (an ERK inhibitor) or 20 mmol/L SP600125 (an inhibitor of JNK) did not inhibit cell death, the addition of 20 mmol/L SB203580 (a p38 MAPK inhibitor) partially rescued cells from apoptosis. Desipramine-induced caspase 3 activation required p38 MAPK activation. 3. Pretreatment of cells with BAPTA/AM (20 mmol/L) to prevent desipramine-induced increases in [Ca(2+)](i) did not protect cells from death. 4. The results of the present study suggest that, in MG63 human osteosarcoma cells, desipramine causes Ca(2+)-independent apoptosis by inducing p38 MAPK-associated activation of caspase 3.


Assuntos
Antidepressivos Tricíclicos/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Desipramina/farmacologia , Osteossarcoma/enzimologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Cálcio/metabolismo , Linhagem Celular Tumoral , Quelantes/farmacologia , Relação Dose-Resposta a Droga , Ativação Enzimática , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Osteossarcoma/patologia , Inibidores de Proteínas Quinases/farmacologia , Fatores de Tempo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
14.
J Recept Signal Transduct Res ; 28(6): 567-79, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19061074

RESUMO

The effects of econazole, an antifungal drug applied for treatment of keratitis and mycotic corneal ulcer, on cytosolic-free Ca(2+) concentrations ([Ca(2+)](i)) and viability of corneal cells was examined by using SIRC rabbit corneal epithelial cells as model. [Ca(2+)](i) and cell viability were measured by using the fluorescent dyes fura-2 and WST-1, respectively. Econazole at concentrations > or = 1 microM increased [Ca(2+)](i) in a concentration-dependent manner. The Ca(2+) signal was reduced partly by removing extracellular Ca(2+). The econazole-induced Ca(2+) influx was insensitive to L-type Ca(2+) channel blockers and protein kinase C modulators. In Ca(2+)-free medium, after pretreatment with 20 microM econazole, [Ca(2+)](i) rises induced by 1 microM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor) were abolished. Conversely, thapsigargin pretreatment also abolished econazole-induced [Ca(2+)](i) rises. Inhibition of phospholipase C with 2 microM U73122 did not change econazole-induced [Ca(2+)](i) rises. At concentrations between 10 and 80 microM, econazole killed cells in a concentration-dependent manner. The cytotoxic effect of 20 microM econazole was not reversed by prechelating cytosolic Ca(2+) with BAPTA. This shows that in SIRC cells econazole induces [Ca(2+)](i) rises by causing Ca(2+) release from the endoplasmic reticulum and Ca(2+) influx from unknown pathways. Econazole-caused cytotoxicity was independent from a preceding [Ca(2+)](i) rise.


Assuntos
Antifúngicos/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Cálcio/metabolismo , Córnea/efeitos dos fármacos , Econazol/farmacologia , Animais , Bloqueadores dos Canais de Cálcio/metabolismo , Morte Celular , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Córnea/metabolismo , Retículo Endoplasmático/metabolismo , Inibidores Enzimáticos/farmacologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Proteína Quinase C/metabolismo , Coelhos , Tapsigargina/farmacologia
15.
J Chin Med Assoc ; 71(10): 523-7, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18955187

RESUMO

Nodular regenerative hyperplasia (NRH), characterized by diffuse hepatic micronodular transformation in groups without fibrous septa between the nodules, is a rare benign liver lesion that has many synonyms in previous literature. Pathologic evaluation is the mainstay of accurate diagnosis. Treatment is focused on its underlying conditions and complications of portal hypertension. A 39-year-old man visited our hospital due to right upper quadrant pain and a palpable liver mass. Magnetic resonance examination revealed a slightly hyperintense tumor on T2-weighted images, and focal nodular hyperplasia was diagnosed by the radiologists. Atypical radiologic findings could not yield an accurate diagnosis. Surgical intervention was therefore performed. Pathologic examination of the resected liver tumor confirmed the diagnosis of NRH. We conclude that NRH should be included in the differential diagnosis of benign liver tumor.


Assuntos
Neoplasias Hepáticas/patologia , Fígado/patologia , Adulto , Diagnóstico Diferencial , Humanos , Hiperplasia , Neoplasias Hepáticas/diagnóstico , Regeneração Hepática , Masculino
16.
J Formos Med Assoc ; 107(8): 616-26, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18678545

RESUMO

BACKGROUND/PURPOSE: Hepatectomy remains the standard treatment for primary hepatocellular carcinoma (HCC). However, its role in the treatment of multinodular HCC (MNHCC) is unknown. METHODS: The study consisted of 599 patients undergoing curative hepatic resection for HCC between October 1990 and June 2006, in which 112 patients had MNHCC (tumor number > or = 2). The type of MNHCC was classified into: A, nodules involving one or two adjoining segments; B, large tumor with satellite nodules involving three or more segments; C, three or fewer nodules that are scattered in remote segments; and D, more than three separate tumors. Univariate and multivariate analyses were used to identify the prognostic factors related to postoperative survival. During the same period of time, and from our database of 178 patients with pathologically proven MNHCC who were undergoing nonsurgical multidisciplinary therapy, 48 patients with serum albumin level > or = 3.5 g/dL, total bilirubin < 2 mg/dL, tumor number < or = 3, and tumor size < or = 5 cm were compared with 38 patients with the same condition treated with hepatectomy, in which 16 received one-block resection and 22 underwent multiple-site resection. RESULTS: The overall 1-, 3- and 5-year survival rates for patients with single-tumor HCC and MNHCC were 88.0%, 69.2% and 58.4%, and 86.1%, 55.5% and 29.9%, respectively (p < 0.001). Alpha-fetoprotein > 400 ng/mL, total tumor size > 5 cm, largest tumor size > 5 cm, total tumor number > 3, microvascular invasion, non-A type MNHCC and multiple-site resection were poor prognostic factors for MNHCC in the hepatectomy group. Multivariate analysis revealed that only multiple-site hepatic resection was an independent adverse factor related to postoperative survival. In addition, patients who underwent one-block resection had significantly better survival compared with the nonsurgical group (p = 0.0016), but the multiple-site resection subgroup did not. CONCLUSION: The prognosis of MNHCC is poor in comparison with that of single-nodular HCC. Hepatectomy is the treatment of choice if the tumors can be removed by one-block resection and liver function reserve is acceptable.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Prognóstico
17.
J Chin Med Assoc ; 70(8): 352-5, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17698438

RESUMO

Angiosarcoma is a rare soft-tissue neoplasm that occurs most often in the skin and the subcutaneous tissues but very rarely in the gastrointestinal tract. We report a case of primary intestinal angiosarcoma with severe gastrointestinal bleeding. This patient was referred to our institute for shock with tarry-bloody stool and severe anemia. Panendoscopy revealed multiple duodenal polypoid tumors, and initial biopsy specimen showed poorly differentiated adenocarcinoma. The tumors were treated with pancreaticoduodenectomy, but the patient died 2 weeks after the operation as a result of acute respiratory distress syndrome. The pathology was consistent with angiosarcoma of the duodenum. In our experience, this tumor may cause severe bleeding, and surgery should be performed as soon as possible to prevent complications of hypovolemic shock.


Assuntos
Neoplasias Duodenais/complicações , Hemorragia Gastrointestinal/etiologia , Hemangiossarcoma/complicações , Idoso , Neoplasias Duodenais/patologia , Hemangiossarcoma/patologia , Humanos , Masculino
18.
Toxicol Sci ; 100(1): 109-17, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17698513

RESUMO

Thimerosal is a mercury-containing preservative in some vaccines. The effect of thimerosal on human gastric cancer cells is unknown. This study shows that in cultured human gastric cancer cells (SCM1), thimerosal reduced cell viability in a concentration- and time-dependent manner. Thimerosal caused apoptosis as assessed by propidium iodide-stained cells and caspase-3 activation. Although immunoblotting data revealed that thimerosal could activate the phosphorylation of extracellular signal-regulated kinase, c-Jun NH2-terminal protein kinase, and p38 mitogen-activated protein kinase (p38 MAPK), only SB203580 (a p38 MAPK inhibitor) partially prevented cells from apoptosis. Thimerosal also induced [Ca2+](i) increases via Ca2+ influx from the extracellular space. However, pretreatment with (bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetate)/AM, a Ca2+ chelator, to prevent thimerosal-induced [Ca2+](i) increases did not protect cells from death. The results suggest that in SCM1 cells, thimerosal caused Ca2+-independent apoptosis via phosphorylating p38 MAPK resulting in caspase-3 activation.


Assuntos
Apoptose/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Caspase 3/metabolismo , Conservantes Farmacêuticos/toxicidade , Neoplasias Gástricas/patologia , Timerosal/toxicidade , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Antracenos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quelantes/farmacologia , Relação Dose-Resposta a Droga , Ácido Egtázico/análogos & derivados , Ácido Egtázico/farmacologia , Ativação Enzimática , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Flavonoides/farmacologia , Humanos , Imidazóis/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/metabolismo , Fatores de Tempo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
19.
World J Gastroenterol ; 13(26): 3645-8, 2007 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-17659720

RESUMO

Inflammatory myofibroblastic tumor (IMT) of the alimentary tract often occurs in children or young adults, but may occur at any age. Symptoms are nonspecific and depend on the location of the tumor. The most often involved sites are small bowel mesentery especially the distal ileum, mesotransverse colon, or great omentum. Recurrence appears to be more frequent in the extrapulmonary lesion. Herein we demonstrate a 63-year-old male patient with mesenteric IMT, with an early recurrence after his first operation. We should be aware that if the tumor is larger than 8 cm, multinodular, omental, with ill-defined margin, with pathologically atypia, or ganglion-like cells, a close surveillance after primary surgery with image study might be necessary to detect the tumor recurrence early. Tumor recurrence may be asymptomatic, and it may act like a malignant tumor with a poor prognosis.


Assuntos
Mesentério , Recidiva Local de Neoplasia/cirurgia , Neoplasias Peritoneais/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Humanos , Laparotomia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias Peritoneais/patologia , Prognóstico , Reoperação , Neoplasias de Tecidos Moles/patologia
20.
J Chin Med Assoc ; 68(7): 327-32, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16038373

RESUMO

BACKGROUND: Intestinal obstruction is one of the most common surgical emergencies. The aim of this study was to identify important management information from the evaluation of patients with intestinal obstruction who had undergone previous laparotomy for non-malignancy. METHODS: Data from 176 patients with previous laparotomy for non-malignancy, and who were operated on for intestinal obstruction, were collected and analyzed retrospectively. RESULTS: Gastroduodenal operations, appendectomy, and obstetric/gynecologic procedures were the 3 most common previous abdominal surgeries. More than half of all bowel obstructions developed within 10 years after previous laparotomy, and particularly within the first 5 years. Most obstructions were related to adhesion, although their etiologies were diverse. The rate of bowel strangulation was much higher in patients with internal herniation, volvulus, intussusception, closed loop, and diaphragmatic hernia than in patients with simple adhesion, bezoar, tumor, and inflammation (48.3% vs 12.2%). The surgical mortality rate correlated significantly with bowel strangulation: the overall rate was 6.8%, that in patients with strangulation was 18.8%, and that in patients without strangulation was 4.2%. CONCLUSION: The etiologies of intestinal obstruction were not only significantly related to bowel strangulation, but were also an important determinant of therapeutic strategy.


Assuntos
Obstrução Intestinal/etiologia , Laparotomia/efeitos adversos , Adulto , Idoso , Seguimentos , Humanos , Pessoa de Meia-Idade
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