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1.
Proc Natl Acad Sci U S A ; 118(6)2021 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-33495363

RESUMEN

As all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO-based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA-anthracycline for low-/intermediate-risk patients, or ATRA-ATO-anthracycline versus ATRA-anthracycline-cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of -5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI -0.07 to 6.97), confirming noninferiority (P < 0.001). Using the Kaplan-Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups (P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA-chemotherapy (https://www.clinicaltrials.gov/, NCT01987297).


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trióxido de Arsénico/administración & dosificación , Leucemia Promielocítica Aguda/tratamiento farmacológico , Tretinoina/administración & dosificación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trióxido de Arsénico/efectos adversos , Quimioterapia de Consolidación/efectos adversos , Citarabina/administración & dosificación , Citarabina/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Resultado del Tratamiento , Tretinoina/efectos adversos
2.
Acta Haematol ; 145(4): 419-429, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35231903

RESUMEN

INTRODUCTION: The overall outcome of patients with refractory AML (rAML) remains poor. Though allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered as the only curative therapy, it is routinely recommended only for patients after remission with salvage chemotherapy. OBJECTIVE: In this study, we evaluated the impact of salvage chemotherapy or allo-HSCT on the overall outcome in rAML. METHODS: We collected the clinical data of 220 patients from 4 medical centers and performed retrospective analysis of prognosis factors, including salvage chemotherapy, intensity of chemotherapy, and allo-HSCT. RESULTS: A total of 29 patients received allo-HSCT directly without salvage chemotherapy, 26 patients achieved complete remission (CR) or complete remission with incomplete hematological recovery (CRi) after transplantation and 4-year leukemia-free survival (LFS) and overall survival (OS) were 45.0 ± 10.7 and 51.0 ± 10.6%, respectively. Another 191 patients received salvage chemotherapy and 81 (42.2%) achieved CR or CRi. Thirty-four patients among them underwent subsequent allo-HSCT with 4-year LFS and OS of 46.0 ± 8.8 and 46.2 ± 9.0%. The 4-year LFS and OS in 26 patients who failed to obtain CR or CRi but received allo-HSCT with active disease were 32.9 ± 10.0 and 36.9 ± 10.8%, respectively. For patients who received salvage chemotherapy but not allo-HSCT, few of them became long-term survivors. In multivariate analysis, salvage chemotherapy and the intensity of chemotherapy failed to have significant impact on both OS and LFS. Allo-HSCT was the only prognostic factor for improved OS and LFS in multivariate analysis. CONCLUSIONS: These results indicate the benefit of allo-HSCT in patients with rAML and direct allo-HSCT without salvage chemotherapy could be treatment option.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Leucemia Mieloide Aguda/terapia , Inducción de Remisión , Estudios Retrospectivos , Terapia Recuperativa/métodos
3.
Mol Cancer ; 18(1): 54, 2019 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-30925928

RESUMEN

BACKGROUND: MicroRNAs (miRs) are involved in lymphoma progression by regulating tumor cell interaction with microenvironment. MiR155 is overexpressed in diffuse large B-cell lymphoma (DLBCL) and its biological effect on tumor microenvironment needs to be futher investigated. METHODS: MiR155 was detected by quantitative real-time PCR in patients with newly diagnosed DLBCL. The mechanism of action of miR155 on lymphoma progression and tumor microenvironment was examined in vitro in B-lymphoma cell lines and in vivo in a murine xenograft model. RESULTS: Serum miR155 was significantly elevated, correlated with tumor miR155 expression, and indicated poor disease outcome in DLBCL. MiR155 overexpression was associated with decreased peripheral blood CD8+T cells and inhibition of T-cell receptor signaling. Of note, EBV-positive patients showed higher serum miR155 than EBV-negative patients. In co-culture systems of B-lymphoma cells with immune cells, miR155 induced Fas-mediated apoptosis of CD8+T cells, which could be targeted by anti-PD-1 and anti-PD-L1 antibodies. Moreover, miR155 enhanced lymphoma cell PD-L1 expression, recruited CD8+T cells by PD-1/PD-L1 interaction and inhibited CD8+T cell function via dephosphorylating AKT and ERK. MiR155-induced AKT/ERK inactivation was more obvious in CD8+T cells co-cultured with EBV-infected B-lymphoma cells. In vivo in a murine xenograft model established with subcutaneous injection of A20 cells, PD-L1 blockade particularly retarded miR155-overexpressing tumor growth, consistent with maintenance of CD8+T cells and their function. CONCLUSIONS: As a oncogenic biomarker of B-cell lymphoma, serum miR155 was related to lymphoma progression through modulating PD-1/PD-L1-mediated interaction with CD8+T cells of tumor microenvironment, indicating the sensitivity of B-cell lymphoma to PD-L1 blockade. Also CD8+T cells could be a therapeutic mediator of immune checkpoint inhibitors in treating EBV-associated lymphoid malignancies.


Asunto(s)
Antineoplásicos Inmunológicos/farmacología , Antígeno B7-H1/antagonistas & inhibidores , Linfocitos T CD8-positivos/inmunología , Comunicación Celular , Resistencia a Antineoplásicos/genética , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , MicroARNs/genética , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Animales , Apoptosis , Antígeno B7-H1/inmunología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Linfocitos T CD8-positivos/efectos de los fármacos , Estudios de Casos y Controles , Proliferación Celular , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Linfocitos/metabolismo , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Pronóstico , Receptor de Muerte Celular Programada 1/inmunología , Transducción de Señal , Tasa de Supervivencia , Células Tumorales Cultivadas , Microambiente Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto
4.
Exp Hematol Oncol ; 10(1): 10, 2021 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-33549147

RESUMEN

BACKGROUND: Arsenic trioxide [ATO, inorganic arsenite (iAsIII) in solution] plays an important role in the treatment of acute promyelocytic leukemia (APL). However, the long-term adverse effects (AEs) and the retention of arsenic among APL patients are rarely reported. In this study, we focused on arsenic methylation metabolism and its relationship with chronic hepatic toxicity, as we previously reported, among APL patients who had finished the treatment of ATO. METHODS: A total of 112 de novo APL patients who had completed the ATO-containing treatment were enrolled in the study. Arsenic species [iAsIII, inorganic arsenate (iAsV), and their organic metabolites, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)] in patients' plasma, urine, hair and nails were detected by high-performance liquid chromatography combined with inductively coupled plasma mass spectrometry (HPLC-ICP-MS). Eighteen single nucleotide polymorphisms (SNPs) of the arsenic (+ 3 oxidative state) methylation transferase (AS3MT) gene, which was known as the main catalyzer for arsenic methylation, were tested with the polymerase chain reaction method. RESULTS: The study showed the metabolic pattern of arsenic in APL patients undergoing and after the treatment of ATO, in terms of total arsenic (TAs) and four species of arsenic. TAs decreased to normal after 6 months since cessation of ATO. But the arsenic speciation demonstrated significantly higher portion of iAsIII in patient's urine (40.08% vs. 1.94%, P < 0.001), hair (29.25% vs. 13.29%, P = 0.002) and nails (30.21% vs. 13.64%, P = 0.003) than the healthy controls', indicating a decreased capacity of arsenic methylation metabolism after the treatment of ATO. Urine primary methylation index (PMI) was significantly lower in patients with both chronic liver dysfunction (0.14 vs. 0.28, P = 0.047) and hepatic steatosis (0.19 vs. 0.3, P = 0.027), suggesting that insufficient methylation of arsenic might be related to chronic liver disorders. Two SNPs (A9749G and A27215G) of the AS3MT gene were associated with impaired urine secondary methylation index (SMI). CONCLUSIONS: The long-term follow-up of arsenic speciation indicated a decreased arsenic methylation metabolism and a probable relationship with chronic hepatic disorders among APL patients after the cessation of ATO. Urine PMI could be a monitoring index for chronic AEs of ATO, and the SNPs of AS3MT gene should be considered when determining the dosage of ATO.

5.
Medicine (Baltimore) ; 97(33): e11872, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30113483

RESUMEN

The long-term survival benefit of treating unresectable hepatocellular carcinoma (HCC) patients with transarterial chemoembolization (TACE) rather than conservative treatment remains controversial. This retrospective case-control study evaluated the survival of patients with unresectable HCC treated with TACE, relative to that of patients who received best supportive care.From January 2002 to December 2010, 522 of 2386 consecutive patients with unresectable HCC were enrolled. Patients were treated with TACE (n = 347) or best supportive care (non-TACE; n = 175). A survival analysis compared the survival of the 2 groups, as well as only those at Barcelona Clinic Liver Cancer Classification (BCLC)-C and Child-Pugh-B (39 TACE, 61 non-TACE).The median follow-up was 5 months (0.15-106 months).The overall median survival of the TACE group (8.0 months) was significantly longer than that of the non-TACE (2.0 months; P ≤ .01). Of the patients at BCLC-C and Child-Pugh-B, the overall median survivals of the TACE and non-TACE patients were 6.0 and 2.0 months, respectively (P ≤ .01); and the 1, 2, 3, 5, and 8-year overall survival rates were significantly superior in the TACE group (P ≤ .01). For all the patients, the independent predictors of survival were treatment modalities, portal vein tumor thrombosis, alpha-fetoprotein, and BCLC stage. Regarding the TACE patients, contributors to prognosis were portal vein tumor thrombosis, alpha-fetoprotein level, and the number of TACE procedures.TACE for unresectable HCC was associated with longer survival compared with best supportive care, especially for patients at BCLC-C and Child-Pugh-B.


Asunto(s)
Carcinoma Hepatocelular/mortalidad , Quimioembolización Terapéutica/mortalidad , Neoplasias Hepáticas/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/terapia , Estudios de Casos y Controles , Quimioembolización Terapéutica/métodos , Femenino , Humanos , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
6.
Artículo en Inglés | WPRIM | ID: wpr-967101

RESUMEN

Background@#and Purpose Orthostatic hypotension (OH) is common in patients with Parkinson’s disease (PD). Early recognition OH is required with sensitive assessments. The purpose of this study was to determine whether blood pressure (BP) changes during exercise can predict the occurrence of OH in PD. @*Methods@#This prospective cohort study included 80 consecutive patients with PD. All patients agreed to participate in a baseline evaluation and cardiopulmonary exercise test (CPET).According to the initial active standing test (AST), those without OH (PD-nonOH) at baseline had their AST results followed up for 6 months. The main outcome was defined as whether patients without OH at baseline would develop OH after 6 months. Logistic regression analysis was applied to identify the relevant variables. A nomogram was constructed based on clinical features and identified variables. The concordance index (C-index) and area under the receiver operating characteristic curve (AUC) were used to evaluate the accuracy and predictive ability of the nomogram, respectively. @*Results@#CPET results indicated that peak load, peak heart rate, heart rate recovery at 1 min, and systolic BP change (ΔSBP) were lower in those with OH than in the PD-nonOH group (p<0.05) at baseline. Logistic regression analysis indicated that peak load and ΔSBP during CPET had significant effects on OH (p<0.05). Age, sex, peak load, and ΔSBP were used to construct the nomogram model (C-index=0.761). The prediction model had an AUC of 0.782 (95% confidence interval=0.649–0.889) and a specificity and sensitivity of 70.0% and 81.8%, respectively. @*Conclusions@#This study has identified predictive factors for OH development in patients with PD. CPET could be used as a complementary examination to identify patients at a high risk of OH.

7.
J Exp Clin Cancer Res ; 36(1): 82, 2017 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-28637496

RESUMEN

BACKGROUND: MicroRNAs (miRs) are involved in tumor progression by regulating tumor cells and tumor microenvironment. MiR21 is overexpressed in diffuse large B-cell lymphoma (DLBCL) and its biological impact on tumor microenvironment remains unclear. METHODS: MiR21 was assessed by quantitative RT-PCR in patients with newly diagnosed DLBCL. The mechanism of action of miR21 on lymphoma progression and tumor angiogenesis was examined in vitro in B-lymphoma cell lines and in vivo in a murine xenograft model. RESULTS: Serum miR21 was significantly elevated in patients and associated with advanced disease stage, International Prognostic Index indicating intermediate-high and high-risk, and increased tumor angiogenesis. When co-cultured with immune cells and endothelial cells, miR21-overexpressing B-lymphoma cells were resistant to chemotherapeutic agents, but sensitive to Bcl-2 inhibitor ABT-199, irrespective of Bcl-2 expression on lymphoma cells. In both co-culture systems of Bcl-2positive and Bcl-2negative B-lymphoma cells, miR21 induced inducible co-stimulator (ICOS) expression on regulatory T (Treg) cells. Through crosstalking with Treg cells by ICOS ligand (ICOSL), endothelial cells were activated, resulting in stimulation of Bcl-2 expression and vessel formation. ABT-199 directly targeted Bcl-2 on endothelial cells, induced endothelial cell apoptosis and inhibited tumor angiogenesis. In a murine xenograft model established with subcutaneous injection of B-lymphoma cells, ABT-199 particularly retarded the growth of miR21-overexpressing tumors, consistent with the induction of endothelial cell apoptosis and inhibition of tumor angiogenesis. CONCLUSIONS: As a serum oncogenic biomarker of B-cell lymphoma, miR21 indicated B-lymphoma cell sensitivity to ABT-199 via ICOS/ICOSL-mediated interaction of Treg cells with endothelial cells.


Asunto(s)
Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Endotelio Vascular/inmunología , Ligando Coestimulador de Linfocitos T Inducibles/metabolismo , Proteína Coestimuladora de Linfocitos T Inducibles/metabolismo , Linfoma de Células B Grandes Difuso/inmunología , MicroARNs/genética , Sulfonamidas/farmacología , Linfocitos T Reguladores/inmunología , Animales , Apoptosis , Proliferación Celular , Células Cultivadas , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Femenino , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/sangre , Persona de Mediana Edad , Pronóstico , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
8.
Artículo en Inglés | WPRIM | ID: wpr-827481

RESUMEN

OBJECTIVE@#To investigate the effects of Composition of Ophiopogon polysaccharide, Notoginseng total saponins and Rhizoma Coptidis alkaloids (CONR) on myocardial apoptosis of diabetic atherosclerosis (DA) rabbits METHODS: Sixty male New Zealand white rabbits were randomly divided into 6 groups [control group, model group, CONR high-dose group (450 mg/kg), CONR medium-dose group (150 mg/kg), CONR low-dose group (50 mg/kg), and simvastatin group] by using a completely random method, 10 in each group. DA model was established by intravenously injected alloxan combined with high-fat diet and abdominal aortic balloon injury. After mediation for 10 weeks, fasting blood glucose (FBG), glycosylated hemoglobin (GHB), glycosylated serum protein (GSP), fructoseamine (FRA), aldose reductase (AR), advanced glycation end products (AGEs) in serum were measured by enzyme linked immunosorbent assay (ELISA) method; the expression of receptor of AGEs (RAGE) in myocardial tissue were observed by immunohistochemical method; and p-Jun N-terminal kinase (p-JNK), caspase-3, B-cell lymphoma-2 (bcl-2) protein expression in myocardial tissue were measured by Western blotting. The myocardial apoptosis was detected by TdT-mediated dUTPnick-end labeling (TUNEL) method, and apoptosis index (AI) was calculated.@*RESULTS@#Compared with the control group, serum FBG, GHB, GSP, FRA, AR, AGEs and the expression of myocardium RAGE, p-JNK, caspase-3 proteins, as well as apoptosis index (AI) were significantly increased and bcl-2 protein was significantly decreased in the model group (P<0.01). Compared with the model group, the levels of serum FBG, GHB, GSP, FRA and AR showed a significant decline in CONR high- and medium-dose groups (P<0.01). FBG and GHB showed a significant decline in CONR low-dose group (P<0.01). Compared with the model group, the expression of serum AGEs and myocardium RAGE, p-JNK and caspase-3 protein as well as AI were significantly decreased and bcl-2 protein was significantly up-regulated in all treatment groups (P<0.01); high-dose CONR had the most significant effect on abovementioned indices compared with other treatment groups (P<0.01). Middle-dose CONR had better effect on serum AGEs compared with the low-dose group (P<0.01); middle-dose CONR and simvastatin groups had better effect on the expression of caspase-3, bcl-2 protein, myocardium apoptosis compared with the CONR low-dose group (P<0.01).@*CONCLUSION@#CONR may effectively inhibit myocardial apoptosis on DA rabbits by intervening AGEs-RAGE and JNK, caspase-3, and bcl-2 protein expressions.


Asunto(s)
Animales , Masculino , Conejos , Alcaloides , Farmacología , Apoptosis , Aterosclerosis , Diabetes Mellitus Experimental , Angiopatías Diabéticas , Quimioterapia , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Farmacología , Corazón , Ophiopogon , Química , Panax notoginseng , Química , Polisacáridos , Farmacología , Saponinas , Farmacología
9.
Artículo en Inglés | WPRIM | ID: wpr-773631

RESUMEN

Ginsenoside Rh2 (Rh2) is one of the major bioactive ginsenosides in Panax ginseng. However, the oral bioavailability of Rh2 is low, with P-glycoprotein (P-gp) and CYP3A4 being reported to be the main factors. The purpose of the present study was to determine the enhancing effect of piperine on the oral bioavailability as well as bioactivity of Rh2. The inhibitory effect of piperine on P-gp and CYP3A4 was determined using a Caco-2 monolayer model and a recombinant CYP3A4 metabolic system, respectively. The pharmacokinetics of oral Rh2 (10 mg·kg) administered alone or in combination with piperine (10 and 20 mg·kg) was performed in rats. The immune boosting effect of Rh2 was assessed in rats by measuring IL-12 level after treated by Rh2 alone or co-administered with piperine. The results indicated that piperine significantly increased the permeability of Rh2 and inhibited the metabolism of Rh2. The pharmacokinetic study results showed that the AUC of Rh2 was significantly increased in combination with piperine at high dose (20 mg·kg) when compared to the control group, with relative bioavailability of 196.8%. The increase of Rh2 exposure led to increased serum levels of IL-12. In conclusion, piperine may be used as a bioenhancer to improve pharmacological effect of Rh2 when given orally.


Asunto(s)
Animales , Humanos , Ratas , Administración Oral , Alcaloides , Benzodioxoles , Disponibilidad Biológica , Células CACO-2 , Citocromo P-450 CYP3A , Metabolismo , Medicamentos Herbarios Chinos , Ginsenósidos , Farmacocinética , Interleucina-2 , Metabolismo , Panax , Química , Piperidinas , Alcamidas Poliinsaturadas , Ratas Sprague-Dawley
10.
Artículo en Inglés | WPRIM | ID: wpr-812421

RESUMEN

Ginsenoside Rh2 (Rh2) is one of the major bioactive ginsenosides in Panax ginseng. However, the oral bioavailability of Rh2 is low, with P-glycoprotein (P-gp) and CYP3A4 being reported to be the main factors. The purpose of the present study was to determine the enhancing effect of piperine on the oral bioavailability as well as bioactivity of Rh2. The inhibitory effect of piperine on P-gp and CYP3A4 was determined using a Caco-2 monolayer model and a recombinant CYP3A4 metabolic system, respectively. The pharmacokinetics of oral Rh2 (10 mg·kg) administered alone or in combination with piperine (10 and 20 mg·kg) was performed in rats. The immune boosting effect of Rh2 was assessed in rats by measuring IL-12 level after treated by Rh2 alone or co-administered with piperine. The results indicated that piperine significantly increased the permeability of Rh2 and inhibited the metabolism of Rh2. The pharmacokinetic study results showed that the AUC of Rh2 was significantly increased in combination with piperine at high dose (20 mg·kg) when compared to the control group, with relative bioavailability of 196.8%. The increase of Rh2 exposure led to increased serum levels of IL-12. In conclusion, piperine may be used as a bioenhancer to improve pharmacological effect of Rh2 when given orally.


Asunto(s)
Animales , Humanos , Ratas , Administración Oral , Alcaloides , Benzodioxoles , Disponibilidad Biológica , Células CACO-2 , Citocromo P-450 CYP3A , Metabolismo , Medicamentos Herbarios Chinos , Ginsenósidos , Farmacocinética , Interleucina-2 , Metabolismo , Panax , Química , Piperidinas , Alcamidas Poliinsaturadas , Ratas Sprague-Dawley
11.
Zhonghua Xue Ye Xue Za Zhi ; 29(4): 252-7, 2008 Apr.
Artículo en Zh | MEDLINE | ID: mdl-18843980

RESUMEN

OBJECTIVE: To reassess the prognostic factors of diffuse large B cell lymphoma (DLBCL) treated with R-CHOP therapy. METHODS: One hundred and twenty five patients were enrolled in this study from Feb. 2000 to Sep. 2006. They received 6 courses of R-CHOP regimen consisting of rituximab 375 mg/ m2, intravenously, d 1; cyclophosphamide 750 mg/m2, bolus intravenously, d 2; doxorubicin 50 mg/m2, bolus intravenously, d 2; vincristine 1.4 mg/m2, bolus intravenously, d 2 and prednisone 60 mg, orally, d 2 - 6. All the patients were evaluated and followed up after the treatment. RESULTS: Eighty six patients (68.8%) achieved complete response (CR), 16 (12.8%) partial response (PR), 11 (12.8%) stable disease (SD) and 12 (9.6%) progressive disease (PD). In univariate analysis, performance status (PS), clinical stage, LDH level, extranodal disease, international prognostic index (IPI) and bulky disease were statistically significantly correlated with the induction of CR; however, only PS, clinical stage and bulky disease remained significant in multi-variate analysis (P = 0.0098, 0.000 and 0.004, respectively). Twenty four month for time to treatment failure (TTF) rate, overall survival (OS) rate, and disease free survival (DFS) rate was (59.7 +/- 5. 3)%, (67.1 +/- 5.6)% and (77.6 +/- 5.8)%, respectively. In univariate analysis, LDH, clinical stage and PS exerted significant effect on TTF and OS rate, but not on DFS rate; age and extranodal disease was not related with TTF, OS and DFS rate. In multi-variate analysis, achieved CR was the only prognostic factor for TTF (P =0.001) and bulky disease had influence on DFS rate. LDH level, PS, and achieved CR was correlated with the OS rate in multi-variate setting (P = 0.002, 0.009 and 0.001 respectively). CONCLUSION: IPI score has its limitation in predicting the prognosis in the R-CHOP era in DLBCL. Other two relevant prognostic factors are bulky disease and achieved CR after 6 courses of treatment.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Adolescente , Adulto , Anciano , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Pronóstico , Resultado del Tratamiento , Vincristina/uso terapéutico , Adulto Joven
12.
Chinese Medical Journal ; (24): 3942-3946, 2012.
Artículo en Inglés | WPRIM | ID: wpr-339922

RESUMEN

<p><b>BACKGROUND</b>Topping-off surgery is a newly-developed surgical technique which combines rigid fusion with an interspinous process device in the adjacent segment to prevent adjacent segment degeneration. There are few reports on Topping-off surgery and its rationality and indications remains highly controversial. Our study aims to investigate the short-term and mid-term clinical results of Topping-off surgery in preventing adjacent segment degeneration when mild or moderate adjacent segment degeneration existed before surgery.</p><p><b>METHODS</b>The 25 cases that underwent L5-S1 posterior lumbar interbody fusion (PLIF) + L4-L5 interspinous process surgeries between April 2008 and March 2010 formed Topping-off group. The 42 cases undergoing L5-S1 PLIF surgery formed PLIF group. Both groups matched in gender, age, body mass index and Pfirrmann grading (4 to 6). The patients were evaluated with visual analogue scale (VAS) and Japanese orthopaedic association (JOA) scores before surgery and in the last follow-up. Modic changes of endplates were recorded.</p><p><b>RESULTS</b>The follow-up averaged 24.8 and 23.7 months. No symptomatic or radiological adjacent segment degeneration was observed. There was no significant difference in intraoperative blood loss or postoperative drainage. VAS and lumbar JOA scores improved significantly in both groups (t = 12.1 and 13.5, P < 0.05). Neither anterior nor posterior disc height was significantly changed. Segmental lordosis of L4-L5 and total lordosis were all increased significantly (Topping-off group: t = -2.30 and -2.24,P < 0.05; PLIF group: t = -2.76 and -1.83, P < 0.01). In the hyperextension and hyperflexion view, Topping-off group's range of motion (ROM) and olisthesis in the L4-L5 segment did not significantly change in flexion, but decreased in extension. In PLIF group, ROM (t = -7.82 and -4.90, P < 0.01) and olisthesis (t = -15.67 and -18.58, P < 0.01) both significantly increased in extension and flexion.</p><p><b>CONCLUSIONS</b>Compared with single segment PLIF surgery, Topping-off surgery can achieve similar symptomatic improvement in cases with pre-existing mild or moderate adjacent segment degeneration, restrict the adjacent segment's ROM in extension and prevent excessive olisthesis of adjacent segment in both extension and flexion.</p>


Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Degeneración del Disco Intervertebral , Diagnóstico por Imagen , Cirugía General , Vértebras Lumbares , Diagnóstico por Imagen , Cirugía General , Radiografía , Estudios Retrospectivos , Enfermedades de la Columna Vertebral , Diagnóstico por Imagen , Cirugía General , Estenosis Espinal , Diagnóstico por Imagen , Cirugía General
13.
Chinese Journal of Surgery ; (12): 115-119, 2012.
Artículo en Zh | WPRIM | ID: wpr-257544

RESUMEN

<p><b>OBJECTIVE</b>To investigate the early-middle stage clinical results of Topping-off surgery in preventing adjacent segment degeneration when mild or moderate adjacent segment degeneration exists before surgery.</p><p><b>METHODS</b>All the cases that received L(5)-S(1) posterior lumbar interbody fusion (PLIF)+L(4)-L(5) interspinous process (ISP) surgeries between April 2008 and March 2010 (Topping-off group) were analyzed retrospectively. The cases received L(5)-S(1) PLIF surgery and whose intervertebral disc degeneration using modified Pfirrmann's grading system were grade 4 - 6 were analyzed retrospectively at the same time (PLIF group). Both groups matched in gender, age, body mass index and Pfirrmann's grading of disc. All the patients were evaluated with visual analogue scale (VAS) and Japanese orthopaedic association (JOA) scores before the surgery and in the last follow-up. The X-ray films before and after surgery were measured.</p><p><b>RESULTS</b>There were 25 patients in Topping-off group and 42 patients in PLIF group were included in the final analysis. The follow-up averaged 24.8 and 23.7 months. No symptomatic or radiological adjacent segment degeneration was observed. The average surgery time was (120 ± 24) min and (106 ± 21) min. There was no significant difference in the blood loss during surgery or post-operation drainage (P > 0.05). VAS and lumbar JOA score improved in both groups (P < 0.01). In the lateral view of lumbar spine, neither of anterior or posterior disk height was significantly changed (P > 0.05), segmental lordosis of L(4)-L(5), total lordosis were all increased (Topping-off group: t = -2.30 and -2.24, P < 0.05; PLIF group: t = -2.76 and -1.83, P < 0.05). In the hyperextension and hyperflexion view, Topping-off group's range of motion (ROM) and olisthesis in the L(4-5) segment did not significantly change in flexion (P > 0.05), but decreased in extension (t = 5.83 and 4.92, P < 0.01). In PLIF group, the ROM (t = -7.82 and -4.90, P < 0.01) and olisthesis (t = -15.67 and -18.58, P < 0.01) both significantly increased in extension and flection.</p><p><b>CONCLUSIONS</b>Compared with single segmental PLIF surgery, Topping-off surgery can achieve similar symptomatic improvement in cases with pre-existing mild or moderate adjacent segment degeneration, restrict the adjacent segment's range of motion in extension and prevent excessive olisthesis of adjacent segment in both extension and flexion. Topping-off surgery has a potential effect of preventing adjacent segmental degeneration.</p>


Asunto(s)
Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Estudios de Seguimiento , Degeneración del Disco Intervertebral , Cirugía General , Vértebras Lumbares , Cirugía General , Estudios Retrospectivos , Fusión Vertebral , Métodos
14.
Chinese Journal of Surgery ; (12): 26-30, 2010.
Artículo en Zh | WPRIM | ID: wpr-254835

RESUMEN

<p><b>OBJECTIVE</b>To discuss the surgical treatment of multilevel lumbar degenerative spondylolisthesis.</p><p><b>METHODS</b>From March 2005 to September 2008, 25 cases of multilevel lumbar degenerative spondylolisthesis were treated with total laminectomy, reduction of spondylolisthesis and 360 degrees circumferential fusion through interbody (PLIF), transverse process (PLF) and pedicle screw fixation. All cases were followed up for 0.5 - 4 years. The Lenke grading system was used to assess the spinal fusion and Henderson grading system was used to assess the clinical outcomes.</p><p><b>RESULTS</b>Complete reduction of spondylolisthesis was achieved in all cases. The bone fusion was grade A in 23 cases, grade B in 2 cases. The clinical outcome was excellent in 16 cases, good in 6 cases and poor in 3 cases.</p><p><b>CONCLUSIONS</b>The pathogenesis of lumbar degenerative multilevel spondylolisthesis is different from that of single-level spondylolisthesis. Complete decompression, reduction of spondylolisthesis sufficient fusion and reliable pedicle screw fixation can provide successful interbody fusion and satisfactory clinical results.It's crucial to reduce multilevel spondylolisthesis by proper techniques based on different types of listhesis.</p>


Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tornillos Óseos , Descompresión Quirúrgica , Estudios de Seguimiento , Vértebras Lumbares , Estudios Retrospectivos , Fusión Vertebral , Métodos , Espondilolistesis , Cirugía General , Resultado del Tratamiento
15.
Chinese Journal of Surgery ; (12): 481-483, 2008.
Artículo en Zh | WPRIM | ID: wpr-237782

RESUMEN

<p><b>OBJECTIVE</b>To analyze the possible reasons for proximal junctional lordosis (PJL) after short-segment posterior pedicle screw fixation in lumbar spine and discuss its proper management.</p><p><b>METHODS</b>From December 2001 to August 2005, 345 patients were treated by short-segment pedicle screw fixation and these patients were reviewed. Clinical outcome was evaluated according to Oswestry Disability Index (ODI). Proximal junctional lordosis was assessed evaluated on radiographs, by measuring lumbar lordosis angle, segmental angle at proximal level and lumbar-sacral angle. Risk factors of proximal junctional lordosis were analyzed.</p><p><b>RESULTS</b>All patients were followed-up for 2 to 6 years (average 3.8 years). ODI after lumbar surgery was 9.7-46.2 ( average 19.6 +/- 10.7). PJL was noted in 78 patients (22.6%), 37 (10.7%) of whom were symptomatic and 21 (6.1%) received revision surgery. PJL was more commonly occurred in patients over 60 years old, with reduced lumbar lordosis or vertical sacrum. The number of fusion-segment was not correlated to the occurrence of PJL.</p><p><b>CONCLUSIONS</b>Short-segment posterior pedicle screw fixation can not improve lumbar sagittal alignment. Age over of 60 years, reduced lumbar lordosis and vertical sacrum are possible risk factors of PJL sacrum.</p>


Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tornillos Óseos , Estudios de Seguimiento , Fijadores Internos , Lordosis , Vértebras Lumbares , Cirugía General , Estudios Retrospectivos , Fusión Vertebral , Resultado del Tratamiento
16.
Chinese Journal of Surgery ; (12): 484-487, 2008.
Artículo en Zh | WPRIM | ID: wpr-237781

RESUMEN

<p><b>OBJECTIVE</b>To evaluate the clinical outcome of posterior corrective operation for degenerative scoliosis and analyze the possible reasons for its late complications and their proper management.</p><p><b>METHODS</b>Thirty-five patients with degenerative scoliosis, who were treated by posterior pedicle screw fixation and interbody fusion with cage implantation from September 1997 to September 2002, were reviewed. Their clinical outcomes were determined according to Oswestry Disability Index (ODI). The fusion area and its adjacent segments were evaluated through radiographic measurements of coronal Cobb angle, lumbar lordosis and coronal balance of the spine. The association of late complications, spinal alignment, and range of fusion was analyzed.</p><p><b>RESULTS</b>At final follow-up, ODI was 17.8 - 62.2 (average 34.7). Late complications occurred in 13 patients, accounting for 37.1%. Among the 13 cases, 10 were symptomatic and 6 received revision surgery. The late complications were proximal junctional scoliosis in 4 patients, proximal junctional kyphosis in 4 patients, proximal compressed vertebral fracture in 1 patient, pseudarthrosis in 1 patient, pedicle screw loosening in 1 patient, and distal segment degeneration in 1 patient. Junctional kyphosis had no obvious relationship with abnormality of spinal alignment. Adjacent segment degeneration occurred more commonly in the cases with the proximal ultimate vertebra below L1 (9/ 18) than above T12 (4/17).</p><p><b>CONCLUSIONS</b>The rate of late complications is relatively high after posterior corrective operation for degenerative scoliosis. Spinal alignment should be evaluated carefully in preoperative planning. The proximal ultimate vertebra should be extended to the level above T12 to avoid late complications.</p>


Asunto(s)
Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tornillos Óseos , Estudios de Seguimiento , Complicaciones Posoperatorias , Estudios Retrospectivos , Escoliosis , Cirugía General , Fusión Vertebral , Métodos , Resultado del Tratamiento
17.
Artículo en Zh | WPRIM | ID: wpr-331956

RESUMEN

<p><b>OBJECTIVE</b>To investigate the characteristic of colonic transmission in functional constipation (FC) and the effect of traditional Chinese medicine (TCM) Sini Powder (SP) on it.</p><p><b>METHODS</b>The colonic transmission time (CTT) of 36 patients with FC (the FC group) and 22 healthy subjects (control group) was measured through colonic transmission test, and CTT of entire colon and that of various subsections was calculated with Hinton method and Arhan method respectively. After then, the FC group was treated with SP for 7 days, and CTT was detected again after treatment.</p><p><b>RESULTS</b>Before treatment, body mass index (BMI) was higher, CTT of entire colon, left half colonic section, and sigmoid-rectal section were longer in the FC group than those in the control group (P < 0.05), no statistical difference in CTT of right half colon was found between the two groups (P > 0.05). After FC patients being treated with SP, their CTT of whole colon, left half colonic section and sigmoid-rectal section were significantly shortened (P < 0.05).</p><p><b>CONCLUSION</b>FC patients were characterized by increased BMI and CTT prolonged and unevenly distributed in subsections, especially in the left half colon, sigmoid and rectum; SP could shorten the CTT in FC patients.</p>


Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Masa Corporal , Colon , Colon Sigmoide , Estreñimiento , Quimioterapia , Medicamentos Herbarios Chinos , Usos Terapéuticos , Tránsito Gastrointestinal , Fitoterapia , Factores de Tiempo , Resultado del Tratamiento
18.
Chinese Journal of Surgery ; (12): 33-36, 2003.
Artículo en Zh | WPRIM | ID: wpr-257737

RESUMEN

<p><b>OBJECTIVES</b>To investigate the techniques of posterior lumbar interbody fusion and pedicle screws in the treatment of degenerative scoliosis and evaluate their clinical significance.</p><p><b>METHODS</b>Twenty five patients with degenerative scoliosis were treated operatively during 1997 - 2002. Among the 25 patients, 13 patients were treated with Brantigan I/F carbon cages in 28 intervertebral spaces, 7 patients were treated with Prospace cages in 15 spaces, 1 patient was treated with CONTACT cages in 2 spaces. The correcting effects, complications and follow-up results were analyzed retrospectively.</p><p><b>RESULTS</b>The average correction rate of scoliosis was 59% and the rate of pain relief was 88%. There was a case of pseudoarthritis and a case of embolism. During follow-up, correction rate and height of disc spaces were not lost nor shift of interbody cages.</p><p><b>CONCLUSION</b>Posterior pedicle screws combined with interbody fusion is a safe and effective treatment for degenerative scoliosis.</p>


Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tornillos Óseos , Fijadores Internos , Estudios Retrospectivos , Escoliosis , Cirugía General , Fusión Vertebral
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