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Extreme drought events are becoming frequent globally, resulting in widespread plant mortality and forest dieback. Although savanna vegetation cover ~20% of the earth's land area, their responses to extreme drought have been less studied than that of forests. Herein, we quantified branch dieback, individual mortality and the associated physiological responses of four evergreen shrubs (Tarenna depauperate Hutch., Maytenus esquirolii (H. Lév.) C.Y. Cheng, Murraya exotica L., Jasminum nudiflorum Lindl.) in a savanna ecosystem in Southwest China to an incidence of extreme drought during 2019 and 2020. We found that 80-100% of the individuals of these species exhibited branch dieback, whereas individual mortality was only found in T. depauperate (4.5%). All species showed high resistance to stem embolism (P50, water potential at 50% loss of hydraulic conductivity ranged from -5.62 to -8.6 MPa), whereas the stem minimum water potentials reached -7.6 to ca -10.0 MPa during the drought. The low water potential caused high native embolism levels (percentage loss of hydraulic conductivity (PLC) 23-65%) in terminal branches, and the remaining stems maintained 15-35% PLC at the end of the drought. Large within-individual variations in stem vulnerability to embolism were detected, and shedding of vulnerable branches could be a mechanism for shrubs to reduce water and carbon consumption. Overall, the content of total nonstructural carbohydrates (NSC) and their components in the stem were generally comparable to or higher than those in the rainy season in three of the four species. Because the leaves were turgor-less for most time during the drought, high NSC levels during the drought could be due to recycling of NSC from dead branches or translocation from roots. Our results suggest high tolerance of savanna shrub species to extreme drought, which could be facilitated by high embolism resistance in some stems and shedding of vulnerable branches to maintain individual water and carbon balance.
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Sequías , Embolia , Carbohidratos , Carbono , Ecosistema , Pradera , Incidencia , Hojas de la Planta/fisiología , Árboles/fisiología , Agua , Xilema/fisiologíaRESUMEN
Hydraulic failure caused by severe drought contributes to aboveground dieback and whole-plant death. The extent to which dieback or whole-plant death can be predicted by plant hydraulic traits has rarely been tested among species with different leaf habits and/or growth forms. We investigated 19 hydraulic traits in 40 woody species in a tropical savanna and their potential correlations with drought response during an extreme drought event during the El Niño-Southern Oscillation in 2015. Plant hydraulic trait variation was partitioned substantially by leaf habit but not growth form along a trade-off axis between traits that support drought tolerance versus avoidance. Semi-deciduous species and shrubs had the highest branch dieback and top-kill (complete aboveground death) among the leaf habits or growth forms. Dieback and top-kill were well explained by combining hydraulic traits with leaf habit and growth form, suggesting integrating life history traits with hydraulic traits will yield better predictions.
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Sequías , Agua , Hábitos , Hojas de la Planta , ÁrbolesRESUMEN
OBJECTIVE: Data regarding direct comparison of contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) and Computed Tomography/Magnetic Resonance Imaging (CT/MR) LI-RADS in diagnosis of non-hepatocelluar carcinoma (non-HCC) malignancies remain limited. Our study aimed to compare the diagnostic performance of the CEUS LI-RADS version 2017 and CT/MRI LI-RADS v2018 for diagnosing non-HCC malignancies in patients with risks for HCC. MATERIALS AND METHODS: In this retrospective study, 94 liver nodules pathologically-confirmed as non-HCC malignancies in 92 patients at risks for HCC from January 2009 to December 2018 were enrolled. The imaging features and the LI-RADS categories on corresponding CEUS and CT/MRI within 1 month were retrospectively analyzed according to the ACR CEUS LI-RADS v2017 and ACR CT/MRI LI-RADS v2018 by two radiologists in consensus for each algorithm. The sensitivity of LR-M category, inter-reader agreement and inter-modality agreement was compared between these two standardized algorithms. RESULTS: Ninety-four nodules in 92 patients (mean age, 54 years ± 10 [standard deviation] with 65 men [54 years ± 11] and 27 women [54 years ± 8]), including 56 intrahepatic cholangiocarcinomas, 34 combined hepatocellular cholangiocarcinomas, two adenosquamous carcinomas of the liver, one primary hepatic neuroendocrine carcinoma and one hepatic undifferentiated sarcoma were included. On CEUS, numbers of lesions classified as LR-3, LR-4, LR-5 and LR-M were 0, 1, 10 and 83, and on CT/MRI, the corresponding numbers were 3, 0, 14 and 77. There was no significant difference in the sensitivity of LR-M between these two standardized algorithms (88.3% of CEUS vs 81.9% of CT/MRI, p = 0.210). Seventy-seven lesions (81.9%) were classified as the same LI-RADS categories by both standardized algorithms (five for LR-5 and 72 for LR-M, kappa value = 0.307). In the subgroup analysis for ICC and CHC, no significant differences were found in the sensitivity of LR-M category between these two standardized algorithms (for ICC, 94.6% of CEUS vs 89.3% of CT/MRI, p = 0.375; for CHC, 76.5% of CEUS vs 70.6% of CT/MRI, p = 0. 649). CONCLUSION: CEUS LI-RADS v2017 and CT/MRI LI-RADS v2018 showed similar value for diagnosing non-HCC primary hepatic malignancies in patients with risks.
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OBJECTIVES: To develop a radiomics algorithm, improving the performance of detecting recurrence, based on posttreatment CT images within one month and at suspicious time during follow-up. MATERIALS AND METHODS: A total of 114 patients with 228 images were randomly split (7:3) into training and validation cohort. Radiomics algorithm was trained using machine learning, based on difference-in-difference (DD) features extracted from tumor and liver regions of interest on posttreatment CTs within one month after resection or ablation and when suspected recurrent lesion was observed but cannot be confirmed as HCC during follow-up. The performance was evaluated by area under the receiver operating characteristic curve (AUC) and was compared among radiomics algorithm, change of alpha-fetoprotein (AFP) and combined model of both. Five-folded cross validation (CV) was used to present the training error. RESULTS: A radiomics algorithm was established by 34 DD features selected by random forest and multivariable logistic models and showed a better AUC than that of change of AFP (0.89 [95% CI: 0.78, 1.00] vs 0.63 [95% CI: 0.42, 0.84], Pâ¯=â¯.04) and similar with the combined model in detecting recurrence in the validation set. Five-folded CV error in the validation cohort was 21% for the algorithm and 26% for the changes of AFP. CONCLUSIONS: The algorithm integrated radiomic features of posttreatment CT showed superior performance to that of conventional AFP and may act as a potential marker in the early detecting recurrence of HCC.
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PURPOSE: To test the technical reproducibility of acquisition and scanners of CT image-based radiomics model for early recurrent hepatocellular carcinoma (HCC). METHODS: We included primary HCC patient undergone curative therapies, using early recurrence as endpoint. Four datasets were constructed: 109 images from hospital #1 for training (set 1: 1-mm image slice thickness), 47 images from hospital #1 for internal validation (sets 2 and 3: 1-mm and 10-mm image slice thicknesses, respectively), and 47 images from hospital #2 for external validation (set 4: vastly different from training dataset). A radiomics model was constructed. Radiomics technical reproducibility was measured by overfitting and calibration deviation in external validation dataset. The influence of slice thickness on reproducibility was evaluated in two internal validation datasets. RESULTS: Compared with set 1, the model in set 2 indicated favorable prediction efficiency (the area under the curve 0.79 vs. 0.80, P = 0.47) and good calibration (unreliability statistic U: P = 0.33). However, in set 4, significant overfitting (0.63 vs. 0.80, P < 0.01) and calibration deviation (U: P < 0.01) were observed. Similar poor performance was also observed in set 3 (0.56 vs. 0.80, P = 0.02; U: P < 0.01). CONCLUSIONS: CT-based radiomics has poor reproducibility between centers. Image heterogeneity, such as slice thickness, can be a significant influencing factor.
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Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Recurrencia Local de Neoplasia/diagnóstico por imagen , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Tomografía Computarizada por Rayos X/instrumentación , Adulto , Anciano , Algoritmos , Biomarcadores de Tumor/análisis , Carcinoma Hepatocelular/cirugía , Medios de Contraste , Femenino , Hepatectomía , Humanos , Yohexol/análogos & derivados , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Factores de RiesgoRESUMEN
OBJECTIVES: We used the status of microvascular invasion (MVI) at primary resection to help treatment selection for hepatitis B virus-positive (HBV+) recurrent hepatocellular carcinoma (rHCC) patients in Barcelona Clinic Liver Cancer (BCLC) stage B-C. METHODS: From 2009 to 2017, we enrolled 221 consecutive HBV+ rHCC patients at BCLC stage B-C who underwent re-resection (RR), radiofrequency ablation (RFA), or transarterial chemoembolization (TACE). Post recurrence survival (PRS) and overall survival (OS) were compared between RR/RFA and TACE according to MVI status. A one-to-one propensity score matching analysis was performed. RESULTS: For MVI(-) patients, the median PRS was 62.3 months for the RR/RFA group and 21.1 months for the TACE group (p = 0.039). The corresponding OS was 71.4 months and 26.6 months, respectively (p = 0.010). For MVI(+) patients, the median PRS in the RR/RFA group and TACE group was 14.7 months and 10.1 months (p = 0.115). The corresponding OS was 23.4 months and 16.4 months, respectively (p = 0.067). After matching, the dominance of RR/RFA over TACE remained in MVI(-) patients for both PRS (62.3 months vs 15.3 months, p = 0.019) and OS (98.1 months vs 33.4 months, p = 0.046). No significant difference was found in MVI(+) patients for either PRS (14.7 months vs 11.8 months, p = 0.593) or OS (23.4 months vs 28.1 months, p = 0.662). CONCLUSIONS: MVI status definitely helps select treatment options in HBV+ rHCC patients. For MVI(-) patients, RR/RFA provided better survival than TACE while for MVI(+) patients, TACE shared similar survival outcomes. KEY POINTS: ⢠This study aimed at the determination of the optimal treatment options (ablation /resection vs TACE) in case of recurrent HBV-related HCC. ⢠It showed that MVI status, established at primary resection of HCC, was a powerful marker for selecting the best treatment option in these patients. ⢠In MVI(-) patients, RR/RFA achieved a better survival than TACE. In MVI(+) patients, TACE shared similar survival.
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Carcinoma Hepatocelular/terapia , Ablación por Catéter , Quimioembolización Terapéutica , Hepatectomía , Hepatitis B Crónica/complicaciones , Neoplasias Hepáticas/terapia , Microvasos/patología , Recurrencia Local de Neoplasia/terapia , Adulto , Anciano , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/patología , Terapia Combinada , Femenino , Virus de la Hepatitis B , Humanos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia/patología , Selección de Paciente , Puntaje de Propensión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: In patients with a large, unresectable hepatocellular carcinoma (HCC), the primary recommendation is for transarterial chemoembolization (TACE) but used alone TACE is not typically curative. Combinations of TACE followed in a delayed fashion by single-applicator thermal ablation have also been suboptimal. As an alternative, we investigated the combination of TACE followed within 1-3 days by multi-antenna microwave ablation (MWA) in patients with a large HCC, to determine the feasibility, safety, local control, and short-term survival rates of this approach. METHODS: We retrospectively studied 43 patients with a large HCC (mean diameter, 8.8 cm; SD, 2.8 cm) treated between July 2015 and July 2018, who underwent TACE followed within 3 days by multi-antenna simultaneous MWA. We measured the liver and renal function before and after treatment, recorded complications, used three-dimensional software and imaging to calculate tumor necrosis rates at 1 month after therapy, and calculated overall survival (OS) and progression-free survival (PFS) using the Kaplan-Meier method. RESULTS: Mean follow up was 12.2 (range, 3.5-35.6) months. All patients completed the treatment protocol. At 1 month after combined therapy, tumor necrosis was complete in 16 (37.2%), nearly complete in 19 (44.2%), and partial in 8 (18.6%) patients. The 1- and 2-year OS rates were 64.0% and 46.8%, respectively, with a median OS of 23.0 months; and the 1- and 2-year PFS rates were 19.9% and 4.4%, respectively, with a median PFS of 4.2 months. A transient change in liver function occurred 3 days after MWA but resolved within 1 month. Only two patients had major complications, which were treatable and resolved. CONCLUSION: Multi-antenna MWA-oriented combined therapy is feasible and well tolerated, and it results in satisfactory initial local control and short-term survival in some but not all patients with a large HCC.
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BACKGROUND: Recurrent hepatocellular carcinoma (rHCC) patients with microvascular invasive (MVI) positive at first resection usually had poorly differentiated tumors and worse survivals. The optimal treatment for this population remains to be elucidated. METHODS: We retrospectively analyzed 319 rHCC patients with MVI-positive at first resection from June, 2009 to June, 2017. Survival and costs between curative treatments [re-resection (RR) and radiofrequency ablation (RFA)] and transarterial chemoembolization (TACE) were compared. Subgroup comparisons were made in patients in Barcelona Clinic Liver Cancer (BCLC) stage 0-A and BCLC stage B-C, respectively. A one-to-one propensity score matching (PSM) was used to diminish bias. RESULTS: In BCLC stage 0-A, 98 received RR/RFA, and 49 received TACE. The median overall survival (OS) of RR/RFA group was not reached, while the OS of TACE group was 26.3 months (P=0.001). After matching, the OS of the RR/RFA group was longer than that of the TACE group (39.5 vs. 26.3 months, P=0.045). In BCLC stage B-C, 137 patients received TACE, 11 received RR and 24 received RFA. The median OS was 29.8 months, 17.9 months and 11.1 months for RR, RFA and TACE group, respectively. No significant difference was found between RR and TACE (P=0.237) or RFA and TACE (P=0.484) after matching. Costs of the TACE group was significantly lower than that of the RR group but similar to that of the RFA group. CONCLUSION: RR/RFA provided better survival outcomes for rHCC patients with MVI-positive at first resection in selected BCLC stage 0-A. In selected BCLC stage B-C, TACE shared a similar efficacy with RR and RFA but a lower cost than RR.
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Background & aims: It remains controversial whether patients with advanced-stage hepatocellular carcinoma could be benefit from transarterial chemoembolization (TACE) treatment. The purpose of the present study is to identify predictors of survival following TACE in patients with advanced HCC. Methods: Overall, 303 patients with Barcelona Clinic Liver Cancer (BCLC) stage C HCC who were first treated with TACE from Sun Yat-sen University Cancer Centre between January 2009 and December 2013 were reviewed and enrolled in this study. We carried out Kaplan-Meier and Cox proportional hazard model analyses of prognostic factors. Results: The median survival of the whole cohort was 8.4 months. Multivariable Cox regression analyses confirmed that four risk factors, high serum levels of gamma-glutamyl transpeptidase (GGT), C-reactive protein (CRP), alkaline phosphatase (ALP) and presence of portal vein tumour thrombosis (PVTT), were independent prognostic factors for overall survival. The expected median survival among patients with 0-1 and 2-4 risk factors were 18.1 (95% CI: 15.5-20.7) and 6.8 (95% CI: 5.8-7.8) months, respectively. Objective tumor response among patients with 0-1 and 2-4 risk factors were 38.9% and 17.3%, respectively. Conclusion: We found four risk factors were associated with dismal overall survival for advanced HCC patients: serum GGT level, serum CRP, serum ALP and presence of PVTT. TACE may be recommended for patients with advanced HCC with 0-1 risk factors due to the favourable prognosis.
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BACKGROUND: Anti-angiogenic therapy combined with chemotherapy could improve the outcomes of patients with platinum-resistant ovarian cancer. Apatinib is an oral tyrosine kinase inhibitor that selectively inhibits VEGF receptor 2. We assessed the efficacy and safety of the combination therapy of apatinib and oral etoposide, considering the potential advantage of home administration without hospital admission, in patients with platinum-resistant or platinum-refractory ovarian cancer. METHODS: In this phase 2, single-arm, prospective study, we recruited patients aged 18-70 years with platinum-resistant or platinum-refractory ovarian cancer at the Sun Yat-sen University Cancer Center (China). The treatment consisted of apatinib at an initial dose of 500 mg once daily on a continuous basis, and oral etoposide at a dose of 50 mg once daily on days 1-14 of a 21-day cycle. Oral etoposide was administered for a maximum of six cycles. Treatment was continued until disease progression, patient withdrawal, or unacceptable toxic effects. The primary endpoint was the proportion of patients achieving an objective response according to Response Evaluation Criteria in Solid Tumors, version 1.1. We used Simon's two-stage design, and analysed efficacy in the intention-to-treat and per-protocol populations. Safety analyses included enrolled patients who had received at least one dose of study medication, but excluded those without any safety data. This study is registered with ClinicalTrials.gov, number NCT02867956. FINDINGS: Between Aug 10, 2016, and Nov 9, 2017, we screened 38 and enrolled 35 patients. At the data cutoff date (Dec 31, 2017), 20 (57%) patients had discontinued the study, and 15 (43%) patients remained on treatment. Objective responses were achieved in 19 (54%; 95% CI 36·6-71·2) of 35 patients in the intention-to-treat population and in 19 (61%; 42·2-78·2) of 31 patients in the per-protocol population. The most common grade 3 or 4 adverse events were neutropenia (17 [50%]), fatigue (11 [32%]), anaemia (ten [29%]), and mucositis (eight [24%]). Serious adverse events were reported in two patients who were admitted to hospital (one patient had anaemia and anorexia; the other patient had increased ascites due to disease progression). No treatment-related deaths were recorded. INTERPRETATION: The combination of apatinib with oral etoposide shows promising efficacy and manageable toxicities in patients with platinum-resistant or platinum-refractory ovarian cancer, and further study in phase 3 trials is warranted. FUNDING: None.
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Inhibidores de la Angiogénesis/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Etopósido/administración & dosificación , Neoplasias Ováricas/tratamiento farmacológico , Compuestos de Platino/administración & dosificación , Piridinas/administración & dosificación , Administración Oral , Adolescente , Adulto , Anciano , Inhibidores de la Angiogénesis/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Progresión de la Enfermedad , Esquema de Medicación , Resistencia a Antineoplásicos , Etopósido/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Compuestos de Platino/efectos adversos , Supervivencia sin Progresión , Estudios Prospectivos , Piridinas/efectos adversos , Factores de Tiempo , Adulto JovenRESUMEN
PURPOSE: To compare the stability of stable and unstable water-in-oil emulsions and the efficacy and safety of these emulsions in a single-center, prospective double-blind trial of transarterial chemoembolization for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 812 patients with inoperable HCC were randomized (stable emulsion, n = 402; unstable emulsion, n = 410). The 2 emulsions were prepared by using the same protocol except that different solvents were used for chemotherapy agents, including epirubicin, lobaplatin, and mitomycin C. The solvent in the stable emulsion arm was contrast medium and distilled water, and the solvent in the unstable emulsion arm was distilled water. The primary endpoint was overall survival (OS), and secondary endpoints were time to progression (TTP), tumor response, adverse events (AEs), and plasma epirubicin concentrations. RESULTS: In vitro, stable emulsions did not occur until 1 day, and unstable emulsions, with a lower peak plasma concentration (P = .001) in vivo, exhibited rapid separation of the oil and aqueous phases after 10 minutes. Median OS times in the stable and unstable emulsion arms were 17.7 and 19.2 months, respectively (P = .81). No differences were found in TTP, tumor response, and AEs except for myelosuppression (anemia, 3.5% vs 7.6%; thrombocytopenia, 11.5% vs 17.7%), which was significantly more severe and frequent in the unstable emulsion arm (P = .013). CONCLUSIONS: Chemoembolization is equally effective with the use of stable and unstable emulsions, but the use of a stable emulsion has the advantage of less myelosuppression and a favorable pharmacokinetic profile.
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Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Aceite Etiodizado/administración & dosificación , Neoplasias Hepáticas/terapia , Antineoplásicos/efectos adversos , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica/efectos adversos , Quimioembolización Terapéutica/mortalidad , China , Método Doble Ciego , Estabilidad de Medicamentos , Emulsiones , Aceite Etiodizado/efectos adversos , Aceite Etiodizado/farmacocinética , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Sorafenib is recommended for the first-line treatment of advanced hepatocellular carcinoma (HCC). However, the median progression-free survival (PFS) of patients with HCC and major portal vein tumor thrombosis treated with sorafenib monotherapy is no more than 3 months. A prospective single-arm phase II study was conducted to determine whether adding hepatic arterial infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin to sorafenib could improve on these results. METHODS: Thirty five patients were treated with sorafenib 400 mg orally twice a day, oxaliplatin 85 mg/m2 HAI on day 1, leucovorin 400 mg/m2 HAI on days 1, and 5-fluorouracil 2800 mg/m2 on days 1 and 2, repeated every 21 days. The primary end point was the 3-month PFS rate. RESULTS: The 3-, 6-, and 12-month PFS rates were 82.9, 51.4, and 22.9%, respectively. The median PFS and overall survival was 6.7 and 13.2 months, respectively. The objective response rate was 40%, and the disease control rate was 77.1% by RECIST criteria. Five (14.3%) patients achieved conversion to complete resection after the study treatment, and one of them experienced a pathological complete response. Treatment-related deaths did not occur. Grade 3-4 toxicities consisted of increases in aspartate aminotransferase (31.4%), hand-foot syndrome (17.1%), thrombocytopenia (14.3%), and neutropenia (8.6%). CONCLUSIONS: The combination treatment met the pre-specified end point of a 3-month progression free survival rate exceeding 65% and was clinical tolerable. The merits of this approach need to be established with a phase III trial. Clinical trial number http://ClinicalTrials.gov (No. NCT02981498).
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Carcinoma Hepatocelular/tratamiento farmacológico , Fluorouracilo/uso terapéutico , Leucovorina/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos Organoplatinos/uso terapéutico , Compuestos de Fenilurea/uso terapéutico , Trombosis de la Vena/complicaciones , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/complicaciones , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Humanos , Infusiones Intraarteriales/métodos , Leucovorina/administración & dosificación , Neoplasias Hepáticas/complicaciones , Masculino , Persona de Mediana Edad , Niacinamida/administración & dosificación , Niacinamida/uso terapéutico , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Compuestos de Fenilurea/administración & dosificación , Vena Porta/patología , Estudios Prospectivos , Sorafenib , Resultado del TratamientoRESUMEN
PURPOSE: Previous studies reported an association between an increased risk of tongue cancer and radiation treatment for nasopharyngeal carcinoma (NPC). This study compared the clinicopathologic characteristics and outcomes of tongue squamous cell carcinoma (TSCC) in patients with and without a history of radiotherapy for NPC. MATERIALS AND METHODS: From 1965 to 2009, a total of 73 patients were diagnosed with TSCC with a history of radiotherapy for NPC. The patients were matched in a 1:3 ratio with patients with sporadic TSCC according to age, sex, and year of the TSCC diagnosis. The primary endpoint was the overall survival. RESULTS: The median interval from NPC to TSCC was 82 months. The NPC survivors were more likely to be diagnosed with a more advanced T classification, less likely to have lymph node involvement, and more likely to have the tumor located in the dorsum of the tongue than sporadic TSCC. Regarding the histologic characteristics, the NPC survivors were more likely to have a weak lymphocytic host response, low tumor budding, and low risk of a worse pattern of invasion. The sporadic TSCC patients had a better overall survival (hazard ratio, 0.690; p=0.033) than the NPC survivors. In competing risks analysis, the cumulative incidence functions for the competing event (documented non-tongue cancer death) were significantly higher in the NPC survivors (Gray's test, p=0.001). CONCLUSION: TSCC patients with a history of radiotherapy for NPC appear to have particular clinicopathologic features, a poorer survival, and are more likely to die from non-tongue cancer causes than those with sporadic TSCC.
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Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidad , Neoplasias de la Lengua/diagnóstico , Neoplasias de la Lengua/mortalidad , Adulto , Anciano , Carcinoma/complicaciones , Carcinoma/radioterapia , Carcinoma de Células Escamosas/etiología , Estudios de Casos y Controles , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Morbilidad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/complicaciones , Neoplasias Nasofaríngeas/radioterapia , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasias Primarias Secundarias/etiología , Neoplasias Primarias Secundarias/mortalidad , Neoplasias Primarias Secundarias/patología , Pronóstico , Radiografía , Neoplasias de la Lengua/etiología , Adulto JovenRESUMEN
BACKGROUND & AIMS: The discontinuation rules of transarterial chemoembolization (TACE) for patients who were assessed as progressive disease (PD) but stage progression-free (SP-free: still belongs to Barcelona Clinic Liver Cancer B) after TACE are unclear. We aimed to evaluate the impact of the PD-pattern on the survival of these patients retreated with TACE. METHODS: In total, 115 consecutive patients who were assessed as PD but SP-free after TACE and then underwent at least one subsequent TACE session were included. Sixty patients were assessed as PD with target lesion progression (TP), and 55 patients were assessed as PD with target lesion non-progression (TNP). Survival and treatment-related adverse events were compared between the two groups. Additional external validation was performed using a data set (n = 103) from another institution. RESULTS: Patients with TNP had significantly longer median post-progression survival (PPS) than those with TP (21.0 vs. 11.9 months, P = 0.004). After TACE retreatment, the incidence of liver dysfunction was significantly higher for patients with TP than for patients with TNP (45% vs. 20%, P = 0.031). In the multivariate analysis, the target lesion response was one of the most significant prognostic factors for PPS (HR = 2.01; 95% confidence interval: 1.23-3.27; P = 0.005). The findings were supported by an independent external cohort. CONCLUSIONS: Compared to patients with TNP, patients with TP might exhibit no improvement in survival and even present damaged liver function after retreatment with TACE. Target lesion response is useful as a clinical decision for repeated TACE in these patients.
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Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/terapia , Adulto , Anciano , China/epidemiología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVES: To evaluate the outcomes of preoperative transarterial chemoembolization (TACE) for resectable hepatocellular carcinoma (HCC) with portal vein invasion. METHODS: From February 2006 to July 2011, 320 patients initially diagnosed with resectable HCC and portal vein invasion were prospectively non-randomized into two arms. In the immediate resection arm (Arm 1, n = 205) patients received immediate surgical resection. 115 patients were included in the preoperative TACE arm (Arm 2), and eventually 85 patients underwent TACE followed by surgical resection. RESULTS: The 1-, 3- and 5-year overall survival rates were 48.3 %, 18.7 % and 13.9 % for Arm 1 and 61.2 %, 31.7 % and 25.3 % for Arm 2 (P = 0.001), respectively. In the subgroup analysis of types I and II portal vein tumour thrombus (PVTT), the preoperative TACE arm demonstrated significantly better survival rates than the immediate resection arm (P I = 0.001, P II = 0.036). However, no significant difference was found for patients with type III PVTT (P III = 0.684). No significant difference was found between the two arms in terms of complications and mortality. CONCLUSIONS: Preoperative TACE seems to confer a survival benefit for resectable HCC with PVTT, especially for types I and II PVTT, and preoperative TACE should therefore be recommended as a routine procedure. KEY POINTS: ⢠Preoperative TACE improves the clinical outcomes for patients with PVTT ⢠Preoperative TACE could significantly improve the rate of en bloc thrombectomy ⢠Preoperative TACE does not increase the related adverse events.
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Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Vena Porta/patología , Cuidados Preoperatorios/métodos , Neoplasias Vasculares/secundario , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Femenino , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Vena Porta/cirugía , Estudios Prospectivos , Resultado del Tratamiento , Neoplasias Vasculares/cirugíaRESUMEN
Insulin-like growth factor binding protein-3 (IGFBP-3) plays an essential role in radiosensitivity of esophageal squamous cell carcinoma (ESCC). However, the underlying mechanism is not completely understood. Here, we observed that IGFBP-3 had favorable impact on the tumorigenicity of ESCC cells in nude mice by using an in vivo imaging system (IVIS) to monitor tumor growth treated with ionizing radiation (IR). Downregulation of IGFBP-3 expression enhanced tumor growth, inhibited anti-proliferative and apoptotic activity and result in IR resistance in vivo. Cell cycle antibody array suggested that silencing IGFBP-3 promoted transition from G0/G1 to S phase, perhaps though influencing Smad3 dephosphorylation and retinoblastoma protein (Rb) phosphorylation. Downregulation of P21 and P27, and upregulation of p-P27 (phospho-Thr187), cyclin-dependent kinase 2 (CDK2), and cyclin E1 might contribute to the G0/G1 to S phase transition promoted by IGFBP-3. Our results suggest that Smad3-P27/P21-cyclin E1/CDK2-phosphorylated retinoblastoma protein pathways might be involved in this IGFBP-3 mediated radiosensitivity transition in ESCC.
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Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Tolerancia a Radiación/genética , Animales , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/radioterapia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Supervivencia Celular/genética , Supervivencia Celular/efectos de la radiación , Modelos Animales de Enfermedad , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas de Esófago , Puntos de Control de la Fase G1 del Ciclo Celular/genética , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de la radiación , Expresión Génica , Técnicas de Silenciamiento del Gen , Silenciador del Gen , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Modelos Biológicos , Fosforilación , Pronóstico , Interferencia de ARN , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND AND PURPOSE: Genetic single nucleotide polymorphisms (SNP) play a critical role in the development of esophageal squamous cell carcinoma (ESCC). The aim of this study is to investigate the associations between insulin-like growth factor binding protein-3 (IGFBP-3) gene polymorphisms and ESCC patients risk and survival after definitive chemoradiotherapy (CRT). MATERIALS AND METHODS: We undertook a case-control study to analyze two IGFBP-3 polymorphisms (rs2854744 A>C and rs2854746 G>C) in an Han Chinese population, by extraction of genomic DNA from the peripheral blood of 110 ESCC patients treated with CRT and 128 control participants, and performed IGFBP-3 genotyping using DNA sequencing. RESULTS: The obtained results indicated that overall, no statistically significant association was observed in rs2854746 G>C. However, rs2854744 A>C genotype was at increased risk of ESCCs (P=0.032; odds ratio (OR)=1.201, CI 95%:1.014-1.423). Moreover, rs2854744 A>C genotype ESCCs were more significantly common in patients with tumor size of >6cm than A allele ESCC and in cases of lower T stage. Furthermore, ESCC patients with rs2854744CC genotype have the poorer CRT response and shorter survival time than GG+GC genotype ESCC. CONCLUSIONS: In conclusion, polymorphism in IGFBP-3 rs2854744 A>C might be a potential predictor of ESCC risk and patient survival. Nevertheless, further investigation with a larger sample size is needed to support our results.
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Carcinoma de Células Escamosas/patología , Quimioradioterapia/métodos , Neoplasias Esofágicas/patología , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Pueblo Asiatico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Estudios de Casos y Controles , China , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Riesgo , Análisis de Secuencia de ADN , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Insulin-like growth factor-binding protein-3 (IGFBP-3) is suggested to predict the radiosensitivity and/or prognosis of patients with esophageal squamous cell carcinoma (ESCC). The present study was designed to investigate the clinical and prognostic effects of IGFBP-3 on ESCC. METHODS: IGFBP-3 was detected by immunohistochemistry in paraffin-embedded tissues from 70 ESCC patients treated with radiotherapy alone and further examined by western blotting analysis in 10 pairs of fresh ESCC tissues and adjacent non-malignant esophageal specimens. Receiver operating characteristic (ROC) analysis was used to determine cut-off scores for tumor positivity and to evaluate patient survival status. The χ(2) test was performed to analyze the association of IGFBP-3 expression with clinical characteristics and radiotherapy response. Associations between prognostic outcomes and IGFBP-3 expression were investigated using Kaplan-Meier analysis and the Cox proportional hazards model. RESULTS: The threshold for IGFBP-3 positivity was set to greater than 65% [area under the ROC curve (AUC)=0.690, P<0.019]. Of the 70 ESCC patient tissues tested, 32 (45.7%) were defined as having high IGFBP-3 expression. The levels of IGFBP-3 protein expression were decreased in 70.0% (7 of 10) of ESCC tissues compared with adjacent non-malignant esophageal tissue. In addition, IGFBP-3 expression was associated with pathologic classification (P<0.05 for T, N, and M categories and clinical stage). Patients with elevated protein level of IGFBP-3 in the tumor had an improved radiotherapy response and prolonged overall survival (P<0.001). CONCLUSIONS: High level of IGFBP-3 expression in ESCC associates with early clinical stages and are predictive for favorable survival of the patients treated with radiotherapy.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina , Pronóstico , Fármacos Sensibilizantes a Radiaciones , Western Blotting , Carcinoma de Células Escamosas de Esófago , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Modelos de Riesgos Proporcionales , Curva ROCRESUMEN
The prognostic value of the primary lesion pretreatment apparent diffusion coefficient (ADC), which is obtained by diffusion-weighted magnetic resonance imaging (MR-DWI), remains unknown in nasopharyngeal carcinoma (NPC). Thus, to investigate whether the pretreatment ADC value as measured from the primary site on MR-DWI is an independent prognostic factor in NPC, we retrospectively reviewed a cohort of 541 patients with histologically-proven stage I-IVB NPC. All patients underwent MRI using a 3-Tesla system (Trio Tim; Siemens, Erlangen Germany). To calculate ADC, the primary lesion was designated on the ADC map at the level of the largest tumor diameter to cover most of the lesion, avoiding cystic or necrotic components. Median and mean (±SD) pretreatment ADC were 0.713 and 0.716 ± 0.079 × 10(-3) mm(2)/s, respectively. Univariate and multivariate analysis confirmed high pretreatment ADC was a good prognostic factor for poor local relapse-free survival and disease-free survival. Furthermore, the area under the ROC curve for prediction of local failure significantly increased when pretreatment ADC was combined with T classification (P = 0.004). Thus, pretreatment ADC might provide useful information for predicting outcome and selecting high-risk patients appropriate for more aggressive therapy. Further studies are warranted to investigate the biological basis of this observation.
Asunto(s)
Imagen de Difusión por Resonancia Magnética , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/mortalidad , Adolescente , Adulto , Anciano , Carcinoma , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/terapia , Estadificación de Neoplasias , Tomografía de Emisión de Positrones , Pronóstico , Curva ROC , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Insuficiencia del Tratamiento , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The prognostic factors of thoracic esophageal squamous carcinoma with cervical lymph nodal metastasis (CLNM) have not been specifically investigated. This study was performed to analyze the efficacy and prognostic factors of chemoradiotherapy for thoracic esophageal carcinoma with CLNM alone. METHODS: From 2002 to 2011, 139 patients with inoperable esophageal cancer who underwent chemoradiotherapy at the Sun Yat-Sen University were retrospectively analyzed. Median radiation doses were 60 Gy (range: 50-68 Gy). Univariate and multivariate analyses were performed to compare overall survival (OS) and progression-free survival (PFS). RESULTS: The 1- and 3-year OS rates were 68.2% and 27.9%, respectively. The 1- and 3-year PFS rates were 51.9% and 20.1%, respectively. The multivariate analysis demonstrated that response to treatment, T stage, pathological grade, and laterality of cervical lymph nodal metastases were independent prognostic factors for thoracic esophageal carcinoma with CLNM. CONCLUSIONS: Concurrent chemoradiotherapy is an important and hopeful treatment option for patients with esophageal cancer with CLNM alone. Our study has revealed that response to treatment, T stage, pathological grade and laterality of cervical lymph nodal metastases are significant prognostic factors for long-term survival.