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IMPORTANCE: Intra-arterial therapies(IATs) are promising options for unresectable hepatocellular carcinoma(HCC). Stratifying the prognostic risk before administering IAT is important for clinical decision-making and for designing future clinical trials. OBJECTIVE: To develop and validate a machine learning(ML)-based decision support model(MLDSM) for recommending IAT modalities for unresectable HCC. DESIGN, SETTING, AND PARTICIPANTS: Between October 2014 and October 2022, a total of 2,959 patients with HCC who underwent initial IATs were enroled retrospectively from 13 tertiary hospitals. These patients were divided into the training cohort (n = 1700), validation cohort (n = 428), and test cohort (n = 200). MAIN OUTCOMES AND MEASURES: Thirty-two clinical variables were input, and five supervised ML algorithms, including eXtreme Gradient Boosting (XGBoost), Categorical Gradient Boosting (CatBoost), Gradient Boosting Decision Tree (GBDT), Light Gradient Boosting Machine (LGBM) and Random Forest (RF), were compared using the areas under the receiver operating characteristic curve (AUC) with the DeLong test. RESULTS: A total of 1856 patients were assigned to the IAT alone Group(I-A), and 1103 patients were assigned to the IAT combination Group(I-C). The 12-month death rates were 31.9% (352/1103) in the I-A group and 50.4% (936/1856) in the I-C group. For the test cohort, in the I-C group, the CatBoost model achieved the best discrimination when 30 variables were input, with an AUC of 0.776 (95% confidence intervals [CI], 0.833-0.868). In the I-A group, the LGBM model achieved the best discrimination when 24 variables were input, with an AUC of 0.776 (95% CI, 0.833-0.868). According to the decision trees, BCLC grade, local therapy, and diameter as top three variables were used to guide clinical decisions between IAT modalities. CONCLUSIONS AND RELEVANCE: The MLDSM can accurately stratify prognostic risk for HCC patients who received IATs, thus helping physicians to make decisions about IAT and providing guidance for surveillance strategies in clinical practice.
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Transition metal dichalcogenide TiSe2 exhibits a superconducting dome within a low pressure range of 2-4 GPa, which peaks with the maximal transition temperature Tc of ≈1.8 K. Here it is reported that applying high pressure induces a new superconducting state in TiSe2, which starts at ≈16 GPa with a substantially higher Tc that reaches 5.6 K at ≈21.5 GPa with no sign of decline. Combining high-throughput first-principles structure search, X-ray diffraction, and Raman spectroscopy measurements up to 30 GPa, It is found that TiSe2 undergoes a first-order structural transition from the 1T phase under ambient pressure to a new 4O phase under high pressure. Comparative ab initio calculations reveal that while the conventional phonon-mediated pairing mechanism may account for the superconductivity observed in 1T-TiSe2 under low pressure, the electron-phonon coupling of 4O-TiSe2 is too weak to induce a superconducting state whose transition temperature is as high as 5.6 K under high pressure. The new superconducting state found in pressurized TiSe2 requires further study on its underlying mechanism.
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The natural bulk Van der Waals heterostructure compound 6R-TaS_{2} consists of alternate stacking 1T- and 1H-TaS_{2} monolayers, creating a unique system that incorporates charge-density-wave (CDW) order and superconductivity (SC) in distinct monolayers. Here, after confirming that the 2D nature of the lattice is preserved up to 8 GPa in 6R-TaS_{2}, we documented an unusual evolution of CDW and SC by conducting high-pressure electronic transport measurements. Upon compression, we observe a gradual suppression of CDW within the 1T layers, while the SC exhibits a dome-shaped behavior that terminates at a critical pressure P_{c} around 2.9 GPa. By taking account of the fact that the substantial suppression of SC is concomitant with the complete collapse of CDW order at P_{c}, we argue that the 6R-TaS_{2} behaves like a stack of Josephson junctions and thus the suppressed superconductivity can be attributed to the weakening of Josephson coupling associated with the presence of CDW fluctuations in the 1T layers. Furthermore, the SC reversely enhances above P_{c}, implying the development of emergent superconductivity in the 1T layers after the melting of T-layer CDW orders. These results show that the 6R-TaS_{2} not only provides a promising platform to explore emergent phenomena but also serves as a model system to study the complex interactions between competing electronic states.
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OBJECTIVE: To develop and validate a risk scoring scale model (RSSM) for stratifying prognostic risk after intra-arterial therapies (IATs) for hepatocellular carcinoma (HCC). METHODS: Between February 2014 and October 2022, 2338 patients with HCC who underwent initial IATs were consecutively enrolled. These patients were divided into training datasets (TD, n = 1700), internal validation datasets (ITD, n = 428), and external validation datasets (ETD, n = 200). Five-years death was used to predict outcome. Thirty-four clinical information were input and five supervised machine learning (ML) algorithms, including eXtreme Gradient Boosting (XGBoost), Categorical Gradient Boosting (CatBoost), Gradient Boosting Decision Tree (GBDT), Light Gradient Boosting Machine (LGBT), and Random Forest (RF), were compared using the areas under the receiver operating characteristic (AUC) with DeLong test. The variables with top important ML scores were used to build the RSSM by stepwise Cox regression. RESULTS: The CatBoost model achieved the best discrimination when 12 top variables were input, with the AUC of 0.851 (95% confidence intervals (CI), 0.833-0.868) for TD, 0.817 (95%CI, 0.759-0.857) for ITD, and 0.791 (95%CI, 0.748-0.834) for ETD. The RSSM was developed based on the immune checkpoint inhibitors (ICI) (hazard ratios (HR), 0.678; 95%CI 0.549, 0.837), tyrosine kinase inhibitors (TKI) (HR, 0.702; 95%CI 0.605, 0.814), local therapy (HR, 0.104; 95%CI 0.014, 0.747), response to the first IAT (HR, 4.221; 95%CI 2.229, 7.994), tumor size (HR, 1.054; 95%CI 1.038, 1.070), and BCLC grade (HR, 2.375; 95%CI 1.950, 2.894). Kaplan-Meier analysis confirmed the role of RSSM in risk stratification (p < 0.001). CONCLUSIONS: The RSSM can stratify accurately prognostic risk for HCC patients received IAT. On the basis, an online calculator permits easy implementation of this model. CLINICAL RELEVANCE STATEMENT: The risk scoring scale model could be easily implemented for physicians to stratify risk and predict prognosis quickly and accurately, thereby serving as a more favorable tool to strengthen individualized intra-arterial therapies and management in patients with unresectable hepatocellular carcinoma. KEY POINTS: ⢠The Categorical Gradient Boosting (CatBoost) algorithm achieved the optimal and robust predictive ability (AUC, 0.851 (95%CI, 0.833-0.868) in training datasets, 0.817 (95%CI, 0.759-0.857) in internal validation datasets, and 0.791 (95%CI, 0.748-0.834) in external validation datasets) for prediction of 5-years death of hepatocellular carcinoma (HCC) after intra-arterial therapies (IATs) among five machine learning models. ⢠We used the SHapley Additive exPlanations algorithms to explain the CatBoost model so as to resolve the black boxes of machine learning principles. ⢠A simpler restricted variable, risk scoring scale model (RSSM), derived by stepwise Cox regression for risk stratification after intra-arterial therapies for hepatocellular carcinoma, provides the potential forewarning to adopt combination strategies for high-risk patients.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Aprendizado de Máquina , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamento farmacológico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/terapia , Masculino , Feminino , Quimioembolização Terapêutica/métodos , Prognóstico , Pessoa de Meia-Idade , Medição de Risco , Idoso , Estudos RetrospectivosRESUMO
PURPOSE: Intra-arterial conversion therapy (ICT) is a promising option for patients with unresectable hepatocellular carcinoma (uHCC). However, the selection of sequential therapeutic modalities is still controversial. This study compared the efficacy and safety of surgical resection (SR) versus thermal ablation (TA) after patients with uHCC received ICT. METHODS: From May 2008 to November 2021, 3553 consecutive patients were reviewed and 791 patients were downstaged to receive TA or SR. Among them, 340 patients received SR, and 451 received TA after ICTs. The propensity score matching (PSM) method was applied to reduce selection bias between groups. Cumulative overall survival (OS) and progression-free survival (PFS) were compared using the Kaplan-Meier method with the log-rank test. The occurrence of complications and adverse events (AEs) were compared using chi-square test. RESULTS: After PSM 1:1 (n = 185 in both groups), the 10-year OS and PFS rates for patients who underwent SR were comparable to those of patients who underwent TA (OS: 45.2% vs. 36.1%; p = 0.190; PFS: 19.3% vs. 15.9%; p = 0.533). A total of 237 (29.9%) patients (203 males; mean age:57.1 ± 11.0 years) received downstaging therapy, and long-term OS and PFS remained comparable between the two groups (p = 0.718, 0.636, respectively). However, the cumulative OS and PFS rates in the downstaged cohort were significantly higher than those in the nondownstaged cohort (both ps < 0.001). Additionally, there was no difference in major complications between the two groups (SR: 6.3% vs. TA: 8.6%; p = 0.320). CONCLUSIONS: TA might be an acceptable first-line alternative to SR after patients with uHCC receive ICT, especially patients unsuitable for SR. Better long-term survival was observed among patients in the downstaged cohort compared to those who failed to downstage.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , IdosoRESUMO
PURPOSE: This study compares the efficacy and safety of lenvatinib and programmed cell death protein (PD)-1 versus lenvatinib alone for advanced hepatocellular carcinoma (Ad-HCC) refractory to hepatic arterial infusion chemotherapy (HAIC). METHODS: From April 2016 to September 2021, 145 patients with Ad-HCC refractory to HAIC based on modified Response Evaluation Criteria in Solid Tumors criteria were enrolled by two radiologists and classified into the HAIC-lenvatinib group (H-L, n = 87) and HAIC-lenvatinib-PD-1 group (H-L-P, n = 58). A propensity score-matching method was used to reduce selective bias. The overall survival (OS) and postprogression-free survival (PPS) rates were compared using the Kaplan-Meier method with log-rank test. Multivariable analyses of independent prognostic factors were evaluated by means of the forward stepwise Cox regression model. RESULTS: After propensity score matching 1:1, the median OS was 43.6 months in the H-L-P group and was significantly longer than that (18.9 months) of the H-L group (p = .009). The median PPS was 35.6 months in the H-L-P group and was significantly longer than that (9.4 months) of the H-L group (p = .009). Multivariate analyses showed that the factors that significantly affected the OS were α-fetoprotein (hazard ratio [HR], 2.14; 95% CI, 1.26-3.98; p = .006), early response to HAIC (HR, 0.44; 95% CI, 1.20-3.85; p = .009), and H-L treatment (HR, 0.52; 95% CI, 0.30-0.86; p = .012). Modified albumin-bilirubin grade (HR, 1.32; 95% CI, 1.03-1.70; p = .026), early response to HAIC (HR, 0.44; 95% CI, 0.25-0.77; p = .004), and H-L (HR, 0.47 ; 95% CI, 0.28-0.78; p = .003) significantly affected the PPS. CONCLUSIONS: This combination therapy of PD-1 inhibitors plus lenvatinib has promising survival benefits in the management of patients with Ad-HCC refractory to HAIC. PLAIN LANGUAGE SUMMARY: Lenvatinib plus programmed death 1 inhibitor is an effective and safe postprogression treatment and improved significantly overall survival and postprogression-free survival compared with lenvatinib alone in patients with advanced hepatocellular carcinoma refractory to hepatic arterial infusion chemotherapy.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Antineoplásicos/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Sorafenibe , Neoplasias Hepáticas/patologia , Resultado do Tratamento , Infusões Intra-Arteriais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Anemia is the most common manifestation in myelodysplastic syndrome (MDS) patients, but the cause of ineffective hematopoiesis is not fully understood. Enucleation is an important event in the maturation process of erythroblasts. According to a series of morphological phenotypes of the pathological development of MDS erythroblasts, we speculate that there may be enucleation disorders. To verify this hypothesis, we cultured MDS bone marrow CD34+ cells in vitro and induced erythroblast development. The results showed that erythroblast enucleation in MDS was significantly lower than that in the normal group, and the rate of enucleation was positively correlated with hemoglobin concentration. Risk stratification of MDS was performed to further analyze the differences in enucleation among the normal group, low-middle risk group and high-risk group. The results showed that the enucleation rate of the high risk group was higher than that of the low-middle risk group but still lower than that of the normal group. Moreover, the expression of pERK and pAKT in MDS erythroblasts in the high risk group was higher than that in the normal group, while the expression of pERK and pAKT in the low-middle risk group was lower than that in the normal group. Furthermore, the enucleation of MDS was positively correlated with the phosphorylation degree of ERK and AKT. In conclusion, this study reveals that the enucleation of erythroblasts is one of the possible causes of anemia in MDS. Video Abstract.
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Anemia , Síndromes Mielodisplásicas , Humanos , Eritroblastos/metabolismo , Eritroblastos/patologia , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/metabolismo , Anemia/complicações , Anemia/metabolismo , Anemia/patologia , Fatores de Risco , Células da Medula Óssea/patologiaRESUMO
OBJECTIVES: Hepatic arterial infusion chemotherapy (HAIC) using the FOLFOX regimen (oxaliplatin plus fluorouracil and leucovorin) is a promising option for advanced hepatocellular carcinoma (Ad-HCC). As identifying patients with Ad-HCC who would obtain objective response (OR) to HAIC preoperatively remains a challenge, we aimed to develop an automatic and non-invasive model for predicting HAIC response. METHODS: A total of 458 patients with Ad-HCC who underwent HAIC were retrospectively included from three hospitals (310 for training, 77 for internal validation, and 71 for external validation). The deep learning and radiomic features were extracted from the automatically segmented liver region on contrast-enhanced computed tomography images. Then, a deep learning radiomic nomogram (DLRN) was constructed by integrating deep learning scores, radiomic scores, and significant clinical variables with multivariate logistic regression. Model performance was assessed by AUC and Kaplan-Meier estimator. RESULTS: After automatic segmentation, only a few modifications were needed (less than 30 min for 458 patients). The DLRN achieved an AUC of 0.988 in the training cohort, 0.915 in the internal validation cohort, and 0.896 in the external validation cohort, respectively, outperforming other models in HAIC response prediction. Moreover, survival risk stratification was also successfully performed by the DLRN. The overall survival (OS) of the predictive OR group was significantly longer than that of the predictive non-OR group (median OS: 26.0 vs. 12.3 months, p < 0.001). CONCLUSIONS: The DLRN provided a satisfactory performance for predicting HAIC response, which is essential to identify Ad-HCC patients for HAIC and may potentially benefit personalized pre-treatment decision-making. CLINICAL RELEVANCE STATEMENT: This study presents an accurate and automatic method for predicting response to hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma, and therefore help in defining the best candidates for this treatment. KEY POINTS: ⢠Deep learning radiomic nomogram (DLRN) based on automatic segmentation of CECT can accurately predict hepatic arterial infusion chemotherapy (HAIC) response of advanced HCC patients. ⢠The proposed prediction model can perform survival risk stratification and is an easy-to-use tool for personalized pre-treatment decision-making for advanced HCC patients.
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Carcinoma Hepatocelular , Aprendizado Profundo , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Nomogramas , Estudos Retrospectivos , Cisplatino , Resultado do Tratamento , Infusões Intra-ArteriaisRESUMO
BACKGROUND: The macrotrabecular-massive (MTM) is a special subtype of hepatocellular carcinoma (HCC), which has commonly a dismal prognosis. This study aimed to develop a multitask deep learning radiomics (MDLR) model for predicting MTM and HCC patients' prognosis after hepatic arterial infusion chemotherapy (HAIC). METHODS: From June 2018 to March 2020, 158 eligible patients with HCC who underwent surgery were retrospectively enrolled in MTM related cohorts, and 752 HCC patients who underwent HAIC were included in HAIC related cohorts during the same period. DLR features were extracted from dual-phase (arterial phase and venous phase) contrast-enhanced computed tomography (CECT) of the entire liver region. Then, an MDLR model was used for the simultaneous prediction of the MTM subtype and patient prognosis after HAIC. The MDLR model for prognostic risk stratification incorporated DLR signatures, clinical variables and MTM subtype. FINDINGS: The predictive performance of the DLR model for the MTM subtype was 0.968 in the training cohort [TC], 0.912 in the internal test cohort [ITC] and 0.773 in the external test cohort [ETC], respectively. Multivariable analysis identified portal vein tumor thrombus (PVTT) (p = 0.012), HAIC response (p < 0.001), HAIC sessions (p < 0.001) and MTM subtype (p < 0.001) as indicators of poor prognosis. After incorporating DLR signatures, the MDLR model yielded the best performance among all models (AUC, 0.855 in the TC, 0.805 in the ITC and 0.792 in the ETC). With these variables, the MDLR model provided two risk strata for overall survival (OS) in the TC: low risk (5-year OS, 44.9%) and high risk (5-year OS, 4.9%). INTERPRETATION: A tool based on MDLR was developed to consider that the MTM is an important prognosis factor for HCC patients. MDLR showed outstanding performance for the prognostic risk stratification of HCC patients who underwent HAIC and may help physicians with therapeutic decision making and surveillance strategy selection in clinical practice.
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Carcinoma Hepatocelular , Aprendizado Profundo , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Prognóstico , Infusões Intra-ArteriaisRESUMO
In this study, we aimed to explore the potential targets and functional mechanisms of Rk1 combined with Rg5 (Rk1+Rg5) against type II diabetes mellitus (T2DM). Network pharmacology and molecular docking were used to predict and verify the targets and signaling pathways of Rk1+Rg5 against T2DM. The results were further confirmed by a db/db mouse model and a model using PA-induced L6 cells. According to network pharmacology, a total of 250 core targets of Rk1+Rg5 towards T2DM were identified; the insulin resistance signaling pathways were enriched by KEGG. Results of molecular docking indicated good binding affinity of Rk1 and Rg5 to Akt1. In vivo and in vitro studies further showed that Rk1+Rg5 is an inhibitor of skeletal muscle insulin resistance. The results showed that Rk1+Rg5 significantly improved the hyperglycemic state of db/db mice, alleviated dyslipidemia, and promoted skeletal muscle glucose uptake. This phenomenon was closely related to the alleviation of the insulin resistance in skeletal muscles. Finally, the combination activated the Akt signaling pathway and promoted GLUT4 translocation to the cell membrane for glucose uptake. Altogether, our findings, for the first time, demonstrate that the combination of Rk1 and Rg5 could be beneficial for anti-T2DM, possibly involving ameliorated insulin resistance.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Camundongos , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Farmacologia em Rede , Simulação de Acoplamento Molecular , Proteínas Proto-Oncogênicas c-akt/metabolismo , Insulina/uso terapêutico , Glucose/metabolismoRESUMO
PURPOSE: Diagnosis of lymph node metastasis (LNM) is critical for patients with pancreatic ductal adenocarcinoma (PDAC). We aimed to build deep learning radiomics (DLR) models of dual-energy computed tomography (DECT) to classify LNM status of PDAC and to stratify the overall survival before treatment. METHODS: From August 2016 to October 2020, 148 PDAC patients underwent regional lymph node dissection and scanned preoperatively DECT were enrolled. The virtual monoenergetic image at 40 keV was reconstructed from 100 and 150 keV of DECT. By setting January 1, 2021, as the cut-off date, 113 patients were assigned into the primary set, and 35 were in the test set. DLR models using VMI 40 keV, 100 keV, 150 keV, and 100 + 150 keV images were developed and compared. The best model was integrated with key clinical features selected by multivariate Cox regression analysis to achieve the most accurate prediction. RESULTS: DLR based on 100 + 150 keV DECT yields the best performance in predicting LNM status with the AUC of 0.87 (95% confidence interval [CI]: 0.85-0.89) in the test cohort. After integrating key clinical features (CT-reported T stage, LN status, glutamyl transpeptadase, and glucose), the AUC was improved to 0.92 (95% CI: 0.91-0.94). Patients at high risk of LNM portended significantly worse overall survival than those at low risk after surgery (P = 0.012). CONCLUSIONS: The DLR model showed outstanding performance for predicting LNM in PADC and hold promise of improving clinical decision-making.
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Carcinoma Ductal Pancreático , Aprendizado Profundo , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/patologia , Humanos , Metástase Linfática/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Neoplasias PancreáticasRESUMO
OBJECTIVES: This study analyzed and compared CT findings and longitudinal variations after discharge between severe and non-severe coronavirus disease (COVID-19) patients who had residual pulmonary sequelae at pre-discharge. METHODS: A total of 310 patients were included and stratified into severe and non-severe COVID-19 groups. Cross-sectional CT features across different time periods (T0: pre-discharge, T1: 1-4 weeks after discharge, T2: 5-8 weeks after discharge, T3: 9-12 weeks after discharge, T4: > 12 weeks after discharge) were compared, and the longitudinal variations of CT findings were analyzed and compared in both groups. RESULTS: The cumulative absorption rate of fibrosis-like findings in the severe and non-severe groups at T4 was 24.3% (17/70) and 52.0% (53/102), respectively. In both groups, ground-glass opacity (GGO) with consolidation showed a clear decreasing trend at T1, after which they maintained similar lower levels. The GGO in the severe group showed an increasing trend first at T1 and then decreasing at T4; however, the incidence decreased gradually in the non-severe group. Most fibrosis-like findings showed a tendency to decrease rapidly and then remained stable. Bronchial dilatation in the severe group persisted at an intermediate level. CONCLUSIONS: After discharge, the characteristics and changing trends of pulmonary sequelae caused by COVID-19 were significantly different between the two groups. Pulmonary sequelae were more serious and recovery was slower in patients with severe/critical disease than in patients with moderate disease. A portion of the fibrosis-like findings were completely absorbed in patients with moderate and severe/critical diseases. KEY POINTS: ⢠Lung sequelae were more serious and recovery was slower in severe/critical COVID-19 patients. ⢠Complete absorption of fibrosis-like findings after a short-term follow-up was observed in at least 17/70 (24.3%) of COVID-19 patients with severe/critical disease and 53/102 (52.0%) of COVID-19 patients with moderate disease. ⢠The most common fibrosis-like findings was a parenchymal band; irregular interface was a nonspecific sign of COVID-19, and the percentage of bronchial dilatation in patients with severe/critical disease remained at a relatively stable medium level (range, 31.6 to 47.8%) at all stages.
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COVID-19 , Alta do Paciente , Estudos Transversais , Seguimentos , Humanos , Pulmão/diagnóstico por imagem , Estudos Retrospectivos , SARS-CoV-2 , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: We aimed to compare the therapeutic outcomes of radiofrequency ablation (RFA) and microwave ablation (MWA) as first-line therapies in patients with small single perivascular hepatocellular carcinoma (HCC). METHODS: A total of 144 eligible patients with small (≤ 3 cm) single perivascular (proximity to hepatic and portal veins) HCC who underwent RFA (N = 70) or MWA (N = 74) as first-line treatment were included. The overall survival (OS), disease-free survival (DFS), and local tumor progression (LTP) rates between the two ablation modalities were compared. The inverse probability of treatment weighting (IPTW) method was used to reduce selection bias. Subgroup analysis was performed according to the type of hepatic vessels. RESULTS: After a median follow-up time of 38.2 months, there were no significant differences in OS (5-year OS: RFA 77.7% vs. MWA 74.6%; p = 0.600) and DFS (5-year DFS: RFA 24.7% vs. MWA 40.4%; p = 0.570). However, a significantly higher LTP rate was observed in the RFA group than the MWA group (5-year LTP: RFA 24.3% vs. MWA 8.4%; p = 0.030). IPTW-adjusted analyses revealed similar results. The treatment modality (RFA vs. MWA: HR 7.861, 95% CI 1.642-37.635, p = 0.010) was an independent prognostic factor for LTP. We observed a significant interaction effect of ablation modality and type of peritumoral vessel on LTP (p = 0.034). For patients with periportal HCC, the LTP rate was significantly higher in the RFA group than in the MWA group (p = 0.045). However, this difference was not observed in patients with perivenous HCC (p = 0.116). CONCLUSIONS: In patients with a small single periportal HCC, MWA exhibited better tumor control than RFA. KEY POINTS: ⢠Microwave ablation exhibited better local tumor control than radiofrequency ablation for small single periportal hepatocellular carcinoma. ⢠There was a significant interaction between the treatment effect of ablation modality and type of peritumoral vessel on local tumor progression. ⢠The type of peritumoral vessel is vital in choosing ablation modalities for hepatocellular carcinoma.
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Carcinoma Hepatocelular , Ablação por Cateter , Neoplasias Hepáticas , Ablação por Radiofrequência , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/cirurgia , Micro-Ondas/uso terapêutico , Pontuação de Propensão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: To evaluate the incidence, risk factors and clinical significance of four types of tumor progression (TP) after microwave ablation (MWA) of single hepatocellular carcinoma (HCC) of <5 cm. METHODS: The data of 340 treatment-naïve, HCC patients with a single HCC of <5 cm underwent MWA between April 2012 and November 2017 were retrospectively reviewed. TPs including local tumor progression (LTP), intrahepatic distant recurrence (IDR), aggressive intrasegmental recurrence (AIR) and extrahepatic distant recurrence (EDR) were reviewed and compared between BCLC stage 0 and A. Univariate and multivariate analysis were performed on clinicopathological variables and different TPs to identify factors affecting long-term overall survival (OS). RESULTS: In a median follow-up period of 25.6 months (range, 3.1-61.4 months), the rate of LTP, IDR, AIR and EDR was 6.2% (21/340), 29.1% (98/340), 3.2% (11/340) and 7.9% (27/340). The four types of TP occurrence rates in BCLC stage 0 were comparable to those in BCLC stage A (p = 0.492, 0.971, 0.681 and 0.219). Univariate analysis showed that age (p < 0.001, hazard ratio [HR] = 2.783), comorbidities (p = 0.042, HR = 1.864), IDR, AIR and EDR (p = 0.027, HR = 1.719; p = 0.001, HR = 3.628; p = 0.009, HR = 2.638) were independently associated with OS. Multivariate analysis showed older age (p < 0.001, HR = 2.478), the occurrence of AIR (p < 0.001, HR = 2.648) and the occurrence of EDR (p = 0.002, HR = 2.222), were associated with poor OS. CONCLUSIONS: The occurrence rate of IDR is the highest of all TPs following MWA of a single HCC of <5cm. Old age, AIR and EDR had an adverse effect on long-term OS.
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Carcinoma Hepatocelular , Ablação por Cateter , Neoplasias Hepáticas , Idoso , Carcinoma Hepatocelular/cirurgia , Humanos , Incidência , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/cirurgia , Micro-Ondas , Recidiva Local de Neoplasia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
Myelodysplastic syndromes (MDSs) are clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis. Anemia is the defining cytopenia of MDS patients, yet the molecular mechanisms for dyserythropoiesis in MDSs remain to be fully defined. Recent studies have revealed that heterozygous loss-of-function mutation of DNA dioxygenase TET2 is 1 of the most common mutations in MDSs and that TET2 deficiency disturbs erythroid differentiation. However, mechanistic insights into the role of TET2 on disordered erythropoiesis are not fully defined. Here, we show that TET2 deficiency leads initially to stem cell factor (SCF)-dependent hyperproliferation and impaired differentiation of human colony-forming unit-erythroid (CFU-E) cells, which were reversed by a c-Kit inhibitor. We further show that this was due to increased phosphorylation of c-Kit accompanied by decreased expression of phosphatase SHP-1, a negative regulator of c-Kit. At later stages, TET2 deficiency led to an accumulation of a progenitor population, which expressed surface markers characteristic of normal CFU-E cells but were functionally different. In contrast to normal CFU-E cells that require only erythropoietin (EPO) for proliferation, these abnormal progenitors required SCF and EPO and exhibited impaired differentiation. We termed this population of progenitors "marker CFU-E" cells. We further show that AXL expression was increased in marker CFU-E cells and that the increased AXL expression led to increased activation of AKT and ERK. Moreover, the altered proliferation and differentiation of marker CFU-E cells were partially rescued by an AXL inhibitor. Our findings document an important role for TET2 in erythropoiesis and have uncovered previously unknown mechanisms by which deficiency of TET2 contributes to ineffective erythropoiesis.
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Proteínas de Ligação a DNA/genética , Células Precursoras Eritroides/patologia , Mutação com Perda de Função , Síndromes Mielodisplásicas/genética , Proteínas Proto-Oncogênicas/genética , Linhagem Celular Tumoral , Proliferação de Células , Metilação de DNA , Dioxigenases , Células Precursoras Eritroides/citologia , Células Precursoras Eritroides/metabolismo , Eritropoese , Deleção de Genes , Técnicas de Silenciamento de Genes , Humanos , Síndromes Mielodisplásicas/patologia , Proteínas Proto-Oncogênicas c-kit/genética , Regulação para CimaRESUMO
BACKGROUND: The aim of this retrospective study was to compare the feasibility and efficiency of ultrasound-guided percutaneous microwave ablation (US-PMWA) assisted by three-dimensional visualization ablation planning system (3DVAPS) and conventional 2D planning for hepatocellular carcinoma (HCC) (diameter > 3 cm). METHODS: One hundred thirty patients with 223 HCC nodules (5.0 ± 1.5 cm in diameter, [3.0-10.0 cm]) who met the eligibility criteria divided into 3D and 2D planning group were reviewed from April 2015 to August 2018. Ablation parameters and oncological outcomes were compared, including overall survival (OS), recurrence-free survival (RFS), and local tumor progression (LTP). Multivariate analysis was performed on clinicopathological variables to identify the risk factors for OS and LTP. RESULTS: The median follow-up period was 21 months (range 3-44). Insertion number (5.4 ± 1.2 VS. 4.5 ± 0.9, P = 0.034), ablation time (1249.2 ± 654.2 s VS. 1082.4 ± 584.7 s, P = 0.048), ablation energy (57,000 ± 11,892 J VS. 42,600 ± 10,271 J, P = 0.038) and success rate of first ablation (95.0% VS. 85.7%, P = 0.033) were higher in the 3D planning group compared with those in 2D planning group. There was no statistical difference in OS, and RFS between the two groups (P = 0.995, P = 0.845). LTP rate of 3D planning group was less than that of 2D planning group (16.5% VS 41.2%, P = 0.003). Multivariate analysis showed tumor maximal diameters (P < 0.001), tumor number (P = 0.003) and preoperative TACE (P < 0.001) were predictors for OS and sessions (P = 0.024), a-fetoprotein level (P = 0.004), and preoperative planning (P = 0.002) were predictors for LTP, respectively. CONCLUSIONS: 3DVAPS improves precision of US guided ablation resulting in lower LTP and higher 5 mm-AM for patients with HCC lesions larger than 3 cm in diameter.
Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Imageamento Tridimensional/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Micro-Ondas/uso terapêutico , Ablação por Radiofrequência/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , Ablação por Cateter/métodos , Progressão da Doença , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Ultrassonografia/métodosRESUMO
OBJECTIVES: To develop a prognostic nomogram based on the albumin-bilirubin (ALBI) grade for prediction of the long-term survival of patients with intermediate-stage hepatocellular carcinoma (HCC) after transarterial chemoembolization combined with microwave ablation (TACE-MWA). METHODS: We retrospectively studied 546 consecutive patients with intermediate-stage HCC according to the Barcelona Clinic Liver Cancer guidelines who underwent TACE-MWA between January 2000 and December 2016. Overall survival (OS) and progression-free survival (PFS) were analyzed. The predictive value of the ALBI grade was investigated. The prognostic nomogram was constructed using the independent predictors assessed by the multivariate Cox proportional hazards model. RESULTS: After a median follow-up of 35.0 months (range, 4.0-221.0 months), 380 patients had died. The median OS was 35.0 months (95% confidence interval (CI), 30.84-39.16 months), and the median PFS was 6.5 months (95% CI, 6.13-6.87 months). The ALBI grade was validated as an independent predictor of OS (p < 0.001). Multivariate analyses showed that Eastern Cooperative Oncology Group performance status score more than 0, presence of liver cirrhosis, a-fetoprotein level above 400 ng/mL, tumor size greater than 5 cm, tumor number more than 3, advanced ALBI grade, and treatment sessions of TACE or MWA fewer than 3 were independently associated with overall mortality. The prognostic nomogram incorporating these eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770 (95% CI, 0.746-0.795). CONCLUSIONS: The prognostic nomogram based on the ALBI grade resulted in reliable efficacy for prediction of individualized OS in patients with intermediate-stage HCC after TACE-MWA. KEY POINTS: ⢠TACE-MWA was associated with a median overall survival of 35.0 months for patients with intermediate-stage HCC. ⢠A prognostic nomogram was built to predict individualized survival of patients with intermediate-stage HCC after TACE-MWA. ⢠The prognostic nomogram incorporating eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770.
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Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Micro-Ondas/uso terapêutico , Estadiamento de Neoplasias/métodos , Nomogramas , Terapia por Radiofrequência/métodos , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
Objective: To compare the oncological outcomes between microwave ablation (MWA) and surgical resection (SR) in patients with ovarian cancer liver metastasis (OCLM).Materials and methods: In this retrospective study, a total of 29 female patients (mean age, 47.8 ± 12.9 years; range, 21-65 years) diagnosed with forty-three OCLM nodules between September 2008 and July 2016 were included. All patients with ovarian cancer received chemotherapy and cytoreductive surgery (CRS). Fifteen patients with 22 nodules underwent MWA, and 14 patients with 21 nodules underwent SR. Overall survival (OS), local tumor recurrence-free survival (LTRS), and operation-related parameters were compared between the two groups. Multivariate analyses were performed on clinicopathological variables to identify factors affecting OS and LTRS.Results: The median follow-up time was 70.2 months (range, 12.1-107.2 months). Fourteen patients died during this period. The 1-, 3-, and 5-year OS and LTRS rates after MWA were comparable to those after SR (p = .198 and p = .889, respectively). Compared with the SR group, the MWA group had a shorter surgical time (p < .001), less estimated blood loss (p < .001), shorter postoperative hospitalization (p < .001) and fewer costs (p = .015). The multivariate analysis showed that old age (p = .001) was a predictor of poor OS and that intrahepatic tumor size (p = .005) and intrahepatic tumor number (p = .001) were predictors of poor LTRS.Conclusion: Percutaneous MWA had comparable oncologic outcomes with those of SR and could be a safe and effective treatment for OCLM.
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Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/cirurgia , Neoplasias Ovarianas/complicações , Ablação por Radiofrequência/métodos , Adulto , Idoso , Feminino , Humanos , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Objectives: To develop and validate the nomograms to predict survival outcomes after microwave ablation (MWA) in elderly patients(>65 years old) with early-stage hepatocellular carcinoma (EHCC).Methods: This retrospective study was approved by the institutional review board. A total of 265 EHCC patients (76 females, 189 males; average age 71.4 years ± 5.4 [standard deviation]) with 345 nodules subsequently underwent MWA from April 2006 to October 2019. Baseline characteristics were collected to identify the risk factors for the determination of survival outcomes after MWA. The nomograms were based on prognostic factors for overall survival (OS) and recurrence-free survival (RFS) from the multivariate Cox proportional hazards model and validated in external cohorts from another two institutions (n = 130). The nomograms were assessed for their predictive accuracy using Harrell's concordance index (C-index).Results: After a median follow-up time of 28.6 months, 29.8% (79/265) of the patients died, and 54.3% (144/265) of the patients experienced recurrence in the training set. The OS nomogram was developed based on the hepatitis B virus (HBV) presence, α-fetoprotein (AFP), and albumin, with a C-index of 0.757 (95% confidence interval [CI]: 0.645, 0.789).The scores of the nomogram ranged from 0 to 24. The RFS nomogram was developed based on tumor number, abutting major vessels and platelets, with a C-index of 0.733 (CI: 0.672, 0.774). The likelihood of 3- and 5-year OS and RFS were consistent between clinical observations and nomogram predictions in external cohorts.Conclusions: The nomogram models can be useful in determining the risk of OS and RFS in elderly patients with EHCC after MWA, which can guide individual patient management.Key pointsMWA is an effective and feasible treatment for elderly patients with EHCC and can improve survival outcomes.A calibrated and objective nomogram model for the prediction of survival outcomes in elderly patients (>65 years old) may guide patient selection and MWA treatment.Older age was not deemed to be a risk factor for survival outcomes when the elderly patients with EHCC underwent MWA.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Idoso , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Micro-Ondas , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Nomogramas , Prognóstico , Estudos RetrospectivosRESUMO
Purpose: To compare acute kidney injury (AKI) incidence between nephron sparing surgery (NSS) and microwave ablation (MWA) for T1a RCC patients, reveal the effect of AKI on survival prognosis, construct AKI nomogram and use Law of Total Probability for survival probability (SP) prediction.Materials and methods: Patients were studied retrospectively after NSS (n = 1267) or MWA (n = 210) from January 1, 2011 to June 30, 2017. Using one to one Propensity Score Matching (PSM), 158 pairs of patients were identified for the cohort study. AKI incidence, risk factors and impact on survival outcomes were analyzed using Chi-square test, logistic and cox regression analysis. AKI risk and SP were predicted by nomogram and Law of Total Probability. The performance of the nomogram was assessed with respect to its discrimination, calibration, and clinical usefulness.Results: AKI occurred more commonly in NSS (27.85%) cohort, when compared to MWA (17.72%) cohort (p = 0.032), but treatment modality was not independently predictive of AKI occurrence (odds ratio [OR]: 0.598; 95% confidence interval [CI]: 0.282-1.265; p = 0.178). The 5-yr overall survival (OS) was lower in AKI patients (73.5%) compared with non-AKI patients (94.8%; p < 0.001). AKI was an independent risk factor for all-cause mortality in RCC patients (hazard ratio [HR]: 2.820; 95% confidence interval [CI]: 1.110-7.165; p = 0.029). Predictors for both NSS- and MWA-related AKI included tumor diameter, baseline eGFR and CCI score. RENAL score and tumor blood supply can predict AKI after NSS and MWA, respectively. The AKI normograms demonstrated good discrimination, with AUCs >0.86, excellent calibration and net benefits at the decision curve analysis with probabilities ≥5%. SP predicted by Law of Total Probability was comparable to actual OS.Conclusion: AKI was an early indicator for poor overall survival in RCC patients. It can be predicted by several oncological parameters. Nomogram and Law of Total Probability can accurately predict AKI risk and SP.