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1.
Radiol Med ; 129(1): 1-13, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37861978

RESUMEN

PURPOSE: To evaluate the utility of dual-energy CT (DECT) in differentiating non-hypervascular pancreatic neuroendocrine neoplasms (PNENs) from pancreatic ductal adenocarcinomas (PDACs) with negative carbohydrate antigen 19-9 (CA 19-9). METHODS: This retrospective study included 26 and 39 patients with pathologically confirmed non-hypervascular PNENs and CA 19-9-negative PDACs, respectively, who underwent contrast-enhanced DECT before treatment between June 2019 and December 2021. The clinical, conventional CT qualitative, conventional CT quantitative, and DECT quantitative parameters of the two groups were compared using univariate analysis and selected by least absolute shrinkage and selection operator regression (LASSO) analysis. Multivariate logistic regression analyses were performed to build qualitative, conventional CT quantitative, DECT quantitative, and comprehensive models. The areas under the receiver operating characteristic curve (AUCs) of the models were compared using DeLong's test. RESULTS: The AUCs of the DECT quantitative (based on normalized iodine concentrations [nICs] in the arterial and portal venous phases: 0.918; 95% confidence interval [CI] 0.852-0.985) and comprehensive (based on tumour location and nICs in the arterial and portal venous phases: 0.966; 95% CI 0.889-0.995) models were higher than those of the qualitative (based on tumour location: 0.782; 95% CI 0.665-0.899) and conventional CT quantitative (based on normalized conventional CT attenuation in the arterial phase: 0.665; 95% CI 0.533-0.797; all P < 0.05) models. The DECT quantitative and comprehensive models had comparable performances (P = 0.076). CONCLUSIONS: Higher nICs in the arterial and portal venous phases were associated with higher blood supply improving the identification of non-hypervascular PNENs.


Asunto(s)
Carcinoma Ductal Pancreático , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Tomografía Computarizada por Rayos X , Estudios Retrospectivos , Medios de Contraste
2.
Radiol Med ; 2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-39400683

RESUMEN

BACKGROUND: Due to heterogeneity of molecular biology and microenvironment, therapeutic efficacy varies among hepatocellular carcinoma (HCC) patients treated with transcatheter arterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKIs). We examined combined models using clinicoradiological characteristics, mutational burden of signaling pathways, and radiomics features to predict survival prognosis. METHODS: Two cohorts comprising 111 patients with HCC were used to build prognostic models. The training and test cohorts included 78 and 33 individuals, respectively. Mutational burden was calculated based on 17 cancer-associated signaling pathways. Radiomic features were extracted and selected from computed tomography images using a pyradiomics system. Models based on clinicoradiological indicators, mutational burden, and radiomics score (rad-score) were built to predict overall survival (OS) and progression-free survival (PFS). RESULTS: Eastern Cooperative Oncology Group performance status, Child-Pugh class, peritumoral enhancement, PI3K_AKT and hypoxia mutational burden, and rad-score were used to create a combined model predicting OS. C-indices were 0.805 (training cohort) and 0.768 (test cohort). The areas under the curve (AUCs) were 0.889, 0.900, and 0.917 for 1-year, 2-year, and 3-year OS, respectively. To predict PFS, alpha-fetoprotein level, tumor enhancement pattern, hypoxia and receptor tyrosine kinase mutational burden, and rad-score were used. C-indices were 0.782 (training cohort) and 0.766 (test cohort). AUCs were 0.885 and 0.925 for 6-month and 12-month PFS, respectively. Calibration and decision curve analyses supported the model's accuracy and clinical potential. CONCLUSIONS: The nomogram models are hopeful to predict OS and PFS in patients with intermediate-advanced HCC treated with TACE plus TKIs, offering a promising tool for treatment decisions and monitoring patient progress.

3.
Int J Cancer ; 152(1): 90-99, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36111424

RESUMEN

Clinically effective methods to predict the efficacy of sunitinib, for patients with metastatic or locally advanced pancreatic neuroendocrine tumors (panNET) are scarce, making precision treatment difficult. This study aimed to develop and validate a computed tomography (CT)-based method to predict the efficacy of sunitinib in patients with panNET. Pretreatment CT images of 171 lesions from 38 patients with panNET were included. CT value ratio (CT value of tumor/CT value of abdominal aorta from the same patient) and radiomics features were extracted for model development. Receiver operating curve (ROC) with area under the curve (AUC) and decision curve analysis (DCA) were used to evaluate the proposed model. Tumor shrinkage of >10% at first follow-up after sunitinib treatment was significantly associated with longer progression-free survival (PFS; P < .001) and was used as the major treatment outcome. The CT value ratio could predict tumor shrinkage with AUC of 0.759 (95% confidence interval [CI], 0.685-0.833). We then developed a radiomics signature, which showed significantly higher AUC in training (0.915; 95% CI, 0.866-0.964) and validation (0.770; 95% CI, 0.584-0.956) sets than CT value ratio. DCA also confirmed the clinical utility of the model. Subgroup analysis showed that this radiomics signature had a high accuracy in predicting tumor shrinkage both for primary and metastatic tumors, and for treatment-naive and pretreated tumors. Survival analysis showed that radiomics signature correlated with PFS (P = .020). The proposed radiomics-based model accurately predicted tumor shrinkage and PFS in patients with panNET receiving sunitinib and may help select patients suitable for sunitinib treatment.


Asunto(s)
Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Sunitinib/uso terapéutico , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/tratamiento farmacológico , Tomografía Computarizada por Rayos X/métodos , Supervivencia sin Progresión , Estudios Retrospectivos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología
4.
BMC Cancer ; 23(1): 1092, 2023 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-37950223

RESUMEN

OBJECTIVES: Preoperative imaging of vascular invasion is important for surgical resection of pancreatic ductal adenocarcinoma (PDAC). However, whether MRI and CT share the same evaluation criteria remains unclear. This study aimed to compare the diagnostic accuracy of high-resolution MRI (HR-MRI), conventional MRI (non-HR-MRI) and CT for PDAC vascular invasion. METHODS: Pathologically proven PDAC with preoperative HR-MRI (79 cases, 58 with CT) and non-HR-MRI (77 cases, 59 with CT) were retrospectively collected. Vascular invasion was confirmed surgically or pathologically. The degree of tumour-vascular contact, vessel narrowing and contour irregularity were reviewed respectively. Diagnostic criteria 1 (C1) was the presence of all three characteristics, and criteria 2 (C2) was the presence of any one of them. The diagnostic efficacies of different examination methods and criteria were evaluated and compared. RESULTS: HR-MRI showed satisfactory performance in assessing vascular invasion (AUC: 0.87-0.92), especially better sensitivity (0.79-0.86 vs. 0.40-0.79) than that with non-HR-MRI and CT. HR-MRI was superior to non-HR-MRI. C2 was superior to C1 on CT evaluation (0.85 vs. 0.79, P = 0.03). C1 was superior to C2 in the venous assessment using HR-MRI (0.90 vs. 0.87, P = 0.04) and in the arterial assessment using non-HR-MRI (0.69 vs. 0.68, P = 0.04). The combination of C1-assessed HR-MRI and C2-assessed CT was significantly better than that of CT alone (0.96 vs. 0.86, P = 0.04). CONCLUSIONS: HR-MRI more accurately assessed PDAC vascular invasion than conventional MRI and may contribute to operative decision-making. C1 was more applicable to MRI scans, and C2 to CT scans. The combination of C1-assessed HR-MRI and C2-assessed CT outperformed CT alone and showed the best efficacy in preoperative examination of PDAC.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Estudios Retrospectivos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/patología , Imagen por Resonancia Magnética , Neoplasias Pancreáticas
5.
J Magn Reson Imaging ; 58(1): 12-25, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36971442

RESUMEN

This review aimed to perform a scoping review of promising MRI methods in assessing tumor hypoxia in hepatocellular carcinoma (HCC). The hypoxic microenvironment and upregulated hypoxic metabolism in HCC are determining factors of poor prognosis, increased metastatic potential, and resistance to chemotherapy and radiotherapy. Assessing hypoxia in HCC is essential for personalized therapy and predicting prognoses. Oxygen electrodes, protein markers, optical imaging, and positron emission tomography can evaluate tumor hypoxia. These methods lack clinical applicability because of invasiveness, tissue depth, and radiation exposure. MRI methods, including blood oxygenation level-dependent, dynamic contrast-enhanced MRI, diffusion-weighted imaging, MRI spectroscopy, chemical exchange saturation transfer MRI, and multinuclear MRI, are promising noninvasive methods that evaluate the hypoxic microenvironment by observing biochemical processes in vivo, which may inform on therapeutic options. This review summarizes the recent challenges and advances in MRI techniques for assessing hypoxia in HCC and highlights the potential of MRI methods for examining the hypoxic microenvironment via specific metabolic substrates and pathways. Although the utilization of MRI methods for evaluating hypoxia in patients with HCC is increasing, rigorous validation is needed in order to translate these MRI methods into clinical use. Due to the limited sensitivity and specificity of current quantitative MRI methods, their acquisition and analysis protocols require further improvement. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 4.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética/métodos , Hipoxia/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética , Microambiente Tumoral
6.
Eur Radiol ; 33(11): 7595-7608, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37231068

RESUMEN

OBJECTIVES: Differences in clinical adverse outcomes (CAO) based on different intestinal stricturing definitions in Crohn's disease (CD) are poorly documented. This study aims to compare CAO between radiological strictures (RS) and endoscopic strictures (ES) in ileal CD and explore the significance of upstream dilatation in RS. METHODS: This retrospective double-center study included 199 patients (derivation cohort, n = 157; validation cohort, n = 42) with bowel strictures who simultaneously underwent endoscopic and radiologic examinations. RS was defined as a luminal narrowing with wall thickening relative to the normal gut on cross-sectional imaging (group 1 (G1)), which further divided into G1a (without upstream dilatation) and G1b (with upstream dilatation). ES was defined as an endoscopic non-passable stricture (group 2 (G2)). Strictures met the definitions of RS (with or without upstream dilatation) and ES were categorized as group 3 (G3). CAO referred to stricture-related surgery or penetrating disease. RESULTS: In the derivation cohort, G1b (93.3%) had the highest CAO occurrence rate, followed by G3 (32.6%), G1a (3.2%), and G2 (0%) (p < 0.0001); the same order was found in the validation cohort. The CAO-free survival time was significantly different among the four groups (p < 0.0001). Upstream dilatation (hazard ratio, 1.126) was a risk factor for predicting CAO in RS. Furthermore, when upstream dilatation was added to diagnose RS, 17.6% of high-risk strictures were neglected. CONCLUSIONS: CAO differs significantly between RS and ES, and clinicians should pay more attention to strictures in G1b and G3. Upstream dilatation has an important impact on the clinical outcome of RS but may not be an essential factor for RS diagnosis. CLINICAL RELEVANCE STATEMENT: This study explored the definition of intestinal stricture with the greatest significance for the clinical diagnosis and prognosis of patients with CD, and consequently provided effective auxiliary information for clinicians to formulate strategies for the treatment of CD intestinal strictures. KEY POINTS: • The retrospective double-center study showed that clinical adverse outcome is different between radiological strictures and endoscopic strictures in CD. • Upstream dilatation has an important impact on the clinical outcome of radiological strictures but may not be an essential factor for diagnosis of radiological strictures. • Radiological stricture with upstream dilatation and simultaneous radiological and endoscopic stricture were at increased risk for clinical adverse outcomes; thus, closer monitoring should be considered.


Asunto(s)
Enfermedad de Crohn , Obstrucción Intestinal , Humanos , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico por imagen , Constricción Patológica/etiología , Estudios Retrospectivos , Resultado del Tratamiento , Endoscopía/métodos , Obstrucción Intestinal/diagnóstico por imagen , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugía , Dilatación/métodos , Endoscopía Gastrointestinal/métodos
7.
Hepatobiliary Pancreat Dis Int ; 22(6): 594-604, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36456428

RESUMEN

BACKGROUND: Although transarterial chemoembolization (TACE) is the first-line therapy for intermediate-stage hepatocellular carcinoma (HCC), it is not suitable for all patients. This study aimed to determine how to select patients who are not suitable for TACE as the first treatment choice. METHODS: A total of 243 intermediate-stage HCC patients treated with TACE at three centers were retrospectively enrolled, of which 171 were used for model training and 72 for testing. Radiomics features were screened using the Spearman correlation analysis and the least absolute shrinkage and selection operator (LASSO) algorithm. Subsequently, a radiomics model was established using extreme gradient boosting (XGBoost) with 5-fold cross-validation. The Shapley additive explanations (SHAP) method was used to visualize the radiomics model. A clinical model was constructed using univariate and multivariate logistic regression. The combined model comprising the radiomics signature and clinical factors was then established. This model's performance was evaluated by discrimination, calibration, and clinical application. Generalization ability was evaluated by the testing cohort. Finally, the model was used to analyze overall and progression-free survival of different groups. RESULTS: A third of the patients (81/243) were unsuitable for TACE treatment. The combined model had a high degree of accuracy as it identified TACE-unsuitable cases, at a sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of 0.759, 0.885, 0.906 [95% confidence interval (CI): 0.859-0.953] in the training cohort and 0.826, 0.776, and 0.894 (95% CI: 0.815-0.972) in the testing cohort, respectively. CONCLUSIONS: The high degree of accuracy of our clinical-radiomics model makes it clinically useful in identifying intermediate-stage HCC patients who are unsuitable for TACE treatment.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/efectos adversos , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Estudios Retrospectivos , Procedimientos Quirúrgicos Vasculares
8.
Gastroenterology ; 160(7): 2303-2316.e11, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33609503

RESUMEN

BACKGROUND & AIMS: No reliable method for evaluating intestinal fibrosis in Crohn's disease (CD) exists; therefore, we developed a computed-tomography enterography (CTE)-based radiomic model (RM) for characterizing intestinal fibrosis in CD. METHODS: This retrospective multicenter study included 167 CD patients with 212 bowel lesions (training, 98 lesions; test, 114 lesions) who underwent preoperative CTE and bowel resection at 1 of the 3 tertiary referral centers from January 2014 through June 2020. Bowel fibrosis was histologically classified as none-mild or moderate-severe. In the training cohort, 1454 radiomic features were extracted from venous-phase CTE and a machine learning-based RM was developed based on the reproducible features using logistic regression. The RM was validated in an independent external test cohort recruited from 3 centers. The diagnostic performance of RM was compared with 2 radiologists' visual interpretation of CTE using receiver operating characteristic (ROC) curve analysis. RESULTS: In the training cohort, the area under the ROC curve (AUC) of RM for distinguishing moderate-severe from none-mild intestinal fibrosis was 0.888 (95% confidence interval [CI], 0.818-0.957). In the test cohort, the RM showed robust performance across 3 centers with an AUC of 0.816 (95% CI, 0.706-0.926), 0.724 (95% CI, 0.526-0.923), and 0.750 (95% CI, 0.560-0.940), respectively. Moreover, the RM was more accurate than visual interpretations by either radiologist (radiologist 1, AUC = 0.554; radiologist 2, AUC = 0.598; both, P < .001) in the test cohort. Decision curve analysis showed that the RM provided a better net benefit to predicting intestinal fibrosis than the radiologists. CONCLUSIONS: A CTE-based RM allows for accurate characterization of intestinal fibrosis in CD.


Asunto(s)
Enfermedad de Crohn/diagnóstico por imagen , Enfermedad de Crohn/patología , Intestinos/diagnóstico por imagen , Intestinos/patología , Tomografía Computarizada por Rayos X/normas , Adulto , Enfermedad de Crohn/complicaciones , Femenino , Fibrosis , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Reproducibilidad de los Resultados , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X/métodos
9.
BMC Cancer ; 22(1): 709, 2022 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-35761201

RESUMEN

AIMS: With prevalence of hepatocellular carcinoma (HCC) in low-risk population (LRP), establishing a non-invasive diagnostic strategy becomes increasingly urgent to spare unnecessary biopsies in this population. The purposes of this study were to find characterisics of HCC and to establish a proper non-invasive method to diagnose HCC in LRP. METHODS: A total of 681 patients in LRP (defined as the population without cirrhosis, chronic HBV infection or HCC history) were collected from 2 institutions. The images of computed tomography (CT) and magnetic resonance imaging (MRI) were manually analysed. We divided the patients into the training cohort (n = 324) and the internal validating cohort (n = 139) by admission time in the first institution. The cohort in the second institution was viewed as the external validation (n = 218). A multivariate logistic regression model incorporating both imaging and clinical independent risk predictors was developed. C-statistics was used to evaluate the diagnostic performance. RESULTS: Besides the major imaging features of HCC (non-rim enhancement, washout and enhancing capsule), tumor necrosis or severe ischemia (TNSI) on imaging and two clinical characteristics (gender and alpha fetoprotein) were also independently associated with HCC diagnosis (all P < 0.01). A clinical model (including 3 major features, TNSI, gender and AFP) was built to diagnose HCC and achieved good diagnostic performance (area under curve values were 0.954 in the training cohort, 0.931 in the internal validation cohort and 0.902 in the external cohort). CONCLUSIONS: The clinical model in this study developed a satisfied non-invasive diagnostic performance for HCC in LRP.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Medios de Contraste , Humanos , Cirrosis Hepática/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X/métodos
10.
Eur Radiol ; 32(9): 6314-6326, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35420301

RESUMEN

OBJECTIVES: To evaluate the prognostic value of fibrosis for patients with pancreatic adenocarcinoma (PDAC) and preoperatively predict fibrosis using clinicoradiological features. Tumor fibrosis plays an important role in the chemoresistance of PDAC. However, the prognostic value of tumor fibrosis remains contradiction and accurate prediction of tumor fibrosis is required. METHODS: The study included 131 patients with PDAC who underwent first-line surgery. The prognostic value of fibrosis and rounded cutoff fibrosis points for median overall survival (OS) and disease-free survival (DFS) were determined using Cox regression and receiver operating characteristic (ROC) analyses. Then the whole cohort was randomly divided into training (n = 88) and validation (n = 43) sets. Binary logistic regression analysis was performed to select independent risk factors for fibrosis in the training set, and a nomogram was constructed. Nomogram performance was assessed using a calibration curve and decision curve analysis (DCA). RESULTS: Hazard ratios of fibrosis for OS and DFS were 1.121 (95% confidence interval [CI]: 1.082-1.161) and 1.110 (95% CI: 1.067-1.155). ROC analysis identified 40% as the rounded cutoff fibrosis point for median OS and DFS. Tumor diameter, carbohydrate antigen 19-9 level, and peripancreatic tumor infiltration were independent risk factors; areas under the nomogram curve were 0.810 and 0.804 in the training and validation sets, respectively. The calibration curve indicated good agreement of the nomogram, and DCA demonstrated good clinical usefulness. CONCLUSIONS: Tumor fibrosis was associated with poor OS and DFS in patients with PDAC. The nomogram incorporating clinicoradiological features was useful for preoperatively predicting tumor fibrosis. KEY POINTS: • Tumor fibrosis is correlated with poor prognosis in patients with pancreatic adenocarcinoma. • Tumor fibrosis can be categorized according to its association with overall survival and disease-free survival. • A nomogram incorporating carbohydrate antigen 19-9 level, tumor diameter, and peripancreatic tumor infiltration is useful for preoperatively predicting tumor fibrosis.


Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Carbohidratos , Fibrosis , Humanos , Estadificación de Neoplasias , Nomogramas , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Pronóstico , Neoplasias Pancreáticas
11.
Eur Radiol ; 32(12): 8692-8705, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35616733

RESUMEN

OBJECTIVES: Accurate evaluation of bowel fibrosis in patients with Crohn's disease (CD) remains challenging. Computed tomography enterography (CTE)-based radiomics enables the assessment of bowel fibrosis; however, it has some deficiencies. We aimed to develop and validate a CTE-based deep learning model (DLM) for characterizing bowel fibrosis more efficiently. METHODS: We enrolled 312 bowel segments of 235 CD patients (median age, 33 years old) from three hospitals in this retrospective study. A training cohort and test cohort 1 were recruited from center 1, while test cohort 2 from centers 2 and 3. All patients performed CTE within 3 months before surgery. The histological fibrosis was semi-quantitatively assessed. A DLM was constructed in the training cohort based on a 3D deep convolutional neural network with 10-fold cross-validation, and external independent validation was conducted on the test cohorts. The radiomics model (RM) was developed with 4 selected radiomics features extracted from CTE images by using logistic regression. The evaluation of CTE images was performed by two radiologists. DeLong's test and a non-inferiority test were used to compare the models' performance. RESULTS: DLM distinguished none-mild from moderate-severe bowel fibrosis with an area under the receiver operator characteristic curve (AUC) of 0.828 in the training cohort and 0.811, 0.808, and 0.839 in the total test cohort, test cohorts 1 and 2, respectively. In the total test cohort, DLM achieved better performance than two radiologists (*1 AUC = 0.579, *2 AUC = 0.646; both p < 0.05) and was not inferior to RM (AUC = 0.813, p < 0.05). The total processing time for DLM was much shorter than that of RM (p < 0.001). CONCLUSION: DLM is better than radiologists in diagnosing intestinal fibrosis on CTE in patients with CD and not inferior to RM; furthermore, it is more time-saving compared to RM. KEY POINTS: • Question Could computed tomography enterography (CTE)-based deep learning model (DLM) accurately distinguish intestinal fibrosis severity in patients with Crohn's disease (CD)? • Findings In this cross-sectional study that included 235 patients with CD, DLM achieved better performance than that of two radiologists' interpretation and was not inferior to RM with significant differences and much shorter processing time. • Meaning This DLM may accurately distinguish the degree of intestinal fibrosis in patients with CD and guide gastroenterologists to formulate individualized treatment strategies for those with bowel strictures.


Asunto(s)
Enfermedad de Crohn , Aprendizaje Profundo , Humanos , Adulto , Enfermedad de Crohn/patología , Intestino Delgado/patología , Estudios Retrospectivos , Estudios Transversales , Tomografía Computarizada por Rayos X/métodos , Fibrosis , Radiólogos
12.
AJR Am J Roentgenol ; 218(6): 999-1009, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35043668

RESUMEN

BACKGROUND. The 2019 WHO classification of digestive system tumors separates neuroendocrine neoplasms (NENs) into neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs), which are considered to represent pathologically distinct entities warranting different management approaches. Dual-layer spectral-detector CT (DLCT) may aid their differentiation through specific material decomposition. OBJECTIVE. The purpose of this study was to assess the utility of quantitative metrics derived from DLCT for the differentiation of pancreatic NET and NEC. METHODS. This retrospective study included 104 patients (mean age, 51 ± 13 [SD] years; 52 women, 52 men) with pathologically confirmed NEN (89 NET, including 22 grade 1, 48 grade 2, and 19 grade 3; 15 NEC) who underwent multiphase DLCT within 15 days before biopsy or resection. Two radiologists independently placed ROIs to record tumor attenuation, iodine concentration (IC), and effective atomic number (Zeff) across phases and assessed qualitative features (composition, homogeneity, margins, calcifications, main pancreatic duct dilatation, vascular invasion, lymphadenopathy). Interobserver agreement was assessed. Mean and median values of both readers' measurements were obtained for quantitative measures; consensus was reached for qualitative features. NET and NEC were compared using multivariable regression analysis and ROC analysis. RESULTS. Interobserver agreement, expressed as intraclass correlation coefficients, ranged from 0.869 to 0.992 for quantitative metrics and, expressed as kappa coefficients, ranged from 0.723 to 0.816 for qualitative features. In multivariable analysis of qualitative and quantitative features, significant independent predictors of NEC (p < .05) were IC in the portal venous phase (median, 1.3 mg/mL for NEC vs 2.7 mg/mL for NET), Zeff in the portal venous phase (median, 8.1 vs 8.6), and attenuation in the portal venous phase (median, 78.2 vs 113.5 HU). AUC for predicting NEC was 0.897 for IC, 0.884 for Zeff, 0.921 for combination of IC and Zeff, and 0.855 for attenuation. Predicted probability based on a combination of IC and Zeff achieved sensitivity of 93.33% and specificity of 80.90% for predicting NEC. Significant independent predictors (p < .05) for differentiating grade 3 NET and NEC were IC (median, 2.0 vs 1.3 mg/mL; AUC = 0.789) and attenuation (mean, 90.3 vs 78.2 HU; AUC = 0.647), both measured in the portal venous phase. CONCLUSION. Incorporation of DLCT metrics improves differentiation of NET and NEC compared with conventional CT attenuation and qualitative features. CLINICAL IMPACT. DLCT may help select patients with pancreatic NENs for platinum-based chemotherapies.


Asunto(s)
Carcinoma Neuroendocrino , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Adulto , Benchmarking , Carcinoma Neuroendocrino/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/metabolismo , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/metabolismo , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos
13.
BMC Cancer ; 21(1): 1167, 2021 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-34717582

RESUMEN

OBJECTIVES: To develop and validate a radiomics model for evaluating treatment response to immune-checkpoint inhibitor plus chemotherapy (ICI + CT) in patients with advanced esophageal squamous cell carcinoma (ESCC). METHODS: A total of 64 patients with advance ESCC receiving first-line ICI + CT at two centers between January 2019 and June 2020 were enrolled in this study. Both 2D ROIs and 3D ROIs were segmented. ComBat correction was applied to minimize the potential bias on the results due to different scan protocols. A total of 788 features were extracted and radiomics models were built on corrected/uncorrected 2D and 3D features by using 5-fold cross-validation. The performance of the radiomics models was assessed by its discrimination, calibration and clinical usefulness with independent validation. RESULTS: Five features and support vector machine algorithm were selected to build the 2D uncorrected, 2D corrected, 3D uncorrected and 3D corrected radiomics models. The 2D radiomics models significantly outperformed the 3D radiomics models in both primary and validation cohorts. When ComBat correction was used, the performance of 2D models was better (p = 0.0059) in the training cohort, and significantly better (p < 0.0001) in the validation cohort. The 2D corrected radiomics model yielded the optimal performance and was used to build the nomogram. The calibration curve of the radiomics model demonstrated good agreement between prediction and observation and the decision curve analysis confirmed the clinical utility. CONCLUSIONS: The easy-to-use 2D corrected radiomics model could facilitate noninvasive preselection of ESCC patients who would benefit from ICI + CT.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Esofágicas/diagnóstico por imagen , Carcinoma de Células Escamosas de Esófago/diagnóstico por imagen , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Máquina de Vectores de Soporte , Anticuerpos Monoclonales Humanizados/administración & dosificación , Sesgo , Biomarcadores de Tumor , Carboplatino/administración & dosificación , Terapia Combinada/métodos , Docetaxel/administración & dosificación , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nomogramas , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento
14.
Eur Radiol ; 31(7): 4720-4730, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33449173

RESUMEN

OBJECTIVES: To explore the role of quantitative regional liver function assessed by preoperative gadoxetic acid-enhanced MRI with computer-aided virtual hepatectomy to predict short-term outcomes after major hepatectomy for HCC. METHODS: We retrospectively reviewed the records of 133 consecutive patients with HCC who underwent preoperative gadoxetic acid-enhanced MRI and indocyanine green (ICG) test. Forty-five patients received open major hepatectomy. Liver function reserve and the future liver remnant were evaluated by computer-aided virtual hepatectomy. Global liver functional parameters included the T1 relaxation time reduction rate (T1ratio) and functional liver volume (FV), whereas regional parameters included the rT1pos, rT1ratio, remnant FV (rFV), and remnant FV ratio (rFVratio) of the remnant liver. The functional parameters of the MRI and ICG were used to predict the short-term outcomes (liver failure and major complications) after major hepatectomy. RESULTS: The T1ratio and FV were correlated with the ICG test (rho = - 0.304 and - 0.449, p < 0.05). FV < 682.8 ml indicated preoperative ICG-R15 ≥ 14% with 0.765 value of the area under the curve (AUC). No patient who underwent major resection with good liver functional reserve (ICG < 14%) and enough future remnant volume (> 30% standard LV) developed liver failure. Low rT1ratio (< 66.5%) and high rT1pos (> 217.5 ms) may predict major complications (AUC = 0.831 and 0.756, respectively; p < 0.05). The rT1ratio was an independent risk factor for postoperative major complications (odds ratio [OR] = 0.845, 95% CI, 0.736-0.966; p < 0.05). CONCLUSION: Preoperative gadoxetic acid-enhanced MRI with computer-aided virtual hepatectomy may facilitate optimal assessment of regional liver functional reserve to predict short-term outcomes after major hepatectomy for HCC. KEY POINTS: • Preoperative gadoxetic acid-enhanced MRI with virtual hepatectomy and volumetric analysis can provide precise liver volume and regional functional assessment. • Quantitative regional liver function assessed by gadoxetic acid-enhanced MRI can predict the short-term outcomes after major hepatectomy in patients with HCC. • The regional liver function assessed by gadoxetic acid-enhanced MRI is an independent risk factor for postoperative major complications.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Gadolinio DTPA , Hepatectomía , Humanos , Hígado/diagnóstico por imagen , Pruebas de Función Hepática , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Imagen por Resonancia Magnética , Estudios Retrospectivos
15.
Eur Radiol ; 31(11): 8615-8627, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33877387

RESUMEN

OBJECTIVES: Pretreatment evaluation of tumor biology and microenvironment is important to predict prognosis and plan treatment. We aimed to develop nomograms based on gadoxetic acid-enhanced MRI to predict microvascular invasion (MVI), tumor differentiation, and immunoscore. METHODS: This retrospective study included 273 patients with HCC who underwent preoperative gadoxetic acid-enhanced MRI. Patients were assigned to two groups: training (N = 191) and validation (N = 82). Univariable and multivariable logistic regression analyses were performed to investigate clinical variables and MRI features' associations with MVI, tumor differentiation, and immunoscore. Nomograms were developed based on features associated with these three histopathological features in the training cohort, then validated, and evaluated. RESULTS: Predictors of MVI included tumor size, rim enhancement, capsule, percent decrease in T1 images (T1D%), standard deviation of apparent diffusion coefficient, and alanine aminotransferase levels, while capsule, peritumoral enhancement, mean relaxation time on the hepatobiliary phase (T1E), and alpha-fetoprotein levels predicted tumor differentiation. Predictors of immunoscore included the radiologic score constructed by tumor number, intratumoral vessel, margin, capsule, rim enhancement, T1D%, relaxation time on plain scan (T1P), and alpha-fetoprotein and alanine aminotransferase levels. Three nomograms achieved good concordance indexes in predicting MVI (0.754, 0.746), tumor differentiation (0.758, 0.699), and immunoscore (0.737, 0.726) in the training and validation cohorts, respectively. CONCLUSION: MRI-based nomograms effectively predict tumor behaviors in HCC and may assist clinicians in prognosis prediction and pretreatment decisions. KEY POINTS: • This study developed and validated three nomograms based on gadoxetic acid-enhanced MRI to predict MVI, tumor differentiation, and immunoscore in patients with HCC. • The pretreatment prediction of tumor microenvironment may be useful to guide accurate prognosis and planning of surgical and immunological therapies for individual patients with HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagen , Medios de Contraste , Gadolinio DTPA , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Imagen por Resonancia Magnética , Invasividad Neoplásica , Nomogramas , Estudios Retrospectivos , Microambiente Tumoral
16.
BMC Gastroenterol ; 21(1): 215, 2021 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-33971815

RESUMEN

BACKGROUND: The normalization of liver biochemical parameters usually reflects the histological response to treatment for nonalcoholic fatty liver disease (NAFLD). Researchers have not clearly determined whether different liver enzymes exhibit various metabolic changes during the follow-up period in patients with NAFLD. METHODS: We performed a retrospective analysis of patients with NAFLD who were receiving therapy from January 2011 to December 2019. Metabolism indexes, including glucose levels, lipid profiles, uric acid levels and liver biochemical parameters, were measured. Magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) and liver ultrasound were used to evaluate steatosis. All patients received recommendations for lifestyle modifications and guideline-recommended pharmacological treatments with indications for drug therapy for metabolic abnormalities. RESULTS: Overall, 1048 patients with NAFLD were included and received lifestyle modification recommendations and pharmaceutical interventions, including 637 (60.7%) patients with abnormal GGT levels and 767 (73.2%) patients with abnormal ALT levels. Patients with concurrent ALT and GGT abnormalities presented higher levels of metabolism indexes and higher liver fat content than those in patients with single or no abnormalities. After 12 months of follow-up, the cumulative normalization rate of GGT was considerably lower than that of ALT (38% vs. 62%, P < 0.001). Greater weight loss resulted in higher cumulative normalization rates of GGT and ALT. Weight loss (OR = 1.21, 95% CI 1.11-1.32, P < 0.001), ALT normalization (OR = 2.75, 95% CI 1.41-5.36, P = 0.01) and lower TG and HOMA-IR values (OR = 2.03, 95% CI 1.11-3.71, P = 0.02; OR = 2.04, 95% CI 1.07-3.89, P = 0.03) were independent protective factors for GGT normalization. Elevated baseline GGT (OR = 0.99, 95% CI 0.98-0.99, P = 0.01) was a risk factor. CONCLUSIONS: For NAFLD patients with concurrently increased ALT and GGT levels, a lower normalization rate of GGT was observed, rather than ALT. Good control of weight and insulin resistance was a reliable predictor of GGT normalization.


Asunto(s)
Resistencia a la Insulina , Enfermedad del Hígado Graso no Alcohólico , Humanos , Hígado/diagnóstico por imagen , Pruebas de Función Hepática , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Estudios Retrospectivos , gamma-Glutamiltransferasa
17.
BMC Cancer ; 20(1): 322, 2020 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-32293344

RESUMEN

BACKGROUND: Response evaluation of neoadjuvant chemotherapy (NACT) in patients with osteosarcoma is significant for the termination of ineffective treatment, the development of postoperative chemotherapy regimens, and the prediction of prognosis. However, histological response and tumour necrosis rate can currently be evaluated only in resected specimens after NACT. A preoperatively accurate, noninvasive, and reproducible method of response assessment to NACT is required. In this study, the value of multi-parametric magnetic resonance imaging (MRI) combined with machine learning for assessment of tumour necrosis after NACT for osteosarcoma was investigated. METHODS: Twelve patients with primary osteosarcoma of limbs underwent NACT and received MRI examination before surgery. Postoperative tumour specimens were made corresponding to the transverse image of MRI. One hundred and two tissue samples were obtained and pathologically divided into tumour survival areas (non-cartilaginous and cartilaginous tumour viable areas) and tumour-nonviable areas (non-cartilaginous tumour necrosis areas, post-necrotic tumour collagen areas, and tumour necrotic cystic/haemorrhagic and secondary aneurismal bone cyst areas). The MRI parameters, including standardised apparent diffusion coefficient (ADC) values, signal intensity values of T2-weighted imaging (T2WI) and subtract-enhanced T1-weighted imaging (ST1WI) were used to train machine learning models based on the random forest algorithm. Three classification tasks of distinguishing tumour survival, non-cartilaginous tumour survival, and cartilaginous tumour survival from tumour nonviable were evaluated by five-fold cross-validation. RESULTS: For distinguishing non-cartilaginous tumour survival from tumour nonviable, the classifier constructed with ADC achieved an AUC of 0.93, while the classifier with multi-parametric MRI improved to 0.97 (P = 0.0933). For distinguishing tumour survival from tumour nonviable, the classifier with ADC achieved an AUC of 0.83, while the classifier with multi-parametric MRI improved to 0.90 (P < 0.05). For distinguishing cartilaginous tumour survival from tumour nonviable, the classifier with ADC achieved an AUC of 0.61, while the classifier with multi-parametric MRI parameters improved to 0.81(P < 0.05). CONCLUSIONS: The combination of multi-parametric MRI and machine learning significantly improved the discriminating ability of viable cartilaginous tumour components. Our study suggests that this method may provide an objective and accurate basis for NACT response evaluation in osteosarcoma.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/tratamiento farmacológico , Osteosarcoma/diagnóstico por imagen , Osteosarcoma/tratamiento farmacológico , Adolescente , Neoplasias Óseas/patología , Niño , Estudios de Factibilidad , Femenino , Humanos , Aprendizaje Automático , Masculino , Imagen Multimodal , Imágenes de Resonancia Magnética Multiparamétrica , Necrosis , Terapia Neoadyuvante , Osteosarcoma/patología , Periodo Preoperatorio , Estudios Prospectivos , Resultado del Tratamiento , Adulto Joven
18.
BMC Cancer ; 20(1): 54, 2020 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-31969123

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) with hilar bile duct tumor thrombus (HBDTT) often mimic hilar cholangiocarcinoma (hilar CC). The purpose of this study is to analyze the Computed Tomography (CT) characteristics of HCC with HBDTT and to identify imaging features to aid its differentiation from hilar CC on enhanced CT. METHODS: We retrospectively identified 58 cases with pathologically proved HCC with HBDTT between 2011 and 2018. Seventy-seven cases of pathologically proven hilar CCs were selected during the same period. The clinical features and CT findings of the two groups were reviewed and compared. RESULTS: HCC with HBDTTs are more commonly found in men (87.9% vs 63.6%, p = 0.001) with lower age of onset (49.84 vs 58.61 years; p < 0.001) in comparison to hilar CCs. Positive correlation were identified between HCC with HBDTTs and chronic HBV infection (72.4% vs 11.7%; p <  0.001), increased serum AFP (67.2% vs 1.3%; p <  0.001), CA19-9 level (58.6% vs 85.7%; p <  0.001) and CEA level (3.4% vs 29.9%; p = 0.001), parenchymal lesion with intraductal lesion (100% vs 18.2%; p <  0.001), washout during the portal venous phase (84.5% vs 6.5%; p <  0.001), thickened bile duct wall (8.6% vs 93.5%; p <  0.001), intrahepatic vascular embolus (44.8% vs 7.8%; p <  0.001), splenomegaly (34.5% vs 2.6%, p <  0.001). A scoring system consisting of the five parameters obtained from characteristics mentioned above was trialed. The sensitivity and specificity for diagnosing HCC with HBDTT were 96.39, 100 and 92.5% respectively when the total score was 2 or more. CONCLUSIONS: HCC with HBDTTs are often distinguishable from hilar CCs based on washout during portal venous phase without thickened bile duct wall. HBV infection and serum AFP level facilitate the differentiation.


Asunto(s)
Neoplasias de los Conductos Biliares/diagnóstico por imagen , Carcinoma Hepatocelular/diagnóstico por imagen , Tumor de Klatskin/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Trombosis/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos de Investigación , Estudios Retrospectivos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X
19.
BMC Cancer ; 20(1): 468, 2020 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-32450841

RESUMEN

BACKGROUND: Neoadjuvant chemotherapy is a promising treatment option for potential resectable gastric cancer, but patients' responses vary. We aimed to develop and validate a radiomics score (rad_score) to predict treatment response to neoadjuvant chemotherapy and to investigate its efficacy in survival stratification. METHODS: A total of 106 patients with neoadjuvant chemotherapy before gastrectomy were included (training cohort: n = 74; validation cohort: n = 32). Radiomics features were extracted from the pre-treatment portal venous-phase CT. After feature reduction, a rad_score was established by Randomised Tree algorithm. A rad_clinical_score was constructed by integrating the rad_score with clinical variables, so was a clinical score by clinical variables only. The three scores were validated regarding their discrimination and clinical usefulness. The patients were stratified into two groups according to the score thresholds (updated with post-operative clinical variables), and their survivals were compared. RESULTS: In the validation cohort, the rad_score demonstrated a good predicting performance in treatment response to the neoadjuvant chemotherapy (AUC [95% CI] =0.82 [0.67, 0.98]), which was better than the clinical score (based on pre-operative clinical variables) without significant difference (0.62 [0.42, 0.83], P = 0.09). The rad_clinical_score could not further improve the performance of the rad_score (0.70 [0.51, 0.88], P = 0.16). Based on the thresholds of these scores, the high-score groups all achieved better survivals than the low-score groups in the whole cohort (all P < 0.001). CONCLUSION: The rad_score that we developed was effective in predicting treatment response to neoadjuvant chemotherapy and in stratifying patients with gastric cancer into different survival groups. Our proposed strategy is useful for individualised treatment planning.


Asunto(s)
Algoritmos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Neoadyuvante/mortalidad , Nomogramas , Neoplasias Gástricas/mortalidad , Tomografía Computarizada por Rayos X/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Estudios Retrospectivos , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Tasa de Supervivencia
20.
Neuroendocrinology ; 110(5): 338-350, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31525737

RESUMEN

INTRODUCTION: The pathological grading of pancreatic neuroendocrine neoplasms (pNENs) is an independent predictor of survival and indicator for treatment. Deep learning (DL) with a convolutional neural network (CNN) may improve the preoperative prediction of pNEN grading. METHODS: Ninety-three pNEN patients with preoperative contrast-enhanced computed tomography (CECT) from Hospital I were retrospectively enrolled. A CNN-based DL algorithm was applied to the CECT images to obtain 3 models (arterial, venous, and arterial/venous models), the performances of which were evaluated via an eightfold cross-validation technique. The CECT images of the optimal phase were used for comparing the DL and traditional machine learning (TML) models in predicting the pathological grading of pNENs. The performance of radiologists by using qualitative and quantitative computed tomography findings was also evaluated. The best DL model from the eightfold cross-validation was evaluated on an independent testing set of 19 patients from Hospital II who were scanned on a different scanner. The Kaplan-Meier (KM) analysis was employed for survival analysis. RESULTS: The area under the curve (AUC; 0.81) of arterial phase in validation set was significantly higher than those of venous (AUC 0.57, p = 0.03) and arterial/venous phase (AUC 0.70, p = 0.03) in predicting the pathological grading of pNENs. Compared with the TML models, the DL model gave a higher (although insignificantly) AUC. The highest OR was achieved for the p ratio <0.9, the AUC and accuracy for diagnosing G3 pNENs were 0.80 and 79.1% respectively. The DL algorithm achieved an AUC of 0.82 and an accuracy of 88.1% for the independent testing set. The KM analysis showed a statistical significant difference between the predicted G1/2 and G3 groups in the progression-free survival (p = 0.001) and overall survival (p < 0.001). CONCLUSION: The CNN-based DL method showed a relatively robust performance in predicting pathological grading of pNENs from CECT images.


Asunto(s)
Interpretación de Imagen Asistida por Computador/métodos , Aprendizaje Automático , Clasificación del Tumor/métodos , Redes Neurales de la Computación , Tumores Neuroendocrinos/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Tomografía Computarizada Espiral , Adulto , Anciano , Aprendizaje Profundo , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/normas , Masculino , Persona de Mediana Edad , Clasificación del Tumor/normas , Estudios Retrospectivos
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