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PURPOSE: This study aimed to verify the feasibility and short-term prognosis of prostatectomy without biopsy. MATERIALS AND METHODS: Patients with a rising PSA level ranging from 4 to 30 ng/mL were scheduled for multiparametric (mp) MRI and 18F-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET). Forty-seven patients (cT2N0M0) with Prostate Imaging Reporting and Data System ≥ 4 and molecular imaging PSMA score ≥ 2 were enrolled. All candidates underwent robot-assisted laparoscopic radical prostatectomy without biopsy. Prostate cancer detection rate, index tumors localization correspondence rate, positive surgical margin, complications, postoperative hospital stay, and PSA level in a 6-week postoperative follow-up visit were collected. RESULTS: All the patients with positive mpMRI and PSMA PET were diagnosed with clinically significant prostate cancer. A total of 80 lesions were verified as cancer by pathology, of which 63 cancer lesions were clinically significant prostate cancer. Fifty-one lesions were simultaneously found by mpMRI and PSMA PET. A total of 23 lesions were invisible on either image, and all lesions were ≤ International Society of Urological Pathology 2 or ≤ 15 mm. Forty-five (95.7%) index tumors found by mpMRI combined with PSMA PET were consistent with pathology. Nine patients reported positive surgical margin. CONCLUSIONS: Biopsy-free prostatectomy is safe and feasible for patients with evaluation strictly by mpMRI combined with 18F-PSMA PET/CT.
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Imágenes de Resonancia Magnética Multiparamétrica , Tomografía Computarizada por Tomografía de Emisión de Positrones , Prostatectomía , Neoplasias de la Próstata , Humanos , Masculino , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios Prospectivos , Persona de Mediana Edad , Anciano , Estudios de Factibilidad , Glutamato Carboxipeptidasa II , Antígenos de Superficie , Radioisótopos de Flúor , Antígeno Prostático Específico/sangre , Biopsia/métodos , Próstata/patología , Próstata/diagnóstico por imagen , Próstata/cirugía , Selección de Paciente , RadiofármacosRESUMEN
BACKGROUND: Identification of non-diabetic renal disease (NDRD) in patients with type 2 diabetes mellitus (T2DM) may help tailor treatment. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) is a promising tool to evaluate renal function but its potential role in the clinical differentiation between diabetic nephropathy (DN) and NDRD remains unclear. PURPOSE: To investigate the added role of IVIM-DWI in the differential diagnosis between DN and NDRD in patients with T2DM. STUDY TYPE: Prospective. POPULATION: Sixty-three patients with T2DM (ages: 22-69 years, 17 females) confirmed by renal biopsy divided into two subgroups (28 DN and 35 NDRD). FIELD STRENGTH/SEQUENCE: 3 T/ T2 weighted imaging (T2WI), and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). ASSESSMENT: The parameters derived from IVIM-DWI (true diffusion coefficient [D], pseudo-diffusion coefficient [D*], and pseudo-diffusion fraction [f]) were calculated for the cortex and medulla, respectively. The clinical indexes related to renal function (eg cystatin C, etc.) and diabetes (eg diabetic retinopathy [DR], fasting blood glucose, etc.) were measured and calculated within 1 week before MRI scanning. The clinical model based on clinical indexes and the IVIM-based model based on IVIM parameters and clinical indexes were established and evaluated, respectively. STATISTICAL TESTS: Student's t-test; Mann-Whitney U test; Fisher's exact test; Chi-squared test; Intraclass correlation coefficient; Receiver operating characteristic analysis; Hosmer-Lemeshow test; DeLong's test. P < 0.05 was considered statistically significant. RESULTS: The cortex D*, DR, and cystatin C values were identified as independent predictors of NDRD in multivariable analysis. The IVIM-based model, comprising DR, cystatin C, and cortex D*, significantly outperformed the clinical model containing only DR, and cystatin C (AUC = 0.934, 0.845, respectively). DATA CONCLUSION: The IVIM parameters, especially the renal cortex D* value, might serve as novel indicators in the differential diagnosis between DN and NDRD in patients with T2DM. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Femenino , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Nefropatías Diabéticas/diagnóstico por imagen , Cistatina C , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Estudios Prospectivos , Imagen de Difusión por Resonancia Magnética/métodos , Imagen por Resonancia Magnética , Movimiento (Física)RESUMEN
BACKGROUND: Venous tumor thrombus (VTT) consistency of renal cell carcinoma (RCC) is an important consideration in nephrectomy plus thrombectomy. However, evaluation of VTT consistency through preoperative MR imaging is lacking. PURPOSE: To evaluate VTT consistency of RCC through intravoxel incoherent motion-diffusion weighted imaging (IVIM-DWI) derived parameters (Dt , Dp , f, and ADC) and the apparent diffusion coefficient (ADC) value. STUDY TYPE: Retrospective. POPULATION: One hundred and nineteen patients (aged 55.8 ± 11.5 years, 85 male) with histologically-proven RCC and VTT who underwent radical resection. FIELD STRENGTH/SEQUENCES: 3.0-T; two-dimensional single-shot diffusion-weighted echo planar imaging sequence at 9 b-values (0-800 s/mm2 ). ASSESSMENT: IVIM parameters and ADC values of the primary tumor and the VTT were calculated. The VTT consistency (friable vs. solid) was determined through intraoperative findings of two urologists. The accuracy of VTT consistency classification based on the individual IVIM parameters of primary tumors and of VTT, and based on models combining parameters, was assessed. Type of operation, intra-operative blood loss, and operation length were recorded. STATISTICAL TESTS: Shapiro-Wilk test; Mann-Whitney U test; Student's t-test; Chi-square test; Receiver operating characteristic (ROC) analysis. Statistical significance level was P < 0.05. RESULTS: Of the enrolled 119 patients, 33 patients (27.7%) had friable VTT. Patients with friable VTT were significantly more likely to experience open surgery, have significantly more intraoperative blood loss, and significantly longer operative duration. The area under the ROC curve (AUC) values of Dt of the primary tumor and VTT in classifying VTT consistency were 0.758 (95% CI 0.671-0.832) and 0.712 (95% CI 0.622-0.792), respectively. The AUC value of the model combining Dp and Dt of VTT was 0.800 (95% CI 0.717-0.868). Furthermore, the AUC of the model combining Dp and Dt of VTT and Dt of the primary tumor was 0.886 (95% CI 0.814-0.937). CONCLUSION: IVIM-derived parameters had the potential to predict VTT consistency of RCC. EVIDENCE LEVEL: 3 Technical Efficacy: Stage 2.
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Carcinoma de Células Renales , Neoplasias Renales , Trombosis , Humanos , Masculino , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/cirugía , Estudios Retrospectivos , Venas , Imagen de Difusión por Resonancia Magnética/métodos , Movimiento (Física) , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/cirugía , Trombosis/diagnóstico por imagenRESUMEN
BACKGROUND: Clear cell likelihood score (ccLS) is reliable for diagnosing small renal masses (SRMs). However, the diagnostic value of Clear cell likelihood score version 1.0 (ccLS v1.0) and v2.0 for common subtypes of SRMs might be a potential score extension. PURPOSE: To compare the diagnostic performance and interobserver agreement of ccLS v1.0 and v2.0 for characterizing five common subtypes of SRMs. STUDY TYPE: Retrospective. POPULATION: 797 patients (563 males, 234 females; mean age, 53 ± 12 years) with 867 histologically proven renal masses. FIELD STRENGTH/SEQUENCES: 3.0 and 1.5 T/T2 weighted imaging, T1 weighted imaging, diffusion-weighted imaging, a dual-echo chemical shift (in- and opposed-phase) T1 weighted imaging, multiphase dynamic contrast-enhanced imaging. ASSESSMENT: Six abdominal radiologists were trained in the ccLS algorithm and independently scored each SRM using ccLS v1.0 and v2.0, respectively. All SRMs had definite pathological results. The pooled area under curve (AUC), accuracy, sensitivity, and specificity were calculated to evaluate the diagnostic performance of ccLS v1.0 and v2.0 for characterizing common subtypes of SRMs. The average κ values were calculated to evaluate the interobserver agreement of the two scoring versions. STATISTICAL TESTS: Random-effects logistic regression; Receiver operating characteristic analysis; DeLong test; Weighted Kappa test; Z test. The statistical significance level was P < 0.05. RESULTS: The pooled AUCs of clear cell likelihood score version 2.0 (ccLS v2.0) were statistically superior to those of ccLS v1.0 for diagnosing clear cell renal cell carcinoma (ccRCC) (0.907 vs. 0.851), papillary renal cell carcinoma (pRCC) (0.926 vs. 0.888), renal oncocytoma (RO) (0.745 vs. 0.679), and angiomyolipoma without visible fat (AMLwvf) (0.826 vs. 0.766). Interobserver agreement for SRMs between ccLS v1.0 and v2.0 is comparable and was not statistically significant (P = 0.993). CONCLUSION: The diagnostic performance of ccLS v2.0 surpasses that of ccLS v1.0 for characterizing ccRCC, pRCC, RO, and AMLwvf. Especially, the standardized algorithm has optimal performance for ccRCC and pRCC. ccLS has potential as a supportive clinical tool. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.
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BACKGROUND: Prostate biopsy is still unavoidable in patients with a rising prostate-specific antigen even though multiparametric magnetic resonance imaging (MRI) is widely used. 18 F-DCFPyL positron emission tomography (PET)/MRI was proved to be promising both in sensitivity and specificity. But its guiding fusion biopsy and the advantages in the diagnosis of prostate disease is seldom reported. This study aimed to verify the feasibility and advantage of 18 F-DCFPyL PET/MRI-guided fusion targeted biopsy (TB) over whole-mount histopathology (WMH) for prostate cancer diagnosis. METHODS: A prospective study of 94 biopsy-naïve patients were conducted using 18 F-DCFPyL PET/MRI scans and scored on a scale of 1-4. Systematic biopsy was performed for all patients. Patients with suspicious lesions also underwent PET/MRI/transrectal ultrasound-guided fusion biopsy. Patients with pathologically confirmed cancer underwent surgery and WMH sections. Systematic biopsy was compared with TB for the detection of index tumors (ITs). Significant cancer was defined as Grade group (GG) 2 or higher no matter the length of the cancer core. RESULTS: 18 F-DCFPyL PET/MRI detected 30/94 (32%) patients with a score of 4, all of whom were verified to have prostate cancer. While it detected 10 patients with a score of 1 (10.6%), they were shown to have no cancer. The sensitivity and specificity of 18 F-DCFPyL PET/MRI were 94.4% and 75%, respectively, if images with a score of 3 are defined as positive. Systematic biopsy detected 18% (203/1128) samples as prostate cancer; conversely, TB detected 113 samples out of 259 scores (43.6%). A statistically significant difference was seen between the PCa detection rates by TB and SB (p < 0.001). All targeted lesions were pathologically proven to be the IT on WMH. CONCLUSIONS: In biopsy-naïve patients, the ultrasound fusion biopsy targeted by 18 F-DCFPyL PET/MRI is an identical pathway for the detection of prostate cancer.
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Próstata , Neoplasias de la Próstata , Masculino , Humanos , Próstata/diagnóstico por imagen , Próstata/patología , Estudios Prospectivos , Biopsia Guiada por Imagen/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Imagen por Resonancia Magnética/métodos , Tomografía de Emisión de PositronesRESUMEN
PURPOSE: We introduce an intrapericardial control technique using a robotic approach in the surgical treatment of renal tumor with level IV inferior vena cava thrombus to decrease the severe complications associated with cardiopulmonary bypass and deep hypothermic circulatory arrest. MATERIALS AND METHODS: Eight patients with level IV inferior vena cava thrombi not extending into the atrium underwent transabdominal-transdiaphragmatic robot-assisted inferior vena cava thrombectomy obviating cardiopulmonary bypass/deep hypothermic circulatory arrest (cardiopulmonary bypass-free group) by an expert team comprising urological, hepatobiliary, and cardiovascular surgeons. The central diaphragm tendon and pericardium were transabdominally dissected until the intrapericardial inferior vena cava were exposed and looped proximal to the cranial end of the thrombi under intraoperative ultrasound guidance. As controls, 14 patients who underwent robot-assisted inferior vena cava thrombectomy with cardiopulmonary bypass (cardiopulmonary bypass group) and 25 patients who underwent open thrombectomy with cardiopulmonary bypass/deep hypothermic circulatory arrest (cardiopulmonary bypass/deep hypothermic circulatory arrest group) were included. Clinicopathological, operative, and survival outcomes were retrospectively analyzed. RESULTS: Eight robot-assisted inferior vena cava thrombectomies were successfully performed without cardiopulmonary bypass, with 1 open conversion. The median operation time and first porta hepatis occlusion time were shorter, and estimated blood loss was lower in the cardiopulmonary bypass-free group as compared to the cardiopulmonary bypass group (540 vs 586.5 minutes, 16.5 vs 38.5. minutes, and 2,050 vs 3,500 mL, respectively). Severe complications (level IV-V) were also lower in the cardiopulmonary bypass-free group than in cardiopulmonary bypass and cardiopulmonary bypass/deep hypothermic circulatory arrest groups (25% vs 50% vs 40%). Oncologic outcomes were comparable among the 3 groups in short-term follow-up. CONCLUSIONS: Pure transabdominal-transdiaphragmatic robot-assisted inferior vena cava thrombectomy without cardiopulmonary bypass/deep hypothermic circulatory arrest represents as an alternative minimally invasive approach for selected level IV inferior vena cava thrombi.
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Robótica , Vena Cava Inferior , Humanos , Vena Cava Inferior/cirugía , Estudios RetrospectivosRESUMEN
OBJECTIVES: Determine the proportion of malignancy within Bosniak v2019 classes. METHODS: MEDLINE and EMBASE were searched. Eligible studies contained patients with cystic renal masses undergoing CT or MRI renal protocol examinations with pathology confirmation, applying Bosniak v2019. Proportion of malignancy was estimated within Bosniak v2019 class. Risk of bias was assessed using QUADAS-2. RESULTS: We included 471 patients with 480 cystic renal masses. No class I malignant masses were observed. Pooled proportion of malignancy were class II, 12% (6/51, 95% CI 5-24%); class IIF, 46% (37/85, 95% CI 28-66%); class III, 79% (138/173, 95% CI 68-88%); and class IV, 84% (114/135, 95% CI 77-90%). Proportion of malignancy differed between Bosniak v2019 II-IV classes (p = 0.004). Four studies reported the proportion of malignancy by wall/septa feature. The pooled proportion of malignancy with 95% CI were class III thick smooth wall/septa, 77% (41/56, 95% CI 53-91%); class III obtuse protrusion ≤ 3 mm (irregularity), 83% (97/117, 95% CI 75-89%); and class IV nodule with acute angulation, 86% (50/58, 95% CI 75-93%) or obtuse angulation ≥ 4 mm, 83%, (64/77, 95% CI 73-90%). Subgroup analysis by wall/septa feature was limited by sample size; however, no differences were found comparing class III masses with irregularity to class IV masses (p = 0.74) or between class IV masses by acute versus obtuse angles (p = 0.62). CONCLUSION: Preliminary data suggest Bosniak v2019 class IIF masses have higher proportion of malignancy compared to the original classification, controlling for pathologic reference standard. There are no differences in proportion of malignancy comparing class III masses with irregularities to class IV masses with acute or obtuse nodules. KEY POINTS: ⢠The proportion of malignancy in Bosniak v2019 class IIF cystic masses is 46% (37 malignant/85 total IIF masses, 95% confidence intervals (CI) 28-66%). ⢠The proportion of malignancy in Bosniak v2019 class III cystic masses is 79% (138/173, 95% CI 68-88%) and in Bosniak v2019 class IV cystic masses is 84% (114/135, 95% CI 77-90%). ⢠Class III cystic masses with irregularities had similar proportion of malignancy (83%, 97/117, 95% CI 75-89%) compared to Bosniak class IV masses (84%, 114/135, 95% CI 77-90%) overall (p = 0.74) with no difference within class IV masses by acute versus obtuse angulation (p = 0.62).
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Carcinoma de Células Renales , Enfermedades Renales Quísticas , Neoplasias Renales , Humanos , Enfermedades Renales Quísticas/diagnóstico por imagen , Enfermedades Renales Quísticas/epidemiología , Tomografía Computarizada por Rayos X/métodos , Riñón/patología , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/epidemiología , Carcinoma de Células Renales/patología , Estudios RetrospectivosRESUMEN
OBJECTIVE: To evaluate the performance of a multiparametric MRI radiomics-based nomogram for the individualised prediction of synchronous distant metastasis (SDM) in patients with clear cell renal cell carcinoma (ccRCC). METHODS: Two-hundred and one patients (training cohort: n = 126; internal validation cohort: n = 39; external validation cohort: n = 36) with ccRCC were retrospectively enrolled between January 2013 and June 2019. In the training cohort, the optimal MRI radiomics features were selected and combined to calculate the radiomics score (Rad-score). Incorporating Rad-score and SDM-related clinicoradiologic characteristics, the radiomics-based nomogram was established by multivariable logistic regression analysis, then the performance of the nomogram (discrimination and clinical usefulness) was evaluated and validated subsequently. Moreover, the prediction efficacy for SDM in ccRCC subgroups of different sizes was also assessed. RESULTS: Incorporating Rad-score derived from 9 optimal MR radiomics features (age, pseudocapsule and regional lymph node), the radiomics-based nomogram was capable of predicting SDM in the training cohort (area under the ROC curve (AUC) = 0.914) and validated in both the internal and external cohorts (AUC = 0.854 and 0.816, respectively) and also showed a convincing predictive power in ccRCC subgroups of different sizes (≤ 4 cm, AUC = 0.875; 4-7 cm, AUC = 0.891; 7-10 cm, 0.908; > 10 cm, AUC = 0.881). Decision curve analysis indicated that the radiomics-based nomogram is of clinical usefulness. CONCLUSIONS: The multiparametric MRI radiomics-based nomogram could achieve precise individualised prediction of SDM in patients with ccRCC, potentially improving the management of ccRCC. KEY POINTS: ⢠Radiomics features derived from multiparametric magnetic resonance images showed relevant association with synchronous distant metastasis in clear cell renal cell carcinoma. ⢠MRI radiomics-based nomogram may serve as a potential tool for the risk prediction of synchronous distant metastasis in clear cell renal cell carcinoma.
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Carcinoma de Células Renales , Neoplasias Renales , Carcinoma de Células Renales/diagnóstico por imagen , Humanos , Neoplasias Renales/diagnóstico por imagen , Imagen por Resonancia Magnética , Nomogramas , Estudios RetrospectivosRESUMEN
BACKGROUND: A quantitative nephrometry scoring system specifically for renal sinus tumors will assist in classifying surgical complexity and treatment planning. METHODS: By using preoperative computed tomography, magnetic resonance imaging, and 3-dimensional image reconstruction, 5 critical components were assessed: the ratio of the sinus area occupied by the tumor in relation to the whole sinus area (R), the compression of the renal segmental vessels or collection system by the tumor (O), the anteroposterior relation of the tumor relative to the segmental vessels or collection system (A), the tumor diameter (D), and whether the tumor affects a solitary kidney (S) ("ROADS"). The ROADS score, indicating low, moderate, or high surgical complexity, was then used to guide surgical strategy planning, including cooling techniques, surgical approaches, and parenchyma incision techniques. A cohort of 134 patients with renal sinus tumors was treated based on their ROADS score and was retrospectively analyzed. RESULTS: The authors successfully performed 113 nephron-sparing surgeries and 21 radical nephrectomies with a complication rate of 7.9%. During follow-up, 3 cases were classified according to surgical margin status because they lacked an intact tumor capsule. There was only 1 case of local recurrence, and there were no cases of metastasis. A high ROADS score was correlated with greater operative complexity, such as longer operation and ischemia times and higher estimated blood loss and complication rates. However, renal function and short-term oncologic outcomes were not related to the score. CONCLUSIONS: The ROADS scoring system provides a standardized, quantitative, 3-dimensional anatomic classification to guide surgical strategy in renal sinus tumors.
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Carcinoma de Células Renales , Neoplasias Renales , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Femenino , Humanos , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Masculino , Nefrectomía/métodos , Nefronas/patología , Nefronas/cirugía , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
Background The 2019 Bosniak classification (version 2019) of cystic renal masses (CRMs) provides a systematic update to the currently used 2005 Bosniak classification (version 2005). Further validation is required before widespread application. Purpose To evaluate the interobserver agreement of MRI criteria, the impact of readers' experience, and the diagnostic performance between version 2019 and version 2005. Materials and Methods From January 2009 to December 2018, consecutive patients with CRM who had undergone renal MRI and surgical-pathologic examination were included in this retrospective study. On the basis of version 2019 and version 2005, all CRMs were independently classified by eight radiologists with different levels of experience. By using multirater κ statistics, interobserver agreement was evaluated with comparisons between classifications and between senior and junior radiologists. Diagnostic performance between classifications by dichotomizing classes I-IV into lower (I-IIF) and higher (III-IV) classes was compared by using the McNemar test. P < .05 was considered to indicate a statistically significant difference. Results A total of 207 patients (mean age ± standard deviation, 49 years ± 12; 139 male and 68 female patients) with CRMs were included. Overall, interobserver agreement was higher with version 2019 than version 2005 (weighted κ = 0.64 vs 0.50, respectively; P < .001). Interobserver agreement between senior and junior radiologists did not differ between version 2019 (weighted κ = 0.65 vs 0.64, respectively; P = .71) and version 2005 (weighted κ = 0.54 vs 0.46; P < .001). Diagnostic specificity for malignancy was higher with version 2019 than with version 2005 (83% [92 of 111] vs 68% [75 of 111], respectively; P < .001), without any difference in sensitivity (89% [85 of 96] vs 84% [81 of 96]; P = .34). Conclusion In the updated Bosniak classification, interobserver agreement improved and was unaffected by observers' experience. The diagnostic performance with version 2019 was superior to that with version 2005, with higher specificity. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Choyke in this issue.
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Competencia Clínica , Enfermedades Renales Quísticas/clasificación , Enfermedades Renales Quísticas/diagnóstico por imagen , Imagen por Resonancia Magnética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Estudios RetrospectivosRESUMEN
Doxophylline (DOXO) and theophylline are widely used as bronchodilators for treating asthma and chronic obstructive pulmonary disease, and DOXO has a better safety profile than theophylline. How DOXO's metabolism and disposition affect its antiasthmatic efficacy and safety remains to be explored. In this study, the metabolites of DOXO were characterized. A total of nine metabolites of DOXO were identified in vitro using liver microsomes from human and four other animal species. Among them, six metabolites were reported for the first time. The top three metabolites were theophylline acetaldehyde (M1), theophylline-7-acetic acid (M2), and etophylline (M4). A comparative analysis of DOXO metabolism in human using liver microsomes, S9 fraction, and plasma samples demonstrated the following: 1) The metabolism of DOXO began with a cytochrome P450 (P450)-mediated, rate-limiting step at the C ring and produced M1, the most abundant metabolite in human liver microsomes. However, in human plasma, the M1 production was rather low. 2) M1 was further converted to M2 and M4, the end products of DOXO metabolism in vivo, by non-P450 dismutase in the cytosol. This dismutation process also relied on the ratio of NADP+/NADPH in the cell. These findings for the first time elucidated the metabolic sites and routes of DOXO metabolism in human. SIGNIFICANCE STATEMENT: We systematically characterized doxophylline metabolism using in vitro and in vivo assays. Our findings evolved the understandings of metabolic sites and pathways for methylxanthine derivatives with the aldehyde functional group.
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Acetaldehído/metabolismo , Broncodilatadores/farmacocinética , Hígado/enzimología , Teofilina/análogos & derivados , Teofilina/metabolismo , Acetaldehído/química , Adulto , Animales , Asma/tratamiento farmacológico , Broncodilatadores/administración & dosificación , Sistema Enzimático del Citocromo P-450/metabolismo , Femenino , Voluntarios Sanos , Humanos , Macaca fascicularis , Ratones , Microsomas Hepáticos , Oxidación-Reducción , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Conejos , Ratas , Teofilina/administración & dosificación , Teofilina/química , Teofilina/farmacocinéticaRESUMEN
BACKGROUND: Nuclear grade is of importance for treatment selection and prognosis in patients with clear cell renal cell carcinoma (ccRCC). PURPOSE: To develop and validate an MRI-based radiomic model for preoperative predicting WHO/ISUP nuclear grade in ccRCC. STUDY TYPE: Retrospective. POPULATION: In all, 379 patients with histologically confirmed ccRCC. Training cohort (n = 252) and validation cohort (n = 127) were randomly assigned. FIELD STRENGTH/SEQUENCE: Pretreatment 3.0T renal MRI. Imaging sequences were fat-suppressed T2 WI, contrast-enhanced T1 WI, and diffusion weighted imaging. ASSESSMENT: Three prediction models were developed using selected radiomic features, radiomic and clinicoradiologic characteristics, and a model containing only clinicoradiologic characteristics. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were used to assess the predictive performance of these models in predicting high-grade ccRCC. STATISTICAL TESTS: The least absolute shrinkage and selection operator (LASSO) and minimum redundancy maximum relevance (mRMR) method were used for the selection of radiomic features and clinicoradiologic characteristics, respectively. Multivariable logistic regression analysis was used to develop the radiomic signature of radiomic features and clinicoradiologic model of clinicoradiologic characteristics. RESULTS: The radiomic signature showed good performance in discriminating high-grade (grades 3 and 4) from low-grade (grades 1 and 2) ccRCC, with sensitivity, specificity, and AUC of 77.3%, 80.0%, and 0.842, respectively, in the validation cohort. The radiomic model, combining radiomic signature and clinicoradiologic characteristics, displayed good predictive ability for high-grade with sensitivity, specificity, and accuracy of 63.6%, 93.3%, and 88.2%, respectively, in the validation cohort. The radiomic model showed a significantly better performance than the clinicoradiologic model (P < 0.05). DATA CONCLUSION: Multiparametric MRI-based radiomic model can predict WHO/ISUP grade in patients with ccRCC with satisfying performance, and thus could help the physician to improve treatment decisions. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.
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Carcinoma de Células Renales , Neoplasias Renales , Imágenes de Resonancia Magnética Multiparamétrica , Carcinoma de Células Renales/diagnóstico por imagen , Humanos , Neoplasias Renales/diagnóstico por imagen , Estudios Retrospectivos , Organización Mundial de la SaludRESUMEN
The histone H3 N-terminal protein domain (N-tail) is regulated by multiple posttranslational modifications, including methylation, acetylation, phosphorylation, and by proteolytic cleavage. However, the mechanism underlying H3 N-tail proteolytic cleavage is largely elusive. Here, we report that JMJD5, a Jumonji C (JmjC) domain-containing protein, is a Cathepsin L-type protease that mediates histone H3 N-tail proteolytic cleavage under stress conditions that cause a DNA damage response. JMJD5 clips the H3 N-tail at the carboxyl side of monomethyl-lysine (Kme1) residues. In vitro H3 peptide digestion reveals that JMJD5 exclusively cleaves Kme1 H3 peptides, while little or no cleavage effect of JMJD5 on dimethyl-lysine (Kme2), trimethyl-lysine (Kme3), or unmethyl-lysine (Kme0) H3 peptides is observed. Although H3 Kme1 peptides of K4, K9, K27, and K36 can all be cleaved by JMJD5 in vitro, K9 of H3 is the major cleavage site in vivo, and H3.3 is the major H3 target of JMJD5 cleavage. Cleavage is enhanced at gene promoters bound and repressed by JMJD5 suggesting a role for H3 N-tail cleavage in gene expression regulation.
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Daño del ADN , Histona Demetilasas/genética , Histona Demetilasas/metabolismo , Histonas/metabolismo , División del ARN/genética , Células A549 , Acetilación , Regulación de la Expresión Génica , Histonas/genética , Humanos , Metilación , Fosforilación , Procesamiento Proteico-Postraduccional/genética , ProteolisisRESUMEN
Objective To evaluate the value of texture features derived from intravoxel incoherent motion (IVIM) parameters for differentiating pancreatic neuroendocrine tumor (pNET) from pancreatic adenocarcinoma (PAC).Methods Eighteen patients with pNET and 32 patients with PAC were retrospectively enrolled in this study. All patients underwent diffusion-weighted imaging with 10 b values used (from 0 to 800 s/mm 2). Based on IVIM model, perfusion-related parameters including perfusion fraction (f), fast component of diffusion (Dfast) and true diffusion parameter slow component of diffusion (Dslow) were calculated on a voxel-by-voxel basis and reorganized into gray-encoded parametric maps. The mean value of each IVIM parameter and texture features [Angular Second Moment (ASM), Inverse Difference Moment (IDM), Correlation, Contrast and Entropy] values of IVIM parameters were measured. Independent sample t-test or Mann-Whitney U test were performed for the between-group comparison of quantitative data. Regression model was established by using binary logistic regression analysis, and receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic efficiency.Results The mean f value of the pNET group were significantly higher than that of the PAC group (27.0% vs. 19.0%, P = 0.001), while the mean values of Dfast and Dslow showed no significant differences between the two groups. All texture features (ASM, IDM, Correlation, Contrast and Entropy) of each IVIM parameter showed significant differences between the pNET and PAC groups (P=0.000-0.043). Binary logistic regression analysis showed that texture ASM of Dfast and texture Correlation of Dslow were considered as the specific imaging variables for the differential diagnosis of pNET and PAC. ROC analysis revealed that multiple texture features presented better diagnostic performance than IVIM parameters (AUC 0.849-0.899 vs. 0.526-0.776), and texture ASM of Dfast combined with Correlation of Dslow in the model of logistic regression had largest area under ROC curve for distinguishing pNET from PAC (AUC 0.934, cutoff 0.378, sensitivity 0.889, specificity 0.854).Conclusions Texture analysis of IVIM parameters could be an effective and noninvasive tool to differentiate pNET from PAC.
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Adenocarcinoma/diagnóstico por imagen , Algoritmos , Imagen de Difusión por Resonancia Magnética , Neoplasias Pancreáticas/diagnóstico por imagen , Adulto , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Movimiento (Física) , Estudios RetrospectivosRESUMEN
BACKGROUND: To determine whether MRI feature analysis can differentiate benign retroperitoneal extra-adrenal paragangliomas and schwannomas. METHODS: The MRI features of 50 patients with confirmed benign retroperitoneal extra-adrenal paragangliomas and schwannomas were retrospectively reviewed by two radiologists blinded to the histopathologic diagnosis. These features were compared between two types of tumours by use of the Mann-Whitney test and binary logistic regression. The patients' clinical characteristics were reviewed. RESULTS: Analysis of MRI images from 50 patients revealed no significant differences in the quantitative MRI features of lesion size, ratio of diameter and apparent diffusion coefficient. There were significant differences in the qualitative MRI features of location, necrosis, cysts and degree of tumour enhancement for two readers, with no significant differences in the other qualitative MRI features between these tumours. The combination of necrosis with degree of tumour enhancement during the arterial phase increased the probability that a retroperitoneal mass would represent retroperitoneal extra-adrenal paraganglioma as opposed to schwannoma. CONCLUSION: We have presented the largest series of MRI features of both benign retroperitoneal extra-adrenal paragangliomas and schwannomas. Some MRI features assist in the differentiation between these tumours, with imaging features consisting of necrosis and avid enhancement during the arterial phase, suggestive of retroperitoneal extra-adrenal paragangliomas.
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Neurilemoma/diagnóstico por imagen , Paraganglioma/diagnóstico por imagen , Neoplasias Retroperitoneales/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Estudios RetrospectivosRESUMEN
PURPOSE: To assess magnetic resonance imaging (MRI) features after prostatic artery embolization (PAE) for the treatment of medium- and large-volume benign prostatic hyperplasia and to correlate prostate volume with clinical indexes. METHODS: We retrospectively evaluated 28 patients who underwent PAE. MRI examinations of the prostate were performed to evaluate signal intensity changes and the characteristics of infarcted areas. Prostate volume and the apparent diffusion coefficient (ADC) were measured at an average of 10 days post-PAE and at 1, 3, 6, and 12 months post-PAE. Some clinical indexes were evaluated before and 12 months after PAE. The paired t test, ANOVA, and multiple linear correlation analyses were performed by using the statistical software, SPSS. RESULTS: All patients experienced prostatic infarction. The prostate volume decreased continuously (p < 0.05). The ADC values before and after 1, 3, 6, or 12 months of embolization (b = 1000 and 2000 s/mm2) were statistically significantly different. The ADC values (b = 3000 s/mm2) were also statistically significantly different before and at each interval time after embolization (p < 0.05). Prostate volume changes correlated significantly with patient age and post-void residual urine volume (p < 0.05). CONCLUSIONS: MRI can be used for assessing changes in signal intensity and ADC values of infarction as well as the volume of the prostate after PAE. After PAE, ultrahigh b value diffusion-weighted imaging (DWI) can show early infarction better than lower b value DWI.
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Embolización Terapéutica/métodos , Infarto/terapia , Imagen por Resonancia Magnética/métodos , Próstata/irrigación sanguínea , Hiperplasia Prostática/terapia , Anciano , Anciano de 80 o más Años , Imagen de Difusión por Resonancia Magnética , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVES: To compare the performance of diffusion-weighted imaging (DWI) with that of contrast-enhanced MRI in differentiating renal oncocytomas from chromophobe renal cell carcinomas (RCCs). METHODS: We recruited 48 patients with histopathologically confirmed renal oncocytomas (n=16) and chromophobe RCCs (n=32). All patients underwent preoperative DWI and contrast-enhanced MRI. Apparent diffusion coefficient (ADC) and signal intensity were measured in each patient. ADC ratio and percentage of signal intensity change were calculated. RESULTS: Mean ADC values for renal oncoctytomas were significantly higher than those for chromophobe RCCs (1.59±0.21 vs. 1.09±0.29× 10-3 mm2/s, p < 0.001). Area under the ROC curve, sensitivity and specificity were 0.931, 87.5% and 84.4%, respectively, for ADC measurement of DW imaging; 0.825, 87.5% and 75%, respectively, for enhancement ratio (p > 0.05). Adding ADC values to the enhancement ratios in the ROC, analysis to differentiate renal oncocytoma from chromophobe RCCs increased specificity from 75 to 87.5% at 87.5% sensitivity without significantly increasing the AUC (0.930). CONCLUSIONS: Both DWI and contrast-enhanced MRI may assist in differentiating renal oncocytomas from chromophobe RCCs, with DWI showing higher diagnostic value. The combination of the two parameters could potentially provide better performance in distinguishing these two tumours. KEY POINTS: ⢠ADC values can assist in differentiating renal oncocytomas from chromophobe RCCs. ⢠DW imaging possesses better specificity than does contrast-enhanced MR imaging. ⢠Combining the two parameters provides higher specificity regarding the differential diagnosis.
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Carcinoma de Células Renales/diagnóstico , Neoplasias Renales/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Adenoma Oxifílico/diagnóstico por imagen , Adulto , Anciano , Diferenciación Celular , Diagnóstico Diferencial , Imagen de Difusión por Resonancia Magnética/métodos , Femenino , Humanos , Aumento de la Imagen/métodos , Riñón/patología , Masculino , Persona de Mediana Edad , Curva ROC , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Leiomyoma of the prostate is a rare benign tumor arising from smooth muscle fibers. Most cases are incidental findings observed during pathological examinations after resection of the prostate. To the best of our knowledge, only few studies have reported the conventional magnetic resonance imaging (MRI) findings of such tumors; however, no reports have described the ultra-high b-value diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) findings of prostatic leiomyomas. CASE PRESENTATION: We report MR imaging characteristics and surgical pathologic findings of a case of prostatic leiomyoma treated by robot-assisted transperitoneal laparoscopic approach. Typical MR features showed a homogeneous lesion with slightly hypointense signal compared to the skeletal muscle on T2-weighted images, and isointense signal relative to the muscle on T1-weighted images with fat suppression, which collectively demonstrate apparent homogeneous enhancement with a non-enhanced envelope. A slightly hyperintense signal compared to the skeletal muscle was observed on ultra-high b-value DWI, and higher ADC values were observed as compared to the prostate cancer. CONCLUSIONS: Prostatic leiomyoma is a benign tumor. This case indicates that MRI features of prostatic leiomyoma are helpful for the differential diagnosis of prostate cancer.
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Imagen de Difusión por Resonancia Magnética/métodos , Leiomioma/diagnóstico por imagen , Neoplasias de la Próstata/diagnóstico por imagen , Anciano , Diagnóstico Diferencial , Humanos , Laparoscopía , Leiomioma/cirugía , Masculino , Neoplasias de la Próstata/cirugía , Procedimientos Quirúrgicos RobotizadosRESUMEN
PURPOSE: To retrospectively analyze the MR imaging presentation of renal epithelioid angiomyolipoma (EAML). METHODS: Retrospective analysis revealed 12 subjects with histologically proven renal EAML who underwent preoperative MRI at our institution between January 2009 and June 2016. Two radiologists reviewed the images in consensus, describing MR imaging features including size, location, growth pattern, signal intensity of tumor, and dynamic enhancement pattern. RESULTS: Nine women and three men were included. The average maximum tumor diameter was 7.1 cm. Exophytic growth was present in 9/12 cases, mesophytic growth in 2/12, and endophytic growth in 1/12. On T1-weighted images, 2/12 displayed homogeneous isointensity, 1/12 homogeneous hyperintensity, 5/12 heterogeneous hypointensity, and 4/12 heterogeneous hyperintensity. Macroscopic fat was detected in 5/12 cases and microscopic fat in 6/12 cases. On T2-weighted images, 5/12 showed heterogeneous hypointensity, 4/12 heterogeneous hyperintensity, and 3/12 homogeneous hypointensity. On dynamic contrast-enhanced MR images, 7/12 showed a slow washout enhancement pattern, 2/12 a rapid washout pattern, 2/12 progressive enhancement, and 1/12 persistent enhancement. Imaging findings were suggestive of hemorrhage (50%), necrosis (25%), or cystic change (50%) within the tumors. Enlarged vessels were detected in 5/12 cases. One tumor extended into the renal sinus. No metastases were found on the preoperative MR imaging. CONCLUSION: Although MRI appearances of renal EAML were various, some MRI characteristics may contribute to suggest the possibility of renal EAML.