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OBJECTIVE: Assess the added prognostic value of the updated International Federation of Gynecology and Obstetrics (FIGO) 2018 staging system, and to identify clinicopathological and radiological biomarkers for improved FIGO 2018 prognostication. METHODS: Patient data were retrieved from a prospectively collected patient cohort including all consenting patients with cervical cancer diagnosed and treated at Haukeland University Hospital during 2001-2022 (n = 948). All patients were staged according to the FIGO 2009 and FIGO 2018 guidelines based on available data for individual patients. MRI-assessed maximum tumor diameter and stromal tumor invasion, as well as histopathologically assessed lymphovascular space invasion were applied to categorize patients according to the Sedlis criteria. RESULTS: FIGO 2018 stage yielded the highest area under the receiver operating characteristic (ROC) curve (AUC) (0.86 versus 0.81 for FIGO 2009) for predicting disease-specific survival. The most common stage migration in FIGO 2018 versus FIGO 2009 was upstaging from stages IB/II to stage IIIC due to suspicious lymph nodes identified by PET/CT and/or MRI. In FIGO 2018 stage III patients, extent and size of primary tumor (p = 0.04), as well as its histological type (p = 0.003) were highly prognostic. Sedlis criteria were prognostic within FIGO 2018 IB patients (p = 0.04). CONCLUSIONS: Incorporation of cross-sectional imaging increases prognostic precision, as suggested by the FIGO 2018 guidelines. The 2018 FIGO IIIC stage could be refined by including the size and extent of primary tumor and histological type. The FIGO IB risk prediction could be improved by applying MRI-assessed tumor size and stromal invasion.
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Neoplasias del Cuello Uterino , Femenino , Humanos , Estadificación de Neoplasias , Neoplasias del Cuello Uterino/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Pronóstico , Radiografía , Estudios RetrospectivosRESUMEN
OBJECTIVE: The prognostic role of adiposity in uterine cervical cancer (CC) is largely unknown. Abdominal fat distribution may better reflect obesity than body mass index. This study aims to describe computed tomography (CT)-assessed abdominal fat distribution in relation to clinicopathologic characteristics, survival, and tumor gene expression in CC. METHODS: The study included 316 CC patients diagnosed during 2004-2017 who had pre-treatment abdominal CT. CT-based 3D segmentation of total-, subcutaneous- and visceral abdominal fat volumes (TAV, SAV and VAV) allowed for calculation of visceral fat percentage (VAV% = VAV/TAV). Liver density (LD) and waist circumference (at L3/L4-level) were also measured. Associations between CT-derived adiposity markers, clinicopathologic characteristics and disease-specific survival (DSS) were explored. Gene set enrichment of primary tumors were examined in relation to fat distribution in a subset of 108 CC patients. RESULTS: High TAV, VAV and VAV% and low LD were associated with higher age (≥44 yrs.; p ≤ 0.017) and high International Federation of Gynecology and Obstetrics (FIGO) (2018) stage (p ≤ 0.01). High VAV% was the only CT-marker predicting high-grade histology (p = 0.028), large tumor size (p = 0.016) and poor DSS (HR 1.07, p < 0.001). Patients with high VAV% had CC tumors that exhibited increased inflammatory signaling (false discovery rate [FDR] < 5%). CONCLUSIONS: High VAV% is associated with high-risk clinical features and predicts reduced DSS in CC patients. Furthermore, patients with high VAV% had upregulated inflammatory tumor signaling, suggesting that the metabolic environment induced by visceral adiposity contributes to tumor progression in CC.
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Grasa Intraabdominal , Neoplasias del Cuello Uterino , Femenino , Humanos , Adulto , Grasa Intraabdominal/metabolismo , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/complicaciones , Obesidad/complicaciones , Adiposidad/genética , Hígado , Índice de Masa CorporalRESUMEN
BACKGROUND: Recently, two immunoglobulin A (IgA) nephropathy-prediction tools were developed that combine clinical and histopathologic parameters. The International IgAN Prediction Tool predicts the risk for 50% declines in the estimated glomerular filtration rate or end-stage kidney disease up to 80 months after diagnosis. The IgA Nephropathy Clinical Decision Support System uses artificial neural networks to estimate the risk for end-stage kidney disease. We aimed to externally validate both prediction tools using a Norwegian cohort with a long-term follow-up. METHODS: We included 306 patients with biopsy-proven primary IgA nephropathy in this study. Histopathologic samples were retrieved from the Norwegian Kidney Biopsy Registry and reclassified according to the Oxford Classification. We used discrimination and calibration as principles for externally validating the prognostic models. RESULTS: The median patient follow-up was 17.1 years. A cumulative, dynamic, time-dependent receiver operating characteristic analysis showed area under the curve values ranging from 0.90 at 5 years to 0.83 at 20 years for the International IgAN Prediction Tool, while time-naive analysis showed an area under the curve value at 0.83 for the IgA Nephropathy Clinical Decision Support System. The International IgAN Prediction Tool was well calibrated, while the IgA Nephropathy Clinical Decision Support System tends to underestimate risk for patients at higher risk and overestimates risk in the lower risk categories. CONCLUSIONS: We have externally validated two prediction tools for IgA nephropathy. The International IgAN Prediction Tool performed well, while the IgA Nephropathy Clinical Decision Support System has some limitations.
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Glomerulonefritis por IGA , Fallo Renal Crónico , Humanos , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/patología , Estudios de Seguimiento , Fallo Renal Crónico/diagnóstico , Pronóstico , Tasa de Filtración Glomerular , Progresión de la EnfermedadRESUMEN
OBJECTIVE: This study presents the diagnostic performance of four different preoperative imaging workups (IWs) for prediction of lymph node metastases (LNMs) in endometrial cancer (EC): pelvic MRI alone (IW1), MRI and [18F]FDG-PET/CT in all patients (IW2), MRI with selective [18F]FDG-PET/CT if high-risk preoperative histology (IW3), and MRI with selective [18F]FDG-PET/CT if MRI indicates FIGO stage ≥ 1B (IW4). METHODS: In 361 EC patients, preoperative staging parameters from both pelvic MRI and [18F]FDG-PET/CT were recorded. Area under receiver operating characteristic curves (ROC AUC) compared the diagnostic performance for the different imaging parameters and workups for predicting surgicopathological FIGO stage. Survival data were assessed using Kaplan-Meier estimator with log-rank test. RESULTS: MRI and [18F]FDG-PET/CT staging parameters yielded similar AUCs for predicting corresponding FIGO staging parameters in low-risk versus high-risk histology groups (p ≥ 0.16). The sensitivities, specificities, and AUCs for LNM prediction were as follows: IW1-33% [9/27], 95% [185/193], and 0.64; IW2-56% [15/27], 90% [174/193], and 0.73 (p = 0.04 vs. IW1); IW3-44% [12/27], 94% [181/193], and 0.69 (p = 0.13 vs. IW1); and IW4-52% [14/27], 91% [176/193], and 0.72 (p = 0.06 vs. IW1). IW3 and IW4 selected 34% [121/361] and 54% [194/361] to [18F]FDG-PET/CT, respectively. Employing IW4 identified three distinct patient risk groups that exhibited increasing FIGO stage (p < 0.001) and stepwise reductions in survival (p ≤ 0.002). CONCLUSION: Selective [18F]FDG-PET/CT in patients with high-risk MRI findings yields better detection of LNM than MRI alone, and similar diagnostic performance to that of MRI and [18F]FDG-PET/CT in all. KEY POINTS: ⢠Imaging by MRI and [18F]FDG PET/CT yields similar diagnostic performance in low- and high-risk histology groups for predicting central FIGO staging parameters. ⢠Utilizing a stepwise imaging workup with MRI in all patients and [18F]FDG-PET/CT in selected patients based on MRI findings identifies preoperative risk groups exhibiting significantly different survival. ⢠The proposed imaging workup selecting ~54% of the patients to [18F]FDG-PET/CT yield better detection of LNMs than MRI alone, and similar LNM detection to that of MRI and [18F]FDG-PET/CT in all.
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Neoplasias Endometriales , Fluorodesoxiglucosa F18 , Femenino , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía de Emisión de Positrones/métodos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Imagen por Resonancia Magnética/métodos , Neoplasias Endometriales/diagnóstico por imagen , Neoplasias Endometriales/cirugía , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Estadificación de Neoplasias , Radiofármacos/farmacologíaRESUMEN
OBJECTIVES: To evaluate the interobserver agreement for MRI-based 2018 International Federation of Gynecology and Obstetrics (FIGO) staging parameters in patients with cervical cancer and assess the prognostic value of these MRI parameters in relation to other clinicopathological markers. METHODS: This retrospective study included 416 women with histologically confirmed cervical cancer who underwent pretreatment pelvic MRI from May 2002 to December 2017. Three radiologists independently recorded MRI-derived staging parameters incorporated in the 2018 FIGO staging system. Kappa coefficients (κ) for interobserver agreement were calculated. The predictive and prognostic values of the MRI parameters were explored using ROC analyses and Kaplan-Meier with log-rank tests, and analyzed in relation to clinicopathological patient characteristics. RESULTS: Overall agreement was substantial for the staging parameters: tumor size > 2 cm (κ = 0.80), tumor size > 4 cm (κ = 0.76), tumor size categories (≤ 2 cm; > 2 and ≤ 4 cm; > 4 cm) (κ = 0.78), parametrial invasion (κ = 0.63), vaginal invasion (κ = 0.61), and enlarged lymph nodes (κ = 0.63). Higher MRI-derived tumor size category (≤ 2 cm; > 2 and ≤ 4 cm; > 4 cm) was associated with a stepwise reduction in survival (p ≤ 0.001 for all). Tumor size > 4 cm and parametrial invasion at MRI were associated with aggressive clinicopathological features, and the incorporation of these MRI-based staging parameters improved risk stratification when compared to corresponding clinical assessments alone. CONCLUSION: The interobserver agreement for central MRI-derived 2018 FIGO staging parameters was substantial. MRI improved the identification of patients with aggressive clinicopathological features and poor survival, demonstrating the potential impact of MRI enabling better prognostication and treatment tailoring in cervical cancer. KEY POINTS: ⢠The overall interobserver agreement was substantial (κ values 0.61-0.80) for central MRI staging parameters in the 2018 FIGO system. ⢠Higher MRI-derived tumor size category was linked to a stepwise reduction in survival (p ≤ 0.001 for all). ⢠MRI-derived tumor size > 4 cm and parametrial invasion were associated with aggressive clinicopathological features, and the incorporation of these MRI-derived staging parameters improved risk stratification when compared to clinical assessments alone.
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Neoplasias del Cuello Uterino , Femenino , Humanos , Imagen por Resonancia Magnética , Estadificación de Neoplasias , Variaciones Dependientes del Observador , Pronóstico , Estudios Retrospectivos , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/patologíaRESUMEN
BACKGROUND: The Oxford classification/MEST score is an established histopathologic scoring system for patients with IgA nephropathy (IgAN). The objective of this study was to derive a prognostic model for IgAN based on the MEST score and histopathologic features. METHODS: A total of 306 patients with biopsy-proven primary IgAN were included. Histopathologic samples were retrieved from the Norwegian Kidney Biopsy Registry and reclassified according to the Oxford classification. The study endpoint was end-stage renal disease (ESRD). Patients were subclassified into three risk models based on histologic features (Model A), a composite score calculated from the adjusted hazard ratio values (Model B), and on quartiles (Model C). RESULTS: The mean follow-up time was 16.5 years (range 0.2-28.1). In total, 61 (20%) patients reached ESRD during the study period. Univariate analysis of M, E, S, T and C lesions demonstrated that all types were associated with an increased risk of ESRD; however, a multivariate analysis revealed that only S, T and C lesions were associated with poor outcomes. Statistical analysis of 15-year data demonstrated that Models A and B were as predictive as the MEST score, with an area-under-the-curve at 0.85. The Harrel c index values were 0.81 and 0.80 for the MEST score and Models A and B, respectively. In the present cohort, adding C lesions to the MEST score did not improve the models prognostic value. CONCLUSIONS: Patients can be divided into risk classes based on their MEST scores. Histopathologic data provide valuable prognostic information at the time of diagnosis. Model B was the most suitable for clinical practice because it was the most user-friendly.
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Glomerulonefritis por IGA/patología , Adulto , Femenino , Estudios de Seguimiento , Glomerulonefritis por IGA/complicaciones , Humanos , Fallo Renal Crónico/etiología , Masculino , Persona de Mediana Edad , Pronóstico , Factores de TiempoRESUMEN
BACKGROUND: Advanced cervical cancer carries a particularly poor prognosis, and few treatment options exist. Identification of effective molecular markers is vital to improve the individualisation of treatment. We investigated transcriptional data from cervical carcinomas related to patient survival and recurrence to identify potential molecular drivers for aggressive disease. METHODS: Primary tumour RNA-sequencing profiles from 20 patients with recurrence and 53 patients with cured disease were compared. Protein levels and prognostic impact for selected markers were identified by immunohistochemistry in a population-based patient cohort. RESULTS: Comparison of tumours relative to recurrence status revealed 121 differentially expressed genes. From this gene set, a 10-gene signature with high prognostic significance (p = 0.001) was identified and validated in an independent patient cohort (p = 0.004). Protein levels of two signature genes, HLA-DQB1 (n = 389) and LIMCH1 (LIM and calponin homology domain 1) (n = 410), were independent predictors of survival (hazard ratio 2.50, p = 0.007 for HLA-DQB1 and 3.19, p = 0.007 for LIMCH1) when adjusting for established prognostic markers. HLA-DQB1 protein expression associated with programmed death ligand 1 positivity (p < 0.001). In gene set enrichment analyses, HLA-DQB1high tumours associated with immune activation and response to interferon-γ (IFN-γ). CONCLUSIONS: This study revealed a 10-gene signature with high prognostic power in cervical cancer. HLA-DQB1 and LIMCH1 are potential biomarkers guiding cervical cancer treatment.
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Cadenas beta de HLA-DQ/genética , Proteínas con Dominio LIM/genética , Transcriptoma , Neoplasias del Cuello Uterino/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Estudios de Cohortes , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Predisposición Genética a la Enfermedad , Cadenas beta de HLA-DQ/fisiología , Humanos , Proteínas con Dominio LIM/fisiología , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , Análisis de Supervivencia , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patologíaRESUMEN
PURPOSE OF REVIEW: For uterine cervical cancer, the recently revised International Federation of Gynecology and Obstetrics (FIGO) staging system (2018) incorporates imaging and pathology assessments in its staging. In this review we summarize the reported staging performances of conventional and novel imaging methods and provide an overview of promising novel imaging methods relevant for cervical cancer patient care. RECENT FINDINGS: Diagnostic imaging during the primary diagnostic work-up is recommended to better assess tumor extent and metastatic disease and is now reflected in the 2018 FIGO stages 3C1 and 3C2 (positive pelvic and/or paraaortic lymph nodes). For pretreatment local staging, imaging by transvaginal or transrectal ultrasound (TVS, TRS) and/or magnetic resonance imaging (MRI) is instrumental to define pelvic tumor extent, including a more accurate assessment of tumor size, stromal invasion depth, and parametrial invasion. In locally advanced cervical cancer, positron emission tomography-computed tomography (PET-CT) or computed tomography (CT) is recommended, since the identification of metastatic lymph nodes and distant metastases has therapeutic consequences. Furthermore, novel imaging techniques offer visualization of microstructural and functional tumor characteristics, reportedly linked to clinical phenotype, thus with a potential for further improving risk stratification and individualization of treatment. Diagnostic imaging by MRI/TVS/TRS and PET-CT/CT is instrumental for pretreatment staging in uterine cervical cancer and guides optimal treatment strategy. Novel imaging techniques may also provide functional biomarkers with potential relevance for developing more targeted treatment strategies in cervical cancer.
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Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/patología , Femenino , Humanos , Metástasis Linfática , Imagen por Resonancia Magnética/métodos , Estadificación de Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Rayos X/métodos , Ultrasonografía/métodos , Neoplasias del Cuello Uterino/terapiaRESUMEN
Widespread clinical use of MRI radiomic tumor profiling for prognostication and treatment planning in cancers faces major obstacles due to limitations in standardization of radiomic features. The purpose of the current work was to assess the impact of different MRI scanning- and normalization protocols for the statistical analyses of tumor radiomic data in two patient cohorts with uterine endometrial-(EC) (n = 136) and cervical (CC) (n = 132) cancer. 1.5 T and 3 T, T1-weighted MRI 2 min post-contrast injection, T2-weighted turbo spin echo imaging, and diffusion-weighted imaging were acquired. Radiomic features were extracted from within manually segmented tumors in 3D and normalized either using z-score normalization or a linear regression model (LRM) accounting for linear dependencies with MRI acquisition parameters. Patients were clustered into two groups based on radiomic profile. Impact of MRI scanning parameters on cluster composition and prognostication were analyzed using Kruskal-Wallis tests, Kaplan-Meier plots, log-rank test, random survival forests and LASSO Cox regression with time-dependent area under curve (tdAUC) (α = 0.05). A large proportion of the radiomic features was statistically associated with MRI scanning protocol in both cohorts (EC: 162/385 [42%]; CC: 180/292 [62%]). A substantial number of EC (49/136 [36%]) and CC (50/132 [38%]) patients changed cluster when clustering was performed after z-score-versus LRM normalization. Prognostic modeling based on cluster groups yielded similar outputs for the two normalization methods in the EC/CC cohorts (log-rank test; z-score: p = 0.02/0.33; LRM: p = 0.01/0.45). Mean tdAUC for prognostic modeling of disease-specific survival (DSS) by the radiomic features in EC/CC was similar for the two normalization methods (random survival forests; z-score: mean tdAUC = 0.77/0.78; LRM: mean tdAUC = 0.80/0.75; LASSO Cox; z-score: mean tdAUC = 0.64/0.76; LRM: mean tdAUC = 0.76/0.75). Severe biases in tumor radiomics data due to MRI scanning parameters exist. Z-score normalization does not eliminate these biases, whereas LRM normalization effectively does. Still, radiomic cluster groups after z-score- and LRM normalization were similarly associated with DSS in EC and CC patients.
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Neoplasias Endometriales , Imagen por Resonancia Magnética , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/mortalidad , Imagen por Resonancia Magnética/métodos , Pronóstico , Neoplasias Endometriales/diagnóstico por imagen , Neoplasias Endometriales/patología , Persona de Mediana Edad , Anciano , Adulto , RadiómicaRESUMEN
Cervical cancer (CC) is a major global health problem with 570,000 new cases and 266,000 deaths annually. Prognosis is poor for advanced stage disease, and few effective treatments exist. Preoperative diagnostic imaging is common in high-income countries and MRI measured tumor size routinely guides treatment allocation of cervical cancer patients. Recently, the role of MRI radiomics has been recognized. However, its potential to independently predict survival and treatment response requires further clarification. This retrospective cohort study demonstrates how non-invasive, preoperative, MRI radiomic profiling may improve prognostication and tailoring of treatments and follow-ups for cervical cancer patients. By unsupervised clustering based on 293 radiomic features from 132 patients, we identify three distinct clusters comprising patients with significantly different risk profiles, also when adjusting for FIGO stage and age. By linking their radiomic profiles to genomic alterations, we identify putative treatment targets for the different patient clusters (e.g., immunotherapy, CDK4/6 and YAP-TEAD inhibitors and p53 pathway targeting treatments).
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Imagen por Resonancia Magnética , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/patología , Pronóstico , Persona de Mediana Edad , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , RadiómicaRESUMEN
Idiopathic Parkinson's disease (iPD) is believed to have a heterogeneous pathophysiology, but molecular disease subtypes have not been identified. Here, we show that iPD can be stratified according to the severity of neuronal respiratory complex I (CI) deficiency, and identify two emerging disease subtypes with distinct molecular and clinical profiles. The CI deficient (CI-PD) subtype accounts for approximately a fourth of all cases, and is characterized by anatomically widespread neuronal CI deficiency, a distinct cell type-specific gene expression profile, increased load of neuronal mtDNA deletions, and a predilection for non-tremor dominant motor phenotypes. In contrast, the non-CI deficient (nCI-PD) subtype exhibits no evidence of mitochondrial impairment outside the dopaminergic substantia nigra and has a predilection for a tremor dominant phenotype. These findings constitute a step towards resolving the biological heterogeneity of iPD with implications for both mechanistic understanding and treatment strategies.
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ADN Mitocondrial , Complejo I de Transporte de Electrón , Complejo I de Transporte de Electrón/deficiencia , Mitocondrias , Enfermedades Mitocondriales , Enfermedad de Parkinson , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Humanos , Complejo I de Transporte de Electrón/genética , Complejo I de Transporte de Electrón/metabolismo , Enfermedades Mitocondriales/genética , Enfermedades Mitocondriales/metabolismo , Masculino , ADN Mitocondrial/genética , Femenino , Mitocondrias/metabolismo , Mitocondrias/genética , Anciano , Sustancia Negra/metabolismo , Sustancia Negra/patología , Persona de Mediana Edad , Fenotipo , Neuronas/metabolismoRESUMEN
Background: The establishment of the Oxford classification and newly developed prediction models have improved the prognostic information for immunoglobulin A nephropathy (IgAN). Considering new treatment options, optimizing prognostic information and improving existing prediction models are favorable. Methods: We used random forest survival analysis to select possible predictors of end-stage kidney disease among 37 candidate variables in a cohort of 232 patients with biopsy-proven IgAN retrieved from the Norwegian Kidney Biopsy Registry. The predictive value of variables with relative importance >5% was assessed using concordance statistics and the Akaike information criterion. Pearson's correlation coefficient was used to identify correlations between the selected variables. Results: The median follow-up period was 13.7 years. An isolated analysis of histological variables identified six variables with relative importance >5%: T %, segmental glomerular sclerosis without characteristics associated with other subtypes (not otherwise specified, NOS), normal glomeruli, global sclerotic glomeruli, segmental adherence and perihilar glomerular sclerosis. When histopathological and clinical variables were combined, estimated glomerular filtration rate (eGFR), proteinuria and serum albumin were added to the list. T % showed a better prognostic value than tubular atrophy/interstitial fibrosis (T) lesions with C-indices at 0.74 and 0.67 and was highly correlated with eGFR. Analysis of the subtypes of segmental glomerulosclerosis (S) lesions revealed that NOS and perihilar glomerular sclerosis were associated with adverse outcomes. Conclusions: Reporting T lesions as a continuous variable, normal glomeruli and subtypes of S lesions could provide clinicians with additional prognostic information and contribute to the improved performance of the Oxford classification and prognostic tools.
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BACKGROUND: Accurate pretherapeutic prognostication is important for tailoring treatment in cervical cancer (CC). PURPOSE: To investigate whether pretreatment MRI-based radiomic signatures predict disease-specific survival (DSS) in CC. STUDY TYPE: Retrospective. POPULATION: CC patients (n = 133) allocated into training(T) (nT = 89)/validation(V) (nV = 44) cohorts. FIELD STRENGTH/SEQUENCE: T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) at 1.5T or 3.0T. ASSESSMENT: Radiomic features from segmented tumors were extracted from T2WI and DWI (high b-value DWI and apparent diffusion coefficient (ADC) maps). STATISTICAL TESTS: Radiomic signatures for prediction of DSS from T2WI (T2rad ) and T2WI with DWI (T2 + DWIrad ) were constructed by least absolute shrinkage and selection operator (LASSO) Cox regression. Area under time-dependent receiver operating characteristics curves (AUC) were used to evaluate and compare the prognostic performance of the radiomic signatures, MRI-derived maximum tumor size ≤/> 4 cm (MAXsize ), and 2018 International Federation of Gynecology and Obstetrics (FIGO) stage (I-II/III-IV). Survival was analyzed using Cox model estimating hazard ratios (HR) and Kaplan-Meier method with log-rank tests. RESULTS: The radiomic signatures T2rad and T2 + DWIrad yielded AUCT /AUCV of 0.80/0.62 and 0.81/0.75, respectively, for predicting 5-year DSS. Both signatures yielded better or equal prognostic performance to that of MAXsize (AUCT /AUCV : 0.69/0.65) and FIGO (AUCT /AUCV : 0.77/0.64) and were significant predictors of DSS after adjusting for FIGO (HRT /HRV for T2rad : 4.0/2.5 and T2 + DWIrad : 4.8/2.1). Adding T2rad and T2 + DWIrad to FIGO significantly improved DSS prediction compared to FIGO alone in cohort(T) (AUCT 0.86 and 0.88 vs. 0.77), and FIGO with T2 + DWIrad tended to the same in cohort(V) (AUCV 0.75 vs. 0.64, p = 0.07). High radiomic score for T2 + DWIrad was significantly associated with reduced DSS in both cohorts. DATA CONCLUSION: Radiomic signatures from T2WI and T2WI with DWI may provide added value for pretreatment risk assessment and for guiding tailored treatment strategies in CC.
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Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/patología , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Imagen de Difusión por Resonancia Magnética/métodos , PronósticoRESUMEN
Uterine cervical cancer (CC) is the most common gynecologic malignancy worldwide. Whole-volume radiomic profiling from pelvic MRI may yield prognostic markers for tailoring treatment in CC. However, radiomic profiling relies on manual tumor segmentation which is unfeasible in the clinic. We present a fully automatic method for the 3D segmentation of primary CC lesions using state-of-the-art deep learning (DL) techniques. In 131 CC patients, the primary tumor was manually segmented on T2-weighted MRI by two radiologists (R1, R2). Patients were separated into a train/validation (n = 105) and a test- (n = 26) cohort. The segmentation performance of the DL algorithm compared with R1/R2 was assessed with Dice coefficients (DSCs) and Hausdorff distances (HDs) in the test cohort. The trained DL network retrieved whole-volume tumor segmentations yielding median DSCs of 0.60 and 0.58 for DL compared with R1 (DL-R1) and R2 (DL-R2), respectively, whereas DSC for R1-R2 was 0.78. Agreement for primary tumor volumes was excellent between raters (R1-R2: intraclass correlation coefficient (ICC) = 0.93), but lower for the DL algorithm and the raters (DL-R1: ICC = 0.43; DL-R2: ICC = 0.44). The developed DL algorithm enables the automated estimation of tumor size and primary CC tumor segmentation. However, segmentation agreement between raters is better than that between DL algorithm and raters.
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BACKGROUND: Tumor size assessment by MRI is central for staging uterine cervical cancer. However, the optimal role of MRI-derived tumor measurements for prognostication is still unclear. MATERIAL AND METHODS: This retrospective cohort study included 416 women (median age: 43 years) diagnosed with cervical cancer during 2002-2017 who underwent pretreatment pelvic MRI. The MRIs were independently read by three radiologists, measuring maximum tumor diameters in three orthogonal planes and maximum diameter irrespective of plane (MAXimaging). Inter-reader agreement for tumor size measurements was assessed by intraclass correlation coefficients (ICCs). Size was analyzed in relation to age, International Federation of Gynecology and Obstetrics (FIGO) (2018) stage, histopathological markers, and disease-specific survival using Kaplan-Meier-, Cox regression-, and time-dependent receiver operating characteristics (tdROC) analyses. RESULTS: All MRI tumor size variables (cm) yielded high areas under the tdROC curves (AUCs) for predicting survival (AUC 0.81-0.84) at 5 years after diagnosis and predicted outcome (hazard ratios [HRs] of 1.42-1.76, p < 0.001 for all). Only MAXimaging independently predicted survival (HR = 1.51, p = 0.03) in the model including all size variables. The optimal cutoff for maximum tumor diameter (≥ 4.0 cm) yielded sensitivity (specificity) of 83% (73%) for predicting disease-specific death after 5 years. Inter-reader agreement for MRI-based primary tumor size measurements was excellent, with ICCs of 0.83-0.85. CONCLUSION: Among all MRI-derived tumor size measurements, MAXimaging was the only independent predictor of survival. MAXimaging ≥ 4.0 cm represents the optimal cutoff for predicting long-term disease-specific survival in cervical cancer. Inter-reader agreement for MRI-based tumor size measurements was excellent.
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BACKGROUND: Arachnoid cysts yield cognitive deficits that are normalized after surgical cyst decompression. OBJECTIVE: The present study aimed to investigate whether arachnoid cysts also affect symptoms of anxiety and depression, and if surgical cyst decompression leads to reduction of these symptoms. METHODS: Twenty-two adult patients (13 men and 9 women) with symptomatic temporal or frontal cysts were included in this questionnaire (Hospital Anxiety and Depression Scale [HADS])-based prospective study. The mean time between answering the preoperative questionnaire and surgery was 37 days. The patients answered the same HADS questionnaire 3-6 months postoperatively. RESULTS: Preoperatively, both patients with frontal (N = 4) and patients with temporal (N = 18) cyst had higher mean HADS anxiety scores than those found in the general population. For patients with temporal cyst, there was a significant or near-significant difference in anxiety and depression scores and the combined scores between those with right-sided cysts and those with left-sided cysts. Postoperatively, the HADS scores normalized and were no longer different from those of the general population. The difference in scores between patients with right and left temporal cyst also disappeared. CONCLUSIONS: Patients with arachnoid cyst have higher levels of anxiety and depression than do the general population and these scores were normalized after decompressive cyst surgery. We further found a hemispheric asymmetry: patients with a right temporal cyst showed higher anxiety, depression, and combined scores than did patients with a left temporal cyst. Also, this disparity normalized after cyst decompression. Thus, arachnoid cysts seem to affect not only cognition but also the level of affective symptoms.