Screening for exclusion of high-risk bleeding features of esophageal varices in cirrhosis through CT and MRI.

BACKGROUND & AIM: Esophageal varices (EV) screening guidelines have evolved with improved risk stratification to avoid unnecessary esophagogastroduodenoscopy (EGD) in individuals with low bleeding risks. However, uncertainties persist in the recommendations for certain patient groups, particularly those with hepatocellular carcinoma (HCC) and/or receiving non-selective beta-blockers (NSBB) without prior endoscopy. This study assessed the efficacy of imaging in ruling out EVs and their high-risk features associated with bleeding in patients with cirrhosis and with HCC. We also evaluated the impact of NSBB on the detection of these characteristics. METHODS: A total of 119 patients undergoing EGD with CT and/or MRI within 90 days of the procedure were included. 87 patients had HCC. A new imaging grading system was developed utilizing the size of EVs and the extent of their protrusion into the esophagus lumen. The negative predictive value (NPV) of EVimaging(-) versus EVimaging (+) (grades 1-3) in ruling out the presence of EV and/or high-risk features by EGD was calculated. The predictive performance of imaging was determined by logistic regression. RESULTS: The NPV of imaging for detecting EV and high-risk features was 81 % and 92 %, respectively. Among HCC patients, the NPV for EV and high-risk features was 80 % and 64 %, respectively. Being on NSBB didn't statistically impact the imaging detection of EV. Imaging was a better predictor of high-risk EGD findings than Child-Turcotte-Pugh scores. CONCLUSIONS: Our results suggest that imaging can effectively rule out the presence of EV and high-risk features during EGD, even in patients with HCC and/or receiving NSBB.

Incremental value of volumetric multiparametric MRI over Fudan score for prognosis of unresectable intrahepatic cholangiocarcinoma treated with systemic chemotherapy.

BACKGROUND: Individualized patient care requires prognostic models customized to a tumor and an individual's disease profile for reliable survival prediction. MRI has prognostic value for intrahepatic cholangiocarcinoma (ICCA). Existing prognostic models for ICCA exclude imaging-based information about an individual's tumor that may reflect important aspects of tumor's biology. Fudan score, a prognostic model applicable to unresectable ICCA, is limited by subjective morphologic imaging parameters. OBJECTIVES: To assess the prognostic value of baseline volumetric multiparametric MRI in unresectable intrahepatic cholangiocarcinoma (ICCA) treated with systemic chemotherapy and the incremental value of MRI over the Fudan score. METHODS: This retrospective study included 114 ICCA patients treated with systemic chemotherapy between 2007 and 2021 after a baseline MRI. The single largest tumor was volumetrically assessed for anatomic (total tumor volume and diameter) and functional parameters (viable tumor volume, percentage-viable tumor volume, viable tumor burden, and ADC). A derivation cohort of 30 patients was utilized to identify MRI parameters associated with overall survival (OS) using Cox regression analysis. The incremental value of MRI over Fudan score was assessed on an independent sub-cohort of 84 patients using Kaplan-Meier analysis and C-index. RESULTS: 114 patients (64 years +/- 11; 61 women) were evaluated. Pre-treatment high (>1350x10-6 mm2/sec) ADC was the only independent predictor of OS (HR, 8.07; P < 0.001). Replacing subjective tumor boundary with objective ADC value, and using modified biochemical thresholds increased the prognostic stratification for the risk groups in the modified ADC-Fudan model compared to the original Fudan model (median survival 12 and 4.5 months; P = 0.055; vs. 11 and 3 months; P < 0.001). The modified ADC-Fudan model demonstrated an 11 % improvement over the original Fudan model (c-index: 0.80 vs. 0.69; P = 0.044) for survival prediction. CONCLUSIONS: High pre-treatment volumetric ADC was associated with unfavorable prognosis in patients with unresectable intrahepatic cholangiocarcinoma treated with systemic chemotherapy. Supplementing the original Fudan model with ADC and modified serum marker thresholds improved the survival prediction performance by 11% in the resulting modified ADC-Fudan model. CLINICAL IMPACT: Volumetric MRI could improve the survival prediction among ICCA patients prior to receiving potentially toxic and expensive palliative chemotherapies. This could potentially guide individualized therapy for this patient cohort.

Outcome prediction for symptomatic patients with fibroids who underwent uterine artery embolization.

PURPOSE: To predict the clinical outcome of symptomatic patients with uterine leiomyomas who underwent uterine artery embolization (UAE), based on clinical and radiological features. METHODS: Patients with symptomatic uterine leiomyomas who underwent UAE from March 2010 to September 2019 were consecutively included in this retrospective study. Patients with persistent or recurrent symptoms and those who needed repeated UAE, myomectomy, or hysterectomy following the initial treatment were considered to have a poor outcome after UAE. The total and enhancing volume of the dominant leiomyoma in each location and uterine volume were obtained before and after UAE. Univariate and multivariate Cox proportional hazard analyses were used to evaluate the parameters that could predict poor outcome. RESULTS: A total of 116 patients (mean age, 45 ± 5 years) were included. Forty-six patients (46/116, 39.7%) showed poor outcome. Cox regression analysis showed higher hazard of poor outcome for younger patients vs. older patients (HR: 0.92, p-value: 0.01), patients with adenomyosis vs. patients without adenomyosis (HR: 2.47, p-value < 0.01), patients with adenomyosis thickness > 2.5 cm before UAE vs. patients without adenomyosis (HR: 4.2, p-value < 0.01) and for patients with intramural fibroid enhancement volume > 440 cm3 compared to patients with no intramural fibroids (p-value: 0.06). Multivariate Cox regression analysis including age, the thickness of adenomyosis, and intramural leiomyoma volume of enhancement before UAE was chosen as the best model to predict the outcome. CONCLUSIONS: Pretreatment clinical and MRI features could identify patients with a higher risk for poor outcome after UAE.

Differentiation between small hepatocellular carcinoma (<3 cm) and benign hepatocellular lesions in patients with Budd-Chiari syndrome: the role of multiparametric MR imaging.

Objective: To investigate the value of multiparametric MR imaging to differentiate between small hepatocellular carcinoma (s-HCC) versus benign liver lesions in patients with Budd-Chiari syndrome. Methods: 12 patients with benign hepatocellular lesions and 32 patients with small (<3 cm) HCCs were assessed. MRI images were reviewed by two radiologists blinded to the patient background information; lesion T1 and T2 signal intensities and ADC values were compared with the background liver. Enhancement of lesion relative to hepatic parenchyma [(T1Enh-T1liver)/T1liver] in the arterial, venous, and delayed phases was also compared between the two groups. A multivariable logistic model was developed using these categorical measures; the predictive value of the model was tested using the Area Under the Receiver operating characteristic (AU-ROC) curve for logistic models. P-values <0.05 were considered statistically significant. Results: There were consistent differences in T1lesion/T1liver, and T2lesion/T2liver, and ADClesion/ADCliver between benign hepatocellular lesions versus the sHCC group (p<0.001, p<0.001, p = 0.045, respectively). Lesion-to-background liver enhancement in the portal venous and delayed phases was different between the benign lesions versus sHCC (p=0.001). ROC analysis for the logistic model that included the T1 ratio, T2 ratio, and portal venous enhancement ratio demonstrated excellent discriminatory power with the area under the curve of 0.94. Conclusion: Multiparametric MR imaging is a useful method to help differentiate benign liver lesions from sHCC in patients with Budd-Chiari syndrome.

Comparison between Gradient-Echo and Spin-Echo EPI MR Elastography at 3 T in quantifying liver stiffness of patients with and without iron overload; a prospective study.

OBJECTIVES: To compare the maximum axial area of the confidence mask and the calculated liver stiffness (LS) on gradient-echo (GRE) and spin-echo echo planar imaging (SE-EPI) MR elastography (MRE) in patients with and without iron deposition. METHODS: 104 patients underwent MRE by GRE and SE-EPI sequences at 3 T. R2* values >88 Hz in the liver were categorized in the iron overload group. The maximum axial area and the corresponding LS values were measured by manually contouring the whole area on one slice with the largest confidence mask at both GRE and SE-EPI sequences. RESULTS: In patients with iron overload, SE-EPI provided larger maximum axial confidence area in unfailed images (57.6 ± 41.7 cm2) compared to GRE (45.7 ± 29.1 cm2) (p-value = 0.007). In five patients with iron overload, imaging failed at GRE sequence, whereas at the SE-EPI sequence the maximum area of the confidence mask had a mean value of 33.5 ± 54.9 cm2. In livers without iron overload (R2*: 50.7 ± 13.1 Hz), the maximum area on the confidence mask was larger at SE-EPI (118.3 ± 41.2 cm2) than on GRE (105.1 ± 31.7 cm2) (P-value = 0.003). There was no significant difference in mean LS between SE-EPI (2.0 ± 0.3 kPa) and GRE (2.1 ± 0.5 kPa) in livers with iron overload (P value = 0.24). Similarly, in the group without iron overload, mean LS was 2.3 ± 0.7 kPa at SE-EPI and 2.4 ± 0.8 kPa at GRE sequences (P-value = 0.11). CONCLUSIONS: SE-EPI MRE can successfully provide similar LS measurements as GRE MRE. Furthermore, it provides a larger measurable area on the confidence mask in both groups with and without iron overload.

Role of MRI-Derived Radiomics Features in Determining Degree of Tumor Differentiation of Hepatocellular Carcinoma.

Background: To investigate radiomics ability in predicting hepatocellular carcinoma histological degree of differentiation by using volumetric MR imaging parameters. Methods: Volumetric venous enhancement and apparent diffusion coefficient were calculated on baseline MRI of 171 lesions. Ninety-five radiomics features were extracted, then random forest classification identified the performance of the texture features in classifying tumor degree of differentiation based on their histopathological features. The Gini index was used for split criterion, and the random forest was optimized to have a minimum of nine participants per leaf node. Predictor importance was estimated based on the minimal depth of the maximal subtree. Results: Out of 95 radiomics features, four top performers were apparent diffusion coefficient (ADC) features. The mean ADC and venous enhancement map alone had an overall error rate of 39.8%. The error decreased to 32.8% with the addition of the radiomics features in the multi-class model. The area under the receiver-operator curve (AUC) improved from 75.2% to 83.2% with the addition of the radiomics features for distinguishing well- from moderately/poorly differentiated HCCs in the multi-class model. Conclusions: The addition of radiomics-based texture analysis improved classification over that of ADC or venous enhancement values alone. Radiomics help us move closer to non-invasive histologic tumor grading of HCC.

Magnetic Resonance Imaging Predictors of Hepatocellular Carcinoma Progression and Dropout in Patients in Liver Transplantation Waiting List.

With the rising incidence of hepatocellular carcinoma (HCC), more patients are now eligible for liver transplantation. Consequently, HCC progression and dropout from the waiting list are also anticipated to rise. We developed a predictive model based on radiographic features and alpha-fetoprotein to identify high-risk patients. Methods: This is a case-cohort retrospective study of 76 patients with HCC who were listed for liver transplantation with subsequent liver transplantation or delisting due to HCC progression. We analyzed imaging-based predictive variables including tumor margin (well- versus ill-defined), capsule bulging lesions, volumetric analysis and distance to portal vein, tumor numbers, and tumor diameter. Volumetric analysis of the index lesions was used to quantify index tumor total volume and volumetric enhancement, whereas logistic regression and receiver operating characteristic curve (ROC) analyses were used to predict the main outcome of disease progression. Results: In univariate analyses, the following baseline variables were significantly associated with disease progression: size and number of lesions, sum of lesion diameters, lesions bulging the capsule, and total and venous-enhancing (viable) tumor volumes. Based on multivariable analyses, a risk model including lesion numbers and diameter, capsule bulging, tumor margin (infiltrative versus well-defined), and alpha-fetoprotein was developed to predict HCC progression and dropout. The model has an area under the ROC of 82%, which was significantly higher than Milan criteria that has an area under the ROC of 67%. Conclusions: Our model has a high predictive test for patient dropout due to HCC progression. This model can identify high-risk patients who may benefit from more aggressive HCC treatment early after diagnosis to prevent dropout due to such disease progression.

Can Posttransarterial Chemoembolization Volumetric Oil Deposition on Computed Tomography Predict Treatment Response on Magnetic Resonance Imaging in Leiomyosarcoma Metastases to the Liver?

OBJECTIVE: To predict early tumor response to transarterial chemoembolization (TACE) based on volumetric oil deposition on posttreatment computed tomography (CT) in patients with leiomyosarcoma liver metastases. METHODS: This retrospective lesion-by-lesion based study included 32 lesions. The volumetric percent enhancing tumor on pre-TACE and 1-month post-TACE venous phase magnetic resonance imaging (MRI), and the percent oil deposition on CT 1 day after TACE were calculated. The predicted post-TACE enhanced percentage was computed by subtracting percent oil deposition from baseline percent enhanced. RESULTS: Mean percentage of viable tumor on pre-TACE MRI was 90.6% ± 9.3%. Mean oil deposition was calculated as 51.4% ± 26.2%. Mean percentage of measured residual tumor enhancement 1 month after TACE was 58.3% ± 27%, which correlates with predicted enhancement percentage of 43.9% ± 25.1% (r = 0.72, P < 0.001). A threshold of 35.5% for enhancement reduction was determined to predict tumor response with an accuracy of 78.1%. CONCLUSION: Volumetric oil deposition on CT can predict residual enhancement on post-TACE MRI.

Predicting early necrosis of colorectal liver metastases using volumetric enhancement on baseline MRI and oil deposition on post-cTACE unenhanced CT.

PURPOSE: To predict tumor necrosis after conventional TACE (cTACE) in patients with colorectal liver metastasis (CRLM) based on volumetric oil deposition on CT one day after treatment. METHODS: Thirty-four lesions in 20 men and 6 women were included in this IRB-approved HIPAA-compliant, retrospective lesion-by-lesion-based study. Semiautomatic volumetric segmentation of target lesions was performed on baseline MRI and post-treatment CT. Predicted percentage of tumor necrosis was defined as 100%-(%baseline MRI enhancement-%CT oil deposition). Necrosis on post-TACE MRI was measured after volumetric segmentation to assess the accuracy of predicting tumor necrosis. The relationship between predicted necrosis percent and post-cTACE measured necrosis percent on MRI was compared using Pearson correlation analysis. Inter-reader agreement was calculated by intraclass correlation coefficient (ICC) after using the same method. RESULTS: Patients in this cohort had a mean age of 64 ± 14 years. Mean percentage of the viable tumor on pre-cTACE venous phase MRI was 58.5% ± 23.9%. Mean oil deposition was 19.8% ± 14.6%. Mean percentage of calculated necrosis one month after cTACE was 59.2% ± 22.7% on venous phase MRI, which had a significant correlation with predicted necrotic percentage of 61.3% ± 19.3% (r = 0.89, p < 0.0001). ICC for enhancement percentage on pre-cTACE and post-cTACE venous phase MRIs were 0.93 (95% CI 0.83, 0.97) and 0.86 (95% CI 0.66, 0.94), respectively. ICC for oil deposition was 0.92 (95% CI 0.81, 0.96). CONCLUSION: Measuring oil deposition of the whole tumor on CT one day after cTACE can assist to predict post-cTACE tumor necrosis.

Integrating baseline MR imaging biomarkers into BCLC and CLIP improves overall survival prediction of patients with hepatocellular carcinoma (HCC).

OBJECTIVES: We aimed to evaluate the independent predictive role of baseline imaging biomarkers for overall survival (OS) and transplant-free survival (TFS) in patients with HCC and assess the incremental value of these biomarkers to current staging systems. METHODS: In this retrospective IRB approved study, the clinical, laboratory, and imaging parameters of 304 HCC patients were collected. Cox regression model was utilized to identify the potential predictors of survival. Recursive partitioning test was utilized to identify the optimal ADC cutoff for stratifying patients' OS. Patients were stratified based on Barcelona Clinic Liver Cancer (BCLC) and Cancer of the Liver Italian Program (CLIP). Binary ADC value (above vs. below the cutoff) and tumor margin (well- vs. ill-defined) were integrated into BCLC and CLIP. OS and TFS was compared for patients based on standard criteria with and without imaging biomarkers. RESULTS: At baseline, patients with low tumor ADC and well-defined tumor margin (favorable imaging biomarkers) had longer survival, as compared to those with high ADC and ill-defined tumor margin (unfavorable imaging biomarkers) (median OS of 43 months vs. 7 months, respectively) (p < 0.001). Tumor ADC and tumor margin remained strong independent predictors of survival after adjustment for demographics, BCLC and CLIP staging, and tumor burden. Incorporating ADC and tumor margin improved performance of OS prediction by 9% in BCLC group and 6% in CLIP group. CONCLUSION: Incorporating ADC and tumor margin to current staging systems for HCC significantly improve prediction of OS and TFS of these criteria. KEY POINTS: • ADC and tumor margin are predictors of overall survival in HCC patients, independent of clinical, laboratory, and other imaging variables. • Adding ADC and tumor margin improved the prognostic value of BCLC and CLIP criteria by 9% and 6%, respectively. • High ADC and ill-defined tumor margin at baseline predicted poor survival, regardless of patient's liver function and general health status.

Efficacy and safety of biosimilar rituximab in patients with pemphigus vulgaris: a prospective observational study.

Background: The optimal treatment for pemphigus vulgaris (PV) has not been clearly determined yet. Rituximab (RTX) was recently approved for the management of adults with moderate to severe PV. Objectives: This prospective observational study was designed to evaluate the efficacy and safety of biosimilar RTX in PV patients.Methods: The efficacy and safety were evaluated by assessing the pemphigus disease area index (PDAI) score, clinical response and any adverse events (AEs) during at least 12-month follow-up. We evaluated anti-desmoglein (Dsg) 1,3 level at baseline, 3 months and 12 months after RTX infusion.Results: A total of 110 patients treated with biosimilar RTX were enrolled between May 2016 and July 2017. The mean age was 43.58 ± 11.77 years and the mean follow-up time was 16.22 ± 3.45 months. A notable decrease in PDAI score, anti-Dsg 1,3 level and prednisolone dosage was observed. Median delay to achieve complete remission (CR), median duration of CR, and median time to relapse were 3, 9, and 12 months, respectively. Newly diagnosed patients (NDPs) experienced higher rate of CR, longer duration of remission and lower risk of relapse, compared to previously treated patients (PTPs). A total of 47 AEs were observed in 33 (30%) patients, which were mostly mild infusion-related reactions.Conclusion: Administration of biosimilar RTX in PV patients was associated with desirable outcomes in terms of efficacy and safety in both NDPs and PTPs.First-line use of RTX in NDPs was more effective and allowed a rapid tapering of corticosteroid doses compared to PTPs.

Post-TACE changes in ADC histogram predict overall and transplant-free survival in patients with well-defined HCC: a retrospective cohort with up to 10 years follow-up.

OBJECTIVES: To evaluate the role of change in apparent diffusion coefficient (ADC) histogram after the first transarterial chemoembolization (TACE) in predicting overall and transplant-free survival in well-circumscribed hepatocellular carcinoma (HCC). METHODS: Institution database was searched for HCC patients who got conventional TACE during 2005-2016. One hundred four patients with well-circumscribed HCC and complete pre- and post-TACE liver MRI were included. Volumetric MRI metrics including tumor volume, mean ADC, skewness, and kurtosis of ADC histograms were measured. Univariate and multivariable Cox models were used to test the independent role of change in imaging parameters to predict survival. P values < 0.05 were considered significant. RESULTS: In total, 367 person-years follow-up data were analyzed. After adjusting for baseline liver function, tumor volume, and treatment modality, incremental percent change in ADC (ΔADC) was an independent predictor of longer overall and transplant-free survival (p = 0.009). Overall, a decrease in ADC-kurtosis (ΔkADC) showed a strong role in predicting longer survival (p = 0.021). Patients in the responder group (ΔADC ≥ 35%) had the best survival profile, compared with non-responders (ΔADC < 35%) (p < 0.001). ΔkADC, as an indicator of change in tissue homogeneity, could distinguish between poor and fair survival in non-responders (p < 0.001). It was not a measure of difference among responders (p = 0.244). Non-responders with ΔkADC ≥ 1 (homogeneous post-TACE tumor) had the worst survival outcome (HR = 5.70, p < 0.001), and non-responders with ΔkADC < 1 had a fair survival outcome (HR = 2.51, p = 0.029), compared with responders. CONCLUSIONS: Changes in mean ADC and ADC kurtosis, as a measure of change in tissue heterogeneity, can be used to predict overall and transplant-free survival in well-circumscribed HCC, in order to monitor early response to TACE and identify patients with treatment failure and poor survival outcome. KEY POINTS: • Changes in the mean and kurtosis of ADC histograms, as the measures of change in tissue heterogeneity, can be used to predict overall and transplant-free survival in patients with well-defined HCC. • A ≥ 35% increase in volumetric ADC after TACE is an independent predictor of good survival, regardless of the change in ADC histogram kurtosis. • In patients with < 35% ADC change, a decrease in ADC histogram kurtosis indicates partial response and fair survival, while ∆kurtosis ≥ 1 correlates with the worst survival outcome.

Role of volumetric multiparametric MRI in distinguishing between intraductal papillary mucinous neoplasms and serous cystadenoma.

PURPOSE: To evaluate the use of volumetric multiparametric MRI in differentiating pancreatic intraductal papillary mucinous neoplasms (IPMNs) from serous cystadenomas (SCAs) METHODS: Included patients (123 patients with pancreatic cystic neoplasms (PCNs) measuring ≥ 10 mm) were stratified into two groups based on cyst type. Axial cyst size, region of interest (ROI)-based apparent diffusion coefficient (ADC) and volumetric data, including cyst volume, volumetric apparent diffusion coefficient (vADC), and volumetric venous enhancement (vVE) were extracted and compared between the two groups. Univariate and multiple logistic regression was used to develop models for distinguishing between IPMNs and SCAs. RESULTS: Volume and size of the cysts, vVE and vADC and ROI-ADC were significantly different between the two groups. Cyst volume was significantly larger in SCAs (median = 14.1cm3, IQR 3.5-42.5) than in IPMNs (median = 2.5 cm3, IQR 1.1-6) (p < 0.001). IPMNs had a higher volumetric ADC value in comparison to SCAs (2925 ± 294 × 10-6 mm2/s vs 2521 ± 202 × 10-6 mm2/s, p < 0.001). However, IPMNs had lower vVE values compared to SCAs (37 signal intensity (SI) vs 86 SI, p < 0.001). Area under the ROC Curve (AUC) of the model that included vADC and cyst volume had 95% accuracy in distinguishing between the two groups. In comparison, the AUC of the model that included ROI-ADC and axial cyst size had 84% accuracy in distinguishing between the two groups. A threshold of 2615 × 10-6 mm2/s for volumetric ADC resulted in the identification of IPMNs from SCAs with sensitivity and specificity of 90.8% and 73.5%, respectively. CONCLUSION: IPMNs had smaller cyst volume, higher volumetric ADC and lower volumetric VE values compared to SCAs. Volumetric multiparametric MRI could be useful in differentiating between the IPMN and SCA groups.

Target-shaped combined halo and reversed-halo sign, an atypical chest CT finding in COVID-19.

Typical chest CT findings in COVID-19 have been described as bilateral peripheral ground glass opacities, with or without consolidation. Halo sign and reversed halo sign have been reported as atypical imaging findings in this disease. However, to the best of our knowledge, combined presence of these signs has never been reported before. Herein, we present a COVID-19 patient with numerous atypical target-shaped, combined halo and reversed halo pulmonary lesions, in the absence of any other underlying disease.

Role of tumor margin and ADC change in defining the need for additional treatments after the first TACE in patients with unresectable HCC.

PURPOSE: To define the number of TACE sessions needed to improve patients' overall survival (OS) in different subgroups of unresectable HCC. METHODS: This retrospective cohort included 180 patients who got TACE between 2005-2016 as the initial treatment for unresectable HCC. Tumor margin (well- vs. ill-defined) was determined by two radiologists at baseline. Well-defined group was divided into two groups (ADC-responders vs. ADC-nonresponders) based on %ADC change (ΔADC-cutoff = 25 %). Accordingly, patients were categorized into three groups, ill-defined, well-defined ADC-responders, or well-defined ADC-nonresponders. Cox-analysis was used to compare the survival benefit of multiple TACE in different groups. RESULTS: Ill-defined HCC (n = 108) was associated with worse survival (HR = 1.95,p < 0.001). Multiple TACE were associated with increased OS (HR = 0.88,p = 0.033) in these patients, with significant survival improvement after ≥4TACE. ΔADC was not related to OS in ill-defined group. In well-defined group (n = 72), multiple TACE were not associated with improved OS (HR = 0.181,p = 0.090). These patients were categorized into two groups based on ΔADC-cutoff. ADC-responders (ΔADC≥25 %) had the longest survival than other groups(p = 0.015). Multiple TACE sessions were not associated with better OS in this group (HR = 1.004,p = 0.982). By contrast, incremental number of TACE were associated with significantly longer OS in ADC-nonresponders (ΔADC<25 %) (HR = 0.79,p = 0.034). These patients' OS significantly improved after ≥3TACE. CONCLUSION: The survival benefit of sequential TACE sessions varies for different HCC subgroups. There was no significant survival benefit associated with multiple TACE in well-defined lesions responding to the first TACE. The most survival benefit was for ADC-nonresponder well-defined group and it was least for ill-defined HCC group, regardless of ADC-response.

Cross-sectional imaging in patients with primary sclerosing cholangitis: Single time-point liver or spleen volume is associated with survival.

AIM: To evaluate the association between single time-point quantitative liver and spleen volumes in patients with PSC and transplant-free survival, independent of Mayo risk score. MATERIALS AND METHODS: This HIPAA-compliant retrospective study included 165 PSC patients in a hospital. Total (T), and lobar (right [R], left [L], and caudate [C]) liver volumes and spleen volume (S) were measured. Adverse outcome was identified as being on liver transplantation list, transplantation or death (outcome 1), and transplantation or death (outcome 2). Cox-regression was performed to assess the predictive value of volumetric parameters to predict transplant-free survival with and without Mayo risk score. Stratified analysis by Mayo risk score categories was performed to assess the discriminative value of volumes in the model. Prediction models were developed dependent of Mayo score, based on patients demographics, lab values and volumetric measures for both defined outcomes. Kaplan-Meier curves were depicted for different liver and spleen volumes. P value <0.05 was considered statistically significant. RESULTS: In this cohort (age 43 ±â€¯17 years; 59 % men) 51 % of patients had adverse outcome. Cox-regression analysis demonstrated statistically significant association between values of T, L, R, C, S, L/T, and C/T and outcome 1; and also statistically significant association between values C, S, and C/T and outcome 2. Prediction models included age, INR, total bilirubin, AST, variceal bleeding, S, and C for outcome 1 and age, INR, total bilirubin, AST, variceal bleeding, and S for outcome 2. CONCLUSIONS: Based on our observational study, quantitative liver and spleen volumes may be associated with transplant-free survival in patients with PSC and may have the potential for predicting the outcome but this should be validated by randomized clinical trial studies.

Does the change in volumetric functional MR metrics post-TACE predict histopathologic grading of hepatocellular carcinoma?

OBJECTIVES: To evaluate whether the change in volumetric ADC (vADC) and volumetric venous enhancement (vVE) after transarterial chemoembolization (TACE) can predict the histologic grading of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This HIPPA-compliant retrospective study was approved by our institutional review board. The study population included 106 HCC patients (147 index lesions) who had MR imaging within 3 months before and after TACE and pathologic report of the HCC either by biopsy or liver transplantation/resection between 2001 and 2017. Volumetric measurements of venous enhancement (VE) and apparent diffusion coefficient (ADC) were performed on baseline and post-TACE MRI. The tumors were histologically classified into two low-grade and high-grade groups. The parameters between two groups were compared using bivariate and multivariate analyses. RESULTS: Median change in vADC, vVE, and absolute vADC skewness after TACE was higher in low-grade HCCs as compared with high-grade HCCs (p < 0.001, p = 0.005, p = 0.04, respectively). Combining ΔvADC, ΔvVE, and the etiology for background liver disease in multivariate analysis had the highest accuracy in distinguishing high-grade tumors (AUC = 91%). CONCLUSION: ΔvADC and ΔvVE after TACE are potential predictors of HCC histopathological grading. Combining functional MRI biomarkers with the etiology of liver disease can enhance the accuracy in assessing degree of differentiation. KEY POINTS: • Change in volumetric functional MRI biomarkers after TACE can be a non-invasive method to evaluate tumor histopathology in HCC. • The etiology of background liver disease might be a predictor of tumor degree of differentiation.

Advances in Imaging of Diffuse Parenchymal Liver Disease.

There are >1.5 billion people with chronic liver disease worldwide, causing liver diseases to be a significant global health issue. Diffuse parenchymal liver diseases, including hepatic steatosis, fibrosis, metabolic diseases, and hepatitis cause chronic liver injury and may progress to fibrosis and eventually hepatocellular carcinoma. As early diagnosis and treatment of these diseases impact the progression and outcome, the need for assessment of the liver parenchyma has increased. While the current gold standard for evaluation of the hepatic parenchymal tissue, biopsy has disadvantages and limitations. Consequently, noninvasive methods have been developed based on serum biomarkers and imaging techniques. Conventional imaging modalities such as ultrasound, computed tomography scan, and magnetic resonance imaging provide noninvasive options for assessment of liver tissue. However, several recent advances in liver imaging techniques have been introduced. This review article focuses on the current status of imaging methods for diffuse parenchymal liver diseases assessment including their diagnostic accuracy, advantages and disadvantages, and comparison between different techniques.

Clinical, Immunological, and Genetic Features in 49 Patients With ZAP-70 Deficiency: A Systematic Review.

Background: Zeta-Chain Associated Protein Kinase 70 kDa (ZAP-70) deficiency is a rare combined immunodeficiency (CID) caused by recessive homozygous/compound heterozygous loss-of-function mutations in the ZAP70 gene. Patients with ZAP-70 deficiency present with a variety of clinical manifestations, particularly recurrent respiratory infections and cutaneous involvements. Therefore, a systematic review of ZAP-70 deficiency is helpful to achieve a comprehensive view of this disease. Methods: We searched PubMed, Web of Science, and Scopus databases for all reported ZAP-70 deficient patients and screened against the described eligibility criteria. A total of 49 ZAP-70 deficient patients were identified from 33 articles. For all patients, demographic, clinical, immunologic, and molecular data were collected. Results: ZAP-70 deficient patients have been reported in the literature with a broad spectrum of clinical manifestations including recurrent respiratory infections (81.8%), cutaneous involvement (57.9%), lymphoproliferation (32.4%), autoimmunity (19.4%), enteropathy (18.4%), and increased risk of malignancies (8.1%). The predominant immunologic phenotype was low CD8+ T cell counts (97.9%). Immunologic profiling showed defective antibody production (57%) and decreased lymphocyte responses to mitogenic stimuli such as phytohemagglutinin (PHA) (95%). Mutations of the ZAP70 gene were located throughout the gene, and there was no mutational hotspot. However, most of the mutations were located in the kinase domain. Hematopoietic stem cell transplantation (HSCT) was applied as the major curative treatment in 25 (51%) of the patients, 18 patients survived transplantation, while two patients died and three required a second transplant in order to achieve full remission. Conclusion: Newborns with consanguineous parents, positive family history of CID, and low CD8+ T cell counts should be considered for ZAP-70 deficiency screening, since early diagnosis and treatment with HSCT can lead to a more favorable outcome. Based on the current evidence, there is no genotype-phenotype correlation in ZAP-70 deficient patients.

Role of baseline volumetric functional MRI in predicting histopathologic grade and patients' survival in hepatocellular carcinoma.

OBJECTIVES: We aimed to evaluate the role of volumetric ADC (vADC) and volumetric venous enhancement (vVE) in predicting the grade of tumor differentiation in hepatocellular carcinoma (HCC). METHODS: The study population included 136 HCC patients (188 lesions) who had baseline MR imaging and histopathological report. Measurements of vVE and vADC were performed on baseline MRI. Tumors were histologically classified into low-grade and high-grade groups. The parameters between the two groups were compared using Mann-Whitney U and chi-square tests for continuous and categorical parameters, respectively. Area under receiver operating characteristic (AUROC) was calculated to investigate the accuracy of vADC and vVE. Logistic regression and multivariable Cox regression were used to unveil the potential parameters associated with high-grade HCC and patient's survival, respectively. RESULTS: Lesions with higher vADC values and a higher absolute vADC skewness were more likely to be high grade on histopathology assessment (p = 0.001 and p = 0.0291, respectively). Also, vVE showed a trend to be higher in low-grade lesions (p = 0.079). Adjusted multivariable model including vADC, vVE, and vADC skewness could strongly predict HCC degree of differentiation (AUROC = 83%). Additionally, a higher Child-Pugh score (HR = 2.39 [p = 0.02] for score 2 and HR = 3.47 [p = 0.001] for score 3), vADC skewness (HR = 1.52, p = 0.02; per increments in skewness), and tumor volume (HR = 1.1, p = 0.001; per 100 cm3 increments) showed the highest association with patients' survival. CONCLUSIONS: vADC and vVE have the potential to accurately predict HCC differentiation. Additionally, some imaging features in combination with patients' clinical characteristics can predict patient survival. KEY POINTS: • Volumetric functional MRI metrics can be considered as non-invasive measures for determining tumor histopathology in HCC. • Estimating patient survival based on clinical and imaging parameters can be used for modifying management approach and preventing unnecessary adverse events.