Magnetic Resonance Elastography Versus Transient Elastography in the Prediction of Complications After Resection for Hepatocellular Carcinoma.

OBJECTIVE: To compare the performances of MRE and TE for predicting severe complications after HR in patients with HCC. SUMMARY OF BACKGROUND DATA: LSM may have the potential to predict outcomes after HR in HCC patients. METHODS: Consecutive patients who underwent HR for HCC between 2017 and 2019 were retrospectively enrolled. Before HR, LSM was performed in all patients using both MRE and TE. All postoperative complications were assessed using the comprehensive complication index (CCI). Severe postoperative complications were defined as a CCI ≥26.2. The performances of MRE and TE for predicting high CCI and diagnosing liver fibrosis were compared using the area under the receiver-operating-characteristic curve (AUROC). Uni-/multivariable logistic regression analyses were used to identify factors associated with high CCI. RESULTS: Among the 208 enrolled patients, 28 patients (13.5%) had high CCI. For detecting high CCI, MRE had an AUROC of 0.874 [95% confidence interval (CI), 0.821-0.916], which was significantly higher than the AUROC of TE (0.756; 95% CI, 0.692-0.813) ( P = 0.020). MRE outperformed TE in detecting fibrosis of ≥F2 (AUROC: 0.935 vs 0.767; P = 0.008), ≥F3 (AUROC: 0.902 vs 0.774; P = 0.001) and F4 (AUROC: 0.916 vs 0.767; P < 0.001). LSM by MRE was independently associated with high CCI (odds ratio, 4.207 per kPa; 95% CI, 1.862-9.504; P < 0.001), whereas LSM by TE was not. CONCLUSIONS: MRE better predicted severe postoperative complications than TE in HCC patients who underwent HR. LSM by MRE was independently associated with high CCI after HR.

Fate of Patients With Intraductal Papillary Mucinous Neoplasms of Pancreas After Resection According to the Pathology and Margin Status: Continuously Increasing Risk of Recurrence Even After Curative Resection Suggesting Necessity of Lifetime Surveillance.

OBJECTIVE: This study evaluated the associated factors and prognosis according to pathology and margin after surgical resection of intraductal papillary mucinous neoplasms (IPMN). BACKGROUND: There is limited information on recurrence patterns according to pathology and margin in IPMN. METHODS: Total 577 patients who underwent operation for IPMN at a tertiary center were included. Factors associated with recurrence, survival, and recurrence outcomes according to pathology and margin were analyzed. RESULTS: Among 548 patients analyzed, 353 had low-grade dysplasia (LGD), 78 had high-grade dysplasia (HGD), and 117 had invasive IPMN. Total 50 patients developed recurrences, with 4 resection margins, 10 remnant pancreas, 11 locoregional, and 35 distant recurrences. Invasive IPMN showed worse 5-year cumulative recurrence risk (LGD vs HGD vs invasive: 0.7% vs 4.3% vs 37.6%, P < 0.001) and 5-year survival rate (89.0% vs 84.0% vs 48.4%, P < 0.001). Recurrence risk increased after 5 years, even in LGD and HGD. Malignant margin (HGD and invasive) had worse 5-year cumulative recurrence rate (R0 vs LGD vs malignant: 8.3% vs 5.9% vs 50.6%, P < 0.001) and 5-year survival rate (80.7% vs 83.0% vs 30.8%, P < 0.001). Carbohydrate antigen 19-9 >37 ( P = 0.003), invasive IPMN ( P < 0.001), and malignant margin ( P = 0.036) were associated with recurrence. CONCLUSIONS: Invasive IPMN developed more recurrences and had worse survival than LGD or HGD, indicating the need for more efficient postoperative treatment strategies. Patients with LGD and HGD also need regular follow-up for recurrence after 5 years. Malignant margins need additional resection to achieve negative or at least LGD margin.

Accuracy of Two-Dimensional Shear Wave Elastography and Attenuation Imaging for Evaluation of Patients With Nonalcoholic Steatohepatitis.

BACKGROUND & AIMS: We evaluated the accuracy of a multiparametric approach using attenuation imaging and 2-dimensional shear wave elastography (2D-SWE) for the detection of steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: We studied 102 patients with increased levels of liver enzymes or suspicion of NAFLD, examined by attenuation imaging and 2D-SWE, immediately before biopsy collection and analysis (reference standard), from January 2018 to July 2019. We collected data on the attenuation coefficient (dB/cm/MHz) from attenuation imaging, liver stiffness measurements, and shear wave dispersion slope (SWDS, [m/s]/kHz) from 2D-SWE. Multivariate linear regression analysis was performed to identify factors associated with each parameter. Diagnostic performance was determined from area under the receiver operating curve (AUROC) values. RESULTS: The attenuation coefficient was associated with steatosis grade (P < .01) and identified patients with steatosis grades S1 or higher, S2 or higher, and S3 or higher, with AUROC values of 0.93, 0.88, and 0.83, respectively. Liver stiffness associated with fibrosis stage (P < .01) and lobular inflammatory activity was the only factor associated with SWDS (P < .01). SWDS detected inflammation grades I1 or higher, I2 or higher, and I3 or higher with AUROC values of 0.89, 0.85, and 0.78, respectively. We developed a risk scoring system to detect steatohepatitis based on the attenuation coefficient (score of 1 for 0.64 < attenuation coefficient ≤ 0.70; score of 2 for 0.70 < attenuation coefficient ≤ 0.73; and score of 3 for attenuation coefficient >0.73) and SWDS (score of 2 for 10.5 [m/s]/kHz < SWDS ≤ 11.7 [m/s]/kHz; and score of 3 for SWDS >11.7 [m/s]/kHz), using an unweighted sum of each score. Based on histopathology analysis, 55 patients had steatohepatitis. Risk scores correlated with NAFLD activity score (rho = 0.73; P < .01). Our scoring system identified patients with steatohepatitis with an AUROC of 0.93-this value was significantly higher than that of other parameters (P < .05), except SWDS (AUROC, 0.89; P = .18). CONCLUSIONS: In the evaluation of patients with suspected NAFLD, the attenuation coefficient can identify patients with steatosis and liver stiffness can detect fibrosis accurately. SWDS was associated significantly with lobular inflammation. We developed a risk scoring system based on the attenuation coefficient and SWDS that might be used to detect steatohepatitis.

Association between spleen volume and the post-hepatectomy liver failure and overall survival of patients with hepatocellular carcinoma after resection.

OBJECTIVES: Post-hepatectomy liver failure (PHLF) can occur as a major complication after hepatic resection (HR) in patients with hepatocellular carcinoma (HCC) and negatively affects the prognosis. We aimed to retrospectively assess whether the spleen volume (SV) measured from preoperative CT images would be associated with the development of PHLF and overall survival (OS) after HR in patients with HCC. METHODS: We enrolled 317 consecutive patients with very early/early stage HCC who underwent a preoperative CT and HR between January 2010 and December 2016. The SV was obtained from preoperative CT images using semi-automated volumetric software and was divided by body surface area to yield SVBSA. Receiver operating characteristic (ROC) curves and logistic regression analyses were performed to identify factors affecting the development of PHLF. The Cox proportional hazard model was used to identify prognostic factors for OS. RESULTS: PHLF was observed in 72 patients (22.7% [72/317]). SVBSA was associated with the development of PHLF (odds ratio, 2.321; 95% CI, 1.347-4.001; p = 0.002) with the area under the ROC curve of 0.663 using the cutoff value of 107.5 cm3 (p < 0.001). SVBSA was also an influencing factor for OS (hazard ratio, 3.935; 95% CI 1.520-10.184; p = 0.005), with the optimal cutoff of 146 cm3. The 5-year OS rate was higher in 245 patients with a SVBSA ≤ 146 cm3 than in 72 patients with a SVBSA > 146 cm3 (95.0% vs. 78.7%, p < 0.001). CONCLUSIONS: In patients with HCC, a larger SVBSA was associated with a higher rate of PHLF and worse OS after HR. The SVBSA may be useful in selecting good surgical candidates. KEY POINTS: • A significantly higher spleen volume divided by body surface area was observed in patients who experienced post-hepatectomy liver failure than in patients who did not (148 cm3 vs. 112 cm3, p < 0.001). • The area under the receiver operating characteristic curve of spleen volume divided by body surface area to predict the development of post-hepatectomy liver failure was 0.663 (p < 0.001). • Spleen volume divided by body surface area was a significant influencing factor for overall survival (hazard ratio, 3.935; 95% CI, 1.520-10.184; p < 0.001), with the optimal cutoff of 146 cm3.

2D shear wave elastography is better than transient elastography in predicting post-hepatectomy complication after resection.

OBJECTIVES: Both transient elastography (TE) and 2D shear wave elastography (SWE) are accurate methods to evaluate liver fibrosis. We aimed to evaluate the diagnostic performance of 2D-SWE in predicting post-hepatectomy complication and to compare it with TE. METHODS: We prospectively enrolled 125 patients with liver tumors. Liver stiffness (LS) (kilopascal [kPa]) was measured using both TE and 2D-SWE before surgery. All post-operative complication was evaluated using the comprehensive complication index (CCI), and CCI ≥ 26.2 was defined as severe complication. Logistic regression analysis was performed to identify predictive factors for severe complication. Receiver operating characteristic analysis was used to evaluate the diagnostic performance of TE/2D-SWE in detecting liver fibrosis and severe complication. RESULTS: Severe complication developed in 18 patients. The median LS in patients with severe complication was significantly higher for both 2D-SWE (11.4 kPa vs. 7.0 kPa, p < 0.001) and TE (8.9 kPa vs. 6.2 kPa, p = 0.009). LS obtained from 2D-SWE was a significant factor correlated with severe complication (odds ratio: 1.27 per kPa [1.10-1.46], p = 0.001). The diagnostic performance of 2D-SWE was significantly higher than that of TE in detecting both ≥F3 (p = 0.024) and F4 (p = 0.048). The area under the curve of 2D-SWE to predict severe complication was 0.854, significantly higher than 0.692 of TE (p = 0.004). The optimal cut-off LS from 2D-SWE to predict severe complication was 8.6 kPa, with sensitivity of 88.9% (16/18) and specificity of 73.8% (79/107). CONCLUSION: LS obtained from 2D-SWE was a significant predictive factor for severe complication, and 2D-SWE showed significantly a better diagnostic performance than TE in detecting liver fibrosis and severe complication. KEY POINTS: • The diagnostic performance of 2D-SWE was significantly higher than that of TE in detecting both ≥ F3 (AUC: 0.853 vs. 0.779, p = 0.024) and F4 (AUC: 0.929 vs. 0.872, p = 0.048). • Liver stiffness value obtained from 2D-SWE was a significant factor correlated with the development of severe complication defined as CCI ≥ 26.2 after hepatic resection for liver tumors (odds ratio: 1.27 per kPa [1.10-1.46], p = 0.001). • 2D-SWE provided significantly a better diagnostic performance in predicting severe complication after hepatic resection than TE (AUC for 2D-SWE: 0.853 vs. AUC for TE: 0.692, p = 0.004).

Shear-Wave Dispersion Slope from US Shear-Wave Elastography: Detection of Allograft Damage after Liver Transplantation.

Background Allograft damage (hepatic parenchymal damage) after liver transplant is associated with the degree of necroinflammation in graft liver. According to a recent animal study, shear-wave dispersion slope obtained at US shear-wave elastography (SWE) is associated with necroinflammatory activity in the liver. Purpose To evaluate the role of shear-wave dispersion slope in detecting allograft damage after liver transplant. Materials and Methods In this prospective study, 104 liver transplant recipients underwent percutaneous liver biopsy for allograft evaluation from December 2017 to November 2018. All participants underwent allograft SWE examination just before liver biopsy, and liver stiffness and shear-wave dispersion slope were obtained. Allograft damage was diagnosed by histopathologic analysis. Clinical and imaging factors related to liver stiffness and shear-wave dispersion slope were determined by multivariable linear regression analysis. Diagnostic performance of each variable in detecting allograft damage was evaluated by comparing area under the receiver operating curve (AUC) values. Results There were 104 study participants (35 women); median age was 56 years (interquartile range, 50-62 years). Allograft damage was found in 46 of 104 (44.2%) of participants. The median liver stiffness (8.2 kPa vs 6.3 kPa; P < .01) and shear-wave dispersion slope (14.4 [m/sec]/kHz vs 10.4 [m/sec]/kHz; P < .01) were higher in participants with allograft damage than in those without damage, respectively. Fibrosis stage was the only determinant factor for liver stiffness (coefficient, 1.8 kPa per fibrosis stage; 95% confidence interval: 0.1, 3.5; P = .03), whereas both fibrosis stage (coefficient, 1.4 [m/sec]/kHz per fibrosis stage; 95% confidence interval: 0.3, 2.6; P = .02) and necroinflammatory activity (coefficient, 1.6 [m/sec]/kHz per necroinflammatory activity grade; 95% confidence interval: 0.5, 2.7; P < .01) affected shear-wave dispersion slope. The AUC for shear-wave dispersion slope in detecting allograft damage was 0.86, which was higher than that of liver stiffness (AUC, 0.75; P < .01). Conclusion Shear-wave dispersion slope determined at US shear-wave elastography may help in detecting allograft damage after liver transplant. © RSNA, 2019 Online supplemental material is available for this article.

Added Value of sequentially performed gadoxetic acid-enhanced liver MRI for the diagnosis of small (10-19 mm) or atypical hepatic observations at contrast-enhanced CT: A prospective comparison.

BACKGROUND: Small hepatocellular carcinomas (HCCs) often show atypical features at cross-sectional imaging, yet there is no preferred recommendation for the diagnosis or characterization of small observations (10-19 mm) at present. PURPOSE: To determine the added value of sequentially performed gadoxetic acid-enhanced liver MRI for contrast-enhanced computed tomography (CECT)-detected small (10-19 mm) or atypical hepatic observations ≥20 mm in the diagnosis of HCC. STUDY TYPE: Prospective, cross-sectional, intraindividual comparison. POPULATION: In all, 110 patients at high risk of developing HCC. FIELD STRENGTH/SEQUENCE: 1.5T and 3T/T1 -weighted imaging. ASSESSMENT: Hepatic observations were classified into HCCs or benign non-HCCs based on imaging features of arterial phase hyperenhancement (APHE) and portal or delayed washout at CT or APHE and portal washout at MRI. Final diagnoses were established using a composite algorithm and diagnostic performances of MRI and CT were compared in all observations. In addition, in a subgroup of histologically confirmed observations and stable benign observations during follow-up (n = 94), sensitivity and specificity of MRI were compared between the aforementioned criteria and LR-5 of Liver Imaging Reporting and Data System v2014. STATISTICAL TEST: χ2 test. RESULTS: MRI provided higher sensitivity than CT (62.2% vs. 27.0%, P = 0.0001) while maintaining specificity (97.2%, each) at the per-patient level. Among 124 observations, 10-19 mm in size, MRI showed significantly higher sensitivity in diagnosing HCCs (62.5%, 50/80) than CT (25%, 20/80, P < 0.0001) with comparable specificity (97.7% [43/44], each). However, seven atypical observations (≥20 mm) at CT remained atypical at MRI. In the subgroup analysis, the diagnostic criteria of APHE and portal washout showed a significantly higher sensitivity (44.2%, 19/43) than LR-5 (23.2%, 10/43, P = 0.004), without compromising specificity (97.7% vs. 95.5%). DATA CONCLUSION: Sequentially performed gadoxetic acid-enhanced MRI provided added value to CECT for the diagnosis of HCCs in small observations by improving sensitivity while maintaining specificity. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:574-587.

Clinical Outcomes of Radiofrequency Ablation for Early Hypovascular HCC: A Multicenter Retrospective Study.

Purpose To retrospectively evaluate the clinical outcomes of radiofrequency ablation (RFA) for early hypovascular hepatocellular carcinomas (HCCs) and to compare them with those of typical hypervascular HCCs. Materials and Methods This retrospective multicenter study received institutional review board approval, with a waiver of the need to obtain informed consent. A total of 56 patients (male-to-female ratio, 40:16; mean age, 61.8 years; age range, 33-87 years) with pathologically proven early HCCs that did not meet the noninvasive diagnosis criteria and who were initially treated with RFA at one of five university-affiliated hospitals between January 2009 and December 2013 comprised the study group. Thereafter, 240 patients with hypervascular HCCs initially treated with RFA in the same period in a historical cohort were selected as control patients. Overall survival (OS), progression-free survival (PFS), and cumulative incidence of local tumor progression (LTP) were estimated by using Kaplan-Meier analysis and were compared by using the Cox proportional hazard regression model. After the first analysis, propensity score analysis was performed to reduce potential bias. Results Complete ablation was achieved in all 56 patients with early hypovascular HCCs after RFA. The estimated 5-year cumulative incidence of LTP in the 56 patients with early hypovascular HCCs was significantly lower than in the 240 patients with hypervascular HCCs (5.4% for early hypovascular HCCs vs 20.8% for hypervascular HCCs; hazard ratio = 6.57 [95% confidence interval: 1.59, 27.2]; P = .009). After propensity matching, the estimated 5-year cumulative incidence of LTP in patients with early hypovascular HCCs was still significantly lower than that in patients with hypervascular HCCs (5.4% vs 23.0%; P = .025; hazard ratio = 5.71 [95% confidence interval: 1.27, 25.8]). OS was not significantly different between the groups (P = .100). One-year PFS in the 56 patients with early hypovascular HCCs, on the other hand, appeared to be favorable at 92.7%, compared with 79.4% in the 240 patients with hypervascular HCCs, but overall, PFS was not significantly different (P = .066). Conclusion RFA of early hypovascular HCCs provided similar OS and PFS compared with RFA of typical hypervascular HCCs, despite its significantly lower 5-year cumulative incidence of LTP. © RSNA, 2017 Online supplemental material is available for this article.

Protein disulfide isomerase inhibition synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma.

Sorafenib is the only approved targeted drug for hepatocellular carcinoma (HCC), but its effect on patients' survival gain is limited and varies over a wide range depending on pathogenetic conditions. Thus, enhancing the efficacy of sorafenib and finding a reliable predictive biomarker are crucial to achieve efficient control of HCCs. In this study, we utilized a systems approach by combining transcriptome analysis of the mRNA changes in HCC cell lines in response to sorafenib with network analysis to investigate the action and resistance mechanism of sorafenib. Gene list functional enrichment analysis and gene set enrichment analysis revealed that proteotoxic stress and apoptosis modules are activated in the presence of sorafenib. Further analysis of the endoplasmic reticulum stress network model, combined with in vitro experiments, showed that introducing an additional stress by treating the orally active protein disulfide isomerase (PDI) inhibitor (PACMA 31) can synergistically increase the efficacy of sorafenib in vitro and in vivo, which was confirmed using a mouse xenograft model. We also found that HCC patients with high PDI expression show resistance to sorafenib and poor clinical outcomes, compared to the low-PDI-expression group. CONCLUSION: These results suggest that PDI is a promising therapeutic target for enhancing the efficacy of sorafenib and can also be a biomarker for predicting sorafenib responsiveness. (Hepatology 2017;66:855-868).

Evaluation of Hepatic Steatosis by Using Acoustic Structure Quantification US in a Rat Model: Comparison with Pathologic Examination and MR Spectroscopy.

Purpose To determine factors that significantly affect the focal disturbance (FD) ratio calculated with an acoustic structure quantification (ASQ) technique in a dietary-induced fatty liver disease rat model and to assess the diagnostic performance of the FD ratio in the assessment of hepatic steatosis by using histopathologic examination as a standard of reference. Materials and Methods Twenty-eight male F344 rats were fed a methionine-choline-deficient diet with a variable duration (3.5 days [half week] or 1, 2, 3, 4, 5, or 6 weeks; four rats in each group). A control group of four rats was maintained on a standard diet. At the end of each diet period, ASQ ultrasonography (US) and magnetic resonance (MR) spectroscopy were performed. Then, the rat was sacrificed and histopathologic examination of the liver was performed. Receiver operating characteristic curve analysis was performed to assess the diagnostic performance of the FD ratio in the evaluation of the degree of hepatic steatosis. The Spearman correlation coefficient was calculated to assess the correlation between the ordinal values, and multivariate linear regression analysis was used to identify significant determinant factors for the FD ratio. Results The diagnostic performance of the FD ratio in the assessment of the degree of hepatic steatosis (area under the receiver operating characteristic curve: 1.000 for 5%-33% steatosis, 0.981 for >33% to 66% steatosis, and 0.965 for >66% steatosis) was excellent and was comparable to that of MR spectroscopy. There was a strong negative linear correlation between the FD ratio and the estimated fat fraction at MR spectroscopy (Spearman ρ, -0.903; P < .001). Multivariate linear regression analysis showed that the degree of hepatic steatosis (P < .001) and fibrosis stage (P = .022) were significant factors affecting the FD ratio. Conclusion The FD ratio may potentially provide good diagnostic performance in the assessment of the degree of hepatic steatosis, with a strong negative linear correlation with the estimated fat fraction at MR spectroscopy. The degree of steatosis and stage of fibrosis at histopathologic examination were significant factors that affected the FD ratio. © RSNA, 2017 Online supplemental material is available for this article.

Nonhypervascular Pancreatic Neuroendocrine Tumors: Differential Diagnosis from Pancreatic Ductal Adenocarcinomas at MR Imaging-Retrospective Cross-sectional Study.

Purpose To determine useful magnetic resonance (MR) imaging features to differentiate nonhypervascular pancreatic neuroendocrine tumors (PNETs) from pancreatic ductal adenocarcinomas (PDACs). Materials and Methods The institutional review board approved this retrospective study and waived the informed consent requirement. Seventy-four patients with surgically confirmed PNETs and 82 patients with PDACs who underwent gadobutrol-enhanced MR imaging were included. Two radiologists independently evaluated the morphologic characteristics and temporal enhancement patterns of each tumor. Quantitative analysis, including measurement of tumor size, maximal upstream parenchymal thickness (MUPT), contrast-to-noise ratio, and apparent diffusion coefficient values, was performed. Uni- and multivariate logistic regression analyses were performed to identify relevant features to differentiate between PNETs and PDACs. Results On the basis of arterial enhancement, 38 PNETs (51%, 38 of 74) were hypervascular and 36 PNETs (49%, 36 of 74) were nonhypervascular. At MR imaging, nonhypervascular PNETs showed significantly higher frequencies of a well-defined margin, portal hyper- or isoenhancement, and MUPT of 10 mm or greater but lower frequencies of ductal dilatation, vascular invasion, and peripancreatic infiltration when compared with PDACs (P < .05 for all). At multivariate analysis, a well-defined margin and portal hyper- or isoenhancement were independent significant differentiators of PNETs from PDACs (odds ratio, 20.3 and 16.1, respectively). When applying the criteria of a well-defined margin and portal hyper- or isoenhancement, 64% of sensitivity and 99% of specificity were observed for the differential diagnosis of PNETs from PDACs. Conclusion A well-defined margin and hyper- or isoenhancement in the portal venous phase are useful MR imaging features that are more common in nonhypervascular PNETs and may help discriminate nonhypervascular PNETs from PDACs. © RSNA, 2017 Online supplemental material is available for this article.

Macrovascular invasion is not an absolute contraindication for living donor liver transplantation.

The indication of liver transplantation (LT) for the treatment of advanced hepatocellular carcinoma (HCC) is expanding. However, portal vein tumor thrombus (PVTT) has been still accepted as an absolute contraindication. We experienced an unexpectedly good prognosis in selected patients. Therefore, we tried to identify the prognostic factors after LT for HCC with major PVTT. Among 282 patients who underwent living donor liver transplantation (LDLT) for HCC from January 2009 to December 2013, 11 (3.9%) patients with major PVTT that was preoperatively diagnosed were investigated. The 1-, 3-, and 5-year recurrence-free survival rates were 63.6%, 45.5%, and 45.5%, respectively, and all recurrent cases showed intrahepatic and extrahepatic recurrence. The 1-, 3-, and 5-year overall survival rates were 72.7%, 63.6%, and 63.6%, respectively, and 2 patients with delayed recurrence survived approximately 5 years after LT. Main portal vein (PV) invasion (P < 0.01), high alpha-fetoprotein × protein induced by vitamin K absence/antagonist-II (AP) score (≥20,000; P < 0.01), high standardized uptake value (SUV) ratio (tumor/background liver) in positron emission tomography (≥2.1; P < 0.01), and a large original tumor (≥7 cm; P = 0.03) were significant risk factors for recurrence. In conclusion, if the PVTT has not expanded to the main PV and the AP score is not high, we can consider LDLT as a curative treatment option. Liver Transplantation 23:19-27 2017 AASLD.

Hepatic stiffness measurement by using MR elastography: prognostic values after hepatic resection for hepatocellular carcinoma.

PURPOSE: To evaluate prognostic value of hepatic stiffness (HS) measurement using MR elastography (MRE) in patients with hepatocellular carcinoma (HCC) treated by hepatic resection (HR). METHODS: We enrolled 144 patients with Barcelona Clinic Liver Cancer stage A HCCs initially treated by HR who underwent preoperative liver MRE between January 2010 and June 2013. HS values were measured using MRE. Receiver operating characteristics (ROC) and multivariate logistic regression analyses were used to determine significant predictive factors for posthepatecomy liver failure (PHLF). Overall survival (OS) was analyzed by evaluating prognostic factors using the Kaplan-Meier method and Cox proportional hazard regression model. RESULTS: After HR, 43 patients (29.9 %) experienced PHLF. HS values were significant predictive factors for PHLF. In ROC analysis, the area under the curve of HS was 0.740 (P = 0.001) for PHLF. Thirty-one patients had HS values ≥ 4.02 kPa; the estimated 1, 3, 5-year survival were 90.0 %, 74.7 % and 65.4 %, respectively, versus 98.1 %, 96.5 % and 96.5 % in 113 patients with HS values < 4.02 kPa (P = 0.015). An HS value ≥ 4.02 kPa was the only significant affecting factor for OS. CONCLUSION: HS values measured by MRE could predict PHLF development post-HR. Furthermore, an HS value ≥4.02 kPa was a significant predicting factor for poor OS post-HR. KEY POINTS: • Hepatic stiffness value was a predictive factor for developing posthepatectomy liver failure • Hepatic stiffness value was a significant affecting factor for OS • Hepatic stiffness value ≥ 4.02 kPa was a predictive factor for poor OS.

Prediction of Pancreatic Fistula After Distal Pancreatectomy Based on Cross-Sectional Images.

BACKGROUND: Postoperative pancreatic fistula (POPF) is one of the most common and clinically relevant complications after distal pancreatectomy (DP), occurring in 5-40% of patients. Determining risk factors for this complication may aid in its prevention. This study sought to predict the development of POPF after DP preoperatively and objectively based on radiologic findings. METHODS: This study included 60 patients who underwent DP using a stapler for pancreatic division between June 2011 and January 2013. Fatty infiltration, apparent diffusion coefficients (ADC) on preoperative MRI, pathologic fat, and fibrosis were measured. Pancreatic thickness and cross-sectional area of the pancreas stump on CT scan were also measured. RESULTS: Mean patient age was 60.5 years, 26 patients (46.3%) had pancreatic cancer and 20 (33.3%) underwent laparoscopic surgery. Clinically relevant POPF was observed in 12 patients (20.0%). Linear regression analysis showed a significant correlation between fat quantification on MRI and pathologic fat (pathologic fat = 1.978 × MR fat -6.393, p < 0.001, R 2 = 0.777). Univariate analysis showed that ≤8% fat on MRI (p = 0.040), ≤5% pathologic fat (p = 0.002), ADC ≤ 1.3 × 10-3 mm2/s (p = 0.020), thicker pancreas (p = 0.007), and wider cross-sectional area of the pancreas (p = 0.013) were significantly associated with clinically relevant POPF after DP. Multivariate analysis revealed that pancreas thickness >17.6 mm [odds ratio (OR) 6.532, p = 0.064] and cross-sectional area >377 mm2 (OR 12.676, p = 0.052) were marginally related to clinically relevant POPF. CONCLUSIONS: Pancreatic thickness and cross-sectional area of the transected surface of the pancreas are marginally significant risk factors for POPF development after DP. Measuring pancreatic thickness and cross-sectional area can be a promising tool for the preoperative prediction of POPF.

Pancreatic Steatosis and Fibrosis: Quantitative Assessment with Preoperative Multiparametric MR Imaging.

PURPOSE: To evaluate the diagnostic performance of multiparametric pancreatic magnetic resonance (MR) imaging, including the T2*-corrected Dixon technique and intravoxel incoherent motion (IVIM) diffusion-weighted (DW) imaging, in the quantification of pancreatic steatosis and fibrosis, with histologic analysis as the reference standard, and to determine the relationship between MR parameters and postoperative pancreatic fistula. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board, and the informed consent requirement was waived. A total of 165 patients (93 men, 72 women; mean age, 62 years) underwent preoperative 3-T MR imaging and subsequent pancreatectomy (interval, 0-77 days). Fat fractions, IVIM DW imaging parameters (true diffusion coefficient [D], pseudodiffusion coefficient [D*], and perfusion fraction [f]), pancreas-to-muscle signal intensity ratios on unenhanced T1-weighted images, and pancreatic duct sizes were compared with the fat fractions and fibrosis degrees (F0-F3) of specimens. In 95 patients who underwent pancreatoenteric anastomosis, MR parameters were compared between groups with clinically relevant postoperative pancreatic fistula and those without. The relationship between postoperative pancreatic fistula and MR parameters was evaluated by using logistic regression analysis. RESULTS: Fat fractions at MR imaging showed a moderate relationship with histologic findings (r = 0.71; 95% confidence interval: 0.63, 0.78). Patients with advanced fibrosis (F2-F3) had lower D*([39.72 ± 13.64] ×10(-3)mm(2)/sec vs [32.50 ± 13.09] ×10(-3)mm(2)/sec [mean ± standard deviation], P = .004), f (29.77% ± 8.51 vs 20.82% ± 8.66, P < .001), and unenhanced T1-weighted signal intensity ratio (1.43 ± 0.26 vs 1.21 ± 0.30, P < .001) than did patients with F0-F1 disease. Clinically relevant fistula developed in 14 (15%) of 95 patients, and f was significantly associated with postoperative pancreatic fistula (odds ratio, 1.17; 95% confidence interval: 1.05, 1.30). CONCLUSION: Multiparametric MR imaging of the pancreas, including imaging with the T2*-corrected Dixon technique and IVIM DW imaging, may yield quantitative information regarding pancreatic steatosis and fibrosis, and f was shown to be significantly associated with postoperative pancreatic fistulas.

Portal Vein Thrombosis in Patients with Hepatocellular Carcinoma: Diagnostic Accuracy of Gadoxetic Acid-enhanced MR Imaging.

Purpose To assess the diagnostic performance of gadoxetic acid-enhanced magnetic resonance (MR) imaging in the evaluation of portal vein thrombosis (PVT) in patients with hepatocellular carcinoma (HCC). Materials and Methods This retrospective study was approved by the institutional review board. The requirement to obtain informed consent was waived. A total of 366 patients with HCC who underwent gadoxetic acid-enhanced MR imaging between January 2007 and May 2013, including 134 with malignant PVT, 49 with benign PVT, and 183 without PVT matched for age and sex, comprised our study population. PVTs were complete in 125 patients and partial in 58 and were located in a major portal vein (n = 159) or segmental portal vein (n = 24). Two radiologists independently reviewed the MR images and assessed the sensitivity, specificity, and accuracy in the detection and characterization of PVT according to location (major vs segmental) and type (complete vs partial). The Fisher exact or χ(2) test was used to evaluate sensitivity difference between the subsets. Results Gadoxetic acid-enhanced MR imaging showed good sensitivity (reviewer 1, 84% [154 of 183 patients]; reviewer 2, 70% [129 of 183 patients]) and high specificity (reviewer 1, 89% [163 of 183 patients]; reviewer 2, 96% [176 of 183 patients]) in the detection of PVT. Diagnostic accuracy for differentiating malignant PVT from benign PVT was high (reviewer 1, 92% [141 of 154 patients]; reviewer 2, 95% [122 of 129 patients]). However, there was slightly lower sensitivity for detecting segmental PVT compared with that of major PVT in the malignant PVT group (reviewer 1, 95% [104 of 110 patients] vs 88% [21 of 24 patients]; reviewer 2, 82% [90 of 110 patients] vs 79% [19 of 24 patients]; P = .203 and .775 for reviewers 1 and 2, respectively). Conclusion Gadoxetic acid-enhanced MR imaging provided good diagnostic performance in the detection of PVT and the differentiation of malignant from benign PVT in patients with HCC. However, caution is needed when evaluating potential candidates for curative treatment because of the low sensitivity for segmental PVT in the malignant PVT group. (©) RSNA, 2016 Online supplemental material is available for this article.

Combined Use of MR Fat Quantification and MR Elastography in Living Liver Donors: Can It Reduce the Need for Preoperative Liver Biopsy?

PURPOSE: To evaluate the diagnostic performance of magnetic resonance (MR) fat quantification and MR elastography for the assessment of hepatic steatosis and fibrosis in living liver donor candidates. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board, and the requirement of informed consent was waived. Donors who underwent MR fat quantification and MR elastography at 1.5 T, followed by liver biopsy, were chronologically grouped into test and validation groups. In the test group (n = 362), MR fat fraction and liver stiffness were compared among donors with normal parenchyma (n = 244), simple steatosis (n = 71), steatosis with inflammatory activity (n = 21), nonalcoholic steatohepatitis (n = 17), and fibrosis (n = 9). Diagnostic performance of the two techniques was assessed by using receiver operating characteristic curve analysis for the detection of substantial steatosis (macrovesicular fat ≥ 10%) or fibrosis (≥F1) and was tested in a validation group (n = 34). RESULTS: In the test group, donors with steatosis showed significantly higher fat fraction than donors without steatosis (P < .0001), and donors with fibrosis and nonalcoholic steatohepatitis showed significantly higher liver stiffness values than donors without fibrosis (P < .0001). Areas under the curve were 0.93 (cutoff value > 5.8%) for MR fat quantification and 0.85 (cutoff value > 1.94 kPa) for MR elastography. By using those values, the combination of the two techniques could be used to detect substantial steatosis or fibrosis with 100% sensitivity (12 of 12 patients, 95% confidence interval: 73.4%, 100%) and 100% negative predictive value (15 of 15 patients, 95% confidence interval: 78.0%, 100%) in the validation group. CONCLUSION: A combination of MR fat quantification and MR elastography can provide sufficient sensitivity to detect substantial steatosis or fibrosis (≥F1) in liver donor candidates.

Hepatic fibrosis: prospective comparison of MR elastography and US shear-wave elastography for evaluation.

PURPOSE: To compare magnetic resonance (MR) elastography and ultrasonographic shear-wave elastography ( SWE shear-wave elastography ) for the staging of hepatic fibrosis ( HF hepatic fibrosis ) in the same individuals. MATERIALS AND METHODS: This prospective study was approved by the institutional review board, and informed consent was obtained from all patients. The technical success of and reliable liver stiffness ( LS liver stiffness ) measurement rates at MR elastography and SWE shear-wave elastography were compared in 129 patients who underwent both examinations. For mutual validation, LS liver stiffness values measured at both examinations were correlated by using Pearson correlation. The diagnostic performance of the two techniques for the assessment of substantial HF hepatic fibrosis (stage ≥ F2) was compared by using nonparametric receiver operating characteristic analysis. RESULTS: The technical success rates of MR elastography and SWE shear-wave elastography were 95.35% (123 of 129) and 97.67% (126 of 129), respectively (P = .51). MR elastography provided significantly more reliable LS liver stiffness measurements than did SWE shear-wave elastography (95.35% [123 of 129] vs 75.2% [97 of 129], P < .001). The two examinations showed moderate correlation (r = 0.724). In patients with HF hepatic fibrosis stages of F3 or lower, the two examinations showed moderate-to-strong correlation (r = 0.683 in normal livers, 0.754 in livers with stage F0 or F1 HF hepatic fibrosis , and 0.90 in livers with stage F2 or F3 HF hepatic fibrosis ; P < .001); however, they did not show significant correlation for stage F4 HF hepatic fibrosis (r = 0.30, P = .31). MR elastography and SWE shear-wave elastography showed similar diagnostic capability in depicting HF hepatic fibrosis of stage F2 or greater (P = .98) when LS liver stiffness measurements were reliably performed. CONCLUSION: MR elastography and SWE shear-wave elastography showed moderate correlation and similar diagnostic performance in the diagnosis of HF hepatic fibrosis of stage F2 or greater; however, MR elastography yielded more reliable LS liver stiffness measurements than did SWE shear-wave elastography .

MR elastography for noninvasive assessment of hepatic fibrosis: reproducibility of the examination and reproducibility and repeatability of the liver stiffness value measurement.

PURPOSE: To determine the reproducibility of MR elastography (MRE) and the reproducibility and repeatability of the stiffness measurement of MRE in the staging of liver fibrosis. MATERIALS AND METHODS: Ninety-four patients, who underwent liver MRE, were included in this study. The patients were classified into group 1 (n = 47) and group 2 (n = 47) according to our knowledge of their histologic hepatic fibrosis (HF) stage. To analyze the reproducibility of MRE, the group 1 patients underwent MRE twice. In addition, to evaluate the repeatability and reproducibility of the stiffness measurement of MRE, a single observer measured the stiffness values of the second MREs in group 1 twice, and two observers independently measured the stiffness values of MRE in group 2. A 95% Bland-Altman limits of agreement and intraclass correlation coefficients (ICCs) were used to evaluate the reproducibility and repeatability of MRE. RESULTS: In group I, there was no significant difference in the mean liver stiffness values of the first and second MRE examinations, i.e., 3.45 ± 0.25 kPa vs. 3.35 ± 0.23 kPa (p = 0.22). The reproducibility of the MRE examination and the reproducibility and repeatability of the stiffness measurement were high, i.e., the ICCs of each parameter were 0.945, 0.827, and 0.963, respectively, and the 95% limits of agreement were 25.3%, 35.35%, and 18.0%, respectively. CONCLUSION: MRE is a promising tool for evaluating HF and has high reproducibility of the examination as well as reproducibility and repeatability of the stiffness measurements.

Non-hypervascular hypointense nodules ≥1 cm on the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging in cirrhotic livers.

OBJECTIVE: To determine the pathologic nature of non-hypervascular hypointense nodules (≥1 cm) on the hepatobiliary phase (HBP) of gadoxetic acid-enhanced magnetic resonance (MR) imaging and to describe the chronological changes of their imaging features on follow-up MR imaging. PATIENTS AND METHODS: This retrospective study was approved by our Institutional Review Board and the requirement for informed consent was waived. 69 patients with 115 non-hypervascular HBP hypointense nodules (≥1 cm in diameter) in cirrhotic livers were enrolled. 67 nodules were histologically diagnosed (group 1) and 52 nodules were followed up with MR for at least 12 months (group 2); 4 nodules belonged to both groups. Two radiologists reviewed the initial and follow-up MR images to determine the size and signal intensities on unenhanced T1- and T2-weighted images, dynamic phases and HBP images in consensus. In addition, two pathologists reviewed the histologic findings including H&E staining and four kinds of immunohistochemical staining in group 1. RESULTS: In group 1, 73.1% (49/67) of nodules were hepatocellular carcinomas. In group 2, 32.7% (17/52) of nodules developed arterial hypervascularity on follow-up, and 78.8% (41/52) showed at least one of the three imaging features considered to indicate malignant changes during follow-up (mean 19 ± 10 months): increase in diameter by ≥5 mm (23/52, 44.2%), arterialization (17/52, 32.7%) and hyperintensity on T2-weighted images (18/52, 34.6%). CONCLUSION: Our study results demonstrate that a significant proportion of non-hypervascular HBP hypointense nodules (≥1 cm in diameter) in patients with cirrhosis showed either malignant features on pathology (73.1%) or developed hypervascularity (32.7%) during follow-up.