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Surgical indications of main duct-involved intraductal papillary mucinous neoplasm (IPMN), especially for main pancreatic duct (MPD) of 5-9 mm, remain controversial. We aimed to predict malignancy risk of main duct-involved IPMN.Total 258 patients with main duct-involved IPMN between 2000 and 2017 in our institute were retrospectively analyzed. Main duct IPMN was classified into segmental and diffuse-type by dilated MPD pattern. Clinicopathologic features and predictive factors for malignancy were analyzed.Among 258 patients, 47 and 211 had pure main duct (segmental: 27, diffuse type: 20) and mixed type, respectively. Malignant IPMN presented higher in main duct type (66.0%) compared to mixed type (46.9%). The diffuse type (72.2%) had more invasive carcinoma than the segmental type (40.7%). Invasive IPMN risk increased proportionally to the MPD diameter (5 ≤ MPD10 mm vs 10 ≤ MPD 15 mm vs MPD ≥ 15 mm; 23.4% vs 40.0% vs 48.6%). Symptoms, elevated serum carbohydrate antigen, MPD ≥10 mm, mural nodule, thickened wall, and distal atrophy were independent predictive factors for malignancy. Patients with MPD of 5-9 mm with at least one predictive factor had 35.0% of malignancy risk.The invasive IPMN risk was different according to the dilated main duct pattern. Patients with main duct type, diffuse type, MPD ≥10 mm, and MPD 5-9 mm with at least one predictive factor should be candidates for immediate surgery.

The associated publication reports proteogenomic analysis of human pancreatic ductal adenocarcinoma (PDAC), where we provided significantly mutated genes (SMGs)/biomarkers, cellular pathways, and cell types as potential therapeutic targets to improve stratification of patients with PDAC. This protocol describes the detailed methods for whole exome sequencing (WES) and RNA sequencing analyses of PDAC samples, including tissue processing for proteogenomic analysis, DNA and RNA extraction, experimental procedures for WES and RNA sequencing, and WES and RNA sequencing data analyses.

The associated publication reports proteogenomic analysis of human pancreatic ductal adenocarcinoma (PDAC), where we provided significantly mutated genes (SMGs)/biomarkers, cellular pathways, and cell types as potential therapeutic targets to improve stratification of patients with PDAC. This protocol describes the detailed methods for mass spectrometry-based proteomic analysis of PDAC samples, including sample preparation, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, and data analyses (peptide/protein identification and quantitation).

The associated publication reports proteogenomic analysis of human pancreatic ductal adenocarcinoma (PDAC), where we provided significantly mutated genes (SMGs)/biomarkers, cellular pathways, and cell types as potential therapeutic targets to improve stratification of patients with PDAC. This protocol describes the detailed methods for cell-based assays for potential prognostic biomarkers in PDAC, including cell culture, viral transduction, and cell-based assays.

The associated publication reports proteogenomic analysis of human pancreatic ductal adenocarcinoma (PDAC), where we provided significantly mutated genes (SMGs)/biomarkers, cellular pathways, and cell types as potential therapeutic targets to improve stratification of patients with PDAC. This protocol describes the detailed methods for assays for orthotopic PDAC mouse models, including mouse tumour tissue processing, ultrasound imaging, Masson-trichrome staining, and IHC analysis for immune cell markers.

The associated publication reports proteogenomic analysis of human pancreatic ductal adenocarcinoma (PDAC), where we provided significantly mutated genes (SMGs)/biomarkers, cellular pathways, and cell types as potential therapeutic targets to improve stratification of patients with PDAC. This protocol describes the detailed methods for bioinformatics analysis of PDAC subtypes, including tumour purity estimation, subtype prediction for tumour samples in previous cohorts, pathway enrichment analysis, kinase activity analysis, and pan-omics analysis.

Multikinase inhibitors, such as sorafenib, are used for the treatment of advanced carcinomas but the response shows limited efficacy or varies a lot with patients. Here we adopted the systems approach combined with high-throughput data analysis to discover key mechanism embedded in the drug response. When analyzing the transcriptomic data from the Cancer Cell Line Encyclopedia (CCLE) database, endothelin 1 (EDN1) was enriched in cancer cells with low responsiveness to sorafenib. We found that the level of EDN1 is higher in the tissue and blood of hepatocellular carcinoma (HCC) patients showing poor response to sorafenib. In vitro experiment showed that EDN1 not only induces activation of angiogenic-promoting pathways in HCC cells but also stimulates proliferation and migration. Moreover, EDN1 is related with poor responsiveness to sorafenib by mitigating unfolded protein response (UPR), which was validated in both transcriptomic data analysis and in silico simulation. Finally, we found that endothelin receptor B (EDNRB) antagonists can enhance the efficacy of sorafenib in both HCC cells and xenograft mouse models. Our findings provide that EDN1 is a novel diagnostic marker for sorafenib responsiveness in HCC and a basis for testing macitentan, which is currently used for pulmonary artery hypertension, in combination with sorafenib in advanced HCC patients.

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. 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. 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

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. 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. 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 146 cm3 (95.0% vs. 78.7%, p < 0.001). 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. • 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 cm 3 vs. 112 cm 3 , 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 cm 3 .

BACKGROUND The prevalent location and incidence of intraductal papillary neoplasm of the bile duct (IPNB) and invasive carcinoma associated with them have varied markedly among studies due to differences in diagnostic criteria and tumor location. METHODS IPNBs were classified into two types: Type 1 IPNB, being histologically similar to intraductal papillary mucinous neoplasm of the pancreas, and Type 2 IPNB, having a more complex histological architecture with irregular papillary branching or foci of solid-tubular components. Medical data were evaluated. RESULTS Among 694 IPNB patients, 520 and 174 had Type 1 and Type 2, respectively. The levels of AST, ALT, ALP, T. Bil, and CEA were significantly higher in patients with Type 2 than in those with Type 1. Type 1 IPNB was more frequently located in the intrahepatic bile duct than Type 2, whereas Type 2 was more frequently located in the distal bile duct than Type 1 IPNB (P

Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year overall survival rate. Patients with PDAC display limited benefits after undergoing chemotherapy or immunotherapy modalities. Herein, we reveal that chemotherapy upregulates placental growth factor (PlGF), which directly activates cancer-associated fibroblasts (CAFs) to induce fibrosis-associated collagen deposition in PDAC. Patients with poor prognosis have high PIGF/VEGF expression and an increased number of PIGF/VEGF receptor-expressing CAFs, associated with enhanced collagen deposition. We also develop a multi-paratopic VEGF decoy receptor (Ate-Grab) by fusing the single-chain Fv of atezolizumab (anti-PD-L1) to VEGF-Grab to target PD-L1-expressing CAFs. Ate-Grab exerts anti-tumor and anti-fibrotic effects in PDAC models via the PD-L1-directed PlGF/VEGF blockade. Furthermore, Ate-Grab synergizes with gemcitabine by relieving desmoplasia. Single-cell RNA sequencing identifies that a CD141

We report a proteogenomic analysis of pancreatic ductal adenocarcinoma (PDAC). Mutation-phosphorylation correlations identified signaling pathways associated with somatic mutations in significantly mutated genes. Messenger RNA-protein abundance correlations revealed potential prognostic biomarkers correlated with patient survival. Integrated clustering of mRNA, protein and phosphorylation data identified six PDAC subtypes. Cellular pathways represented by mRNA and protein signatures, defining the subtypes and compositions of cell types in the subtypes, characterized them as classical progenitor (TS1), squamous (TS2-4), immunogenic progenitor (IS1) and exocrine-like (IS2) subtypes. Compared with the mRNA data, protein and phosphorylation data further classified the squamous subtypes into activated stroma-enriched (TS2), invasive (TS3) and invasive-proliferative (TS4) squamous subtypes. Orthotopic mouse PDAC models revealed a higher number of pro-tumorigenic immune cells in TS4, inhibiting T cell proliferation. Our proteogenomic analysis provides significantly mutated genes/biomarkers, cellular pathways and cell types as potential therapeutic targets to improve stratification of patients with PDAC.

This report describes a purely laparoscopic/robotic technique for successful living donor liver transplantation (LDLT). Purely laparoscopic explant hepatectomy followed by purely laparoscopic and robotic graft implantation can be performed in LDLT.

Purpose The clinical significance of margin status in pancreatic head cancer is still controversial due to the nonstandardized definition of R status and pathologic reporting. This study aims to evaluate the impact of the margin status including location and the role of radiation therapy in pancreatic head cancer. Methods A total of 314 patients who underwent curative-intent surgery for pancreatic head cancer between 2010 and 2017 were analyzed. Demographics, survival, and local recurrences were compared according to 2 definitions: 0-mm R1 as direct involvement and 1-mm R1 as close resection margin less than 1 mm. The specific margins were divided into 4 groups according to the location around the pancreas: pancreas transection, anterior surface, posterior surface, and vessel (superior mesenteric artery/superior mesenteric vein) margin. Results The 0-mm R1-rate was 15.6%, and increased to 36.3% in 1-mm R1. The median overall survival rate of 0-mm R0 vs. R1 was 26 months vs. 16 months (P = 0.052) and that of 1-mm R0 vs. R1 was 27 months vs. 18 months, respectively (P = 0.016). In individual margins, posterior, anterior surface, and pancreas transection margin involvement were associated with poor outcome, and the 1 mm posterior surface involvement was an independent risk factor for disease-free survival (hazard ratio, 1.63). Adjuvant radiation therapy had oncologic benefits, especially in R1 patients (P = 0.011) compared to R0 patients (P = 0.088). Conclusion Margin status, especially 1-mm R1 status is an important predictive factor, and involved posterior surface has a clinical impact. Patients with positive margins should be considered adjuvant radiation therapy.

Multikinase inhibitors, such as sorafenib, are used for the treatment of advanced carcinomas but the response shows limited efficacy or varies a lot with patients. Here we adopted the systems approach combined with high-throughput data analysis to discover key mechanism embedded in the drug response. When analyzing the transcriptomic data from the Cancer Cell Line Encyclopedia (CCLE) database, endothelin 1 (EDN1) was enriched in cancer cells with low responsiveness to sorafenib. We found that the level of EDN1 is higher in the tissue and blood of hepatocellular carcinoma (HCC) patients showing poor response to sorafenib. In vitro experiment showed that EDN1 not only induces activation of angiogenic-promoting pathways in HCC cells but also stimulates proliferation and migration. Moreover, EDN1 is related with poor responsiveness to sorafenib by mitigating unfolded protein response (UPR), which was validated in both transcriptomic data analysis and in silico simulation. Finally, we found that endothelin receptor B (EDNRB) antagonists can enhance the efficacy of sorafenib in both HCC cells and xenograft mouse models. Our findings provide that EDN1 is a novel diagnostic marker for sorafenib responsiveness in HCC and a basis for testing macitentan, which is currently used for pulmonary artery hypertension, in combination with sorafenib in advanced HCC patients.

Circulating tumor cells (CTCs) are useful biomarkers of many solid tumors, but are infrequently detected in early stage pancreatic ductal adenocarcinomas (PDACs). The first drainage of pancreatic venous blood flow come to portal vein and pass through the liver, and they finally go out for peripheral blood. We thought that comparing CTCs from portal vein and peripheral blood could enable us to understand the clinical meaning of CTCs from each different site in PDACs. Therefore, we aimed to determine 1) whether CTCs could be reliably identified in early stages (operable) of PDACs, 2) if there are any differences in the detected number of CTC in portal vein blood and peripheral blood, and 3) whether CTCs can be sensitive biomarkers for the prognosis of resectable PDAC patients. Newly diagnosed PDAC patients who underwent operation with curative intention between 2013 and 2015 were prospectively enrolled. Blood draws from portal and peripheral vein ran through the microfabricated porous filter, and anti-epithelial cell adhesion molecule (EpCAM) and anti-Plectin-1 antibodies were used for CTC identification. Baseline clinical characteristics, tumor characteristics, treatment, and clinical outcomes were assessed. The clinical stages of the 32 enrolled patients were as follows: IA/IB 1 (3.1%); IIA 9 (28.1%); IIB 17 (53.1%); III 5 (15.6%). Twenty-seven patients (84.4%) received R0 resection, while five patients (15.6%) received R1 resection. EpCAM+ CTCs were detected in 20 portal blood (62.5%) and 22 peripheral blood (68.8%). Plectin-1+ CTCs were identified in 14 portal blood (43.8%) and 16 peripheral blood (50%). Plectin-1-expressing CTCs were picked from CTC platform (microfabricated porous filter) and we could find out all KRAS mutation. Patients with detectable EpCAM+ CTC less than one in peripheral blood showed longer overall survival (OS) compared to patients with detectable CTCs more than one (35.5 months vs. 16.0 months). EpCAM and Plectin-1 successfully identified CTCs at the early stage of PDACs. Also, the number of CTCs could be a prognostic marker for survival in resectable PDACs.

OBJECTIVE To compare the performances of magnetic resonance elastography (MRE) and transient elastography (TE) for predicting severe complications after hepatic resection (HR) in patients with hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA Liver stiffness measurement (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

This study evaluated the associated factors and prognosis according to pathology and margin after surgical resection of intraductal papillary mucinous neoplasms (IPMN).There is limited information on recurrence patterns according to pathology and margin in IPMN.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.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%, P0.001) and 5-year survival rate (89.0% vs 84.0% vs 48.4%, P0.001). 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%, P0.001) and 5-year survival rate (80.7% vs 83.0% vs 30.8%, P0.001). Carbohydrate antigen 19-937 ( P = 0.003), invasive IPMN ( P0.001), and malignant margin ( P = 0.036) were associated with recurrence.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.

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.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.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).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.• 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).

Background This study was conducted to identify patients who may benefit from adjuvant chemoradiotherapy (CRT) for positive or close resection margin (RM) after curative resection of pancreatic adenocarcinoma. Methods From 2004 to 2015, total of 472 patients with pancreatic adenocarcinoma underwent curative resection. After excluding patients with RM > 2 mm or unknown, remaining 217 patients were retrospectively analyzed. Forty-six (21.2%) patients were treated with adjuvant chemotherapy alone (CTx; mainly gemcitabine-based), 142 (65.4%) with adjuvant CRT (mainly upfront), and 29 (13.4%) patients didn’t receive any adjuvant therapy (noTx group). Results Locoregional recurrence rate was significantly lower in the CRT group (43.7%) than in the CTx group (71.7%) or noTx group (65.5%) (p = 0.001). Significant survival benefits of CRT over CTx (HR 0.602, p = 0.020 for overall survival (OS); HR 0.599, p = 0.016 for time to any recurrence (TTR)) were demonstrated in multivariate analysis. CRT group had more 5-year survivors than other groups. In the subgroup analysis, such benefits of adjuvant CRT over CTx was observed only in patients with head tumor & vascular RM > 0.5 mm, but not in patients with body/tail tumor or vascular RM ≤ 0.5 mm. In the CRT group, radiation dose≥54 Gy was significantly associated with better TTR and OS. Conclusions Adjuvant CRT could improve TTR and OS compared to adjuvant CTx alone in patients with close RM under 2 mm. Radiation dose escalation may be beneficial when feasible. Modern CRT regimen–based randomized evidence is needed for these high-risk patients.

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).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.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 0.64attenuation coefficient ≤ 0.70; score of 2 for 0.70attenuation coefficient ≤ 0.73; and score of 3 for attenuation coefficient0.73) and SWDS (score of 2 for 10.5 [m/s]/kHzSWDS ≤ 11.7 [m/s]/kHz; and score of 3 for SWDS11.7 [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).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.

Background/Aims: Although many studies have reported the promising effect of neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC) to increase resectability, only a few studies have recommended the use of first-line chemotherapeutic agents as neoadjuvant treatment for BRPC. The current study compared clinical outcomes between gemcitabine and FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) in patients with BRPC. Methods: In this single-center retrospective study, 100 BRPC patients treated with neoadjuvant chemotherapy and resection from 2008 to 2018 were reviewed. Clinical outcomes included overall survival, resectability, and recurrence patterns after gemcitabine or FOLFIRINOX treatment. Results: For neoadjuvant chemotherapy, gemcitabine was administered to 34 patients and FOLFIRINOX to 66. Neoadjuvant radiotherapy was administered to 27 patients (79.4%) treated with gemcitabine and 19 (28.8%) treated with FOLFIRINOX (p

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

Background The new 8th American Joint Committee on Cancer (AJCC) staging has recently been released and there are major changes in distal bile duct (DBD) cancer staging. However, clinical validation is needed before the changes can be widely implemented. Methods This study was performed to evaluate the prognostic predictability of the 8th AJCC staging compared with that of the 7th using C statistics. Results 293 consecutive patients who had curative-intended surgery were enrolled. There was no significant difference of the 5-year survival rate between 7th T1 and T2 (P=0.123), but significant difference between T2 and T3 (P=0.039). There were significant differences in pairwise comparisons between the 8th T stage (T1 vs. T2, P=0.001; T2 vs. T3, P=0.014). The number of regional lymph node metastases also showed prognostic predictability. The 8th T and N stage both showed comparable prognostic predictability with the 7th (95% confidential intervals for C; T, -0.043 – 0.097, N, -0.001 – 0.008). Conclusions The 8th AJCC staging for DBD cancer does not have better prognostic predictability than the 7th stage does. The previous pathologic results would become useless unless they were reviewed entirely. Therefore, introduction of the AJCC 8th staging has to be reconsidered, especially for new T staging. This article is protected by copyright. All rights reserved.

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).

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with poor prognosis, and the situation has not improved despite extensive clinical and scientific research. Here, we report proteogenomic analysis of PDAC. Mutation-phosphorylation correlations identified signaling pathways associated with somatic mutations in significantly mutated genes. mRNA-protein abundance correlations revealed oncogene and tumor suppressor candidates correlating with patient survival. Integrated clustering of mRNA, protein, and phosphorylation data identified six PDAC subtypes (Sub1-6), which were indistinguishable using mRNA data alone. mRNA and protein signatures defining Sub1-6 revealed that Sub1, Sub2-4, and Sub5-6 were precursor, invasive, and immunogenic tumors, respectively. In the Sub2-4 group, proliferation was highest for Sub4; Sub6 in the Sub5-6 group had an increased pancreatic secretion capacity. Orthotopic mouse PDAC models revealed higher numbers of pro-tumorigenic immune cells in Sub4 tumors, inhibiting T cell proliferation. Our proteogenomic analysis provides therapeutic targets and improves understanding of cancer biology and patient stratification in PDAC.

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.

Introduction: The detection of portal vein tumor thrombosis (PVTT) in patients with hepatocellular carcinoma (HCC) meeting the Milan criteria is of critical importance as PVTT is known to be a contraindication to transplantation and an indicator of a dismal prognosis. Objective: To determine which modality may best detect PVTT, we compared the diagnostic performance of gadoxetic acid-enhanced MRI (GA-MRI) and contrast-enhanced CT (CECT) in HCC patients meeting the Milan criteria. Methods: We retrospectively enrolled 310 patients with HCCs meeting the Milan criteria who underwent both GA-MRI and CECT between June 2007 and May 2017. Among them, 44 patients were demonstrated to have PVTT while 266 patients had no PVTT. Two radiologists then assessed GA-MRI and CECT images for the presence of PVTT on a 5-point scale as well as vessel expansion, continuity with tumors, and enhancement on both modalities, as well as T2 hyperintensity and diffusion restriction on GA-MRI. The McNemar test was used to compare sensitivity and specificity of GA-MRI and CECT for the detection of PVTT, and Fisher’s exact test was used to compare their imaging features. Results: GA-MRI showed higher sensitivity values than CECT in detecting PVTT (reviewer 1, 93.2% [41/44] vs. 77.3% [34/44]; reviewer 2, 88.6% [39/44] vs. 70.5% [31/44]) (both p = 0.039). Specificity of GA-MRI and CECT demonstrated no difference (reviewer 1, 95.5% [254/266] vs. 95.1% [253/266]; reviewer 2, 97.0% [258/266] vs. 97.4% [259/266]) (both p > 0.999). Continuity with tumors and enhancement were more frequently observed on GA-MRI than on CECT (p < 0.050, both reviewers). Conclusion: GA-MRI detected PVTT more often than CECT in HCC patients meeting the Milan criteria and better depicted PVTT in continuity with tumors and those showing enhancement than CECT.

BackgroundHepatic fibrosis is a dynamic, reversible process which can result in liver failure. Diagnosis and monitoring of hepatic fibrosis are clinically important.PurposeTo compare the diagnostic...

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. 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. 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 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. 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.

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

To evaluate prognostic value of hepatic stiffness (HS) measurement using MR elastography (MRE) in patients with hepatocellular carcinoma (HCC) treated by hepatic resection (HR). 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. 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

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.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.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).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.

Alveolar hemorrhage is a life-threatening clinical syndrome often initially thought to be atypical pneumonia. Association with hematopoietic stem cell transplantation is well studied, but not with solid organ transplantation. We report a case of a 54-year-old woman presented with fever and shortness of breath on the third posttransplant day after deceased donor liver transplantation. Imaging studies showed diffuse bilateral pulmonary infiltrates and a positive sequential bronchoalveolar lavage test was revealed during bronchoscopy. Cytomegalovirus antigenemia was present in 8/200,000 white blood cells; Aspergillus galactomannan and Pneumocystis jirovecii were also present. However, only Aspergillus hyphae were found in the sputum culture. Management strategy aimed to treat underlying infections, provide adequate respiratory support, and control inflammation. We proposed that diffuse alveolar hemorrhage should be considered as differential diagnosis in early pulmonary complications after liver transplantation. Early diagnosis and aggressive treatment protocol is the key for a good outcome.

Background Hepatitis B core antibody-positive (HBcAb+) graft is known as a risk for de novo hepatitis B virus (HBV) infection in recipients after liver transplantation (LT). However, little is known about the possibility or incidence of de novo HBV infections after LT in hepatitis B surface antigen-negative (HBsAg−)/HBcAb+ recipients using HBsAg−/HBcAb− grafts. The study aimed to evaluate the prevalence of de novo HBV infection in HBsAg−/HBcAb+ recipients using HBsAg−/HBcAb− grafts. A retrospective review was performed with the records of 1129 adult patients who underwent primary LT at a single institution in an HBV endemic area between January 2000 and December 2013. A total of 78 patients (6.9%) were reviewed for de novo HBV infection after LT. De novo HBV infection was developed in 1 patient (1.28%). The patient was a 65-year-old woman who underwent LT due to alcoholic liver cirrhosis. De novo HBV was not related to graft loss or death and well treated with tenofovir. In conclusion, de novo HBV infections may occur in HBsAg-/HBcAb+ recipients using HBsAg−/HBcAb− grafts, and caution is needed in these patients.

Intraductal papillary neoplasm of bile duct (IPNB) was described as a preinvasive neoplastic lesion of the biliary tract in the 2010 World Health Organization (WHO) classification. Although a number of studies have since been conducted on IPNBs, controversy remains, particularly regarding the standardization of its definition. Meetings by Japanese and Korean expert pathologists were held twice to resolve the pathological diagnostic aspects of IPNB. Through round-table discussions and histological reviews, we reached the common understanding that IPNBs diagnosed according to the criteria of WHO 2010 are characterized by intraductal predominant papillary or villous biliary neoplasms covering delicate fibrovascular stalks and are classified into two types pathologically. One type (type 1 IPNB) is histologically similar to intraductal papillary mucinous neoplasms of pancreas, and typically develops in the intrahepatic bile ducts, while the other (type 2 IPNB) has a more complex histological architecture with irregular papillary branching or with foci of solid-tubular components and typically involves the extrahepatic bile ducts. This report states the diagnostic pathologic features of IPNB proposed by WHO 2010. Since currently, the concept of IPNB is still confusing, the proposed diagnostic pathologic features stated here will be of use for future clinicopathological and molecular analyses toward consensus building of IPNB.

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.

Recurrence and metastasis are major challenges in the management of hepatocellular carcinoma (HCC) patients after resection. To identify a metastasis-associated gene signature, we performed comparative gene expression analysis with recurrent HCC tissues from HCC patients who underwent partial or total hepatectomy and from non-metastatic primary HCC tissues. From this, we were able to identify genes associated with HCC recurrence. TCIRG1 (T-Cell Immune Regulator 1) was one of the aberrantly overexpressed genes in patients with recurrent HCC who had undergone total hepatectomy. The significant overexpression of TCIRG1 was confirmed using the Liver Hepatocellular Carcinoma dataset from The Cancer Genome Atlas. High expression of TCIRG1 was significantly associated with poor 5-year disease-free and recurrence-free survival of HCC patients. TCIRG1 knockdown suppressed tumor cell growth and proliferation in HCC cell lines; caused a significant increase in the proportion of cells in the G1/S phase of cell cycle; induced cell death; suppressed the metastatic potential of HCC cells by selectively regulating the epithelial-mesenchymal transition (EMT) regulatory proteins E-cadherin, N-cadherin, Fibronectin, Snail and Slug; and significantly attenuated the metastatic potential of ras-transformed NIH-3T3 cells in vitro and in vivo. These findings suggest that TCIRG1 functions as a metastatic enhancer by modulating growth, death and EMT in HCC cells. TCIRG1 could be a therapeutic target for the treatment of liver malignancy and metastasis.

Objective The aim of this study was to prospectively evaluate whether liver stiffness (LS) assessments, obtained by two-dimensional (2D)-shear wave elastography (SWE) with a propagation map, can evaluate liver fibrosis stage using histopathology as the reference standard. Materials and Methods We prospectively enrolled 123 patients who had undergone percutaneous liver biopsy from two tertiary referral hospitals. All patients underwent 2D-SWE examination prior to biopsy, and LS values (kilopascal [kPa]) were obtained. On histopathologic examination, fibrosis stage (F0–F4) and necroinflammatory activity grade (A0–A4) were assessed. Multivariate linear regression analysis was performed to determine the significant factors affecting the LS value. The diagnostic performance of the LS value for staging fibrosis was assessed using receiver operating characteristic (ROC) analysis, and the optimal cut-off value was determined by the Youden index. Results Reliable measurements of LS values were obtained in 114 patients (92.7%, 114/123). LS values obtained from 2D-SWE with the propagation map positively correlated with the progression of liver fibrosis reported from histopathology (p < 0.001). According to the multivariate linear regression analysis, fibrosis stage was the only factor significantly associated with LS (p < 0.001). The area under the ROC curve of LS from 2D-SWE with the propagation map was 0.773, 0.865, 0.946, and 0.950 for detecting F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The optimal cut-off LS values were 5.4, 7.8, 9.4, and 12.2 kPa for F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The corresponding sensitivity and specificity of the LS value for detecting cirrhosis were 90.9% and 88.4%, respectively. Conclusion The LS value obtained from 2D-SWE with a propagation map provides excellent diagnostic performance in evaluating liver fibrosis stage, determined by histopathology.

Background The need for liver retransplantation (re-LT) has been increasing. Here we describe the outcome and technical aspects of re-LT during 25 years in a single major center. Methods We retrospectively reviewed patients who underwent LT from March 1988 to February 2013. Among 1,312 LTs during 25 years, 38 (2.9%) were re-LTs, including 28 adults (mean age 52.0 y) and 10 children (mean age 5.7 y). Results The most common indication was primary nonfunction in early re-LT and biliary complication in late re-LT. Preoperative major comorbidity was very common (81.6%). Among them, infection was the most frequent (52.6%). Living-donor re-LT constituted 21.1%. In operative technique, nonconventional methods were substantially performed, including high hilar dissection for hepatectomy (>50%), arterial anastomosis with the use of right gastroepiploic or jump graft (23.7%), and hepaticoenterostomy (60.5%). Several reanastomoses were needed in 10.5% for artery and 5.3% for duct. In adults and children, mean estimated blood losses were 9,541 mL and 977 mL, respectively. Mean operative times for adults and children were 508 and 432 minutes, respectively. In-hospital mortality was 35.7% in adults and 40.0% in children. The main cause of death was sepsis for both adults and children. Survival rates at 1 month and 1, 3, and 5 years were, respectively, 89.4%, 56.5%, 50.3%, and 50.3% in adults, and 70.0%, 60.0%, 60.0%, and 60.0% in children. Conclusions Outcome of re-LT is poorer than primary LT regardless of the cause of graft failure. Therefore, more technical concerns need to be considered. We also need more efforts to control perioperative infections to improve survival after re-LT.

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.

Background/Aims Cluster differentiation 44 standard isoform (CD44s) is a transmembrane glycoprotein. CD44s is a known prognostic factor in various cancers, due to its involvement in tumor cell growth, invasion and metastasis. Its prognostic role, however, is debated because it can be a positive or negative prognostic factor depending on tumor type and is still an ambiguous prognostic indicator in other cancers, especially hepatocellular carcinoma (HCC). We investigated the relationship between CD44s expression and survival in HCC patients. Methods A total of 260 HCC samples were collected to generate a tissue microarray. Staining of the arrays with a primary mouse CD44s monoclonal antibody was followed by evaluation of the relationship between CD44s expression and tumor differentiation. The effect of CD44s expression on patient survival was analyzed. Results CD44s protein expression correlated with histological grade (most and worst Edmondson grade) of the HCC (p=0.029 and p=0.039, respectively) and adversely affected the disease free survival period based on univariate and multivariate analyses (p=0.038 and p=0.077, respectively). Conclusions High CD44s protein expression correlates with shorter disease free survival and poorly differentiated HCC. CD44s-targeted therapy may be efficacious for HCC treatment in the future.

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.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).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 value5.8%) for MR fat quantification and 0.85 (cutoff value1.94 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.A combination of MR fat quantification and MR elastography can provide sufficient sensitivity to detect substantial steatosis or fibrosis (≥F1) in liver donor candidates.