Intraductal papillary neoplasm of the bile duct: diagnostic value of MRI features in differentiating pathologic subclassifications-type 1 versus type 2.

OBJECTIVES: To identify MRI features for differentiating type 2 from type 1 intraductal papillary neoplasms of bile duct (IPNB) and assessing malignant potential of IPNB. METHODS: This retrospective study included 60 patients with surgically proven IPNB who had undergone preoperative MRI between January 2007 and December 2020. All surgical specimens were reviewed retrospectively to classify types 1 and 2 IPNBs and assess tumor grade. Significant MRI features for differentiating type 2 (n = 40) from type 1 IPNB (n = 20); and for IPNB with an associated invasive carcinoma (n = 43) from intraepithelial neoplasia (n = 17) were determined using logistic regression analysis. RESULTS: An associated invasive carcinoma was more frequently found in type 2 than in type 1 IPNB (85.0% [34/40] vs. 45.0% [9/20], p = 0.003). At univariable analysis, MRI features including extrahepatic location, no dilatation of tumor-bearing segment of bile duct, isolated upstream bile duct dilatation, and single lesion were associated with type 2 IPNB (all p ≤ 0.012). At multivariable analysis, significant MRI findings for differentiating type 2 from type 1 IPNB were extrahepatic location and no dilatation of tumor-bearing segment of bile duct (odds ratio [OR], 7.24 and 46.40, respectively). At univariable and multivariable analysis, tumor size ≥ 2.5 cm (OR, 8.45), bile duct wall thickening (OR, 4.82), and irregular polypoid or nodular tumor shape (OR, 6.44) were significant MRI features for differentiating IPNB with an associated invasive carcinoma from IPNB with intraepithelial neoplasia. CONCLUSION: MRI with MR cholangiopancreatography may be helpful in differentiating type 2 IPNB from type 1 IPNB and assessing malignant potential of IPNB. CLINICAL RELEVANCE STATEMENT: Preoperative MRI with MR cholangiopancreatography may be helpful in differentiating type 2 intraductal papillary neoplasms of bile duct (IPNB) from type 1 IPNB and assessing malignant potential of IPNB. KEY POINTS: • In terms of tumor grade, the incidence of invasive carcinoma was significantly higher in type 2 intraductal papillary neoplasm of the bile duct (IPNB) than in type 1 IPNB. • At MRI, extrahepatic location and no dilatation of tumor-bearing segment are significant features for differentiating type 2 IPNBs from type 1 IPNBs. • At MRI, large tumor size, bile duct wall thickening, and irregular polypoid or nodular tumor shape are significant features for differentiating IPNB with an associated invasive carcinoma from IPNB with intraepithelial neoplasia.

LI-RADS Tumor in Vein at CT and Hepatobiliary MRI.

Background Diagnostic performance of the Liver Imaging Reporting and Data System tumor in vein (LR-TIV) category at CT and/or MRI has not yet been evaluated, to the knowledge of the authors. Purpose To assess the diagnostic performance of the LR-TIV category in detecting macroscopic tumors in veins (TIVs) at CT and hepatobiliary contrast agent-enhanced (HBA) MRI, with pathologic results used as the reference standard. Materials and Methods Between January 2010 and December 2019, consecutive patients with or without macroscopic TIV who underwent both CT and HBA MRI before hepatic resection or liver transplant were retrospectively included. Three radiologists independently assessed the LR-TIV features of enhancing soft tissue in vein and features suggestive of TIV (FSTIV) and reached a consensus. Macroscopic TIV at pathologic examination was the reference standard. Sensitivities and specificities of the LR-TIV category without and with FSTIV were calculated, and the added value of FSTIV was evaluated by using the McNemar test. Results In the 1322 patients with (n = 101) or without (n = 1221) macroscopic TIV (median age, 64 years [interquartile range, 58-70 years]; 1053 men), without consideration of FSTIV, the sensitivity and specificity of enhancing soft tissue in vein for detecting macroscopic TIV at pathologic examination were 64.4% (65 of 101) and 99.8% (1218 of 1221) with CT and 62.4% (63 of 101) and 99.8% (1218 of 1221) with HBA MRI, respectively. With consideration of FSTIV, the sensitivity and specificity of the LR-TIV category became 67.3% (68 of 101 patients) and 99.7% (1217 of 1221 patients) at both CT and HBA MRI. No difference was found between measurements without and with FSTIV (sensitivity, 62% vs 67% for CT [P = .45] and 64% vs 67% for HBA MRI [P = .18]; specificity, 99% for both CT and HBA MRI [P > .99 for both]). Conclusion The Liver Imaging Reporting and Data System tumor in vein category showed moderate sensitivity and high specificity in the detection of macroscopic tumors in veins at both CT and hepatobiliary contrast agent-enhanced MRI, with pathologic examination used as the reference standard. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Morrell in this issue.

How to approach pancreatic cancer after neoadjuvant treatment: assessment of resectability using multidetector CT and tumor markers.

OBJECTIVES: To investigate clinical and CT factors associated with local resectability in patients with nonmetastatic pancreatic cancers after neoadjuvant chemotherapy ± radiation therapy (CRT). METHODS: This retrospective study included consecutive patients with nonmetastatic pancreatic cancers who underwent neoadjuvant CRT between June 2009 and June 2019. Tumor size, tumor-vascular contact with artery/vein, and local resectability categories (resectable, borderline resectable, or locally advanced) were assessed at baseline and post-CRT CT. Baseline and post-CRT carbohydrate antigen (CA) 19-9 levels were also assessed. Clinical or imaging features related to R0 resection were determined using logistic regression analysis. RESULTS: A total of 179 patients (mean age, 62.4 ± 9.3 years; 92 men) were included. After neoadjuvant CRT, 105 (58.7%) patients received R0 resection, while 74 (41.3%) did not. R0 resection rates were significantly different according to post-CRT CT resectability categories (p < 0.001): 82.8% (48/58), 70.1% (47/67), and 18.5% (10/54) for resectable, borderline resectable, and locally advanced disease, respectively. For post-CRT borderline resectable disease, ≥ 50% decrease in CA 19-9 was significantly associated with R0 resection (odds ratio (OR), 3.160; p = 0.02). For post-CRT locally advanced disease, small post-CRT tumor size ≤ 2 cm (OR, 9.668; p = 0.026) and decreased tumor-arterial contact (OR, 24.213; p = 0.022) were significantly associated with R0 resection. CONCLUSION: Post-CRT CT resectability categorization may be useful for the assessment of R0 resectability in patients with pancreatic cancer following neoadjuvant CRT. Additionally, ≥ 50% decrease in CA 19-9 was associated with R0 resection in post-CRT borderline resectable disease, while small post-CRT tumor size and decreased tumor-arterial contact were with locally advanced disease. KEY POINTS: • R0 resection rates following neoadjuvant chemotherapy ± radiation therapy (CRT) were 82.8%, 70.1%, and 18.5% in resectable, borderline resectable, and locally advanced disease, respectively, at post-CRT CT (p < 0.001). • For post-CRT borderline resectable disease, ≥ 50% decrease in carbohydrate antigen (CA) 19-9 was significantly associated with R0 resection. • For post-CRT locally advanced disease, small post-CRT tumor size ≤ 2 cm and decreased tumor-arterial contact were significantly associated with R0 resection.

Simultaneous evaluation of perfusion and morphology using GRASP MRI in hepatic fibrosis.

OBJECTIVES: To determine if golden-angle radial sparse parallel (GRASP) dynamic contrast-enhanced (DCE)-MRI allows simultaneous evaluation of perfusion and morphology in liver fibrosis. METHODS: Participants who were scheduled for liver biopsy or resection were enrolled (NCT02480972). Images were reconstructed at 12-s temporal resolution for morphologic assessment and at 3.3-s temporal resolution for quantitative evaluation. The image quality of the morphologic images was assessed on a four-point scale, and the Liver Imaging Reporting and Data System score was recorded for hepatic observations. Comparisons were made between quantitative parameters of DCE-MRI for the different fibrosis stages, and for hepatocellular carcinoma (HCCs) with different LR features. RESULTS: DCE-MRI of 64 participants (male = 48) were analyzed. The overall image quality consistently stood at 3.5 ± 0.4 to 3.7 ± 0.4 throughout the exam. Portal blood flow significantly decreased in participants with F2-F3 (n = 18, 175 ± 110 mL/100 mL/min) and F4 (n = 12, 98 ± 47 mL/100 mL/min) compared with those in participants with F0-F1 (n = 34, 283 ± 178 mL/100 mL/min, p < 0.05 for all). In participants with F4, the arterial fraction and extracellular volume were significantly higher than those in participants with F0-F1 and F2-F3 (p < 0.05). Compared with HCCs showing non-LR-M features (n = 16), HCCs with LR-M (n = 5) had a significantly prolonged mean transit time and lower arterial blood flow (p < 0.05). CONCLUSIONS: Liver MRI using GRASP obtains both sufficient spatial resolution for confident diagnosis and high temporal resolution for pharmacokinetic modeling. Significant differences were found between the MRI-derived portal blood flow at different hepatic fibrosis stages. KEY POINTS: A single MRI examination is able to provide both images with sufficient spatial resolution for anatomic evaluation and those with high temporal resolution for pharmacokinetic modeling. Portal blood flow was significantly lower in clinically significant hepatic fibrosis and mean transit time and extracellular volume increased in cirrhosis, compared with those in no or mild hepatic fibrosis. HCCs with different LR features showed different quantitative parameters of DCE-MRI: longer mean transit time and lower arterial flow were observed in HCCs with LR-M features.

Performance of LI-RADS Version 2018 on CT for Determining Eligibility for Liver Transplant According to Milan Criteria in Patients at High Risk for Hepatocellular Carcinoma.

BACKGROUND. LI-RADS has been investigated primarily in terms of detection of hepatocellular carcinoma (HCC), with less attention given to its performance, particularly on CT, in determining eligibility for liver transplant (LT). OBJECTIVE. The purpose of our study was to assess the performance of LI-RADS version 2018 (v2018) on CT for the diagnosis of HCC and determination of LT eligibility according to the Milan criteria (MC). METHODS. This retrospective study included 136 patients (110 men, 26 women; mean age, 53.9 ± 8.1 [SD] years) at high-risk for HCC who underwent liver protocol CT within 3 months before LT between January 2010 and December 2018. Two radiologists independently reviewed CT examinations using LI-RADS v2018; Organ Procurement and Transplantation Network (OPTN) classes were constructed from the LI-RADS interpretations. Histopathologic analysis of liver explants served as the reference standard for determining the presence of HCC and LT eligibility based on MC. Diagnostic performance was evaluated. Overall survival (OS) was assessed based on medical record review. RESULTS. Based on histopathologic evaluation of liver explants in the 136 patients, 27 patients had no malignancy, 77 were eligible for LT due to HCC within MC, and 32 were unsuitable for LT (i.e., HCC beyond MC in 16 patients, HCC with macrovascular invasion in 12, non-HCC malignancy in four). LR-5 exhibited per-lesion sensitivity and PPV for HCC of 55.9% and 92.8%, respectively, for reader 1 and 39.8% and 86.5% for reader 2. When considering LR-5 observations to represent HCC in assessing MC, LI-RADS had accuracy for determining LT eligibility of 92.7% for reader 1 and 85.3% for reader 2; OPTN criteria had accuracy for determining LT eligibility of 89.0% for reader 1 and 84.4% for reader 2. Five-year OS for patients within MC versus 5-year OS for patients unsuitable for LT was 92.2 months versus 56.0 months for LI-RADS, 92.6 months versus 47.6 months for OPTN criteria, and 93.3 months versus 55.1 months for histopathologic assessment of liver explants. CONCLUSION. LI-RADS v2018, as evaluated on CT in high-risk patients, shows high PPV for HCC detection and high accuracy for determining LT eligibility based on MC. LT eligibility based on preoperative LI-RADS evaluation is associated with post-LT survival. CLINICAL IMPACT. These findings support the use of LI-RADS on CT in assessing eligibility in patients who are candidates for LT.

Evaluation of LI-RADS Version 2018 Treatment Response Algorithm for Hepatocellular Carcinoma in Liver Transplant Candidates: Intraindividual Comparison between CT and Hepatobiliary Agent-enhanced MRI.

Background The Liver Imaging Reporting and Data System (LI-RADS), version 2018, treatment response algorithm (TRA) is used to assess hepatocellular carcinoma (HCC) after local-regional therapy (LRT). However, its diagnostic performance has not yet been fully compared between CT and hepatobiliary agent (HBA)-enhanced MRI in patients who have undergone liver transplant (LT). Purpose To compare the diagnostic performance of LI-RADS TRA when using CT versus using HBA-enhanced MRI in an intraindividual manner according to pathologic results. Materials and Methods Between January 2011 and September 2019, 165 patients with 237 clinically suspected HCCs underwent LRT followed by LT and were retrospectively included. All patients underwent both CT and HBA-enhanced MRI after LRT and before LT. Three radiologists independently assessed tumor viability with both modalities by using LI-RADS TRA and reached a consensus. Pathologic tumor viability categorized as either completely (100%) or incompletely (<100%) necrotic obtained from the explanted liver served as the reference standard. Sensitivity and specificity of the LI-RADS TRA in the consensus reading were then compared between CT and HBA-enhanced MRI by using the ratio estimator approach. Interobserver agreements were calculated by using Fleiss κ statistics. Results There were 165 patients (mean age, 62 years ± 9 [standard deviation]; 135 men) with a total of 237 lesions, of which 107 were viable tumors (45.1%) at pathologic evaluation. With the LI-RADS TRA, sensitivity and specificity of the viable category for detection of viable HCCs at pathologic evaluation were 42.1% (45 of 107 lesions) and 95.4% (124 of 130 lesions) with CT and 52.3% (56 of 107 lesions) and 93.9% (122 of 130 lesions) with HBA-enhanced MRI, with a significant difference in sensitivity but not specificity (P = .009 and P = .42, respectively). Interobserver agreements for the LI-RADS TRA were substantial for both CT and HBA-enhanced MRI (κ, 0.69 for both). Conclusion In patients who underwent local-regional therapy for hepatocellular carcinoma before liver transplant, hepatobiliary agent-enhanced MRI was more sensitive than CT in evaluating tumor viability with the Liver Imaging Reporting and Data System, version 2018, treatment response algorithm. ©RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Bashir and Mendiratta-Lala in this issue.

Important CT and histopathological findings for recurrence and overall survival in patients with pancreatic ductal adenocarcinoma who underwent surgery after neoadjuvant FOLFIRINOX.

OBJECTIVES: To investigate important factors for recurrence-free survival (RFS) and overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDA) who underwent surgery after neoadjuvant FOLFIRINOX using CT and histopathological findings. MATERIALS AND METHODS: Sixty-nine patients with PDA who underwent surgery after neoadjuvant FOLFIRINOX were retrospectively included. All patients underwent baseline and first follow-up CT. Two reviewers assessed the CT findings and resectability based on the NCCN guideline. They graded extrapancreatic perineural invasion (EPNI) using a 3-point scale focused on 5 routes. Clinical and histopathological results, such as T- and N-stage, tumor regression grade (TRG) using the College of American Pathology (CAP) grading system, and resection status, were also investigated. Kaplan-Meier methods were used for RFS and OS. The Cox proportional hazard model and logistic regression model were used to identify significant predictive factors. RESULTS: There were 57 patients (82.6%) without residual tumors (R0) and 12 patients (17.4%) with residual tumors (R1 or R2). The median RFS was 13 months (range 0~22 months). For RFS, EPNI on baseline CT (hazard ratio (HR) 2.53, 95% confidence interval (CI) 1.116-5.733, p = 0.026) and TRG (HR 1.76, 95% CI 1.000-3.076, p = 0.046) were important predictors of early recurrence. The mean OS was 48 months (range 11~35 months). For OS, TRG (HR 1.05, 95% CI 1.251-6.559, p = 0.013) was a significant factor. However, there were no independent predictors for residual tumors according to the CT findings. CONCLUSION: EPNI on baseline CT and TRG were important prognostic factors for tumor recurrence. In addition, TRG was also an important prognostic factor for OS. KEY POINTS: • CT and histopathological findings are helpful for predicting early recurrence and poor survival. • EPNI on baseline CT (HR 2.53, p = 0.026) is an important predictor of early recurrence. • The TRG is an important prognostic factor for early recurrence (HR 1.76, p = 0.046) and poor survival (HR 1.05, p = 0.013).

Preoperative assessment of the resectability of pancreatic ductal adenocarcinoma on CT according to the NCCN Guidelines focusing on SMA/SMV branch invasion.

OBJECTIVES: For patients with pancreatic adenocarcinoma (PAC), adequate determination of disease extent is critical for optimal management. We aimed to evaluate diagnostic accuracy of CT in determining the resectability of PAC based on 2020 NCCN Guidelines. METHODS: We retrospectively enrolled 368 consecutive patients who underwent upfront surgery for PAC and preoperative pancreas protocol CT from January 2012 to December 2017. The resectability of PAC was assessed based on 2020 NCCN Guidelines and compared to 2017 NCCN Guidelines using chi-square tests. Overall survival (OS) was estimated using the Kaplan-Meier method and compared using log-rank test. R0 resection-associated factors were identified using logistic regression analysis. RESULTS: R0 rates were 80.8% (189/234), 67% (71/106), and 10.7% (3/28) for resectable, borderline resectable, and unresectable PAC according to 2020 NCCN Guidelines, respectively (p < 0.001). The estimated 3-year OS was 28.9% for borderline resectable PAC, which was significantly lower than for resectable PAC (43.6%) (p = 0.004) but significantly higher than for unresectable PAC (0.0%) (p < 0.001). R0 rate was significantly lower in patients with unresectable PAC according to 2020 NCCN Guidelines (10.7%, 3/28) than in those with unresectable PAC according to the previous version (31.7%, 20/63) (p = 0.038). In resectable PAC, tumor size ≥ 3 cm (p = 0.03) and abutment to portal vein (PV) (p = 0.04) were independently associated with margin-positive resection. CONCLUSIONS: The current NCCN Guidelines are useful for stratifying patients according to prognosis and perform better in R0 prediction in unresectable PAC than the previous version. Larger tumor size and abutment to PV were associated with margin-positive resection in patients with resectable PAC. KEY POINTS: • The updated 2020 NCCN Guidelines were useful for stratifying patients according to prognosis. • The updated 2020 NCCN Guidelines performed better in the prediction of margin-positive resection in unresectable cases than the previous version. • Tumor size ≥ 3 cm and abutment to the portal vein were associated with margin-positive resection in patients with resectable pancreatic adenocarcinoma.

Prediction of tumor recurrence and poor survival of ampullary adenocarcinoma using preoperative clinical and CT findings.

OBJECTIVES: To predict poor survival and tumor recurrence in patients with ampullary adenocarcinoma using preoperative clinical and CT findings. MATERIALS AND METHODS: A total of 216 patients with ampullary adenocarcinoma who underwent preoperative CT and surgery were retrospectively included. CT was assessed by two radiologists. Clinical and histopathological characteristics including histologic subtypes were investigated. A Cox proportional hazard model and the Kaplan-Meier method were used to identify disease-free survival (DFS) and overall survival (OS). A nomogram was created based on the multivariate analysis. The optimal cutoff size of the tumor was evaluated and validated by internal cross validation. RESULTS: The median OS was 62.8 ± 37.9, and the median DFS was 54.3 ± 41.2 months. For OS, tumor size (hazard ratio [HR] 2.79, p < 0.001), papillary bulging (HR 0.63, p = 0.049), organ invasion on CT (HR 1.92, p = 0.04), male sex (HR 1.59, p = 0.046), elevated CA 19-9 (HR 1.92, p = 0.01), pT stage (HR 2.45, p = 0.001), and pN stage (HR 3.04, p < 0.001) were important predictors of survival. In terms of recurrence, tumor size (HR 2.37, p = 0.04), pT stage (HR 1.76, p = 0.03), pN stage (HR 2.23, p = 0.001), and histologic differentiation (HR 4.31, p = 0.008) were important predictors of recurrence. In terms of tumor size on CT, 2.65 cm and 3.15 cm were significant cutoff values for poor OS and RFS (p < 0.001). CONCLUSION: Preoperative clinical and CT findings were useful to predict the outcomes of ampullary adenocarcinoma. In particular, tumor size, papillary bulging, organ invasion on CT, male sex, and elevated CA 19-9 were important predictors of poor survival after surgery. KEY POINTS: • Clinical staging based on preoperative clinical information and CT findings can be useful to predict the prognosis of ampullary adenocarcinoma patients. • In terms of survival, tumor size (HR 2.79), papillary bulging (HR 0.63), organ invasion on CT (HR 1.92), male sex (HR 1.59), and elevated CA 19-9 (HR 1.92) were important clinical predictors of poor survival. • Tumor size on CT was of special importance for both poor overall survival and disease-free survival, with optimal cutoff values of 2.65 cm and 3.15 cm, respectively (p < 0.001).

A comparison of outcomes in patients with intracholecystic papillary neoplasms or conventional adenocarcinomas of the gallbladder.

BACKGROUND: Intracholecystic papillary neoplasm (ICPN) of the gallbladder (GB) is an exophytic intraepithelial neoplasm. This study aimed to investigate clinicopathologic findings, prognosis and recurrence patterns of patients with ICPN as compared to those patients with conventional adenocarcinoma of the gallbladder (GBC). METHODS: Patients who underwent surgical resection for suspected GB cancer between 2000 and 2018 were included. ICPN was defined as an exophytic papillary mass within the GB lumen with a size ≥1.0 cm. RESULTS: Of 607 patients, 241 patients (40%) were pathologically diagnosed with ICPN. Of the 241 patients with ICPNs, 110 (46%) were T1 or less. Following T stage-matched analysis, the rate of lymph node metastases were comparable (50 [52%] vs. 37 [49%], P = 0.581). The five-year survival rate was higher in ICPN, but after T stage-matching, they were comparable (69.1 vs. 63.2%, P = 0.171). Overall recurrence rates were also comparable, with the exception of lower peritoneal seeding in patients with ICPN. CONCLUSION: Patients with ICPN who underwent resection were more likely to have an earlier T stage. There was no significant difference in prognosis and recurrence between ICPN and conventional GBC after stage matching. Therefore, the treatment strategy for ICPN should follow the same protocols used for conventional GBC.

Progression of Pancreatic Branch Duct Intraductal Papillary Mucinous Neoplasm Associates With Cyst Size.

BACKGROUNDS & AIMS: Most guidelines for management of patients with intraductal papillary mucinous neoplasms (IPMN) vary in proposed surveillance intervals and durations-these are usually determined based on expert opinions rather than substantial evidence. The progression of and optimal surveillance intervals for branch-duct IPMNs (BD-IPMN) has not been widely studied. We evaluated the progression of BD-IPMN under surveillance at a single center, and determined optimal follow-up intervals and duration. METHODS: We performed a retrospective analysis of 1369 patients with BD-IPMN seen at Seoul National University Hospital in Korea from January 2001 through December 2016. We included only patients whose imaging studies showed classical features of BD-IPMN, and collected data from each patient over time periods of at least 3 years. We reviewed radiologic and pathologic findings, and performed linear and binary logistic regressions to estimate cyst growth. RESULTS: The median annual growth rate of the cyst was 0.8 mm over a median follow-up time of 61 months. During surveillance, 46 patients (3.4%) underwent surgery because of disease progression after a median follow-up time (in this group) of 62 months. Worrisome features were observed in 209 patients (15.3%) during surveillance, including cyst size of 3 cm or more (n = 109, 8.0%), cyst wall thickening (n = 51, 3.7%), main pancreatic duct dilatation (n = 77, 5.6%), and mural nodule (n = 43, 3.1%). Along with annual rate of cyst growth, incidences of main pancreatic duct dilatation and mural nodules associated with the sizes of cysts at detection (P < .001). CONCLUSIONS: In a retrospective analysis of patients with BD-IPMN followed for more than 5 years, we found most cysts to be indolent, but some rapidly grew and progressed. Surveillance protocols should therefore be individualized based on initial cyst size and rate of growth.

Combined hepatocellular cholangiocarcinoma: LI-RADS v2017 categorisation for differential diagnosis and prognostication on gadoxetic acid-enhanced MR imaging.

OBJECTIVES: To investigate the performance of the Liver Imaging Reporting and Data System (LI-RADS) v2017 for combined hepatocellular cholangiocarcinoma (cHCC-CCA) in the differential diagnosis from hepatocellular carcinoma (HCC) and prediction of prognosis on gadoxetic acid-enhanced MRI (Gd-EOB-MRI). METHODS: Patients at high risk of HCC with pathologically confirmed cHCC-CCAs (n = 70) and a matched control of HCCs (n = 70) who had undergone Gd-EOB-MRI were included. LI-RADS category was assigned for each lesion by two radiologists. Imaging features and surgical outcomes were compared between cHCC-CCAs of LR-M and LR-5/4 using the χ2 test or Fisher's exact test. Recurrence-free survival (RFS) was estimated using Kaplan-Meier survival curves and compared using the log-rank test. RESULTS: cHCC-CCAs and HCCs were categorised as LR-M, LR-5/4 and LR-TIV in 61.4% (43/70), 37.1% (26/70) and 1.4% (1/70) and 10.0% (7/70), 88.6% (62/70) and 1.4% (1/70), respectively. cHCC-CCAs of LR-5/4, in comparison to LR-M, showed significantly higher frequencies of major HCC features: arterial hyperenhancement (96.2% (25/26) vs. 58.1% (25/43), p = 0.001), washout appearance (80.8% (21/26) vs. 48.8% (21/43), p = 0.011) and enhancing capsule (34.6% (9/26) vs. 11.6% (5/43), p = 0.031). After curative surgery, patients with cHCC-CCAs of LR-M showed a higher early recurrence rate (≤ 6 months) than did those with LR-5/4 (27.8% (10/36) vs. 4.8% (1/21), p = 0.041), whereas no significant difference was observed in RFS (log-rank p = 0.084). CONCLUSIONS: By using LI-RADS on Gd-EOB-MRI, a substantial proportion of cHCC-CCAs can be categorised as non-LR-M. In addition, cHCC-CCAs mimicking HCCs on imaging (LR-5/4) may indicate better surgical outcomes with regard to early recurrence than those of LR-M. KEY POINTS: • cHCC-CCAs can be categorised as either LR-M or non-LR-M on Gd-EOB-MRI. • cHCC-CCAs of LR-5/4 frequently demonstrate major HCC imaging features. • LI-RADS categorisation may provide prognostic information after surgery in cHCC-CCAs.

Reduced expression of the RNA-binding protein HuD in pancreatic neuroendocrine tumors correlates with low p27Kip1 levels and poor prognosis.

For the majority of patients diagnosed with pancreatic neuroendocrine tumors (NETs), there is significant malignant potential with a poor prognosis; however, the molecular abnormalities and pathogenesis of pancreatic NETs have not been firmly established. Here, we report that loss of expression of the RNA-binding protein HuD correlates with low p27Kip1 (p27) levels and poor prognosis in pancreatic NETs. HuD expression was frequently lost in many human pancreatic NETs, and these pancreatic NETs showed aggressive clinicopathological phenotypes with low p27 levels, increased tumor size, higher World Health Organization grade and pT stage of the tumor, and the presence of angioinvasion. Furthermore, loss of HuD was an independent, progression-free prognostic factor in multivariate survival analysis. However, the level of HuR, a member of the same Hu protein family as HuD, was not significantly correlated with pancreatic NET size and progression. Mechanistically, HuD enhanced p27 mRNA translation by interacting with both the 5'-untranslated region (UTR) and the 3'-UTR of p27 mRNA, and consequently suppressed cell cycle progression and tumor growth. In addition, HuD competed with miR-30a-3p for binding to the 3'-UTR of p27 mRNA, suggesting an interplay between HuD and miR-30a-3p in controlling p27 translation. Our results identify HuD as a pivotal suppressor of pancreatic NET growth, and suggest that HuD has potential value as a prognostic factor of pancreatic NETs. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Tumor-Associated Protein Profiles in Kaposi Sarcoma and Mimicking Vascular Tumors, and Their Pathological Implications.

We investigated protein profiles specific to vascular lesions mimicking Kaposi sarcoma (KS), based on stepwise morphogenesis progression of KS. We surveyed 26 tumor-associated proteins in 130 cases, comprising 39 benign vascular lesions (BG), 14 hemangioendotheliomas (HE), 37 KS, and 40 angiosarcomas (AS), by immunohistochemistry. The dominant proteins in KS were HHV8, lymphatic markers, Rb, phosphorylated Rb, VEGF, and galectin-3. Aberrant expression of p53, inactivation of cell cycle inhibitors, loss of beta-catenin, and increased VEGFR1 were more frequent in AS. HE had the lowest Ki-67 index, and the inactivation rates of cell cycle inhibitors in HE were between those of AS and BG/KS. Protein expression patterns in BG and KS were similar. Clustering analysis showed that the 130 cases were divided into three clusters: AS-rich, BG-rich, and KS-rich clusters. The AS-rich cluster was characterized by high caveolin-1 positivity, abnormal p53, high Ki-67 index, and inactivated p27. The KS-rich cluster shared the features of KS, and the BG-rich group had high positive expression rates of galectin-3 and low bcl2 expression. In conclusion, although the rate was different, AS and HE tended to have less cell cycle marker expression than KS, and features of BG and activated KS cell signaling were similar.

Memory T cells are significantly increased in rejected liver allografts of rhesus monkeys.

The rhesus monkey (RM) is an excellent preclinical model in kidney, heart, and islet transplantation that has provided the basis for new immunosuppressive protocols for clinical studies. However, there remain relatively few liver transplantation (LT) models in nonhuman primates. In this study, we analyzed the immune cell populations of peripheral blood mononuclear cells (PBMCs) and secondary lymphoid organs along with livers of normal RMs and compared them with those of rejected LT recipients following withdrawal of immunosuppression. We undertook 5 allogeneic ABO compatible orthotopic LTs in monkeys using 5 normal donor monkey livers. We collected tissues including lymph nodes, spleens, blood, and recipient livers, and we performed flow cytometric analysis using isolated immune cells. We found that CD4 or CD8 naïve T cells were normally seen at low levels, and memory T cells were seen at high levels in the liver rather than lymphoid organs or PBMC. However, regulatory cells such as CD4+ forkhead box P3+ T cells and CD8+ CD28- cells remained in high numbers in the liver, but not in the lymph nodes or PBMC. The comparison of CD4/8 T subpopulations in normal and rejected livers and the various tissues showed that naïve cells were dramatically decreased in the spleen, lymph node, and PBMCs of rejected LT monkeys, but rather, the memory CD4/8 T cells were increased in all tissues and PBMC. The normal liver has large numbers of CD4 regulatory T cells, CD8+ CD28-, and myeloid-derived suppressor cells, which are known immunosuppressive cells occurring at much higher levels than those seen in lymph node or peripheral blood. Memory T cells are dramatically increased in rejected liver allografts of RMs compared with those seen in normal RM tissues. Liver Transplantation 24 256-268 2018 AASLD.

Preoperative MDCT Assessment of Resectability in Borderline Resectable Pancreatic Cancer: Effect of Neoadjuvant Chemoradiation Therapy.

OBJECTIVE: The purpose of this study is to evaluate the diagnostic performance of MDCT in assessing tumor resectability in patients with borderline resectable pancreatic cancers after receiving neoadjuvant chemoradiation therapy (CRT) in comparison with those undergoing upfront surgery. SUBJECTS AND METHODS: Thirty-seven patients with borderline resectable pancreatic cancers were randomly allocated to the neoadjuvant CRT group (arm 1; n = 18) or up-front surgery group (arm 2; n = 19). Three radiologists rated the likelihood of local resectability on a 5-point scale at preoperative MDCT in two separate sessions (session 1: post-CRT of arm 1, baseline of arm 2; session 2: using new imaging criteria reflecting the changes during CRT of arm 1). The AUC of each reviewer, as well as sensitivity, specificity, and accuracy based on consensus interpretation, were compared between arms and sessions. RESULTS: For local resectability (n = 30), AUC values at session 1 were 0.664, 0.669, and 0.588 for reviewers 1, 2, and 3, respectively, and were not significantly different between arms 1 (n = 15; 0.759, 0.713, and 0.593) and 2 (n = 15; 0.852, 0.685, and 0.722) (p > 0.05). In arm 1, MDCT sensitivity, specificity, accuracy were 22%, 100%, and 53%, respectively, at session 1 versus 78%, 67%, and 73%, respectively, at session 2 (p > 0.05). CONCLUSION: In patients with borderline resectable pancreatic cancers, neoadjuvant CRT did not significantly decrease the performance of MDCT for the prediction of local resectability. However, by considering post-CRT changes, such as nonprogression in tumor-vascular contact, MDCT may provide better sensitivity for locally resectable disease.

Intrahepatic Mass-Forming Cholangiocarcinoma: Relationship Between Computed Tomography Characteristics and Histological Subtypes.

OBJECTIVE: The aim of this study was to determine the value of multi-detector row computed tomography (MDCT) in differentiating the small-duct (SD) and large-duct (LD) types of intrahepatic mass-forming cholangiocarcinomas (IMCCs) and predicting patient prognosis. METHODS: The 4-phase MDCT image findings of 82 patients with surgically confirmed IMCCs (60 SD-type and 22 LD-type IMCCs) were compared between 2 types using univariate and multivariate analyses. Overall survival rates for 78 patients with available information were compared using the Kaplan-Meier method. RESULTS: Arterial hyperenhancement, round or lobulated contour, and lack of bile duct encasement were significant MDCT features suggesting the SD type, and lymph node enlargement was significantly associated with the LD type (all P's < 0.05). The presence of those 3 SD-type-suggestive features (MDCT-suggested SD type) demonstrated high specificity (90.9% [20/22]) in differentiating the SD type. Patients of MDCT-suggested SD type without lymph node enlargement (n = 24) demonstrated significantly better overall survival than other groups. CONCLUSIONS: Preoperative MDCT features of IMCCs can help differentiate the SD and LD types and predict patient prognosis.

Comparison of the Clinicopathologic Characteristics of Intraductal Papillary Neoplasm of the Bile Duct according to Morphological and Anatomical Classifications.

BACKGROUND: Intraductal papillary neoplasm of the bile duct (IPNB) is a recently defined entity and its clinical characteristics and classifications have yet to be established. We aimed to clarify the clinical features of IPNB and determine the optimal morphological classification criteria. METHODS: From 2003 to 2016, 112 patients with IPNB who underwent surgery were included in the analysis. After pathologic reexamination by a specialized biliary-pancreas pathologist, previously suggested morphological and anatomical classifications were compared using the clinicopathologic characteristics of IPNB. RESULTS: In terms of histologic subtypes, most patients had the intestinal type (n = 53; 48.6%) or pancreatobiliary type (n = 33; 30.3%). The simple "modified anatomical classification" showed that extrahepatic IPNB comprised more of the intestinal type and tended to be removed by bile duct resection or pancreatoduodenectomy. Intrahepatic IPNB had an equally high proportion of intestinal and pancreatobiliary types and tended to be removed by hepatobiliary resection. Morphologic classifications and histologic subtypes had no effect on survival, whereas a positive resection margin (75.9% vs. 25.7%; P = 0.004) and lymph node metastasis (75.3% vs. 30.0%; P = 0.091) were associated with a poor five-year overall survival rate. In the multivariate analysis, a positive resection margin and perineural invasion were important risk factors for survival. CONCLUSION: IPNB showed better long-term outcomes after optimal surgical resection. The "modified anatomical classification" is simple and intuitive and can help to select a treatment strategy and establish the proper scope of the operation.

Preoperative Assessment of Pancreatic Cancer with FDG PET/MR Imaging versus FDG PET/CT Plus Contrast-enhanced Multidetector CT: A Prospective Preliminary Study.

Purpose To determine the diagnostic performance of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/magnetic resonance (MR) imaging in the preoperative assessment of pancreatic cancer in comparison with that of FDG PET/computed tomography (CT) plus contrast material-enhanced multidetector CT. Materials and Methods This prospective study was approved by the institutional review board; written informed consent was obtained. Thirty-seven patients with 39 pancreatic tumors underwent preoperative FDG PET/MR imaging, PET/CT, and contrast-enhanced multidetector CT. The authors measured maximal and mean standardized uptake values (SUVmax and SUVmean, respectively) of pancreatic cancer at PET/MR imaging and PET/CT. Two radiologists independently reviewed the two imaging sets (set 1, PET/MR imaging; set 2, PET/CT plus multidetector CT) to determine tumor resectability according to a five-point scale, N stage (N0 or N positive), and M stage (M0 or M1). With use of clinical-surgical-pathologic findings as the standard of reference (n = 20), diagnostic performances of the two imaging sets were compared by using the McNemar test. Results Both SUVmax and SUVmean of pancreatic tumors showed strong correlations between PET/MR imaging and PET/CT (r = 0.897 and 0.890, respectively; P < .001). The diagnostic performance of PET/MR imaging was not significantly different from that of PET/CT plus multidetector CT in the assessment of tumor resectability (area under the receiver operating characteristic curve: 0.891 vs 0.776, respectively, for reviewer 1 [P = .109] and 0.859 vs 0.797 for reviewer 2 [P = .561]), N stage (accuracy: 54% [seven of 13 patients] vs 31% [four of 13 patients]; P = .250 for both reviewers), and M stage (accuracy: 94% [16 of 17 patients] vs 88% [15 of 17 patients] for reviewer 1 [P > .999] and 94% [16 of 17 patients] vs 82% [14 of 17 patients] for reviewer 2 [P = .500]). Conclusion FDG PET/MR imaging showed a diagnostic performance similar to that of PET/CT plus contrast-enhanced multidetector CT in the preoperative evaluation of the resectability and staging of pancreatic tumors. © RSNA, 2016 Online supplemental material is available for this article.

COQ6 Mutations in Children With Steroid-Resistant Focal Segmental Glomerulosclerosis and Sensorineural Hearing Loss.

The phenotypic combination of steroid-resistant focal segmental glomerulosclerosis (SR-FSGS) and sensorineural hearing loss has been mainly reported in patients with mitochondrial cytopathies, including primary coenzyme Q10 (CoQ10) deficiency. In this report of 10 children with SR-FSGS and sensorineural hearing loss, we found 6 patients with biallelic COQ6 mutations. Median age at the onset of nephrotic syndrome was 29 (range, 15-47) months. All patients progressed to end-stage renal disease within a median of 13 (range, 1-27) months after the onset. Kidney biopsy revealed abnormal mitochondrial proliferation in podocytes in all 6 patients. None of the 5 patients who underwent kidney transplantation developed recurrence of FSGS. Primary CoQ10 deficiency due to COQ6 mutations should be considered in children presenting with both SR-FSGS and sensorineural hearing loss. An early diagnosis of COQ6 mutations is essential because the condition is treatable when CoQ10 supplementation is started at the early stage. We recommend early kidney biopsy because detection of abnormal mitochondrial proliferation in podocytes might provide an earlier diagnostic clue.