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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.

Background: Preoperative locoregional treatment (LRT) for hepatocellular carcinoma (HCC) often induces intratumoral necrosis without affecting the overall tumor size, and residual viable tumor size (VTS) on imaging is an important clinical parameter for assessing post-treatment response. However, for surgical specimens, it is unclear whether the VTS would be more relevant to prognosis compared to total tumor size (TTS).Methods: A total of 142 surgically resected solitary HCC cases were retrospectively reviewed. The TTS and VTS were assessed by applying the modified Response Evaluation Criteria in Solid Tumors method to the resected specimens, and correlated with the clinicopathological features and survival.Results: As applying VTS, 13/142 cases (9.2%) were down-staged to ypT1a. Although the survival analysis results for overall survival according to TTS or VTS were similar, VTS was superior to predict disease-free survival (DFS; p = .023) compared to TTS (p = .08). In addition, multivariate analysis demonstrated VTS > 2 cm to be an independent predictive factor for decreased DFS (p = .001). In the subpopulation of patients with LRT (n = 54), DFS in HCCs with TTS or VTS > 2 cm were significantly shorter than those with TTS or VTS ≤ 2 cm (p = .047 and p = .001, respectively). Interestingly, HCCs with TTS > 2 cm but down-staged to VTS ≤ 2 cm after preoperative LRT had similar survival to those with TTS ≤ 2 cm.Conclusions: Although the prognostic impact of tumor size was similar regardless of whether TTS or VTS was applied, reporting VTS may help to increase the number of candidates for surgery in HCC patients with preoperative LRT.

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 (

Background Lymph node (LN) metastasis is a well-known poor prognostic factor of pancreatic cancer. LN metastasis, through direct invasion of tumor cell to peritumoral lymph nodes (PTLN), is treated as the same as those which spread through lymphatic channels. This study aimed to evaluate the impact of PTLN invasion on the oncologic outcome of pancreatic cancer. Methods Five hundred and six patients who underwent operation for pancreatic ductal adenocarcinoma from 2012 to 2018 were reviewed. PTLN invasion was defined as direct invasion of tumor cells in contact with main tumor. Results Among the 506 patients, 112 patients (22.1%) had PTLN invasion. PTLN invasion group (PTLNI) showed better disease-free survival than regional LN metastasis group (RLNM) and combined LN metastasis group (CLNM) (PTLNI 21 vs RLNM 11 vs CLNM 12 months, P = .003). There was no significant difference between N0 and PTLNI (PTLNI 21 vs N0 23 months, P = .999). In multivariate analysis, conventional LN metastasis was a significant factor compared to N0, but PTLN invasion was not (hazard ratio 0.786 [0.507-1.220], P = .283). Conclusion Because PTLN invasion does not adversely affect survival in the same way as LN metastasis does, pancreatic cancer-may be overstaged if PTLN invasion were dealt in the same manner as a metastatic LN. Therefore, PTLN invasion should be disregarded from current nodal staging system.

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. 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. 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

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. 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. 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. EPNI on baseline CT and TRG were important prognostic factors for tumor recurrence. In addition, TRG was also an important prognostic factor for OS. • 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).

To predict poor survival and tumor recurrence in patients with ampullary adenocarcinoma using preoperative clinical and CT findings. 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. 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

Background Hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) at gadoxetic acid-enhanced MRI may indicate hepatocellular carcinoma (HCC) or nonmalignant cirrhosis-associated nodules. Purpose To assess the distribution of pathologic diagnoses of HBP hypointense nodules without APHE at gadoxetic acid-enhanced MRI and to evaluate clinical and imaging features in differentiating their histologic grades. Materials and Methods This retrospective multicenter study included pathologic analysis-confirmed HBP hypointense nodules without APHE (≤30 mm) in patients with chronic liver disease or cirrhosis screened between January 2008 and June 2016. Central pathologic review by 10 pathologists determined final histologic grades as progressed HCC, early HCC, high-grade dysplastic nodule (DN), and low-grade DN or regenerative nodule. Gadoxetic acid-enhanced MRI features were analyzed by three radiologists. Multivariable logistic regression analyses with elastic net regularization were performed to identify clinical and imaging features for differentiating histologic grades. Results There were 298 patients (mean age, 59 years ± 10; 226 men) with 334 nodules evaluated, and progressed HCCs were diagnosed in 44.0% (147 of 334), early HCCs in 20.4% (68 of 334), high-grade DNs in 27.5% (92 of 334), and low-grade DNs or regenerative nodules in 8.1% (27 of 334). Serum α-fetoprotein level 100 ng/mL or greater (odds ratio, 2.7; P = .01) and MRI features including well-defined margin (odds ratio, 5.5; P = .003), hypointensity at precontrast T1-weighted imaging (odds ratio, 3.2; P < .001), intermediate hyperintensity at T2-weighted imaging (odds ratio, 3.4; P < .001), and restricted diffusion (odds ratio, 1.9; P = .04) were independent predictors for progressed HCC at multivariable analysis. Conclusion In patients at high risk for hepatocellular carcinoma (HCC), hepatobiliary phase hypointense nodules without arterial phase hyperenhancement at gadoxetic acid-enhanced MRI corresponded mainly to progressed HCCs, early HCCs, and high-grade dysplastic nodules. High α-fetoprotein level and some imaging features at MRI helped to differentiate progressed HCC from lower grade nodules. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Motosugi in this issue.

Bone disorder is a common complication of chronic kidney disease (CKD). The clinical usefulness of bone mineral density (BMD) in CKD is not well known. Our study shows that low BMD is associated with physical activity and dietary Na/K intake ratio and can predict poor renal outcome in non-dialysis CKD. Despite evidence of a link between bone mineral disorders and chronic kidney disease (CKD), the clinical implications of bone mineral density (BMD) in CKD are not well established. We investigated risk factors and renal outcomes of low BMD in CKD. We analyzed data from the KNOW-CKD. BMD measured by dual-energy x-ray absorptiometry was classified by T score: normal (T score ≥ − 1.0), osteopenia (− 1.0 > T score > − 2.5), and osteoporosis (T score ≤ − 2.5) of the lumbar spine, hip, or femoral neck. Logistic regression analysis to assess risk factors of low BMD (T score

Background Liver biopsy is the essential method to diagnose non-alcoholic steatohepatitis (NASH), but histological features of NASH are too subjective to achieve reproducible diagnoses in early stages of disease. We aimed to identify the key histological features of NASH and devise a scoring model for diagnosis. Methods Thirteen pathologists blindly assessed 12 histological factors and final histological diagnoses ('not-NASH,' 'borderline,' and 'NASH') of 31 liver biopsies that were diagnosed as non-alcoholic fatty liver disease (NAFLD) or NASH before and after consensus. The main histological parameters to diagnose NASH were selected based on histological diagnoses and the diagnostic accuracy and agreement of 12 scoring models were compared for final diagnosis and the NAFLD Activity Score (NAS) system. Results Inter-observer agreement of final diagnosis was fair (κ = 0.25) before consensus and slightly improved after consensus (κ = 0.33). Steatosis at more than 5% was the essential parameter for diagnosis. Major diagnostic factors for diagnosis were fibrosis except 1C grade and presence of ballooned cells. Minor diagnostic factors were lobular inflammation ( ≥ 2 foci/ × 200 field), microgranuloma, and glycogenated nuclei. All 12 models showed higher inter-observer agreement rates than NAS and post-consensus diagnosis (κ = 0.52-0.69 vs. 0.33). Considering the reproducibility of factors and practicability of the model, summation of the scores of major (× 2) and minor factors may be used for the practical diagnosis of NASH. Conclusions A scoring system for the diagnosis of NAFLD would be helpful as guidelines for pathologists and clinicians by improving the reproducibility of histological diagnosis of NAFLD.

Acinar cell carcinomas (ACCs) and mixed acinar-neuroendocrine carcinomas (MAcNECs) of the pancreas are extremely rare carcinomas with a significant component with acinar differentiation. To date, the clinicopathological behaviours of these neoplasms remain unclear. In this study, we evaluated the histopathological and molecular characteristics of 20 ACCs and 13 MAcNECs and compared them to a cohort of 269 well-differentiated pancreatic neuroendocrine tumours (PanNETs). Compared to PanNETs, both ACCs and MAcNECs had an advanced pT classification (p

PURPOSE The most recent 2017 World Health Organization (WHO) classification of pancreatic neuroendocrine neoplasms (PanNENs) has refined the three-tiered 2010 scheme by separating grade 3 pancreatic neuroendocrine tumors (G3 PanNETs) from poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs). However, differentiating between G3 Pan- NETs and PanNECs is difficult in clinical practice. Materials and Methods Eighty-two surgically resected PanNENs were collected from 16 institutions and reclassified according to the 2017 WHO classification based on the histological features and proliferation index (mitosis and Ki-67). Immunohistochemical stains for ATRX, DAXX, retinoblastoma, p53, Smad4, p16, and MUC1 were performed for 15 high-grade PanNENs. RESULTS Re-classification resulted in 20 G1 PanNETs (24%), 47 G2 PanNETs (57%), eight G3 well-differentiated PanNETs (10%), and seven poorly differentiated PanNECs (9%). PanNECs showed more frequent diffuse nuclear atypia, solid growth patterns and apoptosis, less frequent organoid growth and regular vascular patterns, and absence of low-grade PanNET components than PanNETs. The Ki-67 index was significantly higher in PanNEC (58.2%± 15.1%) compared to G3 PanNET (22.6%±6.1%, p < 0.001). Abnormal expression of any two of p53, p16, MUC1, and Smad4 could discriminate PanNECs from G3 PanNETs with 100% specificity and 87.5% sensitivity. CONCLUSION Histological features supporting the diagnosis of PanNECs over G3 PanNETs were the absence of a low-grade PanNET component in the tumor, the presence of diffuse marked nuclear atypia, solid growth pattern, frequent apoptosis and markedly increased proliferative activity with homogeneous Ki-67 labeling. Immunohistochemical stains for p53, p16, MUC1, and Smad4 may be helpful in distinguishing PanNECs from G3 PanNETs in histologically ambiguous cases, especially in diagnostic practice when only small biopsied tissues are available.

Background Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is commonly diagnosed as hepatocellular carcinoma (HCC) preoperatively. Therefore, unexpected recurrence occurs in some patients after liver transplantation (LT). The aim of this study was to identify the risk factors of recurrence. Methods We retrospectively reviewed the data of 20 patients who underwent LT for cHCC-CC from January 2005 to December 2015. Results Of the 20 patients, 11 (55%) had concurrent HCC and 10 (50%) had multiple cHCC-CCs. Before LT, 13 patients had undergone transarterial chemoembolization (TACE, n = 9), radiofrequency ablation, and TACE (n = 3) or surgical resection (n = 1). Four of the patients (20%) had the classical type, whereas 16 (80%) had subtypes with stem cell features. Six of the 16 patients (37.5%) with subtypes with stem cell features and 3 of the 4 patients (75%) with the classical type showed recurrence after LT. In multivariate analysis, the classical type was significantly associated with poorer recurrence-free survival (RFS) (hazard ratio [HR]: 8.65, confidence interval [CI]: 1.25–60.05, P = .03) and poorer overall survival (HR: 8.89, CI: 1.37–57.84, P = .02). Spontaneous tumor necrosis also showed significance on RFS (P = .03) among 11 patients with nontreated lesions. Conclusion In cHCC-CC, the classical type and spontaneous tumor necrosis were associated with recurrence. If these risk factors are found after LT, short-interval follow-up and strategies such as chemotherapy and/or use of mammalian target of rapamycin inhibitors to prevent recurrence are needed.

Intrahepatic cholangiocarcinoma is a complex disease with three different histologic subtypes, the large duct, small duct, and bile ductular types. In the present study, we elucidated whether the three histological subtypes have differences in their methylation profiles and developed a DNA methylation marker that might help identify a subset of ICC with a different prognosis. We screened 113 promoter CpG island loci against 10 cases of intrahepatic cholangiocarcinoma and normal cystic ducts using the MethyLight assay and selected 30 CpG island loci with cancer-associated hypermethylation. Then, we analyzed 172 intrahepatic cholangiocarcinomas for the methylation state at these 30 loci. Six loci, including DLEC1, were more frequently methylated in the bile ductular type and small duct type, whereas six loci were more frequently methylated in the large duct type. Of these 30 loci, DLEC1 methylation was found mainly in the bile ductular type and small duct type but rarely in the large duct type. DLEC1 methylation was significantly associated with a better clinical outcome in intrahepatic cholangiocarcinomas of the small duct type but not of the bile ductular type. DLEC1 methylation was an independent prognostic variable in both cancer-specific survival and recurrence-free survival. For patients with intrahepatic cholangiocarcinoma of the small duct type (n = 68), DLEC1 methylation was found in 26 (38.2%) and was associated with a better clinical outcome for both cancer-specific survival and recurrence-free survival. Our findings suggest that DLEC1 methylation can be utilized to identify a subset with a better prognosis in intrahepatic cholangiocarcinomas of the small duct type.

Obtaining ground-truth labels for supervised training is a labor-intensive and time-consuming task. Owning to their large size, only slide-level labels or a handful of coarse annotations are usually provided for pathology images, which makes the training of the classifier challenging. In this study, we propose a conceptually simple, two-stage approach to classify small and large duct types in intrahepatic chalongio-carcinoma using only slide-level labels. Unlike conventional pathology image analysis methods employ multiple instance learning (MIL) applied to overcome the problem of the slide-level label, we introduce a novel label smoothing method to progressively refine the training labels to improve the classification accuracy. The main idea is that we introduce the hidden class, which is assumed to be mutually inclusive of all ground-truth classes and less confident for classification. By iteratively refining (i.e., smoothing) per-patch labels, we can extract and discard the hidden class from the training data. We demonstrate that the proposed label filtering scheme improves the classification accuracy by up to 30% compared to the baseline MIL method and 10% compared to the state-of-the-art noisy label cleaning method. In addition, we demonstrate the effectiveness of gene mutation prior information in the classification of two different duct types. The experimental results suggest that the proposed method may provide pathologists insight into the study of correlations between genetic and histologic subtypes.

Background Artificial intelligence (AI) research is highly dependent on the nature of the data available. With the steady increase of AI applications in the medical field, the demand for quality medical data is increasing significantly. We here describe the development of a platform for providing and sharing digital pathology data to AI researchers, and highlight challenges to overcome in operating a sustainable platform in conjunction with pathologists. Methods Over 3000 pathological slides from five organs (liver, colon, prostate, pancreas and biliary tract, and kidney) in histologically confirmed tumor cases by pathology departments at three hospitals were selected for the dataset. After digitalizing the slides, tumor areas were annotated and overlaid onto the images by pathologists as the ground truth for AI training. To reduce the pathologists’ workload, AI-assisted annotation was established in collaboration with university AI teams. Results A web-based data sharing platform was developed to share massive pathological image data in 2019. This platform includes 3100 images, and 5 pre-processing algorithms for AI researchers to easily load images into their learning models. Discussion Due to different regulations among countries for privacy protection, when releasing internationally shared learning platforms, it is considered to be most prudent to obtain consent from patients during data acquisition. Conclusions Despite limitations encountered during platform development and model training, the present medical image sharing platform can steadily fulfill the high demand of AI developers for quality data. This study is expected to help other researchers intending to generate similar platforms that are more effective and accessible in the future.

To investigate clinical and CT factors associated with local resectability in patients with nonmetastatic pancreatic cancers after neoadjuvant chemotherapy ± radiation therapy (CRT). 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. 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. 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. • 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.

To determine if golden-angle radial sparse parallel (GRASP) dynamic contrast-enhanced (DCE)-MRI allows simultaneous evaluation of perfusion and morphology in liver fibrosis.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.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, p0.05 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 (p0.05). 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 (p0.05).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.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.

BACKGROUND: In the World Health Organization (WHO) classification, gallbladder (GB) intraepithelial lesions are grouped as flat or tumoral, according to their morphological features. The purpose of this study was to investigate the relationship between the morphologies and clinical features of GB cancer (GBC) and to examine the feasibility of using morphologic classification as a prognostic factor. METHODS: From January 2000 to December 2012, the available pathologic slide reviews of 381 patients were analyzed at the Seoul National University Hospital. All pathologic slides were evaluated by two pancreato-biliary tract pathology experts. GBCs were categorized into eight groups (Flat: F1-2, Borderline, Tumoral: Tu1-5), according to the thickness of the mucosal lesion, histologic patterns of the mucosa under microscopy, invasion extent, and patient history of premalignant lesions. According to the morphologic classification, clinical features were compared and survival analysis was performed. RESULTS: In three groups, flat lesions comprised 179 (46.9%) cases and borderline and tumoral comprised 97 (25.4%) and 105 (27.5%) cases, respectively. More favorable pathologic and clinical results were found within the tumoral group. The borderline group had an intermediate tendency between flat and intraluminal in clinicopathologic parameters. In the curative resected T2 stage group, the borderline group demonstrated an intermediate trend compared to that of the flat and tumoral groups, but this was statistically insignificant (P=0.08). CONCLUSIONS: Flat type GBCs show worse prognosis than tumoral GBCs. The morphological classifications between flat and tumoral on the basis of 1 cm and by papillary feature is feasible. Tumor morphology can be used as a reference while deciding the treatment plan, especially in T2 GBC.

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.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.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%) (p0.001). 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.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.• 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.

Intrahepatic cholangiocarcinoma (ICC) is a rare but fatal tumor. The isocitrate dehydrogenase 1 and 2 (IDH1/2) genes are known to be mutated in ICC. IDH1/2 mutations tend to be accompanied by enhanced hypermethylation at a subset of genomic loci. We sought to clarify the clinicopathological features, including prognostic value, of ICCs with IDH1/2 mutation-associated hypermethylation at a subset of genes. The mutation status of IDH1/2 and methylation status of 30 gene CpG island loci were analyzed in 172 cases of ICC using pyrosequencing and the MethyLight assay, respectively. The mutation status of IDH1/2 was correlated with clinicopathological features and the DNA methylation status at 30 gene loci. Then, the clinicopathological characteristics were analyzed regarding three-tiered methylation statuses in genes showing IDH1/2 mutation-associated methylation. IDH1/2 mutations were found in 9.3% of ICCs, and IDH1/2-mutated tumors were associated with the histological subtype, including the bile ductular type and small duct type, and poor differentiation. Eight DNA methylation markers showed associations with IDH1/2 mutations, and ICCs with > 5/8 methylated markers were associated with the bile ductular type or small duct type, absence of mucin production, absence of biliary intraepithelial neoplasia, and presence of chronic liver disease. > 5/8 methylated markers were an independent prognostic marker associated with better survival in both cancer-specific survival and recurrence-free survival. In summary, by analyzing the association between IDH1/2 mutations and DNA methylation in individual genes, we developed a panel of DNA methylation markers that were significantly associated with IDH1/2 mutations and were able to identify a subset of ICC with better clinical outcomes.

Background Perfluorobutane (PFB) and sulfur hexafluoride (SHF) have different physiologic characteristics, but it is unclear whether hepatocellular carcinomas (HCCs) show similar wash-in and washout patterns to both contrast agents at US. Purpose To investigate Contrast-Enhanced US Liver Imaging Reporting and Data System (LI-RADS) version 2017 HCC categorization by comparing PFB-enhanced US and SHF-enhanced US in participants at high risk for HCC. Materials and Methods In this prospective study conducted from February to August 2019, participants at high risk for HCC with treatment-naive hepatic observations (≥1 cm) categorized as LR-3, LR-4, LR-5, or LR-M (intermediate probability of HCC, probable HCC, definitely HCC, and probably malignant but not HCC specific, respectively) on cross-sectional images were screened. They underwent same-day PFB-enhanced US and SHF-enhanced US. Arterial phase hyperenhancement (APHE), washout time and degree, and echogenicity in the Kupffer phase (PFB-enhanced US) were evaluated and categorized by the operator using CEUS LI-RADS, who referred to the radiologist who performed the contrast-enhanced US, and by a reviewer. Diagnostic performance was analyzed using the McNemar test. Results Fifty-nine participants were evaluated (43 with HCC, 10 with non-HCC malignancies, six with benign findings). Nonrim APHE was identically observed in 95% (41 of 43, operator) or 88% (38 of 43, reviewer) of HCCs with both contrast agents. Among 43 HCCs, late (≥60 seconds) and mild washout were more frequent with PFB-enhanced US (34 with operator, 33 with reviewer) than with SHF-enhanced US (24 with operator, 26 with reviewer) (

To predict poor survival and tumor recurrence in patients with ampullary adenocarcinoma using preoperative clinical and CT findings.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.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).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.• 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).

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.

Published data on survival of T2 gallbladder carcinoma (GBC) from different countries show a wide range of 5-year survival rates from 30-> 70%. Recently, studies have demonstrated substantial variation between countries in terms of their approach to sampling gallbladders, and furthermore, that pathologists from different continents apply highly variable criteria in determining stage of invasion in this organ. These findings raised the question of whether these variations in pathologic evaluation could account for the vastly different survival rates of T2 GBC reported in the literature. In this study, survival of 316 GBCs from three countries (Chile n = 137, South Korea n = 105, USA n = 74), all adequately sampled (with a minimum of five tumor sections examined) and histopathologically verified as pT2 (after consensus examination by expert pathologists from three continents), was analyzed. Chilean patients had a significantly worse prognosis based on 5-year all-cause mortality (HR: 1.89, 95% CI: 1.27-2.83, p = 0.002) and disease-specific mortality (HR: 2.41, 95% CI: 1.51-3.84, p < 0.001), compared to their South Korean counterparts, even when controlled for age and sex. Comparing the USA to South Korea, the survival differences in all-cause mortality (HR: 1.75, 95% CI: 1.12-2.75, p = 0.015) and disease-specific mortality (HR: 1.94, 95% CI: 1.14-3.31, p = 0.015) were also pronounced. The 3-year disease-specific survival rates in South Korea, the USA, and Chile were 75%, 65%, and 55%, respectively, the 5-year disease-specific survival rates were 60%, 50%, and 50%, respectively, and the overall 5-year survival rates were 55%, 45%, and 35%, respectively. In conclusion, the survival of true T2 GBC in properly classified cases is neither as good nor as bad as previously documented in the literature and shows notable geographic differences even in well-sampled cases with consensus histopathologic criteria. Future studies should focus on other potential reasons including biologic, etiopathogenetic, management-related, populational, or healthcare practice-related factors that may influence the survival differences of T2 GBC in different regions.

Antibacterial and immune-evasive coating for orthopedic implants reduce infection and infection-induced immune response., Bacterial infection and infection-induced immune response have been a life-threatening risk for patients having orthopedic implant surgeries. Conventional biomaterials are vulnerable to biocontamination, which causes bacterial invasion in wounded areas, leading to postoperative infection. Therefore, development of anti-infection and immune-evasive coating for orthopedic implants is urgently needed. Here, we developed an advanced surface modification technique for orthopedic implants termed lubricated orthopedic implant surface (LOIS), which was inspired by slippery surface of Nepenthes pitcher plant. LOIS presents a long-lasting, extreme liquid repellency against diverse liquids and biosubstances including cells, proteins, calcium, and bacteria. In addition, we confirmed mechanical durability against scratches and fixation force by simulating inevitable damages during surgical procedure ex vivo. The antibiofouling and anti-infection capability of LOIS were thoroughly investigated using an osteomyelitis femoral fracture model of rabbits. We envision that the LOIS with antibiofouling properties and mechanical durability is a step forward in infection-free orthopedic surgeries.

BackgroundHenoch-Schönlein purpura nephritis (HSPN), a small-vessel vasculitis, shares renal pathological features with immunoglobulin A nephropathy. Oxford classification of immunoglobulin A nephropathy pathology has been updated to the MEST-C score, but its application in HSPN remains unresolved.MethodsTwo hundred and thirteen patients with biopsy-proven HSPN were retrieved from the Seoul National University Hospital between 2000 and 2017. Renal outcome risks (i.e., end-stage renal disease or doubling of serum creatinine) were evaluated according to MEST-C scores after stratification by age: 113 children aged ResultsTwenty-one child (19%) and 16 adult (16%) patients reached the renal outcome during the median follow-up periods of 12 years and 13 years, respectively (maximum 19 years). In children, M1 and T1/T2 scores revealed worse renal outcomes than did M0 and T0 scores, respectively, whereas the T score was the only factor related to worse outcomes in adult patients after adjusting for multiple clinical and laboratory variables. The pooled data showed that M1, S1, and T1/T2 in children and E1 and T1/T2 in adults were correlated with poorer renal outcomes than those of their counterpart scores.ConclusionsThe Oxford classification MEST-C scores can predict long-term renal outcomes in patients with HSPN.

PURPOSE To compare tumor vascularity in 4 types of rat hepatocellular carcinoma (HCC) models: N1S1, vascular endothelial growth factor (VEGF)-transfected N1S1 (VEGF-N1S1), McA-RH7777, and VEGF-transfected McA-RH7777 (VEGF-McA-RH777) tumors. MATERIALS AND METHODS The N1S1 and McA-RH7777 cell lines were transfected with expression vectors containing cDNA for rat VEGF. Eighty-eight male Sprague-Dawley rats (weight range, 400-450 g) were randomly divided into 4 groups (ie, 22 rats per model), and 4 types of tumor models were created by using the N1S1, VEGF-N1S1, McA-RH7777, and VEGF-McA-RH777 cell lines. Tumor vascularity was evaluated by perfusion computed tomography (CT), enzyme-linked immunosorbent assay of VEGF, CD34 staining, angiography, and Lipiodol transarterial embolization. Intergroup discrepancies were evaluated by Kruskal-Wallis test. RESULTS Arterial perfusion (P < .001), portal perfusion (P = .015), total perfusion (P < .001), tumor VEGF level (P = .002), and microvessel density (MVD; P = .007) were significantly different among groups. VEGF-McA-RH7777 tumors showed the greatest arterial perfusion (46.7 mL/min/100 mL ± 15.5), total perfusion (60.7 mL/min/100 mL ± 21.8), tumor VEGF level (3,376.7 pg/mL ± 145.8), and MVD (34.5‰ ± 7.5). Whereas most tumors in the N1S1, VEGF-N1S1, and McA-RH7777 groups showed hypovascular staining on angiography and minimal Lipiodol uptake after embolization, 5 of 6 VEGF-McA-RH7777 tumors (83.3%) presented hypervascular tumor staining and moderate to compact Lipiodol uptake. CONCLUSIONS McA-RH7777 tumors were more hypervascular than N1S1 tumors, and tumor vascularity was enhanced further by VEGF transfection. Therefore, the VEGF-McA-RH7777 tumor is recommended to mimic hypervascular human HCC in rats.

Purpose The aim of this animal study was to evaluate the safety and feasibility of a portable, ultrasonography-guided, high-intensity focused ultrasound (USg-HIFU) system to treat the pancreas. Methods Eight swine were included. Using a portable HIFU device (ALPIUS 900, Alpinion Medical Systems), ablations were performed on the pancreas in vivo. Different acoustic intensities were applied (1.7 kW/cm2 or 1.5 kW/cm2 , n=2 [group A for a pilot study]; 1.5 kW/ cm2 , n=3 [group B]; and 1.2 kW/cm2 , n=3 [group C]). Magnetic resonance imaging (MRI) was performed immediately (group A) or 7 days (groups B and C) after HIFU treatment. In groups B and C, serum amylase and lipase levels were measured on days 0 and 7, and performance status was observed every day. Necropsy was performed on days 0 (group A) or 7 (groups B and C) to assess the presence of unintended injuries and to obtain pancreatic and peripancreatic tissue for histological analysis. Results Ablation was noted in the pancreas in all swine on MRI, and all pathologic specimens showed coagulation necrosis in the treated area. The mean ablation areas on MRI were 85.3±38.1 mm2, 90.7±21.2 mm2, and 54.4±30.6 mm2 in groups A, B, and C, respectively (P>0.05). No animals showed evidence of complications, except for one case of a pseudocyst in group B. Conclusion This study showed that pancreas ablation using a portable USg-HIFU system may be safe and feasible, and that coagulation necrosis of the pancreas was successfully achieved with a range of acoustic intensities.

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.

Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) frequently display infiltrative growth into the adjacent normal soft tissue. In this study, we aimed to determine whether the microscopic extension into surrounding normal tissue can influence the local recurrence of MFS and UPS. A total of 42 cases (22 MFS and 20 UPS) were examined. The length of the microscopic extension was measured from the edge of the main tumor mass to the end of infiltration. The length of 5.5 mm was selected as the optimal cut-off value that could predict local recurrence using the receiver operating characteristic (ROC) curve and Youden index. Longer length of microscopic extension was significantly correlated with the status of resection margin (P = 0.032). The group with longer length of microscopic extension (>5.5 mm) had significantly worse recurrence-free survival than the group with shorter length of microscopic extension (≤5.5 mm) (P = 0.000). Multivariate analysis revealed that the length of microscopic extension was independent predictors of recurrence-free survival (P = 0.018). In conclusion, microscopic extensions at the edge of the main mass into the surrounding normal tissue were observed in most MFS and UPS patients, and the length of microscopic extension was associated with local recurrence.

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.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.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) (p0.05). 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 (p0.05).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.

To determine the diagnostic value of the cotton ball sign and other CT features in patients with gallbladder (GB) wall thickenings (WTs). Three blinded readers reviewed the preoperative CT and MR images of 101 patients with pathologically confirmed GB adenomyomatosis (GA) (n = 34) and other benign (n = 29), malignant (n = 41), and premalignant (n = 2) GBWTs. Three readers analysed the morphological features of GBWT and presence of the “cotton ball sign”, defined as fuzzy grey dots in GBWT or a dotted outer border of the inner enhancing layer on contrast-enhanced (CE) CT. In addition, the “pearl necklace sign” on MR was analysed. In the GA group (n = 34), prevalence of the cotton ball sign and pearl necklace sign was 74% (25/34) and 44% (15/34), respectively. Presence of the cotton ball sign, smooth contour of the mucosa, double-layering enhancement, and enhancement degree weaker than the renal cortex on CT images were significant predictors of benign GBWT (p < 0.01). When differentiating GA from GB malignancy or premalignancy, accuracy of the cotton ball sign and pearl necklace sign was 81% (62/77) and 74% (57/77), respectively. The cotton ball sign on CE-CT showed higher sensitivity and comparable specificity to those of the pearl necklace sign in differentiating GA from malignancy. • Prevalence of the cotton ball sign on CT was 74% in gallbladder adenomyomatosis. • The cotton ball sign was useful in differentiating gallbladder adenomyomatosis from gallbladder cancer. • The cotton ball sign was more sensitive than the pearl necklace sign for adenomyomatosis diagnosis.

There is an urgent need to investigate the genetic changes that occur in intraductal papillary mucinous neoplasm (IPMN), which is a well-known precursor of pancreatic cancer. In this study, gene expression profiling was performed by removing unwanted variation to determine the differentially expressed genes (DEGs) associated with malignant progression of IPMN. Among the identified DEGs, zinc finger E-box binding homeobox 1 (ZEB1) and E-cadherin, a crucial regulator of epithelial-to-mesenchymal transition (EMT), was validated among identified DEGs. A total of 76 fresh-frozen tissues were used for gene expression profiling and formalin-fixed, paraffin-embedded blocks from 87 patients were obtained for immunohistochemical analysis. Loss of E-cadherin expression (p = 0.023, odd ratio [OR] = 4.923) and expression of ZEB1 in stromal cells (stromal ZEB1, p < 0.001, OR = 26.800) were significantly correlated with degree of dysplasia. The hazard of death was significantly increased in patients with loss of E-cadherin expression (hazard ratio [HR] = 13.718, p = 0.004), expression of epithelial ZEB1 (HR = 19.117, p = 0.001), and stromal ZEB1 (HR = 6.373, p = 0.043). Based on the results of this study, loss of E-cadherin and expression of stromal ZEB1 are associated with increased risk of malignant progression. Epithelial and stromal ZEB1, as well as E-cadherin may be strong predictors of survival in patients with IPMN. Our finding suggests that these EMT markers may be utilized as potential prognosticators and may be used to improve and personalize treatment of IPMN.

We report a case of adenocarcinoma originating from the duodenal Brunner glands in a 47-year-old female patient. The lesion was 0.8 cm in extent and located at the posterior wall of the first part of the duodenum. Histologically, the tumor showed transition from non-neoplastic Brunner glands through dysplastic epithelium into adenocarcinoma. The carcinoma cells were strongly positive for MUC6 protein, which is an epithelial marker for the Brunner glands. Tumor protein p53 was overexpressed in the carcinoma cells, but not in the non-neoplastic or dysplastic epithelium. Dystrophic calcification was predominant. This is the first case report of duodenal adenocarcinoma of Brunner gland origin in Korea.

Purpose To determine factors that significantly affect the focal disturbance (FD) ratio calculated with an acoustic structure quantification (ASQ) technique in a dietary-induced fatty liver disease rat model and to assess the diagnostic performance of the FD ratio in the assessment of hepatic steatosis by using histopathologic examination as a standard of reference. Materials and Methods Twenty-eight male F344 rats were fed a methionine-choline-deficient diet with a variable duration (3.5 days [half week] or 1, 2, 3, 4, 5, or 6 weeks; four rats in each group). A control group of four rats was maintained on a standard diet. At the end of each diet period, ASQ ultrasonography (US) and magnetic resonance (MR) spectroscopy were performed. Then, the rat was sacrificed and histopathologic examination of the liver was performed. Receiver operating characteristic curve analysis was performed to assess the diagnostic performance of the FD ratio in the evaluation of the degree of hepatic steatosis. The Spearman correlation coefficient was calculated to assess the correlation between the ordinal values, and multivariate linear regression analysis was used to identify significant determinant factors for the FD ratio. Results The diagnostic performance of the FD ratio in the assessment of the degree of hepatic steatosis (area under the receiver operating characteristic curve: 1.000 for 5%-33% steatosis, 0.981 for33% to 66% steatosis, and 0.965 for66% steatosis) was excellent and was comparable to that of MR spectroscopy. There was a strong negative linear correlation between the FD ratio and the estimated fat fraction at MR spectroscopy (Spearman ρ, -0.903; P.001). Multivariate linear regression analysis showed that the degree of hepatic steatosis (P.001) and fibrosis stage (P = .022) were significant factors affecting the FD ratio. Conclusion The FD ratio may potentially provide good diagnostic performance in the assessment of the degree of hepatic steatosis, with a strong negative linear correlation with the estimated fat fraction at MR spectroscopy. The degree of steatosis and stage of fibrosis at histopathologic examination were significant factors that affected the FD ratio.