CT Evaluation of Long-Term Changes in Common Bile Duct Diameter after Cholecystectomy.

Purpose: The present study aimed to investigate the frequency and extent of compensatory common bile duct (CBD) dilatation after cholecystectomy, assess the time between cholecystectomy and CBD dilatation, and identify potentially useful CT findings suggestive of obstructive CBD dilatation. Materials and Methods: This retrospective study included 121 patients without biliary obstruction who underwent multiple CT scans before and after cholecystectomy at a single center between 2009 and 2011. The maximum short-axis diameters of the CBD and intrahepatic duct (IHD) were measured on each CT scan. In addition, the clinical and CT findings of 11 patients who were initially excluded from the study because of CBD stones or periampullary tumors were examined to identify distinguishing features between obstructive and non-obstructive CBD dilatation after cholecystectomy. Results: The mean (standard deviation) short-axis maximum CBD diameter of 121 patients was 5.6 (± 1.9) mm in the axial plane before cholecystectomy but increased to 7.9 (± 2.6) mm after cholecystectomy (p < 0.001). Of the 106 patients with a pre-cholecystectomy axial CBD diameter of < 8 mm, 39 (36.8%) showed CBD dilatation of ≥ 8 mm after cholecystectomy. Six of the 17 patients with longterm (> 2 years) serial follow-up CT scans (35.3%) eventually showed a significant (> 1.5-fold) increase in the axial CBD diameter, all within two years after cholecystectomy. Of the 121 patients without obstruction or related symptoms, only one patient (0.1%) showed IHD dilatation > 3 mm after cholecystectomy. In contrast, all 11 patients with CBD obstruction had abdominal pain and abnormal laboratory indices, and 81.8% (9/11) had significant dilatation of the IHD and CBD. Conclusion: Compensatory non-obstructive CBD dilatation commonly occurs after cholecystectomy to a similar extent as obstructive dilatation. However, the presence of relevant symptoms, significant IHD dilatation, or further CBD dilatation 2-3 years after cholecystectomy should raise suspicion of CBD obstruction.

Suspicious findings observed retrospectively on CT imaging performed before the diagnosis of pancreatic cancer.

Background: Few studies have focused on computed tomography findings before a pancreatic cancer diagnosis. We aimed to investigate the prediagnostic computed tomography findings of patients who had undergone computed tomography within the prediagnostic period of their pancreatic cancer diagnosis. Methods: Between January 2008 and December 2019, 27 patients who underwent contrast-enhanced abdominal or chest computed tomography including the pancreas within 1 year of a pancreatic cancer diagnosis were enrolled in this retrospective study. The prediagnostic computed tomography imaging findings were divided into pancreatic parenchyma and pancreatic duct findings. Results: All patients underwent computed tomography for reasons unrelated to pancreatic cancer. The pancreatic parenchyma and ducts showed normal findings in seven patients and abnormal findings in 20 patients. Hypoattenuating mass-like lesions were detected in nine patients with a median size of 1.2 cm. Six patients had focal pancreatic duct dilatations, and two patients had distal parenchymal atrophy. In three patients, two of these findings were found simultaneously. Taken together, 14 (51.9%) of 27 patients had findings suggestive of pancreatic cancer in prediagnostic computed tomography. Conclusions: In contrast-enhanced computed tomography performed for other purposes, attention should be paid to the presence of a hypoattenuating mass, focal pancreatic duct dilatation, or distal parenchymal atrophy of the pancreas. These features may be clues for an early diagnosis of pancreatic cancer.

Primary hepatic mucosa-associated lymphoid tissue lymphoma mimicking hepatocellular carcinoma in a patient with chronic hepatitis B: a case report.

Primary hepatic lymphoma is a rare disease, and primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma accounts for only 0.3% of all primary hepatic lymphomas. Herein, we report a case of primary hepatic MALT lymphoma in a male patient in his mid-40 s with chronic hepatitis B infection. The patient visited our department for further examination of a hepatic nodule initially visualized through abdominal pelvic computed tomography (CT). Based on imaging studies and elevated levels of tumor markers, the tumor was suspected to be hepatocellular carcinoma. A laparoscopic inferior sectionectomy (segment 5 and 6) was performed, and immunohistochemical staining revealed that the tumor was positive for CD20, B-cell lymphoma 2, pan-cytokeratin (CK), and CK19 markers. Pathological findings revealed it to be a primary hepatic MALT lymphoma. After surgery, bone marrow biopsies and fluorodeoxyglucose-positron emission tomography integrated with CT scanning confirmed that there was no other involvement. The patient did not receive chemotherapy, and there was no recurrence during the 24-month follow-up period. Hepatocellular carcinoma is the most common malignancy in patients with chronic hepatitis B, but rare tumors such as primary MALT lymphoma can also occur, so a careful approach is required for their differentiation.

A preoperative scoring system to predict lymph node metastasis in intrahepatic cholangiocarcinoma.

BACKGROUND: The abnormality of imaging finding of lymph node (LN) has demonstrated unsatisfactory diagnostic accuracy for pathologic lymph node metastasis (LNM). We aimed to develop and validate a simple scoring system predicting LNM in patients with intrahepatic cholangiocarcinoma (iCCA) prior to surgery based on MRI and clinical findings. METHODS: We retrospectively enrolled consecutive patients who underwent surgical resection for treatment-naïve iCCA from six institutions between January 2009 and December 2015. Patients who underwent lymph node dissection (LND) were randomly assigned to the training and validation cohorts at a 2:1 ratio, an¹ìd pathologic LN status was evaluated. Patients who did not undergo LND were assigned to the test cohort, and clinical LN status was evaluated. Using MRI and clinical findings, a preoperative LNM score was developed in the training cohort and validated in the validation and test cohorts. RESULTS: The training, validation, and test cohorts included 102, 53, and 118 patients, respectively. The preoperative LNM score consisted of serum carcinoembryonic antigen and two MRI findings (suspicious LN and bile duct invasion). The preoperative LNM score was associated with pathologic LNM in training (p < 0.001) and validation (p = 0.010) cohorts and clinical LNM in test cohort (p < 0.001). The preoperative LNM score outperformed MRI-suspicious LN alone in predicting pathologic LNM (area under the curve, 0.703 vs. 0.604, p = 0.004). The preoperative LNM score was also associated with overall survival in all cohorts (p < 0.001). CONCLUSIONS: Our preoperative LNM score was significantly associated with pathologic or clinical LNM and outperformed MRI-suspicious LN alone.

Preoperative magnetic resonance imaging-based prognostic model for mass-forming intrahepatic cholangiocarcinoma.

BACKGROUND & AIMS: As most staging systems for intrahepatic cholangiocarcinoma (iCCA) are based on pathological results, preoperative prognostic prediction is limited. This study aimed to develop and validate a prognostic model for the overall survival of patients with mass-forming iCCA (MF-iCCA) using preoperative magnetic resonance imaging (MRI) and clinical findings. METHODS: We enrolled a total of 316 patients who underwent preoperative MRI and surgical resection for treatment-naive MF-iCCA from six institutions, between January 2009 and December 2015. The subjects were randomly assigned to a training set (n = 208) or validation set (n = 108). The MRIs were independently reviewed by three abdominal radiologists. Using MRI and clinical findings, an MRI prognostic score was established. We compared the discrimination performance of MRI prognostic scores with those of conventional pathological staging systems. RESULTS: We developed an MRI prognostic score consisting of serum CA19-9 and three MRI findings (tumour multiplicity, lymph node metastasis and bile duct invasion). The MRI prognostic score demonstrated good discrimination performance in both the training set (C-index, 0.738; 95% confidence interval [CI], 0.698-0.780) and validation set (C-index, 0.605; 95% CI, 0.526-0.680). In the validation set, MRI prognostic score showed no significant difference with AJCC 8th TNM stage, MEGNA score and Nathan's stage. CONCLUSIONS: Our MRI prognostic score for overall survival of MF-iCCA showed comparable discriminatory performance with pathological staging systems and might be used to determine an optimal treatment strategy.

A New Reporting System for Diagnosis of Hepatocellular Carcinoma in Chronic Hepatitis B With Clinical and Gadoxetic Acid-Enhanced MRI Features.

BACKGROUND: Current major guidelines for diagnosis of hepatocellular carcinoma (HCC) based on imaging findings are different from each other and do not include clinical risk factors as a diagnostic criteria. PURPOSE: To developed and validated a new diagnostic score system using MRI and clinical features as applied in chronic hepatitis B patients. STUDY TYPE: Retrospective observational study. SUBJECT: A total of 418 treatment-naïve patients (out of 902 patients) with chronic hepatitis B having 556 lesions suspected for HCC which were eligible for curative treatment. FIELD STRENGTH/SEQUENCE: T1W GRE in- and opposed-phase, T2W FSE, DWI, and T1W 3D-GRE dynamic contrast-enhanced sequences at 1.5  T and 3  T. ASSESSMENT: Six radiologists with 7-22 years of experience independently evaluated MR images based on Liver Imaging Reporting and Data System (LI-RADS) version 2018. STATISTICAL TESTS: Based on logistic regression analysis of MRI features and clinical factors, a risk score system was devised in derivation cohorts (268 patients, 352 lesions) and externally validated (150 patients, 204 lesions). The performance of the new score system was assessed by Harell's c-index. Using cutoff value of 12, maintaining positive predictive value ≥95%, the diagnostic performances of the score system were compared with those of LR-5. RESULTS: The 15-point diagnostic scoring system used MRI features (lesion size, nonrim arterial phase hyperenhancement, portal venous phase hypointensity, hepatobiliary phase hypointensity, and diffusion restriction) and clinical factors (alpha-fetoprotein and platelet). It showed good discrimination in the derivation (c-index, 0.946) and validation cohorts (c-index, 0.907). Using a risk score of 12 as a cut-off, this system yielded higher sensitivity than LR-5 (derivation cohort, 76.8% vs. 52.1%; validation cohort, 73.4% vs. 49.5%) without significant decrease in specificity (derivation cohort, 93.1% vs. 97.2%, P = 0.074; validation cohort, 91.7% vs. 96.1%, P = 0.299). DATA CONCLUSION: A new score system showed improved sensitivity in chronic hepatitis B patients compared to LI-RADS without significant compromise in specificity. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Clinical Staging of Mass-Forming Intrahepatic Cholangiocarcinoma: Computed Tomography Versus Magnetic Resonance Imaging.

We compared the performance of computed tomography (CT) and magnetic resonance imaging (MRI) for preoperative clinical staging of mass-forming intrahepatic cholangiocarcinoma (iCCA), using the eighth American Joint Committee on Cancer (AJCC) system. This retrospective, multicenter, cohort study consecutively identified patients who underwent partial hepatectomy for mass-forming iCCA and had preoperative CT and MRI performed from January 2009 to December 2015. CT and MRI characteristics were used to determine clinical stage based on the eighth AJCC system. Performances of CT and MRI for clinical T and N staging were compared using generalized estimating equations. In 334 patients (median age, 63 years; 221 men), MRI sensitivities were significantly higher than CT sensitivities for detecting T1b or higher stages (91.0% vs. 80.5%, respectively, P < 0.001), T2 or higher stages (89.1% vs. 73.8%, respectively, P < 0.001), and T3 or T4 stage (77.8% vs. 58.0%, respectively, P < 0.001). MRI was also more sensitive at identifying multiple tumors than CT (66.7% vs. 50.0%, respectively, P = 0.026), without a significant difference in specificity (78.1% vs. 80.1%, respectively, P = 0.342). Sensitivities were comparable between CT and MRI for determination of size >5 cm (i.e., T1b for single tumor) and extrahepatic organ invasion (i.e., T4). Sensitivities of CT and MRI were not different for N stage (65.0% vs. 64.0%, respectively, P = 0.808), but the specificity of CT was significantly higher than that of MRI (80.7% vs. 72.9%, respectively, P = 0.001) when using a composite reference standard. Conclusion: MRI showed superior sensitivity to CT for diagnosing T2 and T3 stages, particularly multiple tumors. CT and MRI had comparable sensitivity for N staging, but CT provided higher specificity than MRI.

Effectiveness of Hepatocellular Carcinoma Surveillance and an Optimal Surveillance Interval: Nationwide Cohort of Korea.

PURPOSE: To assess associations between surveillance intervals in a national hepatocellular carcinoma (HCC) surveillance program and receiving curative treatment and mortality using nationwide cohort data for Korea. MATERIALS AND METHODS: Using the National Health Insurance Service Database of Korea, we retrospectively identified 3201852 patients, the target population of the national HCC surveillance program, between 2008 and 2017. After exclusion, a total of 64674 HCC patients were divided based on surveillance intervals: never screened, ≤6 months (6M), 7-12 months (1Y), 13-24 months (2Y), and 25-36 months (3Y). Associations for surveillance interval with the chance to receive curative therapy and all-cause mortality were analyzed. RESULTS: The 6M group (51.9%) received curative therapy more often than the other groups (1Y, 48.3%; 2Y, 43.8%; 3Y, 41.3%; never screened, 34.5%). Odds ratio for receiving curative therapy among the other surveillance interval groups (1Y, 0.87; 2Y, 0.76; 3Y, 0.77; never screened, 0.57; p<0.001) were significantly lower than that of the 6M group. The hazard ratios (HRs) of all-cause mortality were 1.07, 1.14, and 1.37 for 2Y, 3Y, and never screened groups. The HR for the 1Y group (0.96; p=0.092) was not significantly different, and it was lower (0.91; p<0.001) than that of the 6M group after adjustment for lead-time bias. Curative therapy was associated with survival benefits (HR, 0.26; p<0.001). CONCLUSION: HCC surveillance, especially at a surveillance interval of 6 months, increases the chance to receive curative therapy.

Preoperative prediction of postsurgical outcomes in mass-forming intrahepatic cholangiocarcinoma based on clinical, radiologic, and radiomics features.

OBJECTIVES: Current prognostic systems for intrahepatic cholangiocarcinoma (IHCC) rely on surgical pathology data and are not applicable to a preoperative setting. We aimed to develop and validate preoperative models to predict postsurgical outcomes in mass-forming IHCC patients based on clinical, radiologic, and radiomics features. METHODS: This multicenter retrospective cohort study included patients who underwent curative-intent resection for mass-forming IHCC. In the development cohort (single institution data), three preoperative multivariable Cox models for predicting recurrence-free survival (RFS) were constructed, including the clinical-radiologic, radiomics, and clinical-radiologic-radiomics (CRR) models based on clinical and CT findings, CT-radiomics features, and a combination of both, respectively. Model performance was evaluated in the test cohort (data from five institutions) using Harrell's C-index and compared with postoperative prognostic systems. RESULTS: A total of 345 patients (233, development cohort; 112, test cohort) were evaluated. The clinical-radiologic model included five independent CT predictors (infiltrative contour, multiplicity, periductal infiltration, extrahepatic organ invasion, and suspicious metastatic lymph node) and showed similar performance in predicting RFS to the radiomics model (C-index, 0.65 vs. 0.68; p = 0.43 in the test cohort). The CRR model showed significantly improved performance (C-index, 0.71; p = 0.01) than the clinical-radiologic model and demonstrated similar performance to the postoperative prognostic systems in predicting RFS (C-index, 0.71-0.73 vs. 0.70-0.73; p ≥ 0.40) and overall survival (C-index, 0.68-0.71 vs. 0.64-0.74; p ≥ 0.27) in the test cohort. CONCLUSIONS: A model integrating clinical, CT, and radiomics information may be useful for the preoperative assessment of postsurgical outcomes in patients with mass-forming IHCC. KEY POINTS: • The radiomics analysis had incremental value in predicting recurrence-free survival of patients with intrahepatic mass-forming cholangiocarcinoma. • The clinical-radiologic-radiomics model demonstrated similar performance to the postoperatively available prognostic systems (including 8th AJCC system) in predicting recurrence-free survival and overall survival. • The clinical-radiologic-radiomics model may be useful for the preoperative assessment of postsurgical outcomes in patients with mass-forming intrahepatic cholangiocarcinoma.

Comparison of the current guidelines for diagnosing hepatocellular carcinoma using gadoxetic acid-enhanced magnetic resonance imaging.

OBJECTIVES: To compare the performance of current guidelines applicable to the diagnosis of hepatocellular carcinomas (HCCs) using gadoxetic acid-enhanced magnetic resonance imaging (MRI). METHODS: Two hundred and forty-one hepatic lesions (149 HCCs, six other malignancies, 86 benign lesions) in 177 patients at risk of HCC without a history of previous treatment for hepatic malignancy in a tertiary center were retrospectively reviewed. Either histopathology results or long-term (> 24 months) follow-up images were used as a standard of reference. All lesions were categorized according to the Liver Imaging Reporting and Data System (LI-RADS), European Association for the Study of the Liver (EASL), Asian Pacific Association for the Study of the Liver (APASL), and Korean Liver Cancer Study Group-National Cancer Center (KLCSG-NCC) guidelines. The sensitivity and specificity thereof were assessed using a generalized estimation equation. RESULTS: For gadoxetic acid-enhanced MRI, LI-RADS (95%, 95% confidence interval [CI] 88-98) and EASL (94%, 95% CI 86-97) yielded the highest specificity, while EASL yielded the lowest sensitivity (54% [95% CI 46-62]). APASL yielded the highest sensitivity (91% [95% CI 86-95]) with the lowest specificity (78% [95% CI 69-86]). KLCSG-NCC showed balanced sensitivity (85% [79-90]) and specificity (88% [95% CI 80-93]). Differences were more prominent in small nodules between 1 and 2 cm. CONCLUSION: The diagnostic performance of current guidelines for HCC on gadoxetic acid-enhanced MRI was significantly different, and a potential inverse association between sensitivity and specificity was observed. KEY POINTS: • EASL and LI-RADS yielded the highest specificity with the lowest sensitivity, whereas APASL yielded the highest sensitivity with the lowest specificity. • Differences in the diagnostic performances of guidelines were prominent in small nodules between 1 and 2 cm. • Additional evaluation of CT findings improved the diagnostic sensitivity and accuracy of EASL and LI-RADS. Although doing so decreased specificity, it remained above 89-90%.

Subcentimeter hepatocellular carcinoma in treatment-naïve patients: noninvasive diagnostic criteria and tumor staging on gadoxetic acid-enhanced MRI.

OBJECTIVE: It is controversial to adopt non-invasive diagnostic criteria of hepatocellular carcinoma (HCC) in subcentimeter lesions. This study was aimed to define the optimal noninvasive diagnostic criteria of subcentimeter HCC and to evaluate the effect on tumor staging. METHODS: We included 110 treatment-naïve patients at risk of HCC and eligible for curative treatment who had subcentimeter lesions (n = 136) on gadoxetic acid-enhanced magnetic resonance imaging (MRI) performed between January 2013 and December 2013. Modified diagnostic criteria for subcentimeter HCC were developed using logistic regression analysis. Accuracies of MR staging with and without using the modified criteria were compared by generalized estimating equation test using pathologic staging as reference standards. Subgroup analysis was performed for patients with co-existing HCC ≥ 1 cm (co-HCC). RESULTS: The modified criteria (presence of co-HCC, arterial phase hyperenhancement, and hypointensity on transitional phase [TP]) showed 61.5% (95% CI, 41.6-78.2) of sensitivity and 98.2% (95% CI, 93.0-99.5) of specificity. Including subcentimeter HCCs improved the accuracy of MR staging from 84.5 to 94.5% (p = 0.001). Fifty percent of subcentimeter lesions found in patients with co-HCCs were HCC, whereas 5.9% of them without co-HCCs were HCC (p = 0.001). In the subgroup with co-HCCs, the accuracy of MR staging with subcentimeter HCCs was improved from 69.0% to 92.8% (p = 0.001). CONCLUSIONS: Including subcentimeter HCCs based on the modified diagnostic criteria (co-existing HCC ≥ 1 cm, arterial phase hyperenhancement, and hypointensity on TP) improved MR staging accuracy. KEY POINTS: • Fifty percent of non-benign appearing subcentimeter lesions found in patients with co-HCCs were HCC, whereas 5.9% of them without co-HCCs were HCC (p = 0.001). • Including subcentimeter HCCs improved the accuracy of MR staging from 84.5 to 94.5% (p = 0.001).

mTOR-Dependent Role of Sestrin2 in Regulating Tumor Progression of Human Endometrial Cancer.

Oncogenic activation of the mammalian target of rapamycin complex 1 (mTORC1) leads to endometrial cancer cell growth and proliferation. Sestrin2 (SESN2), a highly conserved stress-inducible protein, is involved in homeostatic regulation via inhibition of reactive oxygen species (ROS) and mTORC1. However, the role of SESN2 in human endometrial cancer remains to be investigated. Here, we investigated expression, clinical significance, and underlying mechanisms of SESN2 in endometrial cancer. SESN2 was upregulated more in endometrial cancer tissues than in normal endometrial tissues. Furthermore, upregulation of SESN2 statistically correlated with shorter overall survival and disease-free survival in patients with endometrial cancer. SESN2 expression strongly correlated with mTORC1 activity, suggesting its impact on prognosis in endometrial cancer. Additionally, knockdown of SESN2 promoted cell proliferation, migration, and ROS production in endometrial cancer cell lines HEC-1A and Ishikawa. Treatment of these cells with mTOR inhibitors reversed endometrial cancer cell proliferation, migration, and epithelial-mesenchymal transition (EMT) marker expression. Moreover, in a xenograft nude mice model, endometrial cancer growth increased by SESN2 knockdown. Thus, our study provides evidence for the prognostic significance of SESN2, and a relationship between SESN2, the mTORC1 pathway, and endometrial cancer growth, suggesting SESN2 as a potential therapeutic target in endometrial cancer.

Optimal lexicon of gadoxetic acid-enhanced magnetic resonance imaging for the diagnosis of hepatocellular carcinoma modified from LI-RADS.

PURPOSE: To define the optimal lexicon of major imaging findings on gadoxetic acid-enhanced MRIs to diagnose HCC to improve diagnostic performance of the LI-RADS. METHODS: Two hundred forty-one hepatic lesions (149 HCC, six other malignancies, 86 benign lesions) in 177 treatment-naïve patients at risk of HCC who underwent gadoxetic acid-MRIs from January 2013 to December 2015 were retrospectively reviewed using either histopathological or follow-up imaging findings as a standard reference. Two board-certified radiologists independently evaluated the imaging features and categorized the nodules based on the original and the following modified definitions in LI-RADS: (1) washout appearance in the portal venous phase (PVP) only versus that in the PVP or transitional phase, and (2) enhancing capsule only versus enhancing or non-enhancing capsule. Diagnostic performance and inter-observer agreement of LR-5 were assessed and compared between the algorithms using generalized estimation equation. RESULTS: The sensitivity [79.2% (95% confidence interval 71.9, 85.0)] and accuracy [84.6% (79.5, 88.7)] of LR-5 were significantly higher for modified lexicon compared with original LI-RADS [60.4% (52.3, 67.9) and 73.9% (67.9, 79.0); P < 0.001 in all cases]. There was no significant difference in specificity [93.5% (86.2, 97.0) and 95.7% (89.0, 98.4); P = 0.153]. Subgroups of lesions < or ≥ 2 cm showed similar tendencies. Inter-observer agreement for capsule appearance was fair to moderate, whereas that for other imaging findings was good to excellent. CONCLUSIONS: Compared to original LI-RADS, LI-RADS with modified lexicon showed higher sensitivity for the diagnosis of HCC using gadoxetic acid-MRI, with similar specificity.

Imaging Features of Hepatocellular Carcinoma: Quantitative and Qualitative Comparison Between MRI-Enhanced With Gd-EOB-DTPA and Gd-DTPA.

OBJECTIVES: The aim of this study was to compare the major imaging features of hepatocellular carcinoma (HCC) on magnetic resonance imaging (MRI) scans with Gd-EOB-DTPA (EOB) and extracellular agent (ECA; Gd-DTPA) contrast media. MATERIALS AND METHODS: Among 184 surgically proven HCCs in 169 patients who underwent a liver MRI with either EOB (n = 120) or ECA (n = 49), 55 HCCs were matched according to tumor size, Edmonson grade (major and worst), and gross type for each of the 2 contrast media. For the qualitative analysis, 2 board-certified radiologists independently reviewed arterial phase hyperenhancement, hypointensity on portal venous phase, hypointensity on delayed or transitional phase (DP/TP, 120-150 seconds), and capsule appearance. For the quantitative analysis, a third radiologist measured the signal intensity at each phase by placing the region of interest for tumor and normal liver parenchyma. The lesion-to-liver contrast (LLC) and lesion-to-liver contrast enhancement ratio (LLCER) were calculated. RESULTS: On qualitative analysis, hypointensity on DP/TP was seen more frequently with EOB (91% in reader 1, 89% in reader 2) than with ECA (73% in reader 1, 75% in reader 2; P = 0.026). Capsule appearance was seen less frequently with EOB (31% in reader 1, 44% in reader 2) than with ECA (73% in reader 1, 78% in reader 2; P < 0.001). On quantitative analysis, the LLC on arterial phase (AP) was better with ECA (P = 0.003), whereas LLC on DP was better with EOB (P < 0.001). The LLCER from precontrast to AP was higher with ECA (P = 0.022), whereas the LLCER from portal venous phase to DP was higher with EOB (P < 0.001). CONCLUSIONS: ECA-MRI revealed better LLC on AP and detection rate of capsule appearance than EOB-MRI. EOB-MRI showed superior LLC on TP.

Nafamostat mesilate negatively regulates the metastasis of triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) lacking of oestrogen receptor, progesterone receptor, and epidermal growth factor receptor type 2 is a highly malignant disease which results in a poor prognosis and rare treatment options. Despite the use of conventional chemotherapy for TNBC tumours, resistance and short duration responses limit the treatment efficacy. Therefore, a need exists to develop a new chemotherapy for TNBC. The aim of this study was to examine the anti-cancer effects of nafamostat mesilate (NM), a previously known serine protease inhibitor and highly safe drug on breast cancer cells. Here, we showed that NM significantly inhibits proliferation, migration, and invasion in MDA-MB231 cells, induces G2/M phase cell-cycle arrest, and inhibits the expression of cyclin-dependent kinase 1 (CDK1). Exposure of MDA-MB231 cells to NM also resulted in decreased transcription factor activities accompanied by the regulated phosphorylation of signalling molecules and a decrease in metalloproteinases, the principal modulators of the extracellular environment during cancer progression. Especially, inhibition of TGFß-stimulated Smad2 phosphorylation and subsequent metastasis-related gene expression, and downregulation of ERK activity may be pivotal mechanisms underlying inhibitory effects of NM on NM inhibits lung metastasis of breast cancer cells and growth of colonized tumours in mice. Taken together, our data revealed that NM inhibits cell growth and metastasis of TNBC cells and indicated that NM is a multi-targeted drug that could be an adjunct therapy for TNBC treatment.

Management of subcentimetre arterially enhancing and hepatobiliary hypointense lesions on gadoxetic acid-enhanced MRI in patients at risk for HCC.

OBJECTIVES: To investigate the significance of subcentimetre (≤1 cm) arterially enhancing and hepatobiliary hypointense lesions (SAELs) observed on gadoxetic acid-enhanced magnetic resonance imaging (MRI) of patients at risk of hepatocellular carcinoma (HCC). METHODS: A SAEL was defined as a subcentimetre hypervascular nodule exhibiting a hepatobiliary phase defect on gadoxetic acid-enhanced MRI. We included 52 SAELs from 46 patients in a HCC surveillance population. The HCC reference standard was pathologic confirmation or a nodule >1 cm with typical imaging features of HCC at follow-up imaging. The malignancy rate and HCC-favourable imaging findings of SAELs were evaluated. RESULTS: The malignancy rate among SAELs was 57.7% (30/52). At diagnosis, all SAELs that progressed to overt HCC were treatable with curative intention. Venous or late dynamic phase washout was more frequently observed with malignant SAELs than with benign SAELs (57.7% vs. 30.6%; P = 0.01). If SAELs exhibiting washout were considered as HCC, sensitivity, specificity, and positive predictive value was 83.3%, 50%, and 69.4%, respectively. CONCLUSION: Among patients at risk of HCC, SAELs on gadoxetic acid-enhanced MRI exhibited high malignant potential. However, close observation may be an appropriate strategy for isolated SAELs. A washout appearance may be helpful for predicting malignancy. KEY POINTS: • Gadoxetic acid-enhanced MRI provides hepatobiliary phase (HBP) images. • Screening frequently detects subcentimetre arterially enhancing and hepatobiliary hypointense lesions (SAELs). • A majority of SAELs progressed to overt HCC within 2 years. • A venous-phase washout appearance correlated significantly with malignancy in SAELs.

Curative Resection of Single Primary Hepatic Malignancy: Liver Imaging Reporting and Data System Category LR-M Portends a Worse Prognosis.

OBJECTIVE: The purpose of this study was to examine the associations between preoperative Liver Imaging Reporting and Data System (LI-RADS) categories and prognosis after curative resection of single hepatic malignancies in patients with chronic liver disease. MATERIALS AND METHODS: Between January 2008 and December 2010, 225 patients with chronic liver disease underwent resection of single hepatic malignant tumors (218 hepatocellular carcinomas, three cholangiocarcinomas, four biphenotypic carcinomas) after undergoing gadoxetic acid-enhanced MRI. Two radiologists retrospectively categorized the tumors into LI-RADS categories. Differences in disease-free survival duration between categories were analyzed by the Kaplan-Meier method with the log-rank test. RESULTS: Reviewer 1 categorized two (0.9%) patients as having LR-3, 53 (23.6%) LR-4, 159 (70.7%) LR-5, and 11 (4.9%) LR-M lesions. The corresponding numbers for reviewer 2 were six (2.7%) LR-3, 30 (13.3%) LR-4, 178 (79.1%) LR-5, and 11 (4.9%) LR-M. The 2-year cumulative recurrence or death rates were 15.1% for lesions categorized LR-3 or LR-4 by reviewer 1, 31.7% for LR-5, and 60% for LR-M. For lesions categorized by reviewer 2 the corresponding rates were 20.6% for LR-3 or LR-4, 29% for LR-5, and 54.5% for LR-M. Disease-free survival was significantly worse among patients with lesions categorized as LR-M than for lesions categorized as LR-3 or LR-4 or as LR-5 (p < 0.01 for both reviewers). Disease-free survival did not significantly differ between patients with LR-3 or LR-4 and those with LR-5 lesions (reviewer 1, p = 0.301; reviewer 2, p = 0.291). CONCLUSION: Patients with tumors preoperatively categorized as LR-M may have a worse prognosis than those with tumors categorized LR-3, LR-4, or LR-5 after curative resection of single hepatic malignancy.

Use of Imaging to Predict Complete Response of Colorectal Liver Metastases after Chemotherapy: MR Imaging versus CT Imaging.

Purpose To compare the diagnostic performances of contrast agent-enhanced computed tomography (CT) and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced liver magnetic resonance (MR) imaging (referred to as EOB MR imaging) in the evaluation of disappearing colorectal liver metastases (CRLMs) after chemotherapy. Materials and Methods The eight institutional review boards approved this retrospective study and waived the requirement for informed consent. On the basis of retrospective searches in eight hospitals, 87 patients with 393 CRLMs, each patient with one or more CRLM that later disappeared on contrast-enhanced CT scans after chemotherapy, and subsequently underwent surgery for the CRLMs, were enrolled. The anonymized imaging data and case report forms were sent to the central review system and independently reviewed by four radiologists. All anonymized data were randomly allocated into two groups (groups A and B), which were read by two independent readers. True absence of tumor was defined as pathologic absence of tumor for resected lesions and no in situ recurrence within 1 year after surgery for lesions left unresected at each 3-month follow-up contrast-enhanced CT. Positive predictive values for absence of tumor and for residual tumor on contrast-enhanced CT and EOB MR images were compared by using a generalized estimating equation. Results Among 393 CRLMs, the positive predictive value for absence of tumor on EOB MR images (78.0%; 95% confidence interval [CI]: 63.68%, 87.74%) was significantly higher than that on contrast-enhanced CT scans (35.2%; 95% CI: 25.11%, 46.79%; P < .001). The positive predictive value for residual tumor on CT scans (86.0%; 95% CI: 78.61%, 91.16%) was higher than that on EOB MR images (83.8%; 95% CI: 77.50%, 88.67%) without statistical significance (P = .330). Conclusion EOB MR imaging was superior to contrast-enhanced CT imaging for assessment of disappearing CRLMs after chemotherapy. © RSNA, 2017 Online supplemental material is available for this article.

Added value of smooth hypointense rim in the hepatobiliary phase of gadoxetic acid-enhanced MRI in identifying tumour capsule and diagnosing hepatocellular carcinoma.

OBJECTIVES: To examine the added value of considering smooth hypointense rim in the hepatobiliary phase (HBP) of gadoxetic acid-enhanced MRI as capsule appearance for diagnosing tumour capsules and hepatocellular carcinoma (HCC). METHODS: A total of 377 hepatic lesions (330 HCCs, 35 non-HCC malignancies and 12 benign) were included from 345 patients who underwent resection after MRI between January 2008 and December 2011. Two radiologists assessed the presence or absence of conventional capsule appearance and smooth hypointense rim in the HBP, and categorized each hepatic lesion according to the Liver Imaging Reporting and Data System. Difference in diagnostic performance was evaluated using the generalized estimating equation method. RESULTS: For identifying capsule, the sensitivity and accuracy of HBP hypointense rim were significantly higher than those of conventional capsule appearance (81.5 % vs. 57.8 % and 76.1 % vs. 59.4 %, respectively; P < 0.001). For diagnosing HCC, the sensitivity and accuracy of LR-5 or LR-5 V were significantly higher when the HBP hypointense rim was also considered capsule appearance (83 % vs. 72.7 % and 84.1 % vs. 75.1 %, respectively; P < 0.001), with the same specificity (91.5 %). CONCLUSIONS: Regarding smooth hypointense rim in the HBP as capsule appearance could improve the detection of tumour capsule and the diagnosis of HCC. KEY POINTS: • Identifying tumour capsule is important for diagnosis of hepatocellular carcinoma (HCC). • Gadoxetic acid-enhanced MRI provides hepatobiliary phase (HBP) images. • Smooth hypointense rim seen in HBP may represent tumour capsule. • Regarding smooth hypointense rim as capsule appearance may improve HCC diagnosis.

The accessory proteins REEP5 and REEP6 refine CXCR1-mediated cellular responses and lung cancer progression.

Some G-protein-coupled receptors have been reported to require accessory proteins with specificity for proper functional expression. In this study, we found that CXCR1 interacted with REEP5 and REEP6, but CXCR2 did not. Overexpression of REEP5 and REEP6 enhanced IL-8-stimulated cellular responses through CXCR1, whereas depletion of the proteins led to the downregulation of the responses. Although REEPs enhanced the expression of a subset of GPCRs, in the absence of REEP5 and REEP6, CXCR1 was expressed in the plasma membrane, but receptor internalization and intracellular clustering of ß-arrestin2 following IL-8 treatment were impaired, suggesting that REEP5 and REEP6 might be involved in the ligand-stimulated endocytosis of CXCR1 rather than membrane expression, which resulted in strong cellular responses. In A549 lung cancer cells, which endogenously express CXCR1, the depletion of REEP5 and REEP6 significantly reduced growth and invasion by downregulating IL-8-stimulated ERK phosphorylation, actin polymerization and the expression of genes related to metastasis. Furthermore, an in vivo xenograft model showed that proliferation and metastasis of A549 cells lacking REEP5 and REEP6 were markedly decreased compared to the control group. Thus, REEP5 and REEP6 could be novel regulators of G-protein-coupled receptor signaling whose functional mechanisms differ from other accessory proteins.