Diagnostic Accuracy of CEUS LI-RADS for the Characterization of Liver Nodules 20 mm or Smaller in Patients at Risk for Hepatocellular Carcinoma.

Background American College of Radiology contrast agent-enhanced US Liver Imaging Reporting and Data System (CEUS LI-RADS) was developed to improve the accuracy of hepatocellular carcinoma (HCC) diagnosis at contrast agent-enhanced US. However, to the knowledge of the authors, the diagnostic accuracy of the system in characterization of liver nodules 20 mm or smaller has not been fully evaluated. Purpose To evaluate the diagnostic accuracy of CEUS LI-RADS in diagnosing HCC in liver nodules 20 mm or smaller in patients at risk for HCC. Materials and Methods Between January 2015 and February 2018, consecutive patients at risk for HCC presenting with untreated liver nodules 20 mm or less were enrolled in this retrospective double-reader study. Each nodule was categorized according to the CEUS LI-RADS and World Federation for Ultrasound in Medicine and Biology (WFUMB)-European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) criteria. Diagnostic performance of CEUS LI-RADS and WFUMB-EFSUMB characterization was evaluated by using tissue histologic analysis, multiphase contrast-enhanced CT and MRI, and imaging follow-up as reference standard and compared by using McNemar test. Results The study included 175 nodules (mean diameter, 16.1 mm ± 3.4) in 172 patients (mean age, 51.8 years ± 10.6; 136 men). The sensitivity of CEUS LR-5 versus WFUMB-EFSUMB criteria in diagnosing HCC was 73.3% (95% confidence interval [CI]: 63.8%, 81.5%) versus 88.6% (95% CI: 80.9%, 94%), respectively (P < .001). The specificity of CEUS LR-5 versus WFUMB-EFSUMB criteria was 97.1% (95% CI: 90.1%, 99.7%) versus 87.1% (95% CI: 77%, 94%), respectively (P = .02). No malignant lesions were found in CEUS LR-1 and LR-2 categories. Only two nodules (of 41; 5%, both HCC) were malignant in CEUS LR-3 category. The incidences of HCC in CEUS LR-4, LR-5, and LR-M were 48% (11 of 23), 98% (77 of 79), and 75% (15 of 20), respectively. Two of 175 (1.1%) histologic analysis-confirmed intrahepatic cholangiocarcinomas were categorized as CEUS LR-M by CEUS LI-RADS and misdiagnosed as HCC by WFUMB-EFSUMB criteria. Conclusion The contrast-enhanced US Liver Imaging Reporting and Data System (CEUS LI-RADS) algorithm was an effective tool for characterization of small (≤20 mm) liver nodules in patients at risk for hepatocellular carcinoma (HCC). Compared with World Federation for Ultrasound in Medicine and Biology-European Federation of Societies for Ultrasound in Medicine and Biology criteria, CEUS LR-5 demonstrated higher specificity for diagnosing small HCCs with lower sensitivity. Published under a CC BY 4.0 license. See also the editorial by Crocetti in this issue.

[Application of Multimodal Transcranial Ultrasound in SD Rats of Cerebral Ischemic Model at Super Early Stage].

OBJECTIVE: To determine the value of applying multimodal ultrasound (mUS) in SD rats of cerebral ischemic model at super early stage (5-15 min after modeling). METHODS: Fifteen focal cerebral ischemic models were established in SD rats with thinning skulls using the suture method. Gray-scale ultrasound, contrast-enhanced ultrasound, and enhanced color Doppler (CECDUS) were performed before and immediately after the modeling to observe the location of the in-cranial suture, perfusion of the right hemisphere, and color flow signal of the middle cerebral artery and the anterior cerebral artery, respectively.A modified neurological deficit score (mNSS) and 2, 3, 5-triphenyltetrazolium chloride (TTC) stains were obtained three hours later to confirm the successful modeling as the gold standard. The positive rate detected by mUS was compared with the gold standard using McNemar tests. RESULTS: One rat died and 14 rats completed the experiment.mUS imaging detected 71% (10/14) positive signals, no significant difference compared with the gold standard (64%, 9/14) ( P>0.05). A hyperechoic double-line at the bottom of the right brain and focal hypoperfused areas in the right hemisphere were observed by gray scale ultrasound and contrast-enhanced ultrasound in the successfully modeled rats, respectively. The CECDUS found no blood flow in the anterior and middle cerebral arteries. Time intensity curve (TIC) analyses indicated significant changes in peak intensity (PI), area under the curve (AUC), wash in slope (WIS), and time to peak (TTP) after successful modeling. CONCLUSION: Multimodal ultrasound can assess modeling success quickly and accurately immediately after the establishment of ischemic model of SD rats.

Contrast-enhanced ultrasound of a traumatic neuroma of the extrahepatic bile duct: A case report and review of literature.

BACKGROUND: Traumatic neuromas result from nerve injury after trauma or surgery but rarely occur in the bile duct. However, it is challenging to diagnose traumatic neuromas correctly preoperatively. Although some previous reports have described the imaging features of traumatic neuroma in the bile duct, no features of traumatic neuromas in the bile duct have been identified by using contrast-enhanced ultrasound (CEUS) imaging before. CASE SUMMARY: A 55-year-old male patient presented to our hospital with a 3-mo history of abdominal distension and anorexia and history of cholecystectomy 4 years ago. Grayscale ultrasound demonstrated mild to moderate intrahepatic bile duct dilatation. Meanwhile, a hyperechoic nodule was found in the upper extrahepatic bile duct. The lesion approximately 0.8 cm × 0.6 cm with a regular shape and clear margins. The nodule of the bile duct showed slight hyperenhancement in the arterial phase and isoenhancement in the venous phase on CEUS. Laboratory tests showed that alanine aminotransferase and aspartate aminotransferase were increased significantly, while the tumor marker carbohydrate antigen 19-9 was increased slightly. Then, hilar bile duct resection and end-to-end bile ductal anastomosis were performed. The histological examination revealed traumatic neuroma of the extrahepatic bile duct. The patient had an uneventful recovery after surgery. CONCLUSION: The current report will help enhance the current knowledge regarding identifying traumatic neuromas by CEUS imaging and review the related literature.

Cavernous hemangioma of an intrapancreatic accessory spleen mimicking a pancreatic tumor: A case report.

BACKGROUND: Intrapancreatic accessory spleen (IPAS) is an uncommon condition, with the majority of cases presenting as solid lesions. Thus, this condition is frequently misdiagnosed as pancreatic solid neoplasm. Moreover, splenic cavernous hemangioma is a rare disorder, whereas lesions with a cystic appearance arising from IPAS have not been reported. CASE SUMMARY: Herein, we present a case involving a 32-year-old male who had a complex cystic lesion in the tail of the pancreas revealed by conventional ultrasound. The lesion was misdiagnosed as a pancreatic cystadenoma because of its confusing anatomic location, as well as due to its peripheral nodular and internal septal enhancement patterns on contrast-enhanced ultrasound. After multidisciplinary discussion, the patient finally underwent laparoscopic pancreatic body and tail resections. Postoperative pathology demonstrated the lesion to be a cavernous hemangioma arising from the IPAS. CONCLUSION: Cavernous hemangioma in the intrapancreatic accessory spleen may mimic pancreatic cystadenoma, which is a condition with the potential to be malignant. Imaging follow-ups or surgical interventions may be helpful for the exclusion of malignant risks in complicated cystic lesions, especially those with parietal and septal enhancements.

Differentiating malignant and benign focal liver lesions in children using CEUS LI-RADS combined with serum alpha-fetoprotein.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) can be used to diagnose focal liver lesions (FLLs) in children. The America College of Radiology developed the CEUS liver imaging reporting and data system (LI-RADS) for standardizing CEUS diagnosis of FLLs in adult patients. Until now, no similar consensus or guidelines have existed for pediatric patients to improve imaging interpretation as adults. AIM: To evaluate the performance of CEUS LI-RADS combined with alpha-fetoprotein (AFP) in differentiating benign and malignant FLLs in pediatric patients. METHODS: Between January 2011 and January 2021, patients ≤ 18 years old who underwent CEUS for FLLs were retrospectively evaluated. The following criteria for diagnosing malignancy were proposed: Criterion I considered LR-4, LR-5, or LR-M lesions as malignancies; criterion II regarded LR-4, LR-5 or LR-M lesions with simultaneously elevated AFP (≥ 20 ng/mL) as malignancies; criterion III took LR-4 Lesions with elevated AFP or LR-5 or LR-M lesions as malignancies. The sensitivity, specificity, accuracy and area under the receiver operating characteristic curve (AUC) were calculated to determine the diagnostic value of the aforementioned criteria. RESULTS: The study included 63 nodules in 60 patients (mean age, 11.0 ± 5.2 years; 26 male). There were no statistically significant differences between the specificity, accuracy, or AUC of criterion II and criterion III (95.1% vs 80.5%, 84.1% vs 87.3%, and 0.794 vs 0.902; all P > 0.017). Notably, criterion III showed a higher diagnostic sensitivity than criterion II (100% vs 63.6%; P < 0.017). However, both the specificity and accuracy of criterion I was inferior to those of criterion II and criterion III (all P < 0.017). For pediatric patients more than 5 years old, the performance of the three criteria was overall similar when patients were subcategorized by age when compared to all patients in aggregate. CONCLUSION: CEUS LI-RADS combined with AFP may be a powerful diagnostic tool in pediatric patients. LR-4 with elevated AFP, LR-5 or LR-M lesions is highly suggestive of malignant tumors.

Contrast-enhanced ultrasound in association with serum biomarkers for differentiating combined hepatocellular-cholangiocarcinoma from hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

BACKGROUND: Combined hepatocellular-cholangiocarcinoma (CHC) is a rare type of primary liver cancer. Due to its complex histopathological characteristics, the imaging features of CHC can overlap with those of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). AIM: To investigate the possibility and efficacy of differentiating CHC from HCC and ICC by using contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) and tumor biomarkers. METHODS: Between January 2016 and December 2019, patients with histologically confirmed CHC, ICC and HCC with chronic liver disease were enrolled. The diagnostic formula for CHC was as follows: (1) LR-5 or LR-M with elevated alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9); (2) LR-M with elevated AFP and normal CA19-9; or (3) LR-5 with elevated CA19-9 and normal AFP. The sensitivity, specificity, accuracy and area under the receiver operating characteristic curve were calculated to determine the diagnostic value of the criteria. RESULTS: After propensity score matching, 134 patients (mean age of 51.4 ± 9.4 years, 108 men) were enrolled, including 35 CHC, 29 ICC and 70 HCC patients. Based on CEUS LI-RADS classification, 74.3% (26/35) and 25.7% (9/35) of CHC lesions were assessed as LR-M and LR-5, respectively. The rates of elevated AFP and CA19-9 in CHC patients were 51.4% and 11.4%, respectively, and simultaneous elevations of AFP and CA19-9 were found in 8.6% (3/35) of CHC patients. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and area under the receiver operating characteristic curve of the aforementioned diagnostic criteria for discriminating CHC from HCC and ICC were 40.0%, 89.9%, 58.3%, 80.9%, 76.9% and 0.649, respectively. When considering the reported prevalence of CHC (0.4%-14.2%), the positive predictive value and NPV were revised to 1.6%-39.6% and 90.1%-99.7%, respectively. CONCLUSION: CHCs are more likely to be classified as LR-M than LR-5 by CEUS LI-RADS. The combination of the CEUS LI-RADS classification with serum tumor markers shows high specificity but low sensitivity for the diagnosis of CHC. Moreover, CHC could be confidently excluded with high NPV.

Can contrast enhanced ultrasound differentiate intrahepatic cholangiocarcinoma from hepatocellular carcinoma?

BACKGROUND: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) differ in treatment and prognosis, warranting an effective differential diagnosis between them. The LR-M category in the contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS) was set up for lesions that are malignant but not specific to HCC. However, a substantial number of HCC cases in this category elevated the diagnostic challenge. AIM: To investigate the possibility and efficacy of differentiating ICC from HCC classified in the LR-M category according to the CEUS LI-RADS. METHODS: Patients with complete CEUS records together with pathologically confirmed ICC and LR-M HCC (HCC classified in the CEUS LI-RADS LR-M category) between January 2015 and October 2018 were included in this retrospective study. Each ICC was assigned a category as per the CEUS LI-RADS. The enhancement pattern, washout timing, and washout degree between the ICC and LR-M HCC were compared using the χ 2 test. Logistic regression analysis was used for prediction of ICC. Receiver operating characteristic (ROC) curve analysis was used to investigate the possibility of LR-M criteria and serum tumor markers in differentiating ICC from LR-M HCC. RESULTS: A total of 228 nodules (99 ICCs and 129 LR-M HCCs) in 228 patients were included. The mean sizes of ICC and LR-M HCC were 6.3 ± 2.8 cm and 5.5 ± 3.5 cm, respectively (P = 0.03). Peripheral rim-like arterial phase hyperenhancement (APHE) was detected in 50.5% (50/99) of ICCs vs 16.3% (21/129) of LR-M HCCs (P < 0.001). Early washout was found in 93.4% (93/99) of ICCs vs 96.1% (124/129) of LR-M HCCs (P > 0.05). Marked washout was observed in 23.2% (23/99) of ICCs and 7.8% (10/129) of LR-M HCCs (P = 0.002), while this feature did not show up alone either in ICC or LR-M HCC. Homogeneous hyperenhancement was detected in 15.2% (15/99) of ICCs and 37.2% (48/129) of LR-M HCCs (P < 0.001). The logistic regression showed that rim APHE, carbohydrate antigen 19-9 (CA 19-9), and alpha fetoprotein (AFP) had significant correlations with ICC (r = 1.251, 3.074, and -2.767, respectively; P < 0.01). Rim APHE presented the best enhancement pattern for diagnosing ICC, with an area under the ROC curve (AUC) of 0.70, sensitivity of 70.4%, and specificity of 68.8%. When rim hyperenhancement was coupled with elevated CA 19-9 and normal AFP, the AUC and sensitivity improved to 0.82 and 100%, respectively, with specificity decreasing to 63.9%. CONCLUSION: Rim APHE is a key predictor for differentiating ICC from LR-M HCC. Rim APHE plus elevated CA 19-9 and normal AFP is a strong predictor of ICC rather than LR-M HCC. Early washout and marked washout have limited value for the differentiation between the two entities.

A novel model for predicting posthepatectomy liver failure in patients with hepatocellular carcinoma.

Posthepatectomy liver failure (PHLF) is the most leading cause of mortality following hepatectomy in patients with hepatocellular carcinoma (HCC). Platelet count was reported to be a simple but useful indicator of liver cirrhosis and function of spleen. Spleen stiffness (SS) was used to evaluate the morphological change of spleen and was reported to be related to liver cirrhosis and portal hypertension. However, the predictive value of platelet to spleen stiffness ratio (PSR) on PHLF remains unknown. A retrospective study was performed to analyze 158 patients with HCC following hepatectomy from August 2015 to February 2016. Univariate and multivariate analyses were performed to evaluate the value of each risk factor for predicting PHLF. The predictive efficiency of the risk factors was evaluated by receiver operating characteristic (ROC) curve. PHLF occured in 23 (14.6%) patients. PSR (P<0.001, odds ratio (OR) = 0.622, 95% confidence interval (CI) 0.493~0.784), hepatic inflow occlusion (HIO) (P = 0.003, OR = 1.044, 95% CI 1.015~1.075) and major hepatectomy (P = 0.019, OR = 5.967, 95% CI 1.346~26.443) were demonstrated to be the independent predictive factors for development of PHLF in a multivariate analysis. Results of the present study suggested PSR is a novel and non-invasive model for predicting PHLF in patients with HCC.

Hepatic Venous Outflow Stenosis After Auxiliary Left Hemiliver Transplantation Diagnosed by Ultrasonic Shear Wave Elastography Combined With Doppler Ultrasonography.

Hepatic vein stenosis after liver transplantation is a relatively rare complication that could even result in graft loss. However, it is difficult to arrive at a definite diagnosis at the early stage of postoperation, and there are few researches on ultrasonic shear wave elastography in the diagnosis of hepatic vein stenosis. We report the case of an 11-year-old male patient with cirrhosis due to hepatolenticular degeneration who received an auxiliary left hemiliver graft from his uncle. Massive ascites developed in 4 days after the operation. Stenosis was suspected at the site of anastomosis by Doppler ultrasonography when elevating the velocity of the left hepatic vein. Meanwhile, increased stiffness of the graft was revealed by ultrasonic shear wave elastography. The stenosis was confirmed by subsequent digital subtraction angiography. Ascites decreased gradually after the stent implantation. Our case indicates that ultrasonic shear wave elastography combined with Doppler ultrasonography is a promising method for noninvasive diagnosis of hepatic venous outflow stenosis following liver transplantation.

Impact of tumor size and cirrhotic background for differentiating HCC and ICC with CEUS: does it matter for patients undergoing hepatectomy?

OBJECTIVES: The aim of this study was to investigate the role of contrast-enhanced ultrasound (CEUS) in differentiating hepatocellular carcinoma (HCC) vs. intrahepatic cholangiocarcinoma (ICC) and primary liver cancer vs. benign liver lesions for surgical decision making. METHODS: Data from 328 patients (296 primary liver cancer patients: 232 HCC and 64 ICC patients and 32 benign hepatic lesion patients) who underwent hepatectomy at our center were retrospectively collected from 2010 to 2015. Conventional ultrasound (US) and CEUS were performed for all patients before hepatectomy. Enhancement patterns in CEUS were classified and compared for HCC vs. ICC and for primary liver cancer vs. benign lesions. RESULTS: Primary liver cancer and hepatic benign lesions could be distinguished by CEUS in different phases. The most obvious differences were in the portal and delayed phases, in which benign lesions could still show hyperenhancement (46.9% vs. 0.0% and p < 0.001 in the portal phase; 43.7% vs. 0.0% and p < 0.001 in the delayed phase). For differentiating HCC and ICC, our results revealed that HCC and ICC displayed different enhancement patterns in the arterial phase (p < 0.001) and the portal phase (p < 0.001). In the subgroup analyses, both HCC and ICC showed a high rate of homogeneous hyperenhancement during the arterial phase when tumors were ≤5 cm (87.2% vs. 64.0% and p = 0.008) or the Ishak score was ≥5 (75.8% vs. 42.9% and p = 0.023), although there was statistical difference. However, during the portal phase, ICC > 5 cm showed significantly more frequent hypoenhancement (92.3% vs. 54.5% and p < 0.001) and less isoenhancement (7.7% vs. 45.5% and p < 0.001) than HCC; additionally, during the portal phase, there was no statistical difference in the enhancement patterns of ICC with different hepatic backgrounds. CONCLUSIONS: Tumor size and hepatic background should be taken into consideration when distinguishing HCC and ICC before surgery. However, CEUS is a helpful tool for differentiating malignant and benign hepatic lesions. For patients who require surgical treatment, CEUS may help with surgical decision making.

Liver Stiffness and Serum Alpha-Fetoprotein in Discriminating Small Hepatocellular Carcinoma from Cirrhotic Nodule.

AIM: This study aimed to investigate the clinical significance of liver stiffness and serum alpha-fetoprotein (AFP) in differentiating small hepatocellular carcinoma (HCC) from cirrhotic nodule. METHODS: A total of 95 chronic hepatitis B patients who were diagnosed with small HCC (n = 53) or cirrhotic nodule (n = 42) underwent ultrasound elastography point quantification (ElastPQ) examinations on lesion and background liver. Three stiffness parameters, lesion stiffness value (SV), absolute stiffness difference (ASD) of lesion and background liver, stiffness ratio (lesion/background liver) (SR), and serum AFP were retrospectively analyzed. Then, the capabilities of lesion SV, ASD, SR, AFP, and the combination of each individual stiffness parameter with AFP were evaluated in differentiating small HCC from cirrhotic nodule. RESULTS: Significantly higher lesion SV, ASD, SR, and serum AFP were observed in small HCC compared with cirrhotic nodule patients (all P ≤ 0.0001). By comparing the stiffness parameters on the patients with AFP greater than 20 ng/mL and AFP of 20 ng/mL or smaller, a higher lesion SV and comparable ASD and SR were found in the small HCC patients. The diagnostic accuracy of lesion SV, ASD, SR, and AFP in the discrimination of small HCC and cirrhotic nodule was 0.731, 0.825, 0.820, and 0.789, respectively. Moreover, the improved sensitivity was observed in the combination of liver stiffness with AFP (83%, 100%, and 92% for lesion SV/AFP, ASD/AFP, and SR/AFP, respectively). CONCLUSIONS: This study illustrated that the combination of liver stiffness and serum AFP has considerable clinical value in detecting suspicious small HCC from cirrhotic nodule.