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 alphafetoprotein(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 theχ2 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.

Non-invasive evaluation of liver steatosis with imaging modalities:New techniques and applications

In the world,nonalcoholic fatty liver disease(NAFLD)accounts for majority of diffuse hepatic diseases.Notably,substantial liver fat accumulation can trigger and accelerate hepatic fibrosis,thus contributing to disease progression.Moreover,the presence of NAFLD not only puts adverse influences for liver but is also associated with an increased risk of type 2 diabetes and cardiovascular diseases.Therefore,early detection and quantified measurement of hepatic fat content are of great importance.Liver biopsy is currently the most accurate method for the evaluation of hepatic steatosis.However,liver biopsy has several limitations,namely,its invasiveness,sampling error,high cost and moderate intraobserver and interobserver reproducibility.Recently,various quantitative imaging techniques have been developed for the diagnosis and quantified measurement of hepatic fat content,including ultrasound-or magnetic resonancebased methods.These quantitative imaging techniques can provide objective continuous metrics associated with liver fat content and be recorded for comparison when patients receive check-ups to evaluate changes in liver fat content,which is useful for longitudinal follow-up.In this review,we introduce several imaging techniques and describe their diagnostic performance for the diagnosis and quantified measurement of hepatic fat content.

Contrast-enhanced ultrasound manifestations of synchronous combined hepatocellular-cholangiocarcinoma and hepatocellular carcinoma:A case report

BACKGROUND Synchronous combined hepatocellular-cholangiocarcinoma(CHC)and hepatocellular carcinoma(HCC)is very rare,with few literature reports and poor clinical outcomes associated with the disorder.Surgical resection is the main treatment,which makes the preoperative diagnosis very important.However,due to imaging manifestations overlapping with HCC,diagnosis of this type of synchronous cancer is challenging and it tends to be misdiagnosed as multiple HCC.Herein,we report the contrast-enhanced ultrasound(CEUS)manifestations of a case of synchronous CHC and HCC,aiming at adding to the understanding of this disease.CEUS displayed exquisite vascularity and tissue perfusion in real time with good spatial and temporal resolution and more accurately reflect tumor washin and washout times than contrast-enhanced computed tomography(CT)in this case.CASE SUMMARY The patient was a 69-year-old female with a 20-year history of chronic hepatitis B.Due to months of epigastric pain and anorexia,she reffered to our hospital for treatment.Five days before hospitalization,abdominal magnetic resonance imaging performed at another hospital detected a space-occupying lesion in the liver.After her hospitalization,laboratory tests showed elevated alpha-fetoprotein and carbohydrate antigen 19-9 level.Two suspicious liver lesions located in S4 and S6,respectively,were identified in a cirrhotic background by abdominal contrast-enhanced CT(CECT).Furthermore,the lesion in S4 and S6 were detected by CEUS and assigned to CEUS LI-RADS 5 and M categories,respectively.The patient underwent tumor radical resections.Post-operative pathology confirmed the S4 and S6 lesions to be HCC and CHC,respectively.A newly-found suspicious liver nodule with potential malignancy was detected in liver S1 by both CEUS and CECT 7 mo after operation.CONCLUSION The CEUS characteristics of CHC and HCC are different.CEUS features in combination with clinical information could help in effective diagnosis,clinical decision-making and better prognosis.

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 LRM 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.

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.

Cost-effectiveness analysis of malaria rapid diagnostic tests:a systematic review

Background:Rapid diagnostic tests(RDT)can effectively manage malaria cases and reduce excess costs brought by misdiagnosis.However,few studies have evaluated the economic value of this technology.The purpose of this study is to systematically review the economic value of RDT in malaria diagnosis.Main text:A detailed search strategy was developed to identify published economic evaluations that provide evidence regarding the cost-effectiveness of malaria RDT.Electronic databases including MEDLINE,EMBASE,Biosis Previews,Web of Science and Cochrane Library were searched from Jan 2007 to July 2018.Two researchers screened studies independently based on pre-specified inclusion and exclusion criteria.The Consolidated Health Economic Evaluation Reporting Standards(CHEERS)checklist was applied to evaluate the quality of the studies.Then cost and effectiveness data were extracted and summarized in a narrative way.Fifteen economic evaluations of RDT compared to other diagnostic methods were identified.The overall quality of studies varied greatly but most of them were scored to be of high or moderate quality.Ten of the fifteen studies reported that RDT was likely to be a cost-effective approach compared to its comparisons,but the results could be influenced by the alternatives,study perspectives,malaria prevalence,and the types of RDT.Conclusions:Based on available evidence,RDT had the potential to be more cost-effective than either microscopy or presumptive diagnosis.Further research is also required to draw a more robust conclusion.

Cost-effectiveness analysis of malaria rapid diagnostic test in the elimination setting

Background:As more and more countries approaching the goal of malaria elimination,malaria rapid diagnostic tests(RDT)was recomendated to be a diagnostic strategy to achieve and maintain the statute of malaria free,as it’s less requirments on equipment and experitise than microscopic examination.But there are very few economic evaluations to confirm whether RDT was cost-effective in the setting of malaria elimination.This research aimed to offer evidence for helping decision making on malaria diagnosis strategy.Methods:A cost-effectiveness analysis was conducted to compare RDT with microscopy examination for malaria diagnosis,by using a decision tree model.There were three strategies of malaria diagnostic testing evaluated in the model,1)microscopy,2)RDT,3)RDT followed by microscopy.The effect indicator was defined as the number of malaria cases treated appropriately.Based on the joint perspective of health sector and patient,costs data were collected from hospital information systems,key informant interviews,and patient surveys.Data collection was conducted in Jiangsu from September 2018 to January 2019.Epidemiological data were obtained from local malaria surveillance reports.A hypothetical cohort of 300000 febrile patients were simulated to calculate the total cost and effect of each strategy.One-way,two-way,and probabilistic sensitivity analysis were performed to test the robustness of the result.Results:The results showed that RDT strategy was the most effective(245 cases)but also the most costly(United States Dollar[USD]4.47 million)compared to using microscopy alone(238 cases,USD 3.63 million),and RDT followed by microscopy(221 cases,USD 2.75 million).There was no strategy dominated.One-way sensitivity analysis reflected that the result was sensitive to the change in labor cost and two-way sensitivity analysis indicated that the result was not sensitive to the proportion of falciparum malaria.The result of Monte Carlo simulation showed that RDT strategy had higher effects and higher cost than other strategies with a high probability.Conclusions:Compared to microscopy and RDT followed by microscopy,RDT strategy had higher effects and higher cost in the setting of malaria elimination.

Evaluating the implementation of rapid diagnostic tests in a malaria elimination setting

Background It was recommended that malaria rapid diagnostic tests(RDTs)should be available in all epidemiological situations.But evidence was limited on the implementation of RDTs and its effectiveness in malaria elimination settings.This study examined the implementation of RDTs and how it affected the diagnosis of imported malaria patients in Jiangsu Province,China.Methods To scale up RDTs,this study developed an intervention package with four major elements covering the supply of RDT test,the training on RDTs,the monitoring and management of RDT use,and the advocacy of RDTs.By using a pretest-posttest control group design,we implemented the interventions in 4 cities in Jiangsu Province with the rest nine cities as controlled areas,from January 2017 to January 2018.Difference-in-Difference approach was used to evaluate the impact of the scale-up of RDTs on the identification of malaria cases.Three binary outcome measures were included to indicate delayed malaria diagnosis,malaria cases with confirmed malaria diagnosis at township-level institutions,and severe malaria cases,respectively.Linear probability regression was performed with time and group fixed effects and the interaction term between time and group.Results Intervention areas received sufficient RDT test supply,regular professional training programs,monthly tracking and management of RDT supply and use,and health education to targeted population.The implementation of interventions was associated with 10.8%(P=0.021)fewer patients with delayed diagnosis.But intervention areas did not see a higher likelihood of having confirmed diagnosis from township-level institutions(coefficient=-0.038,P=0.185)or reduced severe malaria cases(coef.=0.040,P=0.592).Conclusions The comprehensive package of RDT implementation in this study is promising in scaling up RDT use and improving access to care among malaria patients,especially in malaria elimination settings.