Application Value Of Contrastenhanced Ultrasound Imaging Report And Data System In Hepatocellular Carcinoma Diagnosis And TCM Syndrome Differentiation

Background and ObjectiveHepatocellular carcinoma is one of the most common malignant tumors in the world,and its morbidity and mortality are still increasing year by year.The prognosis of HCC patients depends on the stage of the tumor,and curative therapy is only appropriate for patients with early detection.Therefore,early diagnosis is very important for improving the prognosis and survival of HCC patients,and imaging examination is an important method for early diagnosis.American Radiological Society’s contrast-enhanced ultrasound liver imaging reporting and data system(LI-RADS)provides the qualitative diagnosis for hepatocellular carcinoma(HCC).LI-RADS proposes a separate category that refers to possible or confirmed malignant nodules,but not HCC specific.There are many differences between.HCC and non-HCC,such as differences in biological behavior,prognosis and treatment options,and it is of great clinical significance to identify HCC in LR-M nodules.The auxiliary signs of HCC proposed in previous studies are helpful for the differentiation of HCC from non-HCC,but they are not included in LI-RADS.Therefore,this study focused on the typical Contrast-Enhanced Ultrasonography(CEUS)features of LR-M(CEUS LI-RADSv2017)nodules were analyzed retrospectively,and the value of CEUS additional features in the differential diagnosis of HCC and non-HCC was emphasized.TCM clinical diagnosis and treatment of HCC plays an important role in the prognosis and survival of patients,TCM syndrome differentiation and classification of HCC mainly rely on clinical symptoms,with relatively few objectifying indicators,while imaging examinations can provide more objectifying information for the disease.Therefore,by observing the CEUS characteristics of HCC under different TCM syndrome types under high-frequency ultrasound,the correlation between TCM syndrome types of HCC and the imaging characteristics of CEUS LI-RADS can provide new ideas and objectified basis for TCM dialectical HCC,thus improving the accuracy of clinical TCM syndrome differentiation,further enriching and improving TCM syndrome differentiation system of HCC,and helping clinical TCM physicians to make more accurate treatment plans.Method1.The value of contrast-enhanced ultrasonography(CEUS)in the differential diagnosis of LR-M nodules.Patients with focal hepatic lesions who underwent CEUS examinations at the First Affiliated Hospital of Guangzhou University of traditional Chinese medicine and the first affiliated hospital of Sun Yat-sen University between October 2015 and September 2021.A total of 206 patients with LR-M nodules diagnosed according to CEUS LI-RADS v2017 criteria were enrolled.Analyze the ultrasound images:enhancement level in the arterial phase(classified as hyper-or isoenhancement);enhancement pattern in the arterial phase(classified as homogeneous/inhomogeneous or rim/peripheral discontinuous globular);onset of washout(classification as early or late,and the threshold is 60s);degree of washout(classified as mild or marked).the patients were divided into HCC group and non-HCC group according to the pathological results.The clinical features,main signs and auxiliary signs of CEUS were further compared between the HCC group and the non-HCC group.Independent predictors of HCC were identified by a stepwise selective multivariate regression analysis.With histopathological diagnosis as the gold standard,diagnostic tests with statistically significant CEUS signs will be performed.The accuracy,sensitivity,specificity,positive predictive value(PPV)and negative predictive value(NPV)of different CEUS signs in the diagnosis of HCC were calculated,the receiver operating characteristic(ROC)curve was drawn and the area under the curve(AUC)was calculated.To further explore the diagnostic value of additional signs for HCC,2 diagnostic criteria were self-defined based on the above signs.Criterion Ⅰ:PPV in the above statistics was close to 95.0%for any additional signs of CEUS.Criterion Ⅱ:predictors of HCC in multivariate Logistic regression analysis.Standard Ⅲ:non-marginal annular arterial phase with high enhancement(APHE),early(<60 s)clearance and no clearance within 5 min;Standard Ⅳ:non-marginal annular arterial phase with late(≥45 s)and mild clearance.The LR-M nodules were then re-evaluated according to the above criteria to compare the diagnostic performance of the four criteria.The sensitivity,specificity,PPV,NPV and AUC of the four criteria were calculated.2.Correlation analysis between CEUS LI-RADS sign of hepatocellular carcinoma and Traditional Chinese medicine certificate type.From October 2015 to September 2021 in the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine and the First Affiliated Hospital of Sun Yat-sen University,patients were diagnosed as hepatocellular carcinoma,and a total of 135 patients were included.Patient clinical data(name,gender,age,course of disease,etc.),contrast findings(CEUS)and TCM patterns were collected.Comparison of TCM syndrome type and ultrasound contrast examination(CEUS)signs(including arterial phase enhancement level,enhanced morphology,clearance time,disordered vessels,peritumoral annular arteries,intratumoral veins,tumor enhancement boundaries,and intratumoral zone boundaries),and then analysis of statistically significant characteristics.Results1.The value of contrast-enhanced ultrasonography(CEUS)in the differential diagnosis of LR-M nodules.1.1 Of the 206 LR-M nodule results,166(80.6%)were ultimately diagnosed as HCC and 40(19.4%)as non-HCC.Among the non-HCC,there were 24 Intrahepatic Cholangiocarcinoma(ICC),5 Combined Hepatocellular-Cholangiocarcinoma(CHC)and 4 metastatic liver cancer and 7 benign lesions(including 2 atypical hyperplastic nodules,2 hamartoma,1 cholangioadenoma,1 intraductal papilloma,1 hepatic abscess).1.2 Comparison of characteristics of HCC and non-HCC patients:There is a higher proportion of male patients among the clinical characteristics of HCC patients(86.7%vs.72.5%),a higher proportion of nodules with a diameter of 3.1-5.0 cm(39.8%vs.17.5%),a greater proportion of AFP(>35 U/mL)(62.6%vs.35.1%;P=0.004)and CA19-9 elevations(>20 μg/l)(62.2%vs.9.3%).The following CEUS signs were more frequent in the HCC group compared with the non-HCC group:homogeneous/heterogeneous enhancement in arterial phase(95.2%vs 50.5%),mild clearance(71.7%vs 35.0%),intratumoral disorganized vessels(38.0%vs 10.0%),presence of circumferential circumferential arteries(34.3%vs 2.5%),clear margin of tumor enhancement(69.3%vs 47.5%),and clear margin of intratumoral unenhanced areas(34.3%vs 15.0%).All the above differences were statistically significant(P<0.05).1.3 The efficacy of a single CEUS sign in the diagnosis of HCC in LR-M nodules.Intratumoral disordered vessels(sensitivity 38.0%,specificity 90.0%,PPV 94.0%and NPV 25.9%)and peripheral circular vessels(sensitivity 34.3%,specificity 97.5%,PPV 98.3%and NPV 26.4%)had the highest PPV for the diagnosis of HCC.Thus,standard I was defined as the presence of intratumoral disorganized vessels and/or peripheral circumferential vessels.1.4 The main signs of CEUS and the additional signs and the variables with P<0.1 were included in the multivariate Logistic regression analysis,which showed that homogeneous/heterogeneous enhancement(odds ratio=11.76,P<0.001)was the only independent predictor for the diagnosis of HCC.Thus,Standard Ⅱ is defined as the presence of homogeneous/heterogeneous enhancement.1.5 The results of ROC showed that the sensitivity of standard Ⅰ,Ⅱ,Ⅲ and Ⅳ was 48.2%,97.0%,66.3%and 41.6%respectively,the specificity was 90.0%,47.5%,67.5%and 80.0%respectively,PPV and NPV were 95.2%,88.5%,89.4%,89.6%and 29.5%,79.2%,32.5%,24.8%,respectively.AUC of the 4 standard was 0.67,0.72,0.66,0.61 respectively.The NPV and specificity of standard I were the highest among the 4 standard.%).The above differences were statistically significant(P<0.05).206 LR-M nodules were reclassified according to standard I,84 were classified as LR-5,and 122 maintained the LR-M classification.Of the 84 nodules reclassified as LR-5 according to standard I,80 were HCC and 4 were non-HCC(2 ICC,2 CHCC-CC).2.Correlation analysis between CEUS LI-RADS sign of hepatocellular carcinoma and Traditional Chinese medicine certificate type.2.1 A total of 135 HCC patients were included in this study,including 22 female(16.3%)and 113 male(83.7%)patients with a male to female ratio of 5.14:1.Patients covered 23～80 years,with an overall mean age of 56.74 years.2.2 Analysis of TCM syndrome type distribution in hepatocellular carcinoma patientsIn this study,135 patients with hepatocellular carcinoma had the maximum number of 45(33.33%),followed by 36(26.67%),30(22.22%),and 24 with qi stagnation and blood stasis(17.78%).2.3 Analysis of the results of contrast-enhanced ultrasound imaging(CEUS)for hepatocellular carcinoma.Of the 135 HCC patients who were included in this study,128 patients(94.81%),5 intermediate booster patients(3.70%),Low enhancement in 2 cases(1.50%);The uniform/heterogeneous pattern in the arterial phase was 126(93.33%)and 9(6.67%);In the early stage,58 cases(53.33%),72 cases(42.96%),and 5 cases(3.70%)without resolved;In the clearance degree,102 cases of mild clearance(75.56%),28 cases(20.74%),and 5 cases of no resolution(3.7%)were significant;85(62.96%),negative 50(37.04%);94(69.60%)and negative 41(30.37%);92(68.15%),43(31.85%);83(61.48%),11(8.1%)and 41(30.37%).2.4 Correlation analysis between CEUS LI-RADS signs and TCM syndrome types.2.4.1 This study included 135 patients with hepatocellular carcinoma,and the chi-square test results showed no statistical difference in gender between different TCM syndrome types(P>0.05).The results of one-way ANOVA showed that there was no statistical difference in age between different TCM syndrome types(P>0.05).2.4.2 There were no statistical differences in arterial enhancement level,arterial enhancement pattern,clearance time,clearance degree,intratumoral disorder vessels,and strong tumor boundary in 135 patients included in this study(P>0.05).The positive rate of periannular vessels in HCC was significantly different among different TCM types(P<0.01),and the positive rate of periannular vessels in patients with liver and kidney Yin deficiency was lower than that of patients with liver depression and spleen deficiency and qi stagnation,which showed statistical difference(P<0.05),and there was no statistical difference between the other types(P>0.05).There were significant differences between different TCM types(P<0.001);the most differences compared with liver and kidney Yin deficiency,qi stagnation and blood stasis,liver and kidney Yin deficiency(P<0.05).Conclusions1.The main clinical features of the HCC group in LR-M nodules include:higher proportion of males,3.1-5.0cm nodule diameter,and higher proportion of AFP and CA19-9 elevation.The main CEUS characteristics of HCC group were:uniform/uneven enhancement during arterial phase,slight clearance,intratumoral disorganized vessels,presence of peritumoral ring artery,clear boundary of tumor enhancement,clear boundary of non-enhancement area.2.Standard I,which contains signs of intratumoral disordered vessels and/or peripheral circumferential vessels,has a highest specificity and PPV for re-evaluating HCC in LR-M,potentially avoiding the need for biopsy of LR-M nodules.3.There was some correlation between CEUS LI-RADS signs of hepatocellular carcinoma and TCM syndrome:the positive rate of peritumor annular vessels in patients with liver and kidney Yin deficiency was lower than that of patients with liver and spleen deficiency and qi stagnation and blood stasis.Compared with other types,the boundary of the area is more blurred.However,there were no significant differences in the arterial enhancement level,arterial enhancement pattern,clearance time,hepatocellular carcinoma clearance degree,intratumoral disorder blood vessels,and strong tumor boundary.CEUS imaging features can provide some objective basis for the TCM dialectical classification of HCC,provide new ideas for the dialectical HCC,and further enrich and improve the TCM syndrome differentiation system of hepatocyte carcinoma.