Clinical Study Of CEUS In Early Diagnosis Of Hepatocellular Carcinoma

Primary liver cancer is the most serious complications of liver cirrhosis and more than90% of primary liver cancer is hepatocellular carcinoma, which is on the second place ofmalignant tumors.Hepatocellular carcinoma often occurs on the foundation of livercirrhosis, and its formation process is generally believed that regeneration nodular livercirrhosis are gradually developed into atypical regenerative nodule and liver cancernodules.The treatment of liver cancer and its theraputic effects are different on different stagesof liver cancer.It is very important for clinicians to diagnosis and treat small hepatocellularcarcinoma early, which is valuable for its prognosis.Small hepatocellular carcinoma couldreceive long-term survival after surgical resection, so early diagnosis and treatment are keyfactors of improving survival rates in patients with liver cancer.The poorer the tumor differentiation is, more disorders the tumor tissue and vascularstructure are, more sinister the biological behavior is.Knowing the degree of differentiationof hepatocellular carcinoma has important role in the guidance ofits clinical treatment.A large number of studies have shown that tumor-specific hemodynamics is veryimportant for differenciaton of benign tumors and malignant tumor in liver.Withdevelopment of contrast-enhanced ultrasound technology, especially the emergence ofcontrast-enhanced ultrasound harmonic imaging technologies and the new ultrasoundcontrast agents, CEUS is sensitive to show the low velocity blood flow within tumor by useof microbubble nonlinear effect and easy to observe the whole process of tumor blood perfusion in real time view of significantly, improving the detection rate, sensitivity andspecificity, especially in small hepatic lesions.At present, no quantitative indicators of CEUS is available for diagnosis of smallheptacellular carcinoma which is diagnosised mainly according to the characterastics oflesions' imaging at each phase.Different lesions have different enhancement-mode, and then judge the nature oflesions.Enhancement-mode relies on subjective judgments of doctors, lacking ofobjectivity, the current contrast-enhanced ultrasound for liver cancer diagnosis meaningfulparameters has not yet formed a unified quantitative angiography parameters.The degreeof differentiation of liver cancer -related research is still in its infancy stage.Time - intensity curve so that access to ultrasound contrast from qualitative toquantitative become possible, we can get enhanced lesion characteristics, andenhancement-mode, and enhancement curves, while lesions to draw basic strength,maximum strength, rising slope of curve, arrival time, peak time, peak intensity, such asquantitative data.So diagnostic sensitivity and specificity significantly are improved, andultrasonic diagnosis of liver cancer has quantitative indicators, more objective and moreaccurate.In this study, contrast-enhanced ultrasound and ACQ time - intensity curves are usedto explore meaningful parameters, improve the accuracy of the early diagnosis of smallhepatocellular carcinoma.Study the correlation of imaging parameters and the degree ofdifferentiation of hepatocellular carcinoma to judge the degree of differentiation ofhepatocellular carcinoma.Provide important information fbyor clinical treatment programsand prognostic assessment.The present study was divided into the following two parts: Part 1.Clinical Value of CEUS in Differentiating Regeneration and CancerationNodules of Cirrhosis LiverObjective To explore the clinical value of Contrast enhanced ultrasound (CEUS)and ACQ time intensity curve (TIC) in differentiating regeneration and canceration nodulesof cirrhosis liver.Get the significant parameters to differentiate small hepatocellularcarcinoma and hepatocirrhosis regenerative nodule, in order to improving the veracity ofdiagnosing small hepatocellular carcinoma early.Methods This study included 100 patients from 2006.4 to 2009.3.There were 51small hepatocellular carcinoma, 49 regenerative nodule.There were 42 men and 9 womenwith small hepatocellular carcinoma (age range, 31～81 years; mean age, 58+-12 years).There were 44 men and 5 women with regenerative nodule (age range, 34～69 years; meanage, 49+-12 years).The diameters of all the lesions are smaller than 3 centimeter.All ofsmall hepatocellular carcinoma were confirmed by operations or ultrasonic-guided liverpuncture biopsies.Part of regenerative nodule was confirmed by ultrasonic-guided liverpuncture biopsies.The others of the regenerative nodule were confirmed by contrastenhanced CT (CECT) or contrast enhanced MRI (CEMRI).After CEUS, ACQ was used toanalysis t the Arrive Time (AT), Time To Peak (TTP), Peak Intensity (PI), Median and QRof all the lesions and the hepatic tissue around the lesions, then run statistics analyzebetween them.RESULTS All the cases were separated into 2 groups: small hepatocellularcarcinoma and regenerative nodule.In CEUS, small hepatocellular carcinoma showedwhole-lesion enhancement in the artery phade, while the microbubble signal is absent inthe portal vein phade, sonogram obtained during the late phade shows the lesions to behypoechoic relaticve to the liver parenchyma.The ACQ curve shows the range of themicrobubble arrive time (AT) is 0.67s-12.65s, the average is 3.52±3.36s.The range of themicrobubble time to peak (TTP) is 11.63s-70.84s, the average is 21.02±17.91s.The range of the microbubble peak intensity (PI) is 25.29dB-34.02dB, the average is 28.75±2.41dB.The range of the contrast-enhanced time is 25.29dB-34.02dB, the average is 28.75±2.41dB.The range of the enhancement slope is 25.29dB-34.02dB, the average is 28.75±2.41dB.The range of the microbubble Median is 14.45-35.63, the average is 27.78±5.65.The rangeof the microbubble Quartile range (QR) is 2.49-16.16, the average is 6.69±4.07.In CEUS,regenerative nodule showed the same enhancement as the liver parenchyma in the arteryphade, while the microbubble signal is absent in the portal vein and the late phade, which isstill the same as the liver parenchyma.The ACQ curve shows the range of the microbubbleAT is 0.67s-5.06s, the average is 2.40±2.17s, the range of the microbubble TTP is22.78s-60.23s, the average is 34.66±12.20s, the range of the microbubble PI is6.57dB-27.24dB, the average is 22.33±7.10dB.The range of the microbubble Median is12.01-26.43, the average is 22.944±4.21.The range of the microbubble Quartile range (QR)is 2.11-4.73, the average is 3.27±1.27.The statistics results between regenerative noduleand small hepatocellular carcinoma lesions are as follows: AT P=0.37 (F=0.14, p=0.72)and TTP P=0.054 (F=0.08, p=0.79) show no significant statistics difference, while PI P=0.04 (F=4.77, p=0.04), Median P=0.04 (F=0.18, p=0.67) and QR P=0.004 (F=13.35,p=0.01) were of highly statistics significant.The optimization point of ROC results of PIbetween regenerative nodule and small hepatocellular carcinoma is 26.77dB, in this point,PI had the sensitivety is 90%, the specificity is 82%.The optimization point of ROC resultsof Median between regenerative nodule and small hepatocellular carcinoma is 3.56, in thispoint, Median had the sensitivety is 60%, the specificity is 82%.The optimization point ofROC results of QR between regenerative nodule and small hepatocellular carcinoma is25.51, in this point, QR had the sensitivety is 90%, the specificity is 73%.Conclusion The enhancement patterns of small hepatocellular carcinoma andregenerative nodule are obviously different.PI, Median and QR have statistic significant.They can be used to differentiate small hepatocellular carcinoma and regenerative nodulein CEUS, and diagnose the small hepatocellular carcinoma as early as possible.AT, TTP don't have statistic significant. Part 2.Evaluation of Hepatocellular Carcinoma with Contrast-enhanced Ultrasound:Correlation with Pathological DifferentiationObjective To evaluate the relationship between enhancement patterns ofhepatocellular carcinoma (HCC) and tumor differentiation with contrast-enhancedultrasound (CEUS) and explore the significant parameters between different differentiatedHCC.Methods This study included 54 patients from 2006.4 to 2009.3.There were 49 menand 5 women with hepatocellular carcinoma (age range, 18～70years; mean age,49±13years).The diameters of all the lesions range from70×21mm to 15×13mm.All theHCC lesions underwent examinations of CEUS, and autotraking contrast quantification(ACQ) was used to analyze the arrive time (AT), time to peak (TTP), peak intensity (PI),get the contrast-enhanced time,wash out time,enhancment slope,clearance slope of thelesions.All of the lesions were confirmed by operations.Each histopathological diagnosiswas performed by a pathologist, and all the HCC lesions were divided into two groupsaccording to the WHO grading system, and then run statistics analysis between them.RESULTS All the cases were separated into 2 groups: well differentiated HCC andmoderate to poor differentiated HCC.16 of 21 well-differentiated HCCs appearedenhancement pattern as"fast-in and slow-out", 5 of 21 well-differentiated HCCs appearedas "fast-in and fast-out"; 30 of 33 moderate to poor differentiated HCCs appeared as"fast-in and fast-out", 3 of 33 moderate to poor differentiated HCCs appeared as "fast-inand slow-out".The data of the well differentiated HCCs: the microbubble arrive time (AT)is 7.76±3.47s, time to peak (TTP) is 25.73±4.04s, peak intensity (PI) is 29.14±3.67dB,contrast-enhanced time is 17.10±4.94s, wash out time is 46.34±11.48s, the enhancementslope is 1.73±0.54, clearance slope is 1.27±0.81.The data of moderate to poordifferentiated HCCs: the microbubble arrive time (AT) is 3.97±3.87s, time to peak (TTP)is 16.78±7.57s, peak intensity (PI) is 27.03±3.84dB, contrast-enhanced time is 11.43±2.09s, wash out time is16.64±2.04s, enhancement slope is 2.70±1.14, clearance slope is 1.87±0.41.The statistical results between well differentiated HCC and moderate to poor differentiatedHCC lesions are as follows: AT (t=2.10, p=0.052) and PI(t=1.16, p=0.26) show nosignificant statistics difference, while TTP (t=2.86, p=0.01), congtrast-enhanced time(t=3.40, p=0.004), wash out time (t=8.02, p=0.000), enhancement slope (t=2.48, p=0.02)and clearance slope (t=2.286, p=0.034)are of statistics significant.Conclusion Well differentiated HCC and moderate to poor differentiated HCCperformance different on CEUS, the TTP, contrast-enhanced time, wash out time,enhancement slope and clearance slope between the two groups are of statistics significant,thus CEUS offers an effective way to judge the pathologic grading of HCC.