| BackgroundHepatocellular Carcinoma (HCC) was one of the most common malignant tumor allover the world and imaging was an important method on diagnosis it. Due to thecharacteristic of double blood supply of the liver, microbubble contrast agent could providethe special phase images, which made Contrast-enhanced Ultrasound (CEUS) widelyapplied in the differential diagnosis of the focal liver lesions. In recent years, the diagnosisand treatment of HCC had made great progress, especially in surgical and targeted therapy.But the high frequency of recurrence of HCC was a difficulty problem. The metastasis andrecurrence of postoperative HCC lack special treatment at present. Therefore, to seek theimaging parameters which can prompt the prognostic information of HCC may help topredict early metastasis and recurrence. Recently, some scholars had researched thecorrelation between the CEUS enhancement pattern and parameters on breast cancer withpathological prognostic factors. The study reported a few CEUS parameters have obviouscorrelation with the prognosis of breast cancer[1]; another study found that it was closelyrelated to the HCC cell proliferation activity and poor prognosis, according to observeintraoperative ultrasound imaging of HCC vascular supply,[2].These studies about thecorrelation of CEUS pattern with prognostic factors on HCC were rarely reported. Weplaned to analyze the relationship between CEUS parameters and pathological prognosticfactors or clinical outcomes on HCC, and to probe the value and clinical significance injudging the prognosis of HCC.ObjectivesTo analyze the correlation between the Contrast-enhanced Ultrasound (CEUS) parameters and the prognostic factors on Hepatocellular Carcinoma (HCC), which couldhelp us further explore the relationship of the CEUS parameters and the prognosticfactors on HCC.Methods1. Collecting Hepatocellular Carcinoma (HCC) cases confirmed by surgery or biopsywhich has been underwent Contrast-enhanced Ultrasound (CEUS) pre-operatively inSouthwest Hospital of Third Military Medical University. Screening HCC patients withcirrhosis and these tumor specimen sections had Ki-67, CD34, α-fetoprotein (AFP) orCytokeratin19(CK19) immunohistochemical stained as the research objects. Moreover,clinical data, CEUS and pathological data had been collected.2. Two groups were classified on the basis of different CK19expression in HCCpatients: positive CK19expression group and negative CK19expression group. The arterialphase of CEUS enhancement pattern and portal phase enhanced intensity of two groupswere observed. DFY-II Ultrasound Imaging Analysis Software was utilized to measureCEUS parameters quantitatively, including the arterial phase enhancement intensity andheterogeneity of the tumor, the enhancement intensity of tumor and the ratio of the tumor/adjacent the liver parenchyma during the portal phase. The differences between the twogroups were compared.3. Tumor specimens of HCC which had Ki-67, CD34and AFP immunohistochemicalstained had been selected. To observe the tumor specimen slice and then record whetherMicrovessel Invasion (MVI) could be found or not.Immunohistochemical CD34staining ofthe tumor specimen were used to count Microvessel Density (MVD). Postoperativefollow-up had been taken to detect recurrence.To observe the change of tumor size byconventional ultrasound and CEUS in arterial phase; CEUS arterial phase enhancementpattern, enhanced shape and presence of clutter twisted blood vessels internal; Portal phaseenhanced degree and wash out were recorded. Finally, the relationship between CEUSparameters and tumor differentiated degree, Ki-67, MVD, MVI, AFP and the recurrencewas analyzed.Results1.(1)There were no significant differences in age, gender, tumor size and theproportion of hepatitis B serum marker between the two groups(P>0.05). The proportion of well differentiated HCC was higher in negative CK19expression group(17.65%) thananother group(2.53%), the proportion of poorly differentiated HCC was lower in negativeCK19expression group(3.53%) than another group(15.19%)(χ2=15.172, p=0.001).(2) HCC cases with inhomogeneous enhancement in arterial phase had higher positiveCK19expression rate (60.58%) than homogeneous enhanced cases (26.67%)(χ2=17.524,p=0.000). HCC cases with hypoenhancement in portal phase had higher positive CK19expression rate (52.20%) than cases with hyper or iso-enhancement (28.57%)(χ2=5.195,p=0.023).(3) DFY-ⅡUltrasound Imaging Analysis Software measured the results. The arterialphase enhancement heterogeneity of tumor in positive CK19expression group (2.64±0.64)was higher than that of the negative group (2.29±0.31)(W=4.4, p=0.000). The arterialphase enhancement intensity of tumor in positive CK19expression group(102.83±29.78dB)was lower than that of the negative group (120.65±25.49dB)(t=3.887,p=0.000).The portal phase enhancement intensity of tumor in positive CK19expression group(66.83±20.13dB) was lower than that of the negative group(79.99±27.15dB)(t=3.115,p=0.002).The ratio of the tumor/adjacent the liver parenchyma during theportal phase was lower in positive CK19expression group(0.74±0.03)than that in thenegative group(0.92±0.22)(t=5.221,p=0.000).2.(1)There were no significant differences in age, gender, tumor size and theproportion of hepatitis B serum marker with tumor tissue differentiation degree, Ki-67positive rate, MVI detection rate, MVD high-low, AFP positive rate andrecurrence(p>0.05).(2) The size of tumor was increased obviously in CEUS arterial phase of HCC caseshad higher Ki-67positive detection rate (χ2=7.126, p=0.008) and higher MVI detection rate(χ2=4.087, p=0.043). HCC cases with inhomogeneous enhancement in arterial phase hadlower differentiated degree(χ2=7.654, p=0.006), higher Ki-67positive detection rate(χ2=9.659, p=0.002), higher early recurrence rate(χ2=7.485, p=0.024).HCC cases withirregular shape in arterial phase had lower differentiated degree (χ2=4.414, p=0.036),higher Ki-67positive detection rate (χ2=6.443, p=0.011), higher MVI detection rate(χ2=6.985, p=0.008). HCC cases with internal clutter blood vessels in arterial phase hadlower differentiated degree (χ2=6.210, p=0.013) and higher MVI detection rate (χ2=6.985, p=0.008).(3) HCC cases with hypo-enhancement in CEUS portal phase had lower differentiateddegree (χ2=7.450, p=0.006) and higher Ki-67positive detection rate (χ2=5.349,p=0.021).HCC cases with contrast agent washing out faster in portal phase had lowerdifferentiated degree(χ2=3.963, p=0.047), higher Ki-67positive detection rate(χ2=6.018,p=6.018), higher MVI detection rate(χ2=5.379, p=0.020). The contrast agent wash outobviously of HCC cases in portal phase had lower differentiated degree (χ2=8.268,p=0.004) and higher Ki-67positive detection rate (χ2=5.782, p=0.016).(4) Logistic regression results showed that inhomogeneous enhancement in arterialphase was closely related to the Ki-67positive detection rate and the early recurrence;tumor with irregular shape prone to MVI in the arterial phase; portal phase withhypo-enhancement may indicate that the differentiated degree of tumor was poor.Conclusion1. The CEUS enhancement parameters had significant difference between the CK19expressed positive HCC and negative HCC in the setting of cirrhosis. HCC cases withinhomogeneous enhancement in arterial phase and contrast agent faded obviously in portalphase had higher CK19positive incidence which may indicate poor prognosis.2. CEUS enhancement patterns and parameters of HCC could be used to predict theprognosis of HCC preoperatively. The tumor presented heterogeneous enhancement inarterial phase can predict tumor cell proliferation activity and recurrence time. The tumorwith irregular shape may indicate microvessel invasion. Portal phase withhypo-enhancement may have lower degree of tumor cell differentiation, high malignantdegree and poor prognosis. |
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