Objective:To investigate the application value of contrast-enhanced ultra-sound, enhanced computed tomography (CT) and enhanced magnetic resonance imaging (MRI) in the diagnosis of small hepatocellular carcinoma.Methods:The clinical diagnositic trial was con-ducted. The clinicopathological data of 145 patients with small hepatocellular carcinoma who were admitted to the First Affiliated Hospital of Amy Medical University from January 2019 to June 2021 were collected. There were 121 males and 24 females, aged from 26 to 78 years, with a median age of 54 years. All patients were examined with contrast-enhanced ultrasound, enhanced CT and enhanced MRI, and underwent surgical resection of liver lesions within one month. Observation indicators: (1) postoperative histopathological examinations of patients with small hepatocellular carcinoma; (2) examination of small hepatocellular carcinoma by contrast-enhanced ultrasound, enhanced CT and enhanced MRI; (3) imaging features of small hepatocellular carcinoma in the contrast-enhanced ultrasound, enhanced CT and enhanced MRI; (4) enhancement mode distribution of small hepatocellular carcinoma in the arterial, portal and delayed phases of contrast-enhanced ultrasound, enhanced CT and enhanced MRI; (5) the efficacy of contrast-enhanced ultrasound, enhanced CT and enhanced MRI in the diagnosis of small hepatocellular carcinoma. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the Cochran′s Q test or the chi-square test. The sensitivity, specificity and accuracy were used to analyze the efficacy of contrast-enhanced ultrasound, enhanced CT and enhanced MRI in the diagnosis of small hepatocellular carcinoma. Results:(1) Postoperative histopathological examinations of patients with small hepatocellular carcinoma. There were 154 lesions detected in the postoperative histopathological examinations for the 145 small hepatocellular carcinoma patients, with the tumor diameter as (2.2±0.6)cm. (2) Examination of small hepatocellular carcinoma by contrast-enhanced ultrasound, enhanced CT and enhanced MRI. There were 153, 154 and 154 lesions detected in contrast-enhanced ultrasound, enhanced CT and enhanced MRI for the 145 patients with small hepatocellular carcinoma, respectively, with the detection rate as 99.35%(153/154), 100.00%(154/154) and 100.00%(154/154), showing no significant difference among the 3 imaging examination methods ( Q=2.00, P>0.05). (3) Imaging features of small hepatocellular carcinoma in the contrast-enhanced ultrasound, enhanced CT and enhanced MRI. Of the 153 lesions reported in contrast-enhanced ultrasound for patients with small hepatocellular carcinoma, 140 lesions showed "fast-in and fast-out" enhancement, 12 lesions showed "fast-in and slow-out" enhancement and 1 lesion showed isoenhancement in arterial phases and hypoenhancement in portal and delayed phase. Of the 154 lesions reported in enhanced CT for patients with small hepatocellular carcinoma, 112 lesions showed "fast-in and fast-out" enhancement, 13 lesions showed "fast-in and slow-out" enhancement, 14 lesions showed isoenhancement in arterial phase and hypoenhancement in portal and delayed phases, 5 lesions showed rim-like hyperenhancement in arterial phase and hypoenhancement in portal and delayed phases, 5 lesions showed hypoenhancement in the three phases, 3 lesions showed hyperenhancement in the three phases, 1 lesion showed isoenhancement in the three phases and 1 lesion showed isoenhancement in arterial and portal phases and hypoenhancement in delayed phase. Of the 154 lesions reported in enhanced MRI for patients with small hepatocellular carcinoma, 134 lesions showed "fast-in and fast-out" enhancement, 1 lesion showed "fast-in and slow-out" enhancement, 8 lesions showed isoenhancement in arterial phase and hypoenhance-ment in portal and delayed phases, 5 lesions showed rim-like hyperenhancement in arterial phase and hypoenhancement in portal and delay phases, 2 lesions showed rim-like hyperenhancement in the three phases, 1 lesion showed hyperenhancement in the three phases, 1 lesion showed hypoenhancement in the three phases, 1 lesion showed isoenhancement in arterial and portal phases and hypoenhancement in delayed late phase, 1 lesion showed edge delay enhancement in the three phases. (4) Enhancement mode distribution of small hepatocellular carcinoma in the arterial, portal and delayed phases of contrast-enhanced ultrasound, enhanced CT and enhanced MRI. Of the 153 lesions reported in contrast-enhanced ultrasound for patients with small hepatocellular carcinoma, there were 152 lesions with hyperenhancement and 1 lesion with iso or hypoenhance-ment in the arterial phase, there were 55 lesions with hyper or isoenhancement and 98 lesions with hypoenhancement in the portal venous phase, there were 12 lesions with hyper or isoenhancement and 141 lesions with hypoenhancement in the delayed phase. Of the 154 lesions reported in enhanced CT for patients with small hepatocellular carcinoma, there were 133 lesions with hyperen-hancement signal and 21 lesions with iso or hypoenhancement in the arterial phase, there were 53 lesions with hyper or isoenhancement and 101 lesions with hypoenhancement in the portal phase, there were 17 lesions with hyper or isoenhancement and 137 lesions with hypoenhancement in the delayed phase. Of the 154 lesions reported in enhanced MRI for patients with small hepatocellular carcinoma, there were 143 lesions with hyperenhancement and 11 lesions with iso or hypoenhance-ment in the arterial phase, there were 29 lesions with hyper or isoenhancement and 125 lesions with hypoenhancement in the portal phase, there were 5 lesions with hyper or isoenhancement and 149 lesions with hypoenhancement in the delayed phase. There were significant differences in the enhancement mode distribution of lesions in the arterial, portal and delayed phases among contrast-enhanced ultrasound, enhanced CT and enhanced MRI ( χ2=19.47, 13.21, 6.92, P<0.05). (5) The efficacy of contrast-enhanced ultrasound, enhanced CT and enhanced MRI in the diagnosis of small hepatocellular carcinoma. Of the 153 lesions reported in contrast-enhanced ultrasound for patients with small hepatocellular carcinoma, there were 3 lesions misdiagnosed according to the postoperative histopathological examinations. Of the 154 lesions reported in enhanced CT and enhanced MRI for patients with small hepatocellular carcinoma, there were 7 lesions and 2 lesions misdiagnosed according to the postoperative histopathological examinations, respectively. Lesions misdiagnosed in one imaging examination method were correctly diagnosed in the other two imaging examination methods. The sensitivity, specificity, accuracy were 97.4%, 63.0%, 92.3% for contrast-enhanced ultrasound in the diagnosis of small hepatocellular carcinoma. The above indica-tors were 95.5%, 63.0%, 90.6% for enhanced CT and 98.7%, 63.0%, 93.4% for enhanced MRI in the diagnosis of small hepatocellular carcinoma. There was no significant difference in the sensitivity and accuracy among the 3 imaging examination methods ( Q=2.92, 0.00, 1.81, P>0.05). Conclusion:Contrast-enhanced ultrasound, enhanced CT and enhanced MRI all have good diagnostic value in diagnosis of small hepatocellular carcinoma, and they complement each other.

Objective:To investigate the effect of radioactive 125I seed on angiogenesis of subcutaneously transplanted hepatocellular carcinoma in nude mice and underlying mechanism. Methods:The subcutaneous transplanted tumor model of human hepatocellular carcinoma Huh7 cells was established in nude mice. Twelve nude mice were randomly divided into observation group and control group with 6 mice in each group. The 125I seed with activity of 2.96×10 7Bq was implanted into the transplanted tumor of observation group and another with 0 Bq as control group, respectively. The volume of the transplanted tumor was measured every 4 d and the growth curve of the tumor was recorded. The microvessel density (MVD) of the transplanted tumor was evaluated by immunohistochemical detection of CD31. VEGF-A and HIF-1α protein and mRNA were detected by immunohistochemistry and RT-PCR, respectively. Results:The growth rate of tumor in the observation group was slower than that in the control group, and the difference of tumor volume between two groups at 12 d after 125I seed implantation was significantly different( t=3.167, P<0.05). At 28 d after transplantation, the tumor volumes of control and observation group approached to (963.61 ± 89.56) mm 3and (602.10±75.98) mm 3, respectively. The MVD of the observation group was significantly lower than that of the control group ( t=6.361, P<0.05). The relative expression of VEGF-A and HIF-1α mRNA in the observation group was significantly lower than that in the control group ( t=10.480, 6.414, P<0.05). Protein expression levels of VEGF-A and HIF-1α in the observation group were lower than those in the control group ( t=10.890, 12.250, P<0.05). Conclusions:Radioactive 125I seed can inhibit the growth of HCC xenografts by reducing tumor microvessels, which may be related to the decrease of VEGF-A and HIF-1α expression.

Objective:To evaluate the efficacy and prognostic factors of 125I seeds implantation for primary hepatocellular carcinoma. Methods:From December 2011 to January 2021, 102 primary hepatocellular carcinoma patients (86 males, 16 females; median age 61 years) who underwent 125I seeds implantation from 5 hospitals in China were enrolled in this retrospective study. Local progression-free survival (LPFS), overall survival (OS) and the prognostic factors were analyzed. Kaplan-Meier method was used to draw the distribution curve of survival time, and LPFS rate and OS rate were calculated. Log-rank test and Cox regression were used to analyze the influencing factors of survival. Results:The median follow-up time was 38 months until April 2021. The local control rate was 96.1%(98/102). The 1-, 3- and 5-year LPFS rate were 61.3%, 25.5% and 12.7%, and the 1-, 3- and 5-year OS rate were 73.9%, 39.1% and 22.6%, respectively. There were 75 patients with progressive disease, including 42 patients with intrahepatic recurrence and metastasis after seed implantation, and 55 patients died. Multivariate analyses showed that short-term efficacy complete response (CR) (hazard ratio ( HR)=0.34, 95% CI: 0.20-0.58) was protective factor related to LPFS; short-term efficacy CR ( HR=0.25, 95% CI: 0.13-0.47) was the protective factors related to OS; Barcelona clinic liver cancer (BCLC) C stage ( HR=2.33, 95% CI: 1.27-4.27), intrahepatic progression and extrahepatic metastasis ( HR=3.18, 95% CI: 1.28-7.86; HR=3.23, 95% CI: 1.27-8.21) were independent risk factors related to OS. No sever adverse effects were observed. Conclusions:125I seeds implantation is safe and effective for the treatment of primary hepatocellular carcinoma. BCLC stage, short-term efficacy and post-implantation progression are independent factors related to survival time.