Study on the diagnosis of small hepatocellular carcinoma caused by hepatitis B cirrhosis via multi‑slice spiral CT and MRI

  • Authors:
    • Mei Wang
    • Congxin Wei
    • Zhaojuan Shi
    • Jianzhong Zhu
  • View Affiliations

  • Published online on: October 31, 2017     https://doi.org/10.3892/ol.2017.7313
  • Pages:503-508
Metrics: HTML 0 views | PDF 0 views     Cited By (CrossRef): 0 citations

Abstract

The present study compared the diagnostic accuracy of multi‑slice spiral computed tomography (CT) and magnetic resonance imaging (MRI) on small hepatocellular carcinoma (SHCC) caused by hepatitis B cirrhosis. A total of 160 patients with hepatitis B cirrhosis were selected between January 2012 and April 2016, and 183 SHCC lesions were included in the present retrospective study. Patients were divided into the SHCC group (T stage) and the micro hepatocellular carcinoma (MHCC) group (T1 stage). There were a total of 129 SHCC lesions and 54 MHCC lesions identified. All patients underwent multiphasic CT and MRI imaging. The liver acquisition with volume acquisition (LAVA) technique was utilized for MRI. Furthermore, SPSS 20.0 was used for statistical analyses. LAVA in the arterial phase and CT in the arterial phase revealed significantly higher diagnostic rates for the diagnoses of 183 lesions. In addition, standard CT scan exhibited significantly reduced diagnostic rates in SHCC lesions. Results indicated that LAVA in the equilibrium phase had the lowest diagnostic rate in MHCC lesions, which was statistically significant (P<0.05). Overall, the diagnostic rate of CT (79.63%) for MHCC was significantly lower than that of MRI (96.29%) (P<0.05). However, the diagnostic rate of CT for SHCC (96.12%) was significantly higher than that for MHCC (79.63%) (P<0.05). MRI‑LAVA in the arterial phase has the highest diagnostic rate for SHCC and MHCC. However, the diagnostic capability of MRI for MHCC lesions is superior to that of CT.

Introduction

Liver cancer is one of the most common malignant tumors of the digestive system. It has high incidence rates and ranks second in cancer mortality in China (1). It has multiple causes, such as liver cirrhosis, viral infection, chemical carcinogens, alcohol and tobacco, water pollution, and genetic factors (2). Liver cancer caused by hepatitis B infection and cirrhosis is highly prevalent, although it lacks the typical clinical manifestations of liver cancer Moreover, it is particularly important to improve the diagnostic rate of early liver cancer (3). The clinical diagnosis of the hepatocellular cancer involves multiple approaches. Important clinical symptoms like abdominal distension, liver pain, fever, emaciation, debilitation, and jaundice confirms the middle and advanced stage of the disease. The clinically well-established factor being utilized for liver cancer is cirrhosis (4). The diagnosis of hepatocellular carcinoma could frequently, and uniquely, be made on characteristic multiphase contrast based cross-sectional imaging rather than strict need for tissue sampling. Epigentics is another new area showing good potential in clincal diagnosis of liver cancer. Promising results from microRNA (miRNA/miR) profiling and hypermethylation of selected genes have raised hopes of identifying new biomarkers (5). Furthermore, miR-122, a completely conserved liver-specific miRNA in vertebrates, is essential for the maintenance of liver homeostasis. miR-122 is also being explored for its diagnostic abilities for liver cancer (6). Fluorescence in the form of VELscope is contributing signficnatly in the field of cancer diaognsis (7). However, reserarch on concret flouroscent markers specific for liver cancer is in progress.

The presence of small lesions is the characteristic feature of the small hepatocellular carcinoma (SHCC). Early and timely diagnosis, and surgical resection or interventional therapy could help significantly in improving the patient's survival rate, and prolong their survival time (8). Diagnosis of small HCC is acquired solely by imaging as patients with small HCC have no clinical signs. However, ultrasound could help in non-invasive diagnosis of HCC where lesions are greater than 1 cm. Furthermore, computed tomography (CT) and magnetic resonance imaging (MRI) have higher diagnostic rates in the above cases of SHCC (9,10). Guidelines for management of cirrhotic patients, underline that a six-month surveillance with ultrasound must be performed associated with laboratory-chemistry evaluation. In the present study, we applied multi-slice spiral CT and MRI for patients with SHCC caused by hepatitis B cirrhosis, and compared their diagnostic effects.

Materials and methods

The Ethics Committee of the Taishan Medical College (Taian, China) approved the present study. Participants have provided their written informed consent to participate in this study. A total of 160 patients diagnosed with liver cancer caused by hepatitis B cirrhosis in our hospital from January 2012 to April 2016 were selected. Inclusion criteria: i) Patients with hepatitis B cirrhosis; ii) patients diagnosed with SHCC according to the diagnostic criteria of the American Association for the Study of Liver Diseases, and liver biopsy; iii) patients who underwent multi-slice spiral abdominal CT and MRI examinations; and iv) patients who did not undergo any relevant operative treatments before CT and MRI examinations. Exclusion criteria: i) Patients with severe dysfunction of the heart, brain, lung, or kidney; ii) patients with intrahepatic or extrahepatic metastatic lesions; and iii) patients with mental or neurological diseases, and who could not cooperate in examinations. The patients were divided on the basis of tumor diameter into two groups: The SHCC group (tumor diameter, 1–3 cm; n=109, 129 lesions) and the micro hepatocellular carcinoma (MHCC) group (tumor diameter, <1 cm; n=51, 54 lesions). There were no significant differences in the comparison of general parameters between patients in the two groups (P>0.05) (Table I).

Table I.

Comparisons of baseline information of patients in the two groups.

Table I.

Comparisons of baseline information of patients in the two groups.

ItemSmall hepatocellular carcinoma group (n=109)Micro hepatocellular carcinoma group (n=51)t/χ2P-value
Sex (male/female)78/2839/120.0370.846
Age (years)33–7830–80
Average age (years)52.36±4.4952.85±4.510.6420.521
Number of lesions (n)12954
Classification of liver cancer (n, %)
  Primary liver cancer93 (85.32)42 (82.35)0.0610.804
  Liver metastatic carcinoma16 (14.68)  9 (17.65)
Classification of lesion (n, %)
  Single lesion99 (90.82)44 (86.27)0.3540.551
  Multiple lesions10 (9.18)  7 (13.73)

SHCC patients underwent plain scan CT, and arterial phase, portal venous phase, and equilibrium phase CT. The lesions presented as equal density, high density, slightly high density, and equal density, respectively (Fig. 1). These patients underwent MRI examination, including T2 weighted imaging (T2WI), diffusion weighted imaging (DWI), IN-PHASE, OUT-PHASE, liver acquisition with volume acquisition (LAVA) plain scan, and LAVA in arterial phase, portal venous phase, and equilibrium phase. The lesions presented as slightly high signal, high signal, low signal, equal signal, slightly low signal, high signal, slightly high signal, and slightly high signal; and capsular reinforcement was also visible (Fig. 2).

Preparation before examination

Patients were made to fast for 5 h. In addition, they were made to understand the matters requiring attention during examination. They also underwent psychological counseling to relieve tension, fear, anxiety, and other negative emotions. Patients underwent respiratory training also (uniform, calm, and shallow-slow breathing), and were informed of the mild discomfort following injection of the contrast agent. Patients were advised to drink 500 ml of warm water 20 min prior of scanning. Reference standards used were in accordance with the earlier studies.

CT examination

A dual-source 64-slice spiral CT machine (Siemens Healthineers, Erlangen, Germany) was used. Patients were guided to take the supine position. The parameters of the CT machine were set as follows: Msec, 260–300; kv, 120; layer thickness, 5 mm; interlayer spacing, 1 mm; screw pitch, 3. The scanned area was the upper abdomen covering the entire liver; the window width and window center were adjusted, ensuring a clear image. After routine plain scan, patients received bolus injection of iohexol (concentration of 300 mg/ml; Guangzhou Schering Pharmaceutical Co., Ltd., Guangzhou, China), a non-ionic iodinated contrast agent, via the elbow vein using a high-pressure injector (flow rate, 2.8–3.0 ml/sec); the dose of contrast agent was 1.5 ml/kg (body weight); dynamic enhancement scan was performed, followed by observation in three phases (arterial phase, venous phase, and equilibrium phase) in real time: i) Arterial phase, at 20–30 sec after injection of the contrast agent; ii) venous phase, at 60–70 sec after injection of the contrast agent; iii) equilibrium phase, at 150–240 sec after injection of the contrast agent; the reconstructive thickness in the portal venous phase was 1.25 mm with spacing of 0.

MRI examination

An MR 3.0T HDX TWINSP MRI scanner (GE Healthcare, Chicago, IL, USA) was used. Scanning sequences and parameters: An 8-channel phased array coil was used, and the patients were guided to take the supine position with the forearms crossed with the head; the most obvious position of abdominal breathing was observed with the respiratory gating hose, and the fluctuation amplitude of breathing on the magnet was ideally more than one-third of the full length. The body coil was placed in the upper abdomen, the inferior margin of xiphoid was placed in the center of the coil, and the center of the coil was placed in the center of the main magnet. Scanned area: The entire liver from the superior border to the inferior border was scanned. i) Axial T2WI/FRFSE-FS sequence: Time of repetition (TR), 6000–7000 msec; time of echo (TE), 100–130 msec; field of vision (FOV), 34–38 cm; layer thickness, 6 mm; interlayer spacing, 0.6 mm; matrix, 288×224, number of excitation (NEX), 2. ii) Breath-holding axial DWI sequence: The single-shot spin echo and echo planar sequences were used, and the diffusion coefficient b, 0 and 600 sec/mm2; the weighted gradient field was applied in the three spatial axes, X, Y, and Z: TR, 2,500 msec; TE, 65 msec; layer thickness, 6.0 mm; interlayer spacing, 2.0 mm; FOV, 34–38 cm; matrix, 128×128; NEX, 2; scanning time, 20–24 sec. iii) Breath-holding axial T1WI double-echo sequence: Spoiled gradient echo sequence, 2D model; TR, 250 msec; TE, 2.9 msec; FOV, 34–38 cm; layer thickness, 6.0 mm; interlayer spacing, 0.6 mm; matrix, 288×192; NEX, 1; scanning time, 16–22 sec. iv) LAVA; TR, 2.9 msec; TE, 1.3 msec; layer thickness, 4.2 mm; matrix, 224×224; FOV, 36–42 cm ×36-42 cm; reconstruction matrix, 512×512; the scan was performed 12–15 sec after injection of the contrast agent, once every 10 sec, two phases each time, and the scanning time was 120–200 sec.

Observational indexes

Image analysis: Two senior imaging physicians who understood the medical history of patients but did not know the final diagnosis used a double-blind method. They read the images together on a PACS workstation. When they had different diagnostic advice, they had discussions until reaching a consensus. The size and number of lesions, density in each phase of multi-slice spiral CT, and the intensity in each sequence of MRI were recorded. Additionally, whether the subjects had fatty degeneration or capsules was analyzed. Diagnostic rate = (detection number/total number) ×100%.

Statistical analysis

SPSS 20.0 statistical analysis software was used. Quantitative data are presented as ratio, and a χ2-test was used for comparisons; P<0.05 was taken as statistically significant.

Results

Multi-slice spiral CT and MRI examination results of SHCC patients

A total of 183 MHCC/SHCC lesions among 160 patients with liver cancer underwent CT and MRI examinations. The signal distribution in each phase of multi-slice spiral CT and each sequence of MRI showed that a total of 167 liver cancer lesions were found with CT, including 124 SHCC lesions and 43 MHCC lesions. Furthermore, a total of 179 liver cancer lesions were found with MRI, including 127 SHCC lesions and 52 MHCC lesions (Figs. 35).

Analysis of the diagnostic rates of multi-slice spiral CT and MRI for MHCC/SHCC lesions

LAVA in arterial phase (89.92%) and CT in arterial phase (89.14%) had the highest diagnostic rates for SHCC lesions. Plain scan CT had the lowest diagnostic rate (75.96%) and LAVA in arterial phase (90.74%) had the highest diagnostic rate for MHCC lesions. LAVA in equilibrium phase had the lowest diagnostic rate (57.40%). The differences in diagnostic rates for SHCC and MHCC among CT in each phase, MRI IN-PHASE, LAVA plain scan, and LAVA in equilibrium phase were statistically significant (P=0.0198, 0.0184, 0.0002, 0.0003, 0.0019, 0.0011, <0.0001, respectively), while the differences in diagnostic rates of SHCC and MHCC among MR-T2WI, DWI, OUT-PHASE, LAVA in arterial phase, and LAVA in portal venous phase were not significant (P=0.0600, 0.0805, 0.1486, 0.1009, 0.3139, respectively). The overall differences in diagnostic rates of the above 12 detection phases or sequences were not significant (P>0.05) (Table II).

Table II.

Diagnostic rates of multi-slice spiral CT and MRI for micro/small hepatocellular carcinoma lesions.

Table II.

Diagnostic rates of multi-slice spiral CT and MRI for micro/small hepatocellular carcinoma lesions.

MHCC group (n=54)SHCC group (n=129)


Examination sequenceDetection rate of lesions (n, %)Detection rate of lesions (n, %)χ2P-value
CT plain scan32 (59.26)100 (77.51)   5.341   0.0198
Arterial phase40 (74.07)115 (89.14)   5.557   0.0184
Venous phase34 (62.96)114 (88.37)14.288   0.0002
Equilibrium phase32 (59.26)110 (85.27)13.354   0.0003
MRI-T2WI40 (74.07)112 (86.82)   3.538   0.0600
DWI41 (75.93)113 (87.59)   0.280   0.0805
IN-PHASE36 (66.67)113 (87.59)   9.672   0.0019
OUT-PHASE40 (74.07)109 (84.49)   2.086   0.1486
LAVA plain scan36 (66.67)114 (88.37)10.703   0.0011
Arterial phase43 (79.63)116 (89.92)   2.691   0.1009
Portal venous phase43 (79.63)112 (86.82)   1.014   0.3139
Equilibrium phase31 (57.40)113 (87.59)18.923<0.0001
χ211.18110.846
P-value     0.0829     0.0933

[i] CT, computed tomography; MRI, magnetic resonance imaging; DWI, diffusion weighted imaging; T2WI, T2 weighted imaging; MHCC, micro hepatocellular carcinoma group; SHCC, small hepatocellular carcinoma; LAVA, liver acquisition with volume acquisition.

Comparison of the diagnostic rates of multi-slice spiral CT and MRI for MHCC/SHCC lesions

The diagnostic rate of CT for SHCC was 96.12% (124/129), while that of MRI was 98.45% (127/129), and the difference was not significant (P>0.05); the diagnostic rate of CT for MHCC was 79.63% (43/54), while that of MRI was 96.29% (52/54), and the difference was significant (P<0.05); the diagnostic rate of CT for SHCC was significantly higher than that for MHCC (P<0.05); the diagnostic rates of MRI for SHCC and MHCC were over 90%, and there was no significant difference (P>0.05) (Fig. 6).

Discussion

SHCC caused by hepatitis B cirrhosis is an important type of liver cancer. Viral hepatitis caused by hepatitis B develops into cirrhosis, and finally into liver cancer. Increasing the periodic testing of hepatitis B patients, especially those with cirrhosis, can promote the early detection, diagnosis, and treatment of SHCC, and determine the prognosis (11,12). At present, the definition of SHCC has no unified standard, and the criteria used in this study were as follows: The maximum diameter of single cancerous node, ≤3 cm; the number of cancerous nodes, ≤2; and the sum of maximum diameter, ≤3 cm (13). SHCC is closely related to various forms of chronic hepatitis and cirrhosis, and develops from liver cirrhosis. Regenerative nodules of the cirrhotic liver develop into low-grade dysplastic nodules and high-level atypical nodules (including the high-grade atypical nodules of liver cancer). In addition, new tumor blood vessels and capillaries of hepatic sinusoids are generated during development. The blood supply will change, followed by increased nodular arterial blood supply and decreased portal vein blood supply. If there are no more new blood vessels, the tumor diameter will not be more than 3 mm, eventually developing into SHCC (1416).

With the continuous development of medical imaging techniques over recent years, their diagnostic value for liver cancer has far exceeded that of serology. This plays an important role in the detection, qualitative determination, positioning, and staging of liver cancer (17). CT is characterized by clear imaging and fast scanning speed, and is not easily affected by surrounding organs (18). In this study, the diagnostic rate of CT for SHCC was 96.12%. A 64-slice spiral CT machine was used for scanning, and the enhanced scan was performed in three phases according to the characteristics of three forms of SHCC blood supply that could improve the detection rate of SHCC (19,20). However, the disadvantage of CT examination is that even the multiphase enhanced scan could barely diagnose non-typical lesions correctly, demonstrating that it is difficult to make correct diagnoses even with multiphase enhancement scans. Therefore, the diagnostic rate for MHCC in this study was only 79.63%. In addition, the radioactive rays in CT examination cause a certain amount of harm to patients. Therefore, it is inappropriate to perform CT examinations frequently in a short period of time (21).

MRI is a non-radioactive examination with advantages of multi-directional, multi-sequence imaging, along with high spatial resolution, which is widely used for the inspection of liver disease. Through the dynamic enhanced scan of patients, physicians could identify small lesions in the liver as early as possible, and its detection rate for atypical hyperplastic nodules is superior to that of enhanced CT scan (22,23). In this study, the diagnostic rate of MRI for SHCC was as high as 98.45%, and its diagnostic rate for MHCC reached 96.29%. The above results of MRI could be owed to high resolution of MRI scan for lesion tissues. Further, the scanning time in each phase after enhancement is variable and the mutual complementation among T2WI, DWI, dual-echo imaging (IN-PHASE, OUT-PHASE), and LAVA dynamic enhanced imaging so as to clearly observe retroperitoneal lymph node enlargement, the hepatic hilar region, and lymph nodes. Furthermore, MRI has full ability to display the characteristics of lesions, increase the contrast between lesions and the liver, and detect lipid-containing nodules with high sensitivity (24).

In conclusion, the detection rate of MRI for SHCC caused by hepatitis B cirrhosis is superior to that of multi-slice spiral CT. MRI might help physicians analyze the characteristics of SHCC lesions under different sequence images, to improve the clinical effect of SHCC diagnosis.

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APA
Wang, M., Wei, C., Shi, Z., & Zhu, J. (2018). Study on the diagnosis of small hepatocellular carcinoma caused by hepatitis B cirrhosis via multi‑slice spiral CT and MRI. Oncology Letters, 15, 503-508. https://doi.org/10.3892/ol.2017.7313
MLA
Wang, M., Wei, C., Shi, Z., Zhu, J."Study on the diagnosis of small hepatocellular carcinoma caused by hepatitis B cirrhosis via multi‑slice spiral CT and MRI". Oncology Letters 15.1 (2018): 503-508.
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Wang, M., Wei, C., Shi, Z., Zhu, J."Study on the diagnosis of small hepatocellular carcinoma caused by hepatitis B cirrhosis via multi‑slice spiral CT and MRI". Oncology Letters 15, no. 1 (2018): 503-508. https://doi.org/10.3892/ol.2017.7313