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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 33  |  Issue : 1  |  Page : 315-319

Role of multidetector computed tomography in detection of extrahepatic metastases of hepatocellular carcinoma


1 Department of Radiodiagnosis, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Radiodiagnosis, National Liver Institute, Menoufia University, Menoufia, Egypt
3 Department of Radiodiagnosis Fever Hospital, Menoufia, Egypt

Date of Submission02-Aug-2018
Date of Decision08-Oct-2018
Date of Acceptance09-Oct-2018
Date of Web Publication25-Mar-2020

Correspondence Address:
Hanan A Meky
Shebin El Kom, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_241_18

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  Abstract 

Objective
To evaluate the role of multidetector computed tomography (CT) in the detection of hepatocellular carcinoma (HCC) and its metastases regarding its radiological characteristics and sites of metastases.
Background
To discuss radiological criteria of HCC in contrast-enhanced CT. These criteria will help us to detect the tumor in the liver and sites of its extrahepatic metastases.
Patients and methods
We included in this study 218 patients already diagnosed as having HCC. Of them, 139 did not have any extrahepatic metastases and 79 patients had extrahepatic metastases by contrast-enhanced CT assessment. The patients underwent ultrasound examination, clinical examination, and contrast-enhanced CT. Extrahepatic metastases were evaluated by their radiological criteria (enhanced in arterial phase and washout in portal phase and delayed phase) and by their specific sites.
Results
There is a significant relationship between age of the patients and extrahepatic metastases, sites of extrahepatic metastases, grading of extrahepatic metastases according to TNM classification, sensitivity and specificity of CT in detection of metastases of HCC in comparison with the sizes of the detected lesions.
Conclusion
Multidetector CT has the main role in detection of HCC and its extrahepatic metastases.

Keywords: bone metastases, computed tomography, hepatocellular carcinoma, pulmonary metastases, vascular invasion


How to cite this article:
Elwakeel AM, Houseni MM, Hassanein SA, Meky HA. Role of multidetector computed tomography in detection of extrahepatic metastases of hepatocellular carcinoma. Menoufia Med J 2020;33:315-9

How to cite this URL:
Elwakeel AM, Houseni MM, Hassanein SA, Meky HA. Role of multidetector computed tomography in detection of extrahepatic metastases of hepatocellular carcinoma. Menoufia Med J [serial online] 2020 [cited 2020 Mar 30];33:315-9. Available from: http://www.mmj.eg.net/text.asp?2020/33/1/315/281278




  Introduction Top


Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and is estimated to cause more than a quarter million deaths each year all over the world[1].

Multidetector computed tomography (CT) has high sensitivity and specificity for detecting hepatic neoplasm and its deposits. Ultrasonography and MRI also have similar accuracy, but CT is preferred because it outperforms ultrasound and MRI for evaluating the extrahepatic disease[2]. Other benefits of CT are easy access owing to wide availability and patient-friendly protocols, allowing even a chest–abdomen–pelvis CT examination in a less than 20-s breath hold[3]. If radiographic contrast media cannot be administered owing to iodine allergy or renal insufficiency, the accuracy of CT is poor, and MRI should be performed to fully evaluate the liver[4].

Lungs are a very common location for HCC metastasis. Hematogenous dissemination to the pulmonary capillary network is the presumed mechanism of spread[5], and as with hematogenous metastasis from other extrathoracic malignancies, the lower zones are involved more frequently than the upper lung zones.

Lymph nodes also receive metastases from HCC. Regional lymphadenopathy includes portohepatic, peripancreatic, gastroduodenal, portocaval, aortocaval, and para-aortic nodal groups. The aortocaval and para-aortic nodal sites within the upper abdomen were included as regional lymphadenopathy, because 20% of normal lymphatic drainage of the liver typically occurs through the lymphatic vessels along the inferior vena cava[5].

Bone also receives metastases from HCC manifested by bone pain or fracture commonly in iliac bones.

Portal vein tumor thrombosis is a well-known complication of HCC, and the presence of which modifies typical imaging features. It is important to recognize these altered appearances for the purposes of accurate diagnosis and subsequent therapy. When HCC invades a portal vein or its branches, it continues to receive blood supply from the hepatic artery and may drain directly into the portal vein. This direct draining results in arterioportal shunting and changes in portal vein hemodynamics. Large HCC with portal vein thrombosis less often demonstrate the typical arterial phase hypervascularity and subsequent washout diagnostic of HCC. Instead the portal vein thrombosis itself can show arterial phase enhancement and subsequent washout with distension of the vein[5]. The portal vein demonstrates a cast of vessels, which represents neovascularity of the portal vein thrombosis. The arterioportal shunting may also result in poor enhancement of the surrounding liver parenchyma[5].

The detection of extrahepatic metastases of HCC and intrahepatic vascular invasion is crucial for patients with HCC to receive appropriate therapy, which ultimately determines patient survival. The lung, abdominal lymph nodes, and bone are the three most common sites of extrahepatic HCC. Arterial phase enhancement when present can and should be used to differentiate malignant lymphadenopathy and adrenal masses from benign causes. It is not unexpected that most extrahepatic metastases occur in patients with an advanced intrahepatic stage of tumor (stage IVa); incidental extrahepatic lesions may be seen at CT in the brain and gastrointestinal tract but are not common[5].

The study aimed to highlight the role of multidetector CT in the detection of metastases of HCC.


  Patients and Methods Top


This study was conducted on 218 patients with HCC in Radiodiagnosis Department at National Liver Institute, Menoufia University Hospital, from March to October 2017. The study was approved by the Research Ethics Committee in the Faculty of Medicine, Menoufia University, and written informed consent was signed by the patients.

All patients underwent complete physical examination, ultrasound examination, and contrast-enhanced CT.

CT examination of the entire liver was performed with a CT scanner (Somatome definition AS 128; Siemens, Germany, Town/Berlin).

Patients underwent contrast-enhanced CT examination (unenhanced, arterial, venous, and equilibrium phases).

Patients underwent abdomino-pelvis CT scan from diaphragm to symphysis pubis after obtaining unenhanced images through the liver. Triple contrast-enhanced dynamic CT was done after a bolus injection of nonionized contrast material (ultravist) at a rate of 4 ml/s. The contrast medium was injected through an intravenous cannula in the anticubital vein with an automatic power injector. The volume of contrast medium was based on the patient's weight. The volume of contrast medium delivered was 2 ml/kg of body weight with an average of 100–150 ml.

The early arterial phase began immediately after bolus tracking of contrast medium the late arterial phase after 20 s of bolus tracking, the portal phase began 60 s after bolus tracking of contrast medium, and the delayed phase after 7 min after bolus tracking.

The liver was scanned in a single breath hold during each phase with pitch of 1 cm.

When the examination was completed, the patient was asked to wait until the images are verified to be of high enough quality for accurate interpretation.

Additional CT chest was added in the porto-venous phase, with 10-mm interval between slices from lung apex to costophrenic angles.

The acquired images were the axial cuts of the liver in all phases (namely, the nonenhanced, arterial, porto-venous, and equilibrium phases) as well as the images of the chest and abdomen from the lung apex to symphysis pupis in the porto-venous phase.

All the images were assessed in liver window, mediastinal, and lung windows for the lung, as well as bone window for bone metastases.

The liver was assessed for tumor analysis.

Extrahepatic disease was assessed, including the regional and distant lymph nodes, pulmonary nodules, pleural effusion, ascites, and bone metastases.

Reconstructed images in the coronal and sagittal planes were reviewed for any additional information.

Evaluation of HCC metastases by using multidetector computed tomography classified patients into three groups: group 1 included patients with HCC, with no metastases; group 2 included patients with HCC who had intrahepatic vascular metastases; and group 3 included patients with HCC who had extrahepatic metastases.

Patients with intrahepatic vascular metastases were classified into three subgroups: patients who had malignant portal vein invasion, patients who had hepatic vein invasion, and patients who had both hepatic and portal vein invasion.

Patients with HCC who had extrahepatic metastases were classified into six subgroups: patients who had lymph node metastases, patients who had lung metastases, patients who had bone metastases, patients who had peritoneal metastases, patients who had adrenal gland metastases, and patients who had other metastases (brain).

The data collected were tabulated and analyzed by statistical package for the social science, version 17.0 on IBM compatible computer (SPSS Inc., Chicago, Illinois, USA).

Type of statistics were descriptive statistics, for example, percentage, mean, and SD.


  Results Top


Of the 218 patients with HCC, 79 patients showed extrahepatic metastases. Their ages ranged from 20 to 75 years. There were 63 (80%) men and 16 (20%) women [Table 1].
Table 1: Age and sex distribution of the studied 79 patients

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Of the 79 patients with extrahepatic metastases, 44 (55.6%) patients showed lymph node metastases, representing the most common site for metastases. The lungs were the second most common site for HCC metastases, and it was commonly founded as noncalcified soft-tissue nodules. Of the 79 cases, 12 cases were diagnosed as having pulmonary metastases, representing 15% of all cases [Figure 1]. Dissemination through the bone and peritoneum included seven (8%) cases with peritoneal metastases and 10 (12.6%) cases with bone metastases [Figure 2]; adrenal metastases were also recorded in three cases in the study presented, with adrenal invasion in approximately 3.7% of all cases. Other sites also presented with invasion but were very rare, such as brain. These data are represented in [Table 2].
Table 2: Sites of extrahepatic metastases of hepatocellular carcinoma

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Figure 1: A 64-year-old male patient having focal lesion in segment VI showing enhancement in arterial phase (a) and washout in portal phase (b) and delayed phase (c), with bilateral rounded pulmonary nodules in lower lung zones (d).

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Figure 2: A 66.year.old Male patient having focal lesion in left lobe in arterial phase showing enhancement (a) and washout in portal phase (b), with lytic lesion in left iliac bone in venous phase with soft.tissue invasion (c).

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Intrahepatic vascular invasion was found in 22 cases, representing ∼27.8% of all cases; isolated hepatic vein invasion was presented in four cases; isolated portal vein invasion was presented in 14 cases [Figure 3]; and combined hepatic and portal invasion was presented in four cases.
Figure 3: A 56-year-old male patient having multiple heterogeneous focal lesion in both right and left lobe in arterial phase showing enhancement (a) and washout in portal phase (b), with thrombus in right branch of the portal vein (c).

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When assessing the 79 patients with extrahepatic metastases according to the TNM classification regarding the tumor size, 20 patients belonged to T1 (tumor size ≤ 2 cm), 14 patients were considered T2 (size 2–5 cm), and 23 patients with T3 (tumor size ≥5 cm). Patients with HCC had vascular invasion N = 22 (T4) and were considered to have lymph node metastases, 44 patients had lymph node metastases (N1), and 35 did not have lymph node metastases (N0).

CT in the detection of metastases of HCC in comparison with sizes of detected lesions, with an area under the receiver operating characteristic curve of 73%, had a sensitivity of 100%, specificity of 48%, positive predictive value of 95.7, and negative predictive value of 50.1 [Figure 4].
Figure 4: Sensitivity and specificity of computed tomography in detection of metastases of hepatocellular carcinoma in comparison with sizes of detected lesions. The area under the ROC curve was 73%, with sensitivity 100% and specificity 48%, and positive predictive value (PPV) was 95.7 and negative predictive value (NPV) 50.1. ROC, receiver operating characteristic.

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  Discussion Top


Triphasic multidetector computed tomography is an important diagnostic imaging technique for documentation and establishing the diagnosis of metastases of HCC. Clinical examination alone is inaccurate in determining the presence of HCC or its metastases, with a clinical diagnostic accuracy of 20–30%[6].

Triphasic (CT) after bolus injection of contrast medium improves detection and characterization of hepatic tumor and its metastases as the hypervascular HCC and its metastases can be detected by easily evaluating by the enhancement pattern, in arterial (enhanced), veno us (wash out) and delayed phases (washout)[6].

Our study included 79 patients with extrahepatic metastases of HCC. There were 16 females and 63 males, with age range from 20 to 75 years. Male predominance was noted by a ratio of ∼4: 1. The common age group in both males and females is above 60 year. Although the number of our cases is way smaller than those studied by Zhang and Sun[7], the percentage matched. They found in their study of Surveillance, Epidemiology, and End-Results population-based data of liver cases that 70.9% were males and 29.1% were females. The median age was 39 years in the younger age group and 66 years in the older age group.

Twenty-two patients (representing 27.8%) showed intrahepatic vascular invasion, 14 patients had portal vein invasion, four patients had hepatic vein invasion, and four patients had both hepatic and portal vein invasions. Kikuchi et al.[8] on the contrary, found direct invasion of the portal vein in only three of 74 patients. The difference is probably attributed to the fact that their study included only liver lesions below 20 mm.

Our study shows lymph node metastases in 44 cases, representing 55.6%, which is considered the most common site for extrahepatic metastases. This matched with Katyal et al.[9] who found that lymphatic spread of HCC was found with a frequency of 27–42% in three different autopsy series. The most common spread is regional, particularly in perihepatic, peripancreatic, and retroperitoneal locations.

Lung metastases were reported in 12 (15%) of 79 cases without pleural or endobronchial invasion. This matched Katyal et al.[9] who found that hematogenous dissemination to the pulmonary capillary network is the likely mechanism of spread to the lung and has a reported prevalence of 18–60% in the form of noncalcified soft-tissue nodules within the lung parenchyma.

Our study shows that bone metastases also occur with HCC, which were present in 10 (12.6%) case of 79 cases. This matched with Natsuizaka et al.[10] who found that bone metastasis was detected in 6–39% of all extrahepatic metastases and was invariably lytic metastasis.

Three cases with adrenal gland invasion (3.7%) were found: two cases founded in right side and one in left side. Natsuizaka et al.[10] on the contrary reported the adrenal gland as the next most common route of hematogenous spread and was found in 8–17% of cases reviewed. They also reported that adrenal metastases may be the first manifestation of extrahepatic HCC with the right side usually more affected than the left. The difference is probably attributed to the difference in the study population and the number of the studied cases.

Our study included seven (8%) of 79 patients who had peritoneal deposition. This matched with Natsuizaka et al.[10] who found that HCC can directly infiltrate the diaphragm and disseminate into the peritoneum, and this was founded in 5–17% of cases reviewed.

Other reported rare sites of metastases were brain and orbit. Natsuizaka et al.[10] on the contrary reported other sites of metastases, including the kidney and the ovary.

Comparing the tumor size to the associated metastases revealed less nodal metastases and portal vein invasion in tumors more than 3 cm (49 patients with tumor size more than 3 cm showed lymph node metastases in 14 cases and portal vein invasion in 10 cases). However, smaller tumors (≤3 cm, n = 30) were presented by more lymph node metastases (n = 23) and more portal vein invasion (n = 12). On the contrary, distant metastases, including lung metastases (n = 10), bone metastases (n = 6), peritoneal deposition (n = 4), and adrenal invasion (n = 3), were founded to be more common with larger tumors and less in smaller tumors. Our results did not match with Jun et al.[11] who reported that of the 140 patient with small lesions less than 3 cm, there were 66 patient with extrahepatic metastases and 56 patient with vascular invasion; however, with larger lesion above 3 cm, there were 69 patient with extrahepatic metastases and 79 patient with vascular invasion. The difference is probably attributed to the different study population.


  Conclusion Top


As triphasic multidetector computed tomography is considered the gold standard imaging modality for diagnosis of HCC, it also provides a good tool for assessing the expected extrahepatic metastases that may be present at the time of diagnosis, even without clinical manifestations.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Kikuchi LO, Pranagua-Vezozoo DC, Chagas AL. Nodules less than 20mm and vascular invasion are predictors of survival in small hepatocellular carcinoma. J Clin Gastroenterol 2008; 46:2022–2027.  Back to cited text no. 8
    
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Katyal S, Oliver JH, Peterson MS, Ferris JV, Carr BS, Baron RL. Extrahepatic metastases of hepatocellular carcinoma. Radiology 2000; 216:698–703.  Back to cited text no. 9
    
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Natsuizaka M, Omura T, Akaike T. Clinical features of hepatocellular carcinoma with extrahepatic metastases. J Gastroenterol Hepatol 2005; 20:1781–1787.  Back to cited text no. 10
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2]



 

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