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ORIGINAL ARTICLE
Year : 2016  |  Volume : 29  |  Issue : 2  |  Page : 291-296

Multidetector computed tomography in the detection of hepatocellular carcinomas meeting the Milan criteria before liver transplantation


1 Department of Radiology, Faculty of Medicine, Menoufia University, Shebin El Kom, Egypt
2 Department of Radiology, National Liver Institute, Menoufia University, Shebin El Kom, Egypt

Date of Submission22-Feb-2015
Date of Acceptance16-Apr-2015
Date of Web Publication18-Oct-2016

Correspondence Address:
Sarah A Mohammed
Radiology Department, National Liver Institute, Menoufia University, 5 Taisser Street, Shebin El Kom, Menoufia Governorate, 32511
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.192448

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  Abstract 

Objective:
The purpose of this study was to assess the diagnostic performance of multidetector computed tomography (MDCT) in the detection of hepatocellular carcinoma (HCC) in cirrhotic patients who are recommended for liver transplantation according to the Milan criteria.
Background:
Liver transplantation has been considered to be the only causal treatment for patients with liver cirrhosis and HCC because of its theoretical advantage of eliminating both the tumor and liver disease. However, because of the shortage of donor organs, it is strongly recommended that liver transplantations be performed on cirrhotic patients with HCCs only when the patients meet the predetermined criteria. Imaging is thus decisive in the inclusion or exclusion of patients from transplantation lists.
Patients and methods:
This study included 35 patients (29 male and six female) with ages ranging from 39 to 60 years presented to the Transplantation Unit of the National Liver Institute, Menoufia University, during the period between May 2013 and December 2014. Potential recipients with focal lesion on their ultrasound underwent triphasic computed tomography. After liver transplantation, the imaging findings were correlated with histopathological findings in the explanted livers on a patient-by-patient and a lesion-by-lesion basis.
Results
Histopathologic examination revealed 46 HCCs in 31 of 35 patients, whereas MDCT revealed 42 HCCs in 30 of 35 patients. A patient-by-patient analysis showed that the sensitivity of MDCT in the detection of HCC was 90.3%, its specificity was 50%, and its accuracy was 85.7%.
Conclusion:
MDCT has reasonable sensitivity and high diagnostic accuracy in the detection of HCC in cirrhotic patients indicated for liver transplantation according to the Milan criteria.

Keywords: explanted liver, hepatocellular carcinoma, multidetector computed tomography


How to cite this article:
Elsayed EE, Koryem EM, Mohammed SA. Multidetector computed tomography in the detection of hepatocellular carcinomas meeting the Milan criteria before liver transplantation. Menoufia Med J 2016;29:291-6

How to cite this URL:
Elsayed EE, Koryem EM, Mohammed SA. Multidetector computed tomography in the detection of hepatocellular carcinomas meeting the Milan criteria before liver transplantation. Menoufia Med J [serial online] 2016 [cited 2019 Nov 14];29:291-6. Available from: http://www.mmj.eg.net/text.asp?2016/29/2/291/192448


  Introduction Top


Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer-related death; the number of new cases per year is approaching 750 000 [1].

Liver transplantation, in recent times, has become the ultimate solution for decompensating liver diseases, and it has been considered to be the only causal treatment for liver cirrhosis in patients with HCC because of its theoretical advantage of eliminating both the tumor and liver disease. However, because of the shortage of donor organs, it is strongly recommended that liver transplantations be performed on cirrhotic patients with HCCs only when the patients meet the predetermined criteria in terms of the number and extent of HCCs. Imaging is thus decisive in the inclusion or exclusion of patients from transplantation lists. The imaging techniques used are computed tomography (CT), MRI, and ultrasonography [2],[3].

The best indications for liver transplantation according to the Milan criteria are as follows: patients with a single tumor of 5 cm, or patients with fewer than three nodules not exceeding 3 cm in diameter and no macroscopic vascular invasion or extrahepatic metastases [3].

Multidetector computed tomography (MDCT) is currently considered one of the most reliable techniques for evaluating hepatic cancer in the presence of cirrhotic liver disease, and it is primarily involved in patient treatment strategies [4].

HCC can be diagnosed radiologically, without the need for biopsy, if the typical imaging features are present. This requires a contrast-enhanced study (dynamic CT-scan or MRI) [5].

The long waiting time caused by the shortage of donor organs often results in tumor progression and dropout from transplantation candidacy. To that end, United Network of Organ Sharing (UNOS) has adapted the Model for End-stage Liver Disease (MELD) criteria favoring patients with HCC so as to allocate organs according to the clinical urgency, thereby reducing the dropout rate. The diagnostic performances of imaging modalities in evaluating the appropriateness of liver transplant candidates have become of major importance [3].


  Patients and Methods Top


The study was conducted in the National Liver Institute, Menoufia University, during the period from May 2013 to December 2014. It included 35 patients (29 male and six female) with ages ranging from 39 to 60 years presented to the Transplantation Unit of National Liver Institute, Menoufia University. Patients with advanced liver disease and focal lesions on their ultrasound were included in the study. Serum creatinine was evaluated for all patients and we used it to assess glomerular filtration rate (GFR) using the following formula:

MaleGFR (ml/min) = [140 – age (years)] [weight(kg)/(serumcreatinine ×72),

FemaleGFR (ml/min) = [140 – age (years)] [weight(kg)] 0.85/(serumcreatinine ×72).

Patients with a GFR of 45 or greater can undergo CT safely, whereas the risk of dialysis after receiving contrast significantly increases in patients with GFR less than 30.

Consent was taken from patients or their relatives before CT study, and they had the right to refuse at any time. The study was approved by the Research Ethics Committee of the National Liver Institute and the Research Ethics Committee of the Faculty of Medicine, Menoufia University.

All individuals were subjected to clinical assessment including full history taking and clinical examination, laboratory investigation, ultrasound with Doppler study, and triphasic CT scanning.

CT was performed with a Siemens Somatome Definition scanner (Siemens Healthcare GmbH, Henkestr, Erlangen, Germany) (20 detectors). Patient preparation for CT was carried out as follows:

  1. Fasting for 6 h before scan;
  2. No oral contrast;
  3. Creatinine clearance more than 45;
  4. Vigorous oral hydration; and
  5. Introduction of intravenous cannula through the antecubital vein.


The patient was made to lie supine and scanning was started from the lung bases down to the symphysis pubis in all phases. One scout was acquired in the anteroposterior view. The examination was conducted on these scouts from the level of the top of the right diaphragmatic copula (hepatic dome) until the symphysis pubis in the precontrast and postcontrast sequences. The precontrast series were taken by using a section of 10 mm thickness, a slice pitch of 1.5, a gantry rotation period of 0.6 s, and a table speed of 15 mm/rotation. X-ray tube voltage was 120 kV and the current was 240–280 mA.

Multidetector CT scanner was applied to perform arterial, portovenous, and delayed phases on all patients. All patients received 120 ml of nonionic material (Ultravist 300) intravenously at an infusion rate of 4.0 ml/s using a single power injector. Arterial-dominant phase images were acquired at 18 s (collimation, 1.25 mm; pitch, 0.6; kVp, 120; mA, 240–280). Portal-dominant phase images were acquired at 60 s (collimation, 2.5 mm; pitch, 0.6; kVp, 120; mA, 240–280). Delayed phase images were also taken for the entire liver and were acquired at 200 s (collimation, 2.5 mm; pitch, 0.6; kVp, 120; mA, 240–280).

All further data were reconstructed with a standard algorithm and postprocessing was performed on a commercially available workstation (Syngo Work Station) equipped with software tool that allowed generation of three-dimensional images. We used the MIP technique for three-dimensional image reconstruction, which was helpful in the detection of details and orientation of vessels.

All scans were interpreted for the presence of HCC, which was defined as an intensely enhancing nodule in the arterial phase, followed by a well-defined area of hypoattenuation surrounding liver parenchyma in the delayed phase, and for detection of the total number, the size, and the location of nodules in liver segments in addition to the application of the Milan criteria.

Gross and histopathological analyses of the explanted livers of all our patients were performed by an experienced liver pathologist. All explanted livers were fixed in formalin and sectioned at 7–10 mm interval in the transverse plane. Each nodular lesion that was different from the background cirrhotic liver in the morphologic features, color, or size, was fixed in formalin, embedded in paraffin, and further sectioned for additional evaluation.


  Results Top


On histopathological examination of the explanted liver, 46 focal lesions (HCC) were detected, of which eight (17.4%) focal lesions were small in size (≤10 mm), 13 (28.3%) focal lesions were of intermediate size (11–20 mm), and the remaining 25 (54.3%) focal lesions were large in size (>20 mm). On ultrasound, 32 focal lesions were detected, of which six (18.8%) focal lesions were small in size, 10 (31.2%) focal lesions were of intermediate size, and the remaining 16 (50%) focal lesions were large in size. MDCT detected 42 focal lesions (HCC), of which eight (19%) focal lesions were small in size, 12 (28.6%) focal lesions were of intermediate size, and the remaining 22 (52.4%) focal lesions were large in size ([Table 1]).
Table 1 Different measurements for the size of hepatocellular carcinoma nodules among studied cases by ultrasound, multidetector computed tomography, and histopathological examination

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In an analysis based on lesion diameter, the sensitivity and positive predictive value (PPV) of MDCT were calculated for the three size groups (small, intermediate, and large) detected on the histopathological examination of the explanted liver ([Table 2] and [Figure 1]).
Table 2: Evaluation of multidetector computed tomography in the detection of different size of hepatocellular carcinoma nodules among studied cases

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Figure 1: Evaluation of sensitivity and positive predictive value of multidetector computed tomography (MDCT) in the detection of different sizes of hepatocellular carcinoma (HCC) nodules among studied cases.

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The results of the patient-by-patient analysis are reported in [Table 3], which shows sensitivity, specificity, false-positive result, false-negative result, PPV, negative predictive value (NPV), and accuracy ([Table 3] and [Figure 2]).
Table 3: Evaluation of multidetector computed tomography in the detection of hepatocellular carcinoma among studied cases

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Figure 2: Evaluation of multidetector computed tomography (MDCT) in the detection of hepatocellular carcinoma (HCC) among studied cases on a patient-by-patient basis.

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Comparison between the histopathological results and MDCT results revealed that the number of HCC nodules that were detected on histopathology as regards size was 34 (80.9%). The number of HCC nodules underestimated by MDCT was seven (16.7%), and the number of HCC nodules overestimated by MDCT was one (2.4%) ([Table 4]).
Table 4: Measurements of computed tomography for hepatocellular carcinoma nodules versus pathology among studied cases

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Application of the Milan criteria on the basis of CT results and after histopathological finding showed that five patients had no HCC nodules on their CT, three of them proved to have HCC nodules in their explant and the pathology report of the other two patients was identical to the result of CT. The other 30 patients with HCC nodules in their CT were within the Milan criteria after correlation with pathology results. Twenty-six (86.7%) patients had HCC nodules within the Milan criteria, two (6.7%) patients had HCC nodules beyond the Milan criteria, and two patients did not have HCC nodules. On comparison between the Milan criteria after CT and that after pathology we noticed that there was no significant difference (P = 0.09) ([Table 5] and [Figure 3] and [Figure 4]).
Table 5: Comparison between the Milan criteria after computed tomography and that after histopathological findings

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Figure 3: Axial images at arterial, portovenous, and delayed phases, respectively, revealed left lobe focal lesion with enhancement at the arterial phase and washout at the portovenous and the delayed phase.

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Figure 4: Computed tomography axial images at arterial, portovenous, and delayed phases, respectively, revealed right lobe focal with enhancement at the arterial phase and washout at the portovenous and the delayed phase.

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  Discussion Top


HCC is a global health problem, with the incidence of the disease expected to increase in the coming years. Patients who are at increased risk for developing HCC undergo routine imaging surveillance; once a focal abnormality is detected, evaluation with multiphasic contrast material-enhanced CT or MRI is necessary for diagnosis and staging [6].

MDCT is currently considered one of the most reliable techniques for evaluating hepatic cancer in the presence of cirrhotic liver disease, and it is primarily involved in patient treatment strategies [4].

In our study, the comparison of imaging with histopathological findings showed that MDCT has acceptable diagnostic performance in the detection of HCC in patients with cirrhotic liver disease.

The histopathological examination revealed 46 HCCs in 31 of 35 patients, of which eight were small in size (≤10 mm), 13 were of intermediate size (11–20 mm), and the remaining 25 were large in size (>20 mm), whereas MDCT detected 42 HCCs in 30 of 35 patients, of which eight HCC were small in size, 12 were of intermediate size, and the remaining 22 were large in size. Histopathological examination by Kim et al. [3] revealed 139 HCCs in 48 patients, of which 60 HCC were small in size, 42 were intermediate in size, and 37 were large. MDCT correctly depicted 89 of 139 HCCs.

As expected, in our study the performance of MDCT was related to the lesion size. The sensitivity of MDCT for nodules decreased with lesion size. We found very good sensitivity for HCCs larger than 20 mm (88%), acceptable sensitivity for nodules measuring 11–20 mm (84.6%), and low sensitivity for nodules 10 mm or smaller (62.5%). The difference in sensitivities may be due to the altered hepatic structure from cirrhosis, which reduces the conspicuity of small HCC lesions and makes their characterization difficult.

We noticed that not only sensitivity but also the PPV of MDCT decreased with lesion size; these values were quite low for small nodules (62.5%), increased to an acceptable level for nodules of intermediate size (91.7%), and were very good for nodules larger than 20 mm (100%).

In comparison with the study by Ronzoni et al. [7], the results were as follows: the sensitivity for small nodules was 47%, the sensitivity for intermediate nodules was 76%, the sensitivity for large nodules was 89%, the PPV for small nodules was 53%, the PPV for intermediate nodules was 61%, and the PPV for large nodules was 97%. Therefore, small nodules should be strictly monitored for size changes at follow-up, or should be studied with additional imaging, and the histopathologic slice thickness should not be greater than the CT slice thickness.

This study revealed that the sensitivity of MDCT in the detection of HCC using a patient-by-patient analysis was 90.3%, its specificity was 50%, false-positive result was 50%, false-negative result was 9.7%, PPV was 93.3%, NPV was 40%, and its accuracy was 85.7%. A previous study by Lim et al. [8], Libbrecht et al. [9], Teefey et al. [0], and Freeny et al. [1], revealed 80, 50, 67, and 85.5% sensitivity and 96,79, 75, and 92.5% specificity, respectively. Ronzoni et al. [7] reported a sensitivity of 77% and a specificity of 75%, false-negative result of 11%, false-positive result of 10%, PPV of 78.7%, NPV of 73.1%, and accuracy of 76.1%. The low sensitivity reported in this study could be due to the fairly high slice thickness (5–10 mm) and imaging during the early arterial phase. It is well known that, to obtain the best conspicuity of lesions, arterial phase images should be acquired 30–35 s after injection of contrast material. In contrast, the high false-positive rate in our study might have been related to overlooking nodules at histopathological examination, because the histopathological slice thickness was greater than the CT slice thickness.

This study showed that five patients showed no HCC nodule on their CT, three of them proved to have HCC nodules in their explant and the pathology report of the other two patients were identical to the result of CT. The other 30 patients with HCC nodules in their CT were within the Milan criteria after correlation with histopathological results. Twenty-six (86.7%) patients had HCC nodules within the Milan criteria, two (6.7%) patients had HCC nodules beyond the Milan criteria, and two patients did not have HCC nodules. There was no significant difference in our study between the Milan criteria based on CT results and that after histopathological findings (P = 0.09); however; small hypervascular nodules should be strictly monitored for size changes at follow-up, or should be studied with MRI.

In our study, after comparison between the histopathological results and MDCT results, the number of HCC nodules were underestimated in 16.7% of cases and overestimated in 2.4% of cases. Ronzoni et al. [7] showed that the number of HCC nodules was underestimated in 25% of cases and overestimated in 19% cases. Some studies have shown that the Milan criteria may be too strict and that ∼50% of patients receiving transplants outside the Milan criteria survive 5 years. Thus, it is better that MDCT findings lead to an underestimation of disease extent rather than an overestimation, which would exclude patients from transplantation who would benefit from it.


  Conclusion Top


MDCT has reasonable sensitivity and high diagnostic accuracy in the detection of HCC in cirrhotic patients indicated for liver transplantation according to the Milan criteria.

Conflicts of interest

There are no conflicts of interest.[11]

 
  References Top

1.
Mazzaferro V, Bhoori S, Sposito C, Bongini M, Langer M, Miceli R, Mariani L. Milan criteria in liver transplantation for hepatocellular carcinoma: an evidence-based analysis of 15 years of experience. Liver Transpl 2011; 17(Suppl 2):44–57.  Back to cited text no. 1
    
2.
Elkholy M, Elshazly H. Role of three-dimensional multidetector computed tomography angiography of hepatic vessels in the evaluation of living donors. Menoufia Med J 2014; 27:157–163.  Back to cited text no. 2
  Medknow Journal  
3.
Kim SH, Choi BI, Lee JY, Kim SJ, So YH, Eun HW, et al. Diagnostic accuracy of multi-/single-detector row CT and contrast-enhanced MRI in the detection of hepatocellular carcinomas meeting the Milan criteria before liver transplantation. Intervirology 2008; 51(Suppl 1):52–60.  Back to cited text no. 3
    
4.
Mortelé KJ, De Keukeleire K, Praet M, Van Vlierberghe H, de Hemptinne B, Ros PR. Malignant focal hepatic lesions complicating underlying liver disease: dual-phase contrast-enhanced spiral CT sensitivity and specificity in orthotopic liver transplant patients. Eur Radiol 2001; 11:1631–1638.  Back to cited text no. 4
    
5.
Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53:1020–1022.  Back to cited text no. 5
    
6.
Purysko AS, Remer EM, Coppa CP, Leão Filho HM, Thupili CR, Veniero JC. LI-RADS: a case-based review of the new categorization of liver findings in patients with end-stage liver disease. Radiographics 2012; 32:1977–1995.  Back to cited text no. 6
    
7.
Ronzoni A, Artioli D, Scardina R, Battistig L, Minola E, Sironi S, Vanzulli A. Role of MDCT in the diagnosis of hepatocellular carcinoma in patients with cirrhosis undergoing orthotopic liver transplantation. Am J Roentgenol 2007; 189:792–798.  Back to cited text no. 7
    
8.
Lim JH, Cho JM, Kim EY, Park CK. Dysplastic nodules in liver cirrhosis: evaluation of hemodynamics with CT during arterial portography and CT hepatic arteriography. Radiology 2000; 214:869–874  Back to cited text no. 8
    
9.
Libbrecht L, Bielen D, Verslype C, Vanbeckevoort D, Pirenne J, Nevens F, et al. Focal lesions in cirrhotic explant livers: pathological evaluation and accuracy of pretransplantation imaging examinations. Liver Transpl 2002; 8:749–761.  Back to cited text no. 9
    
10.
Teefey SA, Hildeboldt CC, Dehdashti F, Siegel BA, Peters MG, Heiken JP, et al. Detection of primary hepatic malignancy in liver transplant candidates: prospective comparison of CT, MR imaging, US, and PET. Radiology 2003; 226:533–542.  Back to cited text no. 10
    
11.
Freeny PC, Grossholz M, Kaakaji K, Schmiedl UP. Significance of hyperattenuating and contrast-enhancing hepatic nodules detected in the cirrhotic liver during arterial phase helical CT in pre-liver transplant patients: radiologic–histopathologic correlation of explanted livers. Abdom Imaging 2003; 28:333–346.  Back to cited text no. 11
    


    Figures

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

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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