Differentiating small arterial only enhancing hepatocellular carcinoma from nontumorous arteroportal shunt with an emphasis on the precontrast phase

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1 Differentiating small arterial only enhancing hepatocellular carcinoma from nontumorous arteroportal shunt with an emphasis on the precontrast phase Poster No.: C-0739 Congress: ECR 2015 Type: Scientific Exhibit Authors: B. M. Chung, H. J. Park, S. B. Park, J. B. Lee, H. S. Ahn, Y. S. Kim; Seoul/KR Keywords: DOI: Abdomen, CT, Imaging sequences, Cirrhosis /ecr2015/C-0739 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 15

2 Aims and objectives A small arterial enhancing lesion with isoattenuation on portal venous phase or delayed phase (a so-called small arterial enhancing lesion) in patients with chronic liver disease presents diagnostic dilemma because the differential diagnosis includes small hepatocellular carcinoma (HCC) with atypical vascular pattern as well as benign hypervascular lesion, such as non-tumorous arterioportal (AP) shunt [1-4]. Most of the small arterial enhancing lesions are usually further evaluated with followup computed tomography (CT), magnetic resonance imaging (MRI) or core needle biopsy. However, earlier detection of atypical and small HCC with increased diagnostic confidence on preexisting CT imaging tool could achieve long-term survival and lead to lower needs of follow-up CT or MRI, improving cost-effectiveness [5]. We hypothesized that the attenuation of HCC on precontrast phase would be lower than that of liver parenchyma, while the AP shunt would be isoattenuated on precontrast phase. This poster aimed to evaluate the value of the precontrast phase on liver dynamic CT for differentiation of small arterial enhancing HCC from AP shunt in patients with chronic liver disease. Methods and materials Study population Fig. 1 on page 4 is a flowchart that summarizes the inclusion process in this study. [6-10]. The final cohort included 23 patients with 28 HCCs and 25 patients with 28 AP shunts (5-20mm). Five patients with HCCs and 3 patients with AP shunts had two lesions each. CT technique All patients underwent quadriphasic liver CT, including precontrast phase, arterial phase, portal venous phase, delayed phase images. Page 2 of 15

3 Image analysis 1. Qualitative and quantitative analysis 1) Morphologic features [1] - Size: the longest dimension on axial images - Location: 'subcapsular' or 'non-subcapsular' - Shape: 'Irregular' or 'round or oval' - Margin: 'well-defined' or 'ill-defined' - Coexistent HCC: present or absent 2) Visual assessment for attenuation of lesions - Classified as hypo, iso, or hyper compared with the liver parenchyma 3) Quantitative analysis - The attenuation of each lesion and liver parenchyma was measured using ROIs and the lesion-to-liver attenuation ratios were calculated, comparing the attenuation of lesion divided by that of liver parenchyma 2. Evaluation of the added value of precontrast phase for differentiating small HCC from AP shunt Two gastrointestinal radiologists independently reviewed the CT images; two reading sessions for two image sets (triphasic and quadriphasic CT images) with 4-weeks interval. Imaging features that favors HCC or AP shunt are listed in Table 1 on page 4 [1, 3]. Five-point confidence scale was used as follows: 1, definitely HCC; 2, probably HCC; 3, indeterminate; 4, probably AP shunt; 5, definitely AP shunt. Statistical analysis Differences in the imaging features between HCC and AP shunt - Univariate analysis (chi-square test, Fisher's exact test, Student's t-test, and Mann- Whitney test). Page 3 of 15

4 - Multivariate logistic regression analysis. Diagnostic predictive values - McNemar test Analysis of underdiagnosis and overdiagnosis - Overdiagnosis: confidence levels of #3 that were confirmed as AP shunt - Underdiagnosis: confidence levels of #4 that were confirmed as HCC Interobserver agreement: kappa (#) statistics. A p value less than 0.05 was considered significant. Images for this section: Fig. 1: Flow chart of the inclusion process of study group. The numbers in parentheses are number of lesions. Page 4 of 15

5 Table 1: To evaluate the added value of precontrast images, two radiologists reviewed CT images in 2 sessions. At 1st session triphasic CT images were given. Location, shape and margin were used to determine the diagnosis of HCC or AP shunt. At 2nd reading session, additional precontrast images were given. hypoattenuation on precontrast image was regarded to favor HCC and isoattenuation was regarded to favor AP shunt. Page 5 of 15

6 Results 1. Qualitative and quantitative analysis The result of univariate and multivariate analysis for the predictive variables of HCC are summarized in Table 2 on page Evaluation of the added value of precontrast phase for differentiating small HCC from AP shunt Table 3 on page 7 shows the diagnostic predictive values for both observers of each reading session. Additional interpretation of precontrast phase enabled the two observers to correct several diagnostic errors made on the review of triphasic CT (Fig. 2 on page 8). - Eleven cases were overdiagnosed on triphasic CT by both observers, and all these cases were corrected by additional review of precontrast phase with isoattenuation (Fig. 3 on page 9). - Five cases were underdiagnosed on triphasic CT by both observers, two cases were correctly diagnosed by additional review of precontrast phase and the remaining three cases were uncorrected. Both of the corrected lesions revealed hypoattenuation (Fig. 4 on page 10). Whereas all of three uncorrected lesions revealed isoattenuation on precontrast phase (Fig. 5 on page 10). Images for this section: Page 6 of 15

7 Table 2: Univariate and multivariate Analyses for predictive variables of hepatocellular carcinoma in small arterial enhancing nodules of the liver. Round or oval shape, welldefined margin, visual hypoattenuation of the lesion to liver on precontrast phase, and low lesion-to-liver attenuation ratio on precontrast phase were significant parameters associated with HCC on univariate analysis. On multivariate analysis,round or oval shape and visual hypoattenuation of the lesion to liver on precontrast phase were independent predictors for differentiating small HCCs from AP shunts. Page 7 of 15

8 Table 3: Comparison of diagnostic performance and kappa value between triphasic and quadriphasic CT in prediction of AP shunt. The diagnostic performance in the prediction of AP shunt improved significantly for both observers after additional review of the precontrast phase. Interobserver agreement for observers 1 and 2 was fair for the triphasic CT (# = 0.323) but good for the quadriphasic CT (# = 0.740). Az, area under the ROC curve; ROC, receiver operating characteristic. Page 8 of 15

9 Fig. 2: Evaluation of over and underdiagnosis. Eleven AP shunts were overdiagnosed on triphasic CT and all of them were corrected after adding precontrast images with isoattenuation. Five HCCs were underdiagnosed on triphasic CT, After adding precontrast image, 3 cases were still underdiagnosed with isoattenuation, and other 2 cases were corrected due to hypoattenuation on precontrast image. Page 9 of 15

10 Fig. 3: A 68-year-old man with an arterioportal (AP) shunt. A small enhancing lesion (arrow) in hepatic segment 5 is only identified on arterial phase (a) without distinguishing from background liver on delayed phase (b). The arterial enhancing lesion was overdiagnosed as hepatocellular carcinoma on triphasic CT because of non-subcapsular location, round shape, and well-defined margin. After additional review of precontrast phase images (c), it was correctly diagnosed as AP shunt with isoattenuation on precontrast phase. A small hepatic cyst is noted in hepatic segment 6 (arrowheads). Fig. 4: A 53-year-old woman with a hepatocellular carcinoma (HCC). A small enhancing lesion (arrow) in hepatic segment 4 is only identified on arterial phase (a) without distinguishing from background liver on delayed phase (b). The arterial enhancing lesion was underdiagnosed as an arterioportal shunt on triphasic CT because of nonsubcapsular location, irregular shape, and ill-defined margin. After additional review of precontrast phase images (c), it was correctly diagnosed as HCC with hypoattenuation on precontrast phase (arrow). Page 10 of 15

11 Fig. 5: A 76-year-old woman with a hepatocellular carcinoma (HCC). A small enhancing lesion (arrow) in hepatic segment 3 is only identified on arterial phase (a) without distinguishing from background liver on delayed phase (b). The arterial enhancing lesion was underdiagnosed as an arterioportal (AP) shunt on triphasic CT because of subcapsular location, irregular shape, and ill-defined margin. The lesion was interpreted as AP shunt in both observers even after additional review of precontrast phase due to isoattenuation on precontrast phase image (c). This lesion was confirmed as a HCC by gadoxetic acid-enhanced MRI (not shown) and sustaining staining of iodized oil (arrow) after transcatheter arterial chemoembolization (d). Page 11 of 15

12 Conclusion 1. Previous studies that have evaluated the additional role of precontrast phase in the detection of HCC Some investigators found no merit of adding precontrast phase [12, 13]. However, Oliver et al. [14] reported that the additional review of precontrast phase with portal venous phase images led to detection of % additional lesions, which were not identified on the portal venous images. Kim et al. [15] have also demonstrated that the addition of precontrast phase to the biphasic CT increased the detection and diagnostic confidence in assessment of viable tumors in patients with HCC treated with TACE. In our study, eleven of 28 (39%) HCCs demonstrated hypoattenuation on the precontrast phase, whereas no AP shunts showed hypoattenuation. Visual hypoattenuation of the lesion on precontrast phase was an independent predictor for HCC detection with arterial enhancing feature, which is comparable result with two previous studies [14, 15]. The discrepancy among these studies could be explained by the differences in the study design and study populations. In other words, previous two studies [12, 13] only enrolled the cases with washout on portal venous phase or delayed phase and with or without arterial enhancement. Although the role of precontrast image still remains controversial, we believe the precontrast phase is useful tool for the detection of small HCCs with atypical enhancement. 2. Reason that HCCs frequently show hypoattenuation on precontrast phase Although the reason is unclear, Takayasu et al. reported that the amount of fat in tumor cells is closely related with the attenuation of tumor on precontrast phase [16]. In addition, presumably it is because HCCs have heterogeneous organization and can contain hemorrhage, necrosis and fibrous or cystic degeneration according to cellular differentiation. In contrast, AP shunts show a preservation of hepatic structures and cellular compartments because it is only a perfusion gradient between the artery and portal vein that results in a higher arterial inflow [6, 17]. 3. HCCs with atypical vascular pattern Page 12 of 15

13 Several studies reported that small (< 2cm) or well-differentiated HCC frequently shows atypical vascular pattern including arterial enhancement with isoattenuation on the portal venous or delayed phases, as like HCCs included in this study [18-20]. These results also suggest that we cannot easily exclude the diagnosis of HCC when a small arterial enhancing nodule is identified in clinical practice. Therefore, precontrast phase can be helpful to distinguish small arterial enhancing lesions between AP shunts and HCCs. Conclusion Visual hypoattenuation of the lesion on precontrast phase and round or oval shape are independent predictors for differentiating small arterial enhancing HCCs from atypical AP shunts. Therefore, the precontrast phase on quadriphasic CT scans can be helpful in differentiating small HCCs from AP shunts with increased diagnostic accuracy, sensitivity, and improved interobserver agreement. Careful evaluation of the precontrast phase may reduce unnecessary imaging study or procedure, and possibly can achieve earlier diagnosis of small HCCs. Personal information References 1. Park MJ, Kim YS, Lee WJ, Lim HK, Rhim H, Lee J (2010) Outcomes of follow-up CT for small (5-10-mm) arterially enhancing nodules in the liver and risk factors for developing hepatocellular carcinoma in a surveillance population. Eur Radiol 20: Quaia E, Pizzolato R, De Paoli L, Angileri R, Ukmar M, Cova MA (2013) Arterial enhancing-only nodules less than 2 cm in diameter in patients with liver cirrhosis: predictors of hepatocellular carcinoma diagnosis on gadobenate dimeglumine-enhanced MR imaging. J Magn Reson Imaging 37: Hwang SH, Yu JS, Kim KW, Kim JH, Chung JJ (2008) Small hypervascular enhancing lesions on arterial phase images of multiphase dynamic computed tomography in cirrhotic liver: fate and implications. J Comput Assist Tomogr 32:39-45 Page 13 of 15

14 4. O'Malley ME, Takayama Y, Sherman M (2005) Outcome of small (10-20 mm) arterial phase-enhancing nodules seen on triphasic liver CT in patients with cirrhosis or chronic liver disease. Am J Gastroenterol 100: Forner A, Reig ME, de Lope CR, Bruix J (2010) Current strategy for staging and treatment: the BCLC update and future prospects. Semin Liver Dis 30: Ahn JH, Yu JS, Hwang SH, Chung JJ, Kim JH, Kim KW (2010) Nontumorous arterioportal shunts in the liver: CT and MRI findings considering mechanisms and fate. Eur Radiol 20: Choi BI, Lee KH, Han JK, Lee JM (2002) Hepatic arterioportal shunts: dynamic CT and MR features. Korean J Radiol 3: Huppertz A, Haraida S, Kraus A et al (2005) Enhancement of focal liver lesions at gadoxetic acid-enhanced MR imaging: correlation with histopathologic findings and spiral CT--initial observations. Radiology 234: Kim SH, Kim SH, Lee J et al (2009) Gadoxetic acid-enhanced MRI versus triple-phase MDCT for the preoperative detection of hepatocellular carcinoma. AJR Am J Roentgenol 192: McEvoy SH, McCarthy CJ, Lavelle LP et al (2013) Hepatocellular carcinoma: illustrated guide to systematic radiologic diagnosis and staging according to guidelines of the American Association for the Study of Liver Diseases. Radiographics 33: Cohen J (1968) Weighted kappa: nominal scale agreement with provision for scaled disagreement or partial credit. Psychol Bull 70: Iannaccone R, Laghi A, Catalano C et al (2005) Hepatocellular carcinoma: role of unenhanced and delayed phase multi-detector row helical CT in patients with cirrhosis. Radiology 234: Doyle DJ, O'Malley ME, Jang HJ, Jhaveri K (2007) Value of the unenhanced phase for detection of hepatocellular carcinomas 3 cm or less when performing multiphase computed tomography in patients with cirrhosis. J Comput Assist Tomogr 31: Oliver JH, 3rd, Baron RL, Federle MP, Rockette HE, Jr. (1996) Detecting hepatocellular carcinoma: value of unenhanced or arterial phase CT imaging or both used in conjunction with conventional portal venous phase contrast-enhanced CT imaging. AJR Am J Roentgenol 167: Kim HC, Kim AY, Han JK et al (2002) Hepatic arterial and portal venous phase helical CT in patients treated with transcatheter arterial chemoembolization for hepatocellular carcinoma: added value of unenhanced images. Radiology 225: Takayasu K, Furukawa H, Wakao F et al (1995) CT diagnosis of early hepatocellular carcinoma: sensitivity, findings, and CT-pathologic correlation. AJR Am J Roentgenol 164: Yu JS, Kim KW, Jeong MG, Lee JT, Yoo HS (2000) Nontumorous hepatic arterialportal venous shunts: MR imaging findings. Radiology 217: Lee JH, Lee JM, Kim SJ et al (2012) Enhancement patterns of hepatocellular carcinomas on multiphasicmultidetector row CT: comparison with pathological differentiation. Br J Radiol 85:e Page 14 of 15

15 19. Yoon SH, Lee JM, So YH et al (2009) Multiphasic MDCT enhancement pattern of hepatocellular carcinoma smaller than 3 cm in diameter: tumor size and cellular differentiation. AJR Am J Roentgenol 193:W Jang HJ, Kim TK, Burns PN, Wilson SR (2007) Enhancement patterns of hepatocellular carcinoma at contrast-enhanced US: comparison with histologic differentiation. Radiology 244: Page 15 of 15