Diagnostic accuracy of color Doppler in diagnosis of Hepatocellular carcinoma taking histopathology as gold standard

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third most common cause of cancer mortality. Despite the high numbers of patients diagnosed worldwide, HCC continues to pose challenging clinical problems. Good-quality ultra sound with careful evaluation of the entire liver can be a screening examination for HCC in patients at risk. The aim of the study was to determine the diagnostic accuracy of the Doppler sonography for differentiation of hepatocellular carcinoma (HCC) from other focal liver lesions by taking histopathology as a gold standard. It was a cross-sectional survey, conducted in the Department of Diagnostic Radiology, King Edward Medical University/Mayo Hospital, Lahore in one year from 13-12-2010 to 12-12-2011. A total of 70 patients were included in this study with focal lesions on ultrasound are included while pregnant patients are excluded. After evaluating by Doppler sonography and doing core biopsy, the patients were sent to the Department of Pathology, Mayo Hospital for histopathological examination. Histopathology was assessed for confirmation of positive and negative cases. Mean age of the patients was 60.9 ± 4.7 years. Out of 70 patients, 47 patients (67.1%) were male while remaining 23 patients (32.9%) were female. On Doppler sonography 37 cases were positive for hepatocellular carcinoma and 33 cases were negative while 36 cases were positive and 34 negative on histopathology. On Doppler sonography, sensitivity (94.4%), specificity (91.1%), diagnostic accuracy (92.8%), positive predictive value (91.8%) and negative predictive value was 93.9%. We concluded that Doppler sonography is a useful method for differen-

tiation of Hepatocellular carcinoma from other focal liver lesions, detection and characterization of hepatocellular carcinoma.

Share and Cite:

Ali, W. , Saba, K. , Zaidi, N. , Majeed, T. and Bukhari, M. (2013) Diagnostic accuracy of color Doppler in diagnosis of Hepatocellular carcinoma taking histopathology as gold standard. Journal of Biomedical Science and Engineering, 6, 609-614. doi: 10.4236/jbise.2013.66077.

1. INTRODUCTION

Hepatocellular carcinoma (HCC) is a malignancy of the hepatoyte, usually leading to death within 6 - 20 months. Its prevalence is 2% of all malignancies. Hepatocellular carcinoma often arises in the setting of cirrhosis, appearing 20 - 30 years following the initial insult to the liver. However, 25% of patients have no history of risk factor for the development cirrhosis [1].

HCC is the 8th most common cancer in women and 5th most frequent cancer in men world-wide. The incidence of HCC changes according to the occurrence of hepatitis B and C infections. In Asia and sub-Saharan Africa HCC have high rates of infectious hepatitis with incidences of 120 cases per 100,000 [2]. The most common malignancy of the liver is metastases from other organs: 25% - 50% patients with a known non-hematological malignancy have liver metastases at the time of diagnosis [3].

Moreover, differential diagnosis of these liver lesions is difficult, even with clinical, biochemical data, and imaging techniques [4-9]. Recently Doppler sonography has been used to characterize focal hepatic lesions with a higher diagnostic confidence [10]. The detection rate (sensitivity) of colour Doppler sonography to detect the malignant tumours has been reported 92% as compared its Histopathological findings [11,12]. Lin et al. done a study for differential diagnosis of hepatocellular carcinoma and metastasis in 54 patients with at least one lesion measuring diameter <3 cm and found the sensitivity and specificity of Doppler ultrasonography for hepatocellular carcinoma was 80.8% and 96.4%, respectively [13].

In our setup some invasive and costly techniques such as MRI, histopathology and CT scan are used to detect these lesions. Studies on colour Doppler sonography has not been established before, hence this study has been designed to see the diagnostic role of Doppler sonography in detection and differentiation of hepatocellular carcinoma (HCC) by taking histopathology as a gold standard.

This study will help us to choose this non-invasive and cheep diagnostic tool if it will be high effective as reported in the previous literature.

The study was conducted to determine the diagnostic accuracy of the Doppler sonography for differentiation of hepatocellular carcinoma (HCC) from other focal liver lesions by taking histopathology as a gold standard.

2. MATERIAL AND METHODS

A cross sectional study was conducted in the Department of Radiology and Pathology on 70 patients presented with intra hepatic lesions, coming from the indoor and outdoor patents of Mayo Hospital, Lahore.

After meeting inclusion and exclusion criteria about 70 patients, referred from other departments of Mayo Hospital were enrolled in the study. All basic demographic information of each patient was obtained on proforma after informed consent. By using covex probes 2.5 - 3.5 MHz scanning was done at the department of Radiology, Mayo Hospital, Lahore by a single radiologist. The colour Doppler scan was optimized for each patients using low PRF (to obtained accurate results), high gain and filter setting. At first morphological characteristics of lesions including echogenicity, posterior enhancement, echogenic rim and target appearance was seen by Bmode sonography. This presence and or absence of heaptocellular carcinoma (as per operational definition) were assessed. After evaluating by Doppler sonography and doing CORE biopsy, the patients were sent to Department of Pathology Mayo hospital for Histopathological examination. Then the report of histopathology was assessed for confirmation of positive and negative cases.

2.1. Study Design

Cross sectional.

2.2. Study Settings

Department of Diagnostic Radiology, King Edward Medical University/Mayo Hospital, Lahore.

2.3. Duration of Study

Study was carried out over a period of one year from 13-12-2010 to 12-12-2011.

2.4. Sample Size

A total of 70 patients with 95% confidence level, 5% margin of error and expected percentage of HC i.e 48.78% and taking sensitivity and specificity of Doppler USG i.e. 80.8% and 96.4%, respectively taking histopathology as gold standard.

2.5. Sampling Technique

A Non-probability purposive sampling was suggested for this study.

2.6. Sample Selection

The patients were selected according to following criteria.

2.7. Inclusion Criteria

1) Confirmed patients of focal liver lesions diagnosed on ultrasonography (USG) having age 20 - 70 years with either sex with the positive history of hepatitis B hepatictis C and cirrhosis.

2) Lesions of <3 cm of size detected on USG.

2.8. Exclusion Criteria

Pregnant females.

2.9. Hepatocellular Carcinoma

Labeled on Doppler sonography if resistive index value was <0.4.

2.10. Resistive Index (RI)

Measured by formula = (systolic peak frequency – enddiastolic frequency/peak systolic frequency.

2.11. True Positive

Diagnosed as HCC on Doppler sonography and confirmed on histopathology.

2.12. True Negative

Diagnosed as non-HCC on Doppler sonography and also confirmed as non-HCC on histopathology.

2.13. False Negative

Diagnosed non-HCC on Doppler sonography but confirmed as HCC on histopathology.

3. DATA ANALYSIS PROCEDURE

The collected data were analyzed statistically by sing SPSS version 12.0. Quantitative data like age was presented in form of mean ± SD. Qualitative data gender was presented in form of frequency and percentage. A 2 × 2 table was used to calculate sensitivity, specificity, negative predicted value (NPV), positive predicted value (PPV) and accuracy of Doppler sonography taking histopathology as a fold standard.

Fine needle aspiration biopsy was taken and sent to Department of Pathology for cytology and Histopathological evaluation. The slides were stained with hematoxylin and eosin methods.

4. RESULTS

A total of 70 confirmed patients of focal liver lesions diagnosed on ultrasonography (USG) having age 20 - 70 years with either sex with the positive history of hepatitis B hepatitis C and cirrhosis during the study period of six months from 13-12-2010 to 12-12-2011. Majority of the patients i.e., 33 (47.2%) were between 41 - 60 years of age and minimum 11 patients (15.7%) were between 61 - 70 years with mean age of 60.9 ± 4.7 years (Table 1).

Out of 70 patients, 47 patients (67.1%) were male while remaining 23 patients (32.9%) were female (Table 1).

Table 1 also shows distribution of cases by presentation by number of nodules. On Doppler sonography 37 cases were positive for hepatocellular carcinoma and 33 cases were negative while 36 cases were positive and 34 negative on histopathology (Table 2).

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Schottenfeld, D. and Fraumeni, J. (2006) Cancer epidemiology and prevention. 3rd Edition, University Press, New York. doi:10.1093/acprof:oso/9780195149616.001.0001
[2] Stuart, K. (2009) Primary hepatic carcinoma. http://emedicine.medscape.com/article/282814-overview
[3] Albreeht, T. (2005) Sonography of liver metastases. In: Lencioni, R. and Cioni, D., Eds., Focal Liver Lesions, Detection, Characterization, Ablation, Springer-Verlag, Heidelberg, Berlin, 261-274.
[4] Sherman, M. (2005) Diagnosis of small hepatocellular carcinoma. Hepatology, 42, 14-16. doi:10.1002/hep.20790
[5] Stojkovic, M.V., Artiko, V.M., Radoman, I.B., Knezevic, S.J., Lukic, S.M., Kerkez, M.D., et al. (2009) Color Doppler sonography and angioscintigraphy in hepatic Hodgkin’s lymphoma. World Journal of Gastroenterology, 15, 3269-3275. doi:10.3748/wjg.15.3269
[6] SK, B. (2007) Ultrasound differential diagnosis. Jaypee Brothers Medical Publishers Ltd, New Delhi.
[7] Dragoteanu, M., Balea, I.A., Dina, L.A., Piglesan, C.D., Grigorescu, I., Tamas, S., et al. (2008) Staging of portal hypertension and portosystemic shunts using dynamic nuclear medicine investigations. World Journal of Gastroenterology, 14, 3841-3848. doi:10.3748/wjg.14.3841
[8] Artiko, V.M., Sobic-Saranovic, D.P., Pavlovic, S.V., Perisic-Savic, M.S., Stojkovic, M.V., Radoman, I.B., et al. ( 2008) Estimation of the relative liver perfusion using two methods of radionuclide angiography in the patients with hemodynamic disorders in the portal system. Acta Chirurgica Iugoslavica, 55, 11-16. doi:10.2298/ACI0801011A
[9] Artiko, V., Obradovic, V., Petrovic, M., Perisic, M., Stojkovic, M., Sobic-Saranovic, D., et al. (2007). Hepatic radionuclide angiography and Doppler ultrasonography in the detection and assessment of vascular disturbances in the portal system. Hepatogastroenterology, 54, 892897.
[10] Kim, S.H., Lee, J.M., Lee, J.Y., Han, J.K., An, S.K., Han, C.J., et al. (2005) Value of contrast-enhanced sonography for the characterization of focal hepatic lesions in patients with diffuse liver disease: receiver operating characteristic analysis. American Journal of Roentgenology, 184, 1077-1084. doi:10.2214/ajr.184.4.01841077
[11] Wang, Y., Wang, W.P., Ding, H., Huang, B.J., Mao, F. and Xu, Z.Z. (2004) Resistance index in differential diagnosis of liver lesions by color doppler ultrasonography. World Journal of Gastroenterology, 10, 965-967.
[12] Fracanzani, A.L., Burdick, L., Borzio, M., Roncalli, M., Bonelli, N., Borzio, F., et al. (2001).Contrast-enhanced Doppler ultrasonography in the diagnosis of hepatocellular carcinoma and premalignant lesions in patients with cirrhosis. Hepatology, 34, 1109-1112. doi:10.1053/jhep.2001.29373
[13] Lin, Z.Y., Chang, W.Y., Wang, L.Y., Chen, S.C., Chuang, W.L., Hsieh, M.Y., et al. (1992). Duplex pulsed Doppler sonography in the differential diagnosis of hepatocellular carcinoma and other common hepatic tumours. British Journal of Radiology, 65, 202-206. doi:10.1259/0007-1285-65-771-202
[14] But, D.Y., Lai, C.L. and Yuen, M.F. (2008) Natural history of hepatitis-related hepatocellular carcinoma. World Journal of Gastroenterology, 14, 1652-1656. doi:10.3748/wjg.14.1652
[15] Yu, A.S. and Keeffe, E.B. (2003). Management of hepatocellular carcinoma. Reviews in Gastroenterological Disorders, 3, 8-24.
[16] Llovet, J.M., Burroughs, A. and Bruix, J. (2003) Hepatocellular carcinoma. Lancet, 362, 1907-1917. doi:10.1016/S0140-6736(03)14964-1
[17] Qian, J., Feng, G.S. and Vogl, T. (2003) Combined interventional therapies of hepatocellular carcinoma. World Journal of Gastroenterology, 9, 1885-1891.
[18] Qian, J., Vossoughi, D., Woitaschek, D., Oppermann, E., Bechstein, W.O., Li, W.Y., et al. (2003) Combined transarterial chemoembolization and arterial administration of Bletilla striata in treatment of liver tumor in rats. World Journal of Gastroenterology, 9, 2676-2680.
[19] Perry, J.F., Strasser, S.I., George, J., Farrell, G.C. and McCaughan, G.W. (2003). Pharmacotherapy of hepatocellular carcinoma. Expert Opinion on Pharmacotherapy, 4, 2175-2185. doi:10.1517/14656566.4.12.2175
[20] Kudo, M. (2011). Diagnostic imaging of hepatocellular carcinoma: Recent progress. Oncology, 81, 73-85. doi:10.1159/000333265
[21] Bosch, F.X., Ribes, J., Diaz, M. and Cleries, R. (2004) Primary liver cancer: Worldwide incidence and trends. Gastroenterology, 127, S5-S16. doi:10.1053/j.gastro.2004.09.011
[22] Perz, J.F., Armstrong, G.L., Farrington, L.A., Hutin, Y.J. and Bell, B.P. (2006). The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. Journal of Hepatology, 45, 529-538. doi:10.1016/j.jhep.2006.05.013
[23] Llovet, J.M. (2005) Updated treatment approach to hepatocellular carcinoma. Journal of Gastroenterology, 40, 225-235. doi:10.1007/s00535-005-1566-3
[24] Ernst, H., Hahn, E.G., Balzer, T., Schlief, R. and Heyder, N. (1996). Color doppler ultrasound of liver lesions: Signal enhancement after intravenous injection of the ultrasound contrast agent Levovist. Journal of Clinical Ultrasound, 24, 31-35. doi:10.1002/(SICI)1097-0096(199601)24:1<31::AID-JCU5>3.0.CO;2-M
[25] Yasuhara, K., Kimura, K., Ohto, M., Matsutani, S., Ebara, M., Tsuchiya, Y., et al. (1988) Pulsed Doppler in the diagnosis of small liver tumours. British Journal of Radiology, 61, 898-902. doi:10.1259/0007-1285-61-730-898
[26] Taylor, K.J., Ramos, I., Carter, D., Morse, S.S., Snower, D. and Fortune, K. (1998) Correlation of Doppler US tumor signals with neovascular morphologic features. Radiology, 166, 57-62.
[27] Tanaka, S., Kitamura, T., Fujita, M., Nakanishi, K. and Okuda, S. (1990) Color Doppler flow imaging of liver tumors. American Journal of Roentgenology, 154, 509514. doi:10.2214/ajr.154.3.2154912
[28] Lin, Z.Y., Wang, L.Y., Wang, J.H., Lu, S.N., Chen, S.C., Chuang, W.L., et al. (1997) Clinical utility of color Doppler sonography in the differentiation of hepatocellular carcinoma from metastases and hemangioma. Journal of Ultrasound in Medicine, 16, 51-58.

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.