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ORIGINAL ARTICLE
Year : 2020  |  Volume : 13  |  Issue : 5  |  Page : 454-459  

Transabdominal ultrasonographic evaluation of hepatocellular carcinoma and its correlation with cytopathological findings


1 Department of Radiology and Imaging, Sheikh Russel Gastroliver Institute and Hospital, Dhaka, Bangladesh
2 Department of Nuclear Medicine, Institute of Nuclear Medicine and Allied Science, Dhaka Medical College and Hospital, Dhaka, Bangladesh
3 Department of Gynaecology and Obstetrics, Dhaka Medical College and Hospital, Dhaka, Bangladesh
4 Department of Radiology and Imaging, SSMC and Mitford Hospital, Dhaka, Bangladesh
5 Department of Pathology, ICMH, Dhaka, Bangladesh
6 Department of Pathology, Jahurul Islam Medical College, Kishoregonj, Bangladesh
7 Department of General Surgery, Kushtia Medical College, Kushtia, Bangladesh
8 Department of General Medicine, Tairunnessa Memorial Medical College and Hopsital, Gazipur, Bangladesh
9 Department of Cardiology, TMSS Medical College and Rafatullah Community Hospital, Bogura, Bangladesh

Date of Submission02-Oct-2019
Date of Decision12-Nov-2019
Date of Acceptance27-Nov-2019
Date of Web Publication7-Sep-2020

Correspondence Address:
Md Shafiqul Ahsan
Department of Radiology and Imaging, Sheikh Russel Gastroliver Institute and Hospital, Dhaka 1212
Bangladesh
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mjdrdypu.mjdrdypu_272_19

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  Abstract 


Aims and Objectives: To compare the ultrasonographic findings of hepatocellular carcinoma (HCC) with that of cytopathology to asses the diagnostic validity of transabdominal ultrasonography (USG). Settings and Design: Cross-sectional study in Sir Salimullah Medical College and Mitford Hospital, Dhaka. Materials and Methods: This cross-sectional study was carried out in the department of radiology and imaging of Sir Salimullah Medical College and Mitford Hospital, Dhaka, during July, Dhaka, during July 2009–March 2011 to evaluate the transabdominal USG in the detection of HCC and its validity by determining sensitivity, specificity, accuracy, and positive and negative predictive values. For this purpose, a total of fifty patients were enrolled in the study. Cytopathology was done in all these patients. Statistical Analysis: Statistical analyses of the results were obtained using window-based computer software devised with Statistical Package for the Social Sciences (SPSS-13) (SPSS Inc., Chicago, IL, USA). The analysis of the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy was done using online OpenEpi, Version 3, an open-source calculator. Results: The current study found that the mean age of patients was 49.14 ± 13.79 years, ranging from 20 to 79 years. The USG detected HCC in 31 (62%) cases, of which 27 (87.1%) were cytopathologically proven. USG diagnosed 19 (38%) cases as lesions other than HCC, of which 4 (21.1%) cases were diagnosed as HCC cytopathologically (false negative). The rest of the 15 (78.9%) cases were diagnosed as other lesions including metastasis, by both USG and cytopathologically (true negative). The validity of USG was studied by calculating sensitivity, specificity, accuracy, PPV, and NPV, which were 87.1%, 78.95%, 87.1%, 78.95%, and 84%, respectively. Conclusions: In this study, the USG findings and the validity tests were found almost identical as observed by other investigators compared with cytopathological findings. Hence, it can be concluded that the USG is a useful diagnostic modality in the diagnosis of HCC.

Keywords: Cytopathology, hepatocellular carcinoma, sensitivity and specificity, transabdominal ultrasonography, validation study


How to cite this article:
Ahsan MS, Afrin R, Naznin S, Sattar A, Khanam K, Maruf Raza A K, Tulsan SK, Podder V, Islam M. Transabdominal ultrasonographic evaluation of hepatocellular carcinoma and its correlation with cytopathological findings. Med J DY Patil Vidyapeeth 2020;13:454-9

How to cite this URL:
Ahsan MS, Afrin R, Naznin S, Sattar A, Khanam K, Maruf Raza A K, Tulsan SK, Podder V, Islam M. Transabdominal ultrasonographic evaluation of hepatocellular carcinoma and its correlation with cytopathological findings. Med J DY Patil Vidyapeeth [serial online] 2020 [cited 2020 Sep 29];13:454-9. Available from: http://www.mjdrdypv.org/text.asp?2020/13/5/454/294357




  Introduction Top


Hepatocellular carcinoma (HCC) is a common malignancy affecting approximately one million people every year and represents the sixth most common cancer worldwide with an incidence equal to death rate.[1] HCC has the highest incidence in developing countries.[2] For example, the principal reason for the high incidence of HCC in parts of Asia including Bangladesh is the frequency of chronic infection with hepatitis B virus (HBV) and hepatitis C virus. These chronic infections frequently lead to cirrhosis which itself is an important risk factor for HCC. In Bangladesh, it has the prevalence of 35% among all liver diseases.[3],[4]

The major clinical risk factor for the development of HCC is liver cirrhosis, because 70%–90% of HCC develops into a cirrhotic liver. HCC constitutes 75%–85% of primary liver cancers with 80% of HCC cases occurring in Sub-Saharan Africa and eastern part of Asia. During the last four decades, the incidence of HCC has been tripled in the United States.[2],[5] Most HCCs occur after many years of chronic hepatitis that provides the mitogenic and mutagenic environments to precipitate random genetic alterations resulting in malignant transformation of the hepatocytes with subsequent development of HCC. A previous study reported that the 5-year survival rate of HCC is only 9.6%, which is due to late diagnosis, tumor biology, and underlying chronic liver diseases. Therefore, a pressing need exists for biomarkers useful for early cancer detection, accurate pretreatment staging, prediction of response to treatment, and monitoring to disease progression. To attenuate early detection and early treatment, surveillance is necessary for patients at high risk for developing HCC, with or without cirrhosis.[6]

The role of ultrasonography (USG) in detecting and evaluation of hepatic masses is very precise and sensitive.[4] Characterization of a hepatic mass on conventional USG is based on gray-scale imaging. Gray-scale morphology of a mass allows the differentiation of cystic and solid masses. In many instances, a characteristic appearance may suggest the diagnosis without further evaluation. However, definitive diagnosis is not made on the basis of gray-scale information alone, but also on vascular information derived from spectral, color Doppler examination.[7] With recent advent of the high-resolution real-time USG scanner, the whole liver can be scrutinized quickly and a hepatic tumor of as small as 1 cm can be displayed easily.[6]

In patients with chronic liver disease and good hepatic function, USG has a sensitivity of 94%. In the identification of affected patients, but for individual lesions, the sensitivity is only 64%.[2] Currently, the diagnosis of HCC in Bangladesh is based on the detection of raised serum alpha-fetoprotein (AFP) level in suspected patients, with detection of space-occupying lesion (SOL) in liver, suggestive of HCC on abdominal USG and/or computed tomography CT scan, which is then confirmed with fine-needle aspiration (FNA) from hepatic SOL for cytology.[8] The present study is designed to evaluate the role of transabdominal USG in the evaluation of HCC and is correlated with cytopathological findings. The specific aim of the study was to establish the usefulness and specificity of USG in the detection of HCC.


  Materials and Methods Top


This cross-sectional study was done during a period of July 2009–March 2011. The study was carried out on 84 patients on age range between 20 and 79 years referred to the department of radiology and imaging of Sir Salimullah Medical College and Mitford Hospital, Dhaka, for Dhaka, for USG of the abdomen who were clinically suspected as a case of HCC. Among them, 17 patients had only hepatomegaly without any mass. Twelve patients refused to do an FNAC, and in five cases, cytopathology reports were not available. Finally, fifty participants were included in the study after excluding the participants who did not fulfill the exclusion criteria. There were 38 male and 12 female patients. At first, all the participants were evaluated by a detailed history and clinical examination with special emphasis on clinical features. Subsequently, USG of the whole abdomen was done in all cases. In the current study, the patients with multiple small nodules, single large nodule, or diffuse nodules were suspected to have HCC [Supplementary Figure 1], [Supplementary Figure 2], [Supplementary Figure 3], [Supplementary Figure 4], [Supplementary Figure 5]. Reports were checked by an investigator and a competent radiologist of the department of radiology and imaging. FNAC of the masses was done. Cytopathology reports were collected. All this information was collected in a predesigned structured data collection sheet.



All the patients selected in this study underwent USG examination using a real-time scanner equipped with 3.5, 5, and 7.5 KHz transducer of SIEMENS SONOLINE G60S. Abdominal USG was performed with the patients in a supine, right and/or anterior oblique, and/or right lateral decubitus position. The aspirated materials were taken on the slides and then the films were made with the help of a pathologist and sent for cytopathological examinations. All the relevant collected data were compiled on a master chart first. Statistical analyses of the results were obtained using window-based computer software devised with Statistical Package for the Social Sciences (SPSS-13) (SPSS Inc., Chicago, IL, USA). The analysis of the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy was done using online OpenEpi, Version 3, an open-source calculator. The study protocol was approved on 01/11/2010 by the institutional ethical review committee, Dhaka. Written informed consent was obtained from each participant.


  Results Top


The cross-sectional study, which was carried out in in the department of radiology and imaging of Sir Salimullah Medical College and Mitford Hospital, Dhaka, found that the age distribution of 34% of patients was within 40–49 years of age group followed by 18% within 70–79 years of age group. This study showed that the mean age of the patients was 49.14 ± 13.79 years, ranging from 20 to 79 years [Table 1]. The clinical presentation of the study participants is depicted in [Table 2]. USG detected HCC in 31 (62%) cases, of which 27 (87.1%) were proved HCC cytopathologically [Table 3]. USG diagnosed 19 (38%) cases as lesion other than HCC, of which 4 (21.1%) cases were diagnosed as HCC cytopathologically (false negative) [Table 4]. The rest of the 15 (78.9%) cases were diagnosed as other lesion including metastasis by both USG and cytopathologically (true negative) [Table 4]. The validity of USG was studied by calculating sensitivity, specificity, accuracy, PPV, and NPV, which were 87.1% (95% confidence interval [CI]: 71.15–94.87), 78.95% (95% CI: 56.67–91.49), 87.1% (95% CI: 71.15–94.87), 78.95% (95% CI: 56.67–91.49), and 84% (95% CI: 71.49–91.66), respectively [Table 5] and [Table 6].
Table 1: Demographic characteristics of the study subjects (n=50)

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Table 2: Clinical presentation of the study subjects (n=50)

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Table 3: Distribution of cytopathology findings in hepatocellular carcinoma patients on ultrasonography diagnosis (n=31)

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Table 4: Distribution of cytopathology findings in other lesions including metastasis patients on ultrasonography diagnosis (n=19)

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Table 5: Comparison between ultrasonography and cytopathological findings (n=50)

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Table 6: Validity test by calculating sensitivity, specificity, accuracy, and positive and negative predictive values of the ultrasonography findings in diagnosing hepatocellular carcinoma

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  Discussion Top


The current study provides a comprehensive comparison of diagnostic yield of transabdominal USG with cytopathology in the diagnosis of HCC. The detailed analysis of specificity, sensitivity, PPV, NPV, and diagnostic accuracy of transabdominal USG provides better understanding of the use and effectiveness of it as a noninvasive, quick method of screening and diagnosing these patients.

The early detection and accurate characterization of the HCC can offer a therapeutic benefit to affected patients. Previous studies have shown that most patients with HCC survive > years after the diagnosis is made and the prognosis of HCC is largely dependent on the stage of tumor detection.[9] The survival rate of the affected patients has been prolonged since the advancement of hepatic transplantation, resection, and emerging multiple ablative treatments; however, they are most effective when intervened during the early stage of the disease. The National Comprehensive Cancer Network recommends screening and surveillance for HCC as cost-effective for patients with chronic hepatitis B or cirrhosis.[10] The development of HCC is a complex multistep pathological process occurring at molecular, cellular, and tissue levels. Several noninvasive imaging modalities including USG, CT, and magnetic resonance imaging (MRI) have shown to play a role in the HCC assessment. USG is considered among the first line of imaging modality for screening and surveillance of the key pathological changes in hepatocarcinogenesis.[9] The current clinical guidelines recommend 6 monthly ultrasonographic assessment for HCC surveillance as the standard of care in high-risk groups (patients with chronic viral hepatitis B and C infection, nonalcoholic steatohepatitis, and liver cirrhosis) amenable to curative treatment and increased survival.[11] In the current study, majority (76%) of the study subjects were hepatitis B virus surface antigen (HBsAg) positive, whereas 24% were HBsAg negative. Globally, HBV infection constitutes 80% of all virus-associated HCC.[12] The cross-sectional imaging using triple-phase CT or contrast-enhanced MRI can be diagnostic, once the USG detects a nodule on regular surveillance. Most liver nodules are detected initially by unenhanced USG; however, if the liver nodules are not characterized, the microbubble contrast agents may enhance the ability of contrast-enhanced USG (CEUS) to distinguish between HCC and other abnormalities during the same setting and thereby make rapid diagnosis.[13] After injecting the contrast material, CEUS offers a consistent demonstration of washout in malignant lesions, and real-time detection of arterial phase hypervascularity of liver tumors, enabling appropriate evaluation of tumor vascularity. Despite the apparent benefit with CEUS, the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) consider excluding the role of CEUS in HCC diagnosis among cirrhotic patients as CEUS has found to have increased false positives of HCC in patients with cholangiocarcinoma. In contrast, the Italian Association for the Study of the Liver (AISF) still recommends using CEUS for liver nodules of more than 1 cm, together with MRI or CT.[13] CEUS can also be used in patients with renal failure for characterizing liver masses, who otherwise may have contraindication of using CT or MRI.[14] However, the current study could not use CEUS due to lack of adequate resources at the center where the study had been conducted, and therefore, a future study on using CEUS to assess the diagnostic validity is needed to help make evidence informed guidelines.

In our study, the diagnostic accuracy and PPV of the transabdominal USG were found to be 84% and 87%, respectively, when compared with the cytopathological findings. A systematic review previously reported the diagnostic accuracy of ultrasonographic detection of HCC among patients with chronic hepatitis and cirrhosis to be with pooled sensitivity and specificity of 60% and 97%, respectively.[15] However, another meta-analysis found the sensitivity and specificity of USG among cirrhotic patients to be 94% and 94%, respectively.[16] In the current study, the sensitivity and specificity of ultrasonographic detection of HCC was found to be 87.1% and 78.95%, respectively. In addition, the diagnostic accuracy, PPV, and NPV were found to be 84%, 87.1%, and 78.95%, respectively. In a recent meta-analysis, the sensitivity for detecting any stages of HCC was 84%, which is closely similar to this study finding.[13] Another study reported the sensitivity and specificity of USG in detecting HCC ranging from of detecting HCC ranging from 51% to 87% and from 80% to 100%, respectively.[16] It is important to note that the variation in the sensitivity for detecting HCC with USG may occur due to quality of the machine and experience of the operator, coarseness of liver parenchyma, severe fatty liver background, and the subdiaphragmatically localized lesions, cancer staging.[17] Previous studies found that ultrasonographic surveillance of HCC can provide mortality benefit to patients. For example, in a large Chinese randomized controlled trial, Zhang et al. found that among patients of chronic hepatitis B infection with or without cirrhosis, 6 monthly surveillance of HCC with USG and serum AFP levels resulted in a 37% reduction in HCC-related mortality.[18] However, the AASLD or the EASL do not recommend serum AFP for screening and surveillance due to its poor performance in different studies.[19]

In the current study, 36% of patients were aged between 40 and 49 years, and 20% were between 70 and 79 years, with the mean age of 49. Grizzi et al. found that HCC primarily affects older people, with the highest prevalence among those aged between 65 and 69 years old.[20] In the current study, the male–female ratio was found to be 3.17:1. Liu et al. reported that HCC has male predominance with a male-to-female ratio varying between 2:1 and 4:1, which closely matches with the present study.[21]

HCC usually remains asymptomatic and found during the workup of upper abdominal discomfort, rationalizing the current recommendations for regular surveillance and screening with USG among high-risk population. The clinical presentation of HCC has a wide variability depending on the hepatic reserve and often remains asymptomatic or incidentally detected on imaging studies. Previous studies have reported that the most common presenting features are abdominal pain with an abdominal mass in the right upper quadrant. There may be bruit over the liver. Ascites occurs in 20% of cases. Jaundice is rare, unless there is significant deterioration of liver function or mechanical obstruction of the bile ducts.[22]

In the current study, the clinical features encountered by the participants were upper abdominal pain (80%), upper abdominal lump or mass (58%), anorexia and nausea (78%), weight loss (52%), low-grade fever (36%), jaundice (18%), and ascites (14%). The current study also noted that the patients were not aware of these symptoms until late and for a very short duration of 1–2 months, which explains the silent course of the disease during initial stage. A previous study reported that HCC remains asymptomatic until it progresses into an advanced stage. HCC initially develops as small nodules and majority of them grow during the asymptomatic course of the disease process.[23] The initial asymptomatic course of the illness might also be because of the large size of the liver, which requires tumor masses to reach a considerable size to exhibit the classical clinical features. In addition, it might be due to relative inaccessibility of the liver by hand examination and requirement of larger portion of liver before producing jaundice and other signs of hepatic failure. However, each of the patient in the current study had more than one of the above symptoms, usually indicating their delayed reporting to the physician.

In this study, the participants had a tumor involvement in the right (64%) and left (18%) lobe of the liver and both lobes of (18%) the liver. Majority of the participants had right lobe involvement with some tumors being located at its upper most portion unamenable to demonstrate by USG; therefore, the right lobe should be screened by various projection and careful attention. This can be contrasted with a study conducted by Hoque et al., wherein most of the patients (82.9%) had lesions in the right lobe and 11.4% lesions in the left lobe and 5.7% lesions in both the lobes.[24] In addition, the same study also found that maximum lesions (71.4%) were found unifocal and 28% lesions were multifocal.[24] This was similar to the current study current study whereby 70% lesions were unifocal and 30% lesions had multifocal lesions.

It is important to consider the type and pattern of echogenicity, which is an important characteristic. In the current study, the echo patterns of the hepatic lesions diagnosed by USG were hypoechoic (46%), mixed pattern (28%), hyperechoic (18%), and isoechoic pattern (8%). Hoque et al. have shown in a study of suspected HCC where the echogenicity was found to be hypoechoic (45.7%), mixed pattern (37.1%), and hyperechoic (17.2%).[24] The margin of the hepatic lesions in this study was found to be regular in 16 (32%) and irregular in 34 (68%) patients.

In the current study, the patients having HCC diagnosed by USG were compared with cytopathological diagnostic findings. In ultrasonographic findings, HCC constituted 83.6% of cases and other lesions including metastasis constituted 16.1% of cases, whereas cytopathological findings revealed that HCC constituted 85.65% of the cases and other lesions including metastasis constituted 14.35% of the cases.

The results of both USG and cytopathology in the present study were almost similar. Therefore, the inference can be drawn that USG is a useful modality in the detection of HCC. USG is a simple, rapid diagnostic method, which has no radiation hazards and can be advocated for all.


  Conclusions Top


In this study, USG findings and the validity tests were almost identical as observed by other investigators compared with cytopathological findings. Hence, it can be concluded that USG is a useful diagnostic modality in diagnosis of HCC. Therefore, a study of longer period and with larger sample size with the use of contrast agent and newer imaging modalities and more accurate pathological techniques may provide a much better result.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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