Only few pilot studies have evaluated the recent diagnostic imaging system (SWE) for stiffness investigation of focal liver lesions [19].
This study included 75 patients of variable hepatic focal lesions (42 males and 33 females), their age ranged from 19 to 67 years with mean age of 50.13 years. All cases were evaluated by means of B-mode abdominal ultrasound and shear wave sono-elastography, and finally diagnosed by core needle biopsy (39 cases), CE-CT, and CE-MRI (75 cases).
In the current study, the median size of benign focal lesions was 6.7 cm and of malignant focal lesions was 5.3 cm. There was no statistical significance between the lesion size and its nature whether benign or malignant and in turn its stiffness in kPa. This matches with Guibal et al. [17] and Choong et al. [20] who stated that there was no statistical correlation observed between the size of lesions and lesion stiffness value.
Regarding the color-coded elastogram, 46 malignant lesions (88.5%) had mixed color with red foci, while only the 5 benign FNH cases (21.7%) had red foci. There was a statistically significant difference between benign and malignant focal lesions as regard the color-coded elastogram with P value < 0.001, and this matches with the study of Guibal et al. [17] and Park et al. [21] who stated that in the technique setting, dark blue color is indicative of the lowest stiffness and dark red is indicative of the highest stiffness.
Among the benign focal lesions, focal nodular hyperplasia was the stiffest with median stiffness value (26.7 kPa).
The median stiffness value of FNH was (26.7 kPa), while that of hemangioma was (10.5 kPa). These results are in agreement with Guibal et al. [17] who reported that SWE mean stiffness value was for FNH 33 ± 14 kPa, and for the hemangiomas 13.8 ± 5.5, also with Park et al. [21] study results that included that the mean stiffness value for hemangiomas 12.91 ± 9.42 and for FNH 27.02 ± 4.14, while these results do not cope with Gerber et al. [19] who concluded that there was no significant difference could be observed in elasticity values between the different benign FLLs as hemangioma median stiffness value was 16.35 (5.4–71.9) kPa and FNH median stiffness value was 16.55 (2.1–69.7) kPa.
These studies of Guibal et al. [17], Qiang et al. [18], Gerber et al. [19], and Park et al. [21] described that hemangioma had elevated stiffness value in comparison with the surrounding hepatic parenchyma as in Park et al. study [21] hemangioma mean stiffness value was 12.91 ± 9.42, while parenchymal mean stiffness value was 5.5 ± 2.8, as well as in Gerber et al study [19] hemangioma median stiffness value was 16.35 kPa, while parenchymal median stiffness value was 8.5 kPa, and the results of the current study had similar observations as the median stiffness value of hemangioma was 10.5 kPa, the surrounding hepatic parenchymal median stiffness value was 5.84 kPa with statistically significant P value ≤ 0.004.
Kim et al. [22] explained these results by that hemangiomas histologically composed of large blood-filled endothelial-lined spaces separated by fibrous septa, vascular thrombi likely responsible for the high stiffness values.
In the current study, abscess (3 cases) showed elevated stiffness value as median stiffness value was 12.67 kPa, and the surrounding liver parenchyma median stiffness value was 5.97, and this is in agreement with Park et al. [21] as abscess (3 cases) mean stiffness value was 22.13 ± 5.14 and the surrounding liver parenchyma mean stiffness value was 5.77 ± 1.25.
Guibal et al. [17] and Park et al. [21] found that FNH include components significantly higher than other benign hepatic lesions in stiffness. Yu and Wilson [23] added that these elevations in stiffness likely matched to fibrous septations, which results due to central scar formation, and this copes with the results of the current study as FNH was the stiffest benign lesion.
Park et al. [21] fond that SWE mean stiffness values for focal fatty sparing 15.15 ± 11.38, for hematomas 31.05 ± 1.34, and for fibrosis 6.5, Gerber et al. [19] study also included 1 case of adenoma with median stiffness value 8.9, and Guibal et al. [17] mentioned that mean SWE values for focal fatty sparing 6.6 ± 0.3, for scars 53.7 ± 4.7, and for adenomas 9.4 ± 4.3. Guibal et al. [17] explained that adenoma stiffness values were elevated compared with surrounding parenchyma as adenoma are composed of large hepatocytes supported by a weak framework of collagen and they are deficient in biliary canaliculi. Unfortunately, this current study did not include any cases of these categories.
Among the malignant focal lesions: cholangiocarcinoma was the stiffest with median stiffness value (35.9 kPa).
In the current study, the stiffest lesion of all types of focal lesions (benign and malignant) was cholangiocarcinomas (35.9 kPa) and showed more stiffness values comparing with other malignant focal lesions, and this matches with Guibal et al. [17] and Gerber et al. [19] who reported that cholangiocarcinomas were the stiffest malignant FLLs.
Sirica et al. [24] and Okamoto et al. [25] explained these results by the fact that cholangiocarcinoma in histology has a considerable fibrotic component, which is also a significant portion of their malignant progression. Heide et al. [26] added that this fibrotic component is likely resulting in the high stiffness present in cholangiocarcinoma.
Guibal et al. [17] stated that none of the cholangiocarcinomas (56.9 ± 25.6) exhibited a stiffness value like the FNHs (33 ± 14.7) and this copes with the current study results as regard cholangiocarcinoma median stiffness value (35.9 kPa) and FNH (26.7 kPa).
The median stiffness value of HCC (17.6 kPa) was lower than that of metastasis (25.5 kPa) and cholangiocarcinoma (35.9 kPa) and was higher than the median stiffness value of all benign hepatic lesions (10.68 kPa) and lower than the stiffness value of FNH (26.7), and this is in agreement with Guibal et al. [17], Kim et al. [22], and Frulio et al. [27] who reported that generally hepatocellular carcinoma was harder than all benign focal lesions but softer than benign focal lesions that showed high stiffness values such as focal nodular hyperplasia.
Guibal et al. [17] reported that SWE mean stiffness values (in kPa) were for HCCs 14.86 ± 10, for metastasis 28.8 ± 16, and for cholangiocarcinomas 56.9 ± 25.6 kPa with the difference in tissue elasticity between cholangiocarcinoma and HCC statistically significant (P 00.0004). However, Choong et al. [20] stated that the elasticity values of HCC (51.45 ± 14.96 kPa) were statistically non-significant from the values of metastatic lesions (49.89 ± 13.82 kPa).
In this study, HCC (N = 21 cases); 2 cases of HCC showed stiffness value (15.27, 15.1) less than liver parenchyma (18.2, 17.8); however, 19 cases of HCC showed stiffness value more than liver parenchyma. Also, the study of Guibal et al. [17] included 25 cases of HCC; 6 cases showed stiffness value less than liver parenchyma, but 19 cases showed stiffness value more than liver parenchyma.
This is explained by Guibal et al. [17] and Gallotti et al. [28] who reported that HCCs in cirrhotic livers may exhibit a relatively softer values when compared with the stiff surrounding parenchyma. However, some cases of HCC showed stiffness value more than liver parenchyma by the fact that their patients likely had less degree of cirrhosis.
Gerber et al. [19] reported that the median stiffness of all FLLs [28.6 kPa] was significantly higher than that of the surrounding liver [9.9 kPa] (P < 0.0001), whereas the surrounding liver in patients with HCC showed the highest stiffness with (P < 0.0001) in comparison to the surrounding liver of further subgroups, and this matches with the current study results as the median stiffness of all FLLs [18.37 kPa] was significantly higher than that of the surrounding liver median stiffness value [6.47 kPa] (P < 0.001), whereas the surrounding liver in patients with HCC showed the highest median stiffness of 13.2 kPa (P < 0.001) in comparison to the surrounding liver parenchyma of further subgroups.
Guibal et al. [17] and Gerber et al. [19] stated that sometimes cholangiocarcinoma may exhibit similar enhancement criteria in CT and MRI as hepatocellular carcinomas, so discrimination between cholangiocarcinomas and hepatocellular carcinoma can be difficult in these situations, and in Guibal et al. [17], there was a significant difference found between the elasticity of HCCs and CCCs (P 00.0004). These distinct differences in SWE could aid in the differentiation of HCCs and cholangiocarcinomas. Gerber et al. [19] concluded that the use of SWE can aid in the differentiation of HCCs and CCC as the median stiffness of CCC was 70.7, and there was a significant difference in stiffness compared to HCC median stiffness value (44.8).
The current study showed similar observations as cholangiocarcinoma median stiffness value (35.9) was much higher than that of hepatocellular carcinoma (17.6).
In this study, the elasticity values of metastases varied widely depending on the primary tumor type. Colo-rectal metastases (6 cases) median stiffness value (22.54 kPa) was lower than breast cancer metastases (7 cases) median stiffness value (26.25 kPa), this is in agreement with Guibal et al. [17] who reported that mean stiffness value of metastases from carcinoid tumors (30.7 kPa) was higher than metastases from gastro-intestinal tract adenocarcinomas (21.8 kPa).
Lymphoma showed elevated median stiffness value 14.5 kPa comparing to the surrounding liver parenchyma 5.8 kPa, and this matches with Park et al. [21], as lymphoma mean stiffness value was 31.9 kPa, while the surrounding liver parenchyma mean stiffness value was 8.7 kPa.
The lesion to parenchyma stiffness ratio may be of a clinical value in patient with liver fibrosis as, in the current study: HCC lesion/parenchyma stiffness ratio was (1.37) lower than cholangiocarcinoma lesion/parenchyma stiffness ratio (4.6), and also lower than metastasis lesion/parenchyma stiffness ratio (4.2). This was attributed to fibrosis in the surrounding hepatic parenchyma. These results coping with Park et al. [21] and De-Wall et al. [29] who reported that regarding stiffness ratio of FLL to adjacent liver parenchyma, HCC showed lower ratio than all of other malignant FLLs except combined HCC-CCC and showed similar ratio value compared with benign FLLs. This may be attributed to the liver cirrhosis background in most patients with HCC.
In this study, the median benign focal lesion stiffness value (10.68 kPa) was significantly lower than that of malignant focal lesions (20.22 kPa) with a statistical significance P value < 0.001. This matches with Guibal et al. [17] who reported that the mean value for the benign focal lesions was 18.53 ± 13.5 kPa and for the malignant focal lesions was 26.9 ± 18.8 kPa with statistical significance P value = 00.01, and matches also with Park et al. [21] who reported that the malignant focal lesion mean stiffness value was 60.41 ± 47.81 kPa, while that of benign focal lesions was 22.05 ± 17.24 kPa with statistical significance P value = 0.0001. Also, this is in agreement with Gerber et al. [19] results who reported that the benign focal lesion median stiffness value was 16.4 and the malignant focal lesion median stiffness value was 36 with statistically significant P value < 0.0001.
These studies of Guibal et al. [17], Gerber et al. [19], Park et al. [21], Brunel et al. [30], Ferraioli et al. [31], and Xie et al. [32] added that the main role of the technique was to differentiate between adenoma and FNH in benign category and between HCC and cholangiocarcinoma in malignant category as the usual radiological imaging modalities may have overlap and conflict in diagnosis between some cases of these categories.
The results of the current study showed that cholangiocarcinoma median stiffness value (35.9) was much higher than that of hepatocellular carcinoma (17.6). Unfortunately, the current study did not include adenoma cases to differentiate between it and FNH, unlike Guibal et al. [17] study results that included (10 adenoma cases) with mean stiffness value 9.4 ± 4.3 kPa and (16 FNH cases) with mean stiffness value 33 ± −14.7 kPa, and Brunel et al. [30] study that included (57 FNH and 19 adenoma) with mean elasticity value 46.99 ± 31.15 kPa for FNH and 12.08 ± 10.68 kPa for adenoma.
In this study, the receiver operating characteristic (ROC) curve of SWE stiffness values for differentiation of benign from malignant hepatic focal lesions had AUC = 0.834 and using cutoff value 14.165 kPa, yielding 98.1% sensitivity, 78.3% specificity, and 92% accuracy; however, in the study of Park et al. [21], the (ROC) curve showed that using a cutoff value of 30.8 kPa with AUC 0.79, yielding 70.6% sensitivity and 82.4% specificity. This difference in sensitivity may be attributed that there was a sample size difference between the current study (75 lesions) and Park et al. [21] study (136 lesions).
The current study had some limitations
1-Relatively small sample size (75 cases)
2-Failure of SWE acquisitions in left liver lobe focal lesions because of excess tissue movement due to cardiac and respiratory motion and failure in right liver lobe focal lesions with depth greater than 6 cm from the skin because of the lesion location beyond the penetration limits of shear waves. These are the same limitations encountered in conventional ultrasound as mentioned by Guibal et al. [17] and Park et al. [21]. This point needs further assessment.
3-This study is missing some categories (e.g., adenoma and focal fatty sparing) or containing small number of some other categories (e.g., hydatid cyst (3 cases), abscess (3), focal fatty infiltration (4), cholangiocarcinoma (4), and FNH (5)).
Recommendations
Further large scale research is needed to assess the use of shear wave sono-elastography to help in differentiation between malignant and benign hepatic focal lesions.