ReviewLiver Metastases: Sulphur Hexafluoride–Enhanced Ultrasonography for Lesion Detection: A Systematic Review
Introduction
In patients with known primary tumor, B-mode ultrasonography (US) is a valuable, first screening tool for liver lesion detection. However, sensitivity of US in both primary and metastasis detection is low and variable, ranging from 50–76% for metastasis (Albrecht et al., 2004, Cosgrove and Bolondi, 1993, Glover et al., 2002) and 51–91% for primary liver tumors (Charatcharoenwitthaya et al., 2008, Schneider et al., 1999, Teefey et al., 2003).
Contrast-enhanced ultrasonography (CEUS) has recently changed the way of performing ultrasound examinations (Leen et al., 2004, Nicolau and Brú, 2004) and has apparently increased the possibility to detect more metastases compared with B-mode scanning (Lencioni et al., 2007, Solbiati et al., 2001). With CEUS, it is possible to characterize focal liver lesions with patterns of enhancement similar to contrast-enhanced multi-detector computed tomography (MDCT) and magnetic resonance imaging (MRI) with higher than 90% accuracy (Cosgrove, 2007, Lencioni et al., 2007, Solbiati et al., 2001).
Early published papers focused on so called “first-generation” contrast media, with good results in terms of sensitivity and specificity. In particular, multicenter or single-center studies reported lesion detection sensitivity ranging from 87–91% (Albrecht et al., 2001, Albrecht et al., 2003, Blomley et al., 1999).
Despite this positive experience, “first-generation” contrast media had some limitations, including overly rapid transient effect because of instant microbubble destruction after insonation and lack of penetration.
These drawbacks led to the development of “second-generation” contrast media. In particular, SonoVue (Bracco, Milan, Italy) microbubbles are filled with sulfur hexafluoride (SF6), a gas with a low solubility and a great stability and resistance to pressure. Because of the high flexibility of their shell, sulfur hexafluoride microbubbles are strongly echogenic at a wide range of frequencies and acoustic pressure and can therefore be used with both destructive and, more importantly, conservative contrast bubble–specific imaging methods (Lencioni et al. 2002). With the low mechanical index (MI) technique, it is possible to scan the liver in real time during arterial, portal, or late phases, without a significant loss of signal, thus raising the capability of detecting liver lesions (Claudon et al., 2008, Nicolau et al., 2003).
The value of CEUS in liver metastasis detection has been reported by recent reviews and by international guidelines (Albrecht et al., 2004, Claudon et al., 2008, Hohmann et al., 2004, Konopke et al., 2007b). Nevertheless, the diagnostic value of this technique in patients with known neoplasms is still not clear. The key question is whether CEUS should be performed routinely in patients with known neoplasms to detect metastases. The aim of our study was to perform a systematic review of the capability of CEUS in the detection of liver metastases.
Section snippets
Literature search
An extensive electronic search was performed to identify articles about the diagnostic performance of CEUS with sulfur hexafluoride for the detection of liver metastases in patients with an extrahepatic primary tumor, compared with the diagnostic performance of intraoperative findings, intraoperative US, histopathologic analysis (biopsy or surgery) or follow-up with multimodality imaging as the reference standard.
The literature search was performed using the MEDLINE, EMBASE and COCHRANE
Literature search and study selection
An extensive electronic search led to the identification of 718 articles (see Fig. 1). Of these, 481 were found to be not relevant on the basis of their titles.
After assessment of the abstracts of the remaining studies, 123 articles were excluded, mainly because they studied the ability of SonoVue to characterize focal liver lesions.
A further 100 studies were excluded, the most frequent reasons being the study design (review, case report), the contrast agent (Levovist, Sonazoid, Optison) and
Discussion
Only three papers with an overall total of 450 patients fulfilled the inclusion criteria of this review. With only three studies, two of which included a limited number of patients, convincing evidence of the value of second-generation CEUS could not be expected.
The studies included in this systematic review were single- or multicenter studies that compared baseline US versus CEUS, MDCT versus CEUS or MRI versus CEUS. The only three papers accepted fulfilled the criteria. The articles by Larsen
References (39)
- et al.
The role of contrast-enhanced ultrasound for focal liver lesion detection: an overview
Ultrasound Med Biol
(2007) - et al.
The value of contrast enhanced ultrasonography in detection of liver metastases from colorectal cancer: A prospective double-blinded study
Eur J Radiol
(2007) - et al.
Can contrast enhanced ultrasonography replace multidetector-computed tomography in the detection of liver metastases from colorectal cancer?
Eur J Radiol
(2009) - et al.
Ultrasound imaging of focal liver lesions with a second-generation contrast agent
Acad Radiol
(2002) - et al.
Phase-inversion sonography during the liver-specific late phase of contrast enhancement: Improved detection of liver metastases
AJR Am J Roentgenol
(2001) - et al.
Improved detection of hepatic metastases with pulse-inversion US during the liver specific phase of SHU 508A: Multicentric study
Radiology
(2003) - et al.
Detection and characterisation of liver metastases
Eur Radiol
(2004) - et al.
Improved detection of hepatic metastases of adrenocortical cancer by contrast-enhanced ultrasound
Oncol Rep
(2008) - et al.
Colorectal liver metastases: CT, MR imaging, and PET for diagnosis–meta-analysis
Radiology
(2005) - et al.
Diagnostic accuracy of contrast-enhanced ultrasound in focal lesions of the liver using cadence contrast pulse sequencing
Ultraschall Med
(2006)
Improved imaging of liver metastases with stimulated acoustic emission in the late phase of enhancement with the US contrast agent SH U 508A: Early experience
Radiology
Benefits of contrast-enhanced sonography for the detection of liver lesions: Comparison with histologic findings
AJR Am J Roentgenol
Utility of serum tumor markers, imaging, and biliary cytology for detecting cholangiocarcinoma in primary sclerosing cholangitis
Hepatology
Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS)—update 2008
Ultraschall Med
Malignant liver disease
Achieving optimal diagnostic yield through the use of real-time contrast enhanced ultrasonography
Eur Radiol
Assessment of metastatic liver disease in patients with primary extrahepatic tumors by contrast-enhanced sonography versus CT and MRI
World J Gastroenterol
Accuracy of investigations for asymptomatic colorectal liver metastases
Dis Colon Rectum
Detection of hepatic metastases from carcinoid tumor: Prospective evaluation of contrast-enhanced ultrasonography
Dig Dis Sci
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2021, Journal of HepatologyCitation Excerpt :Detection of CRLMs and characterization of FLLs using CEUS seems to be accurate, but prospective studies are limited and cannot be compared due to inhomogeneous cohorts (e.g., different exclusion criteria, including liver metastases in non-colorectal neoplasia, inclusion of patients for characterization of FLLs but not for detection of hepatic metastases, and including patients who received imaging after chemotherapy and local ablative therapy), heterogeneity in different SORs (e.g., intraoperative ultrasound, histology, PET-CT, MRI, CT, and follow-up with various imaging techniques), different study designs (single center vs. multicenter, prospective vs. retrospective, per patient analysis vs. per lesion analysis), different examiners (most of them being radiologists) with different experience levels with ultrasound, resulting in inter-observer variations, and different contrast agents at different dosages (e.g., Sonovue® 1.2–4.8 ml, Sonazoid with 0.01–0.5 ml/kg) (Table S1).22–28 Therefore, data on the detection of FLLs (but not characterization of FLLs) are limited, which also limits a meta-analysis to only 3 studies out of 237 potentially relevant studies.29 In general, the potential influence of the physician's specialty (radiology vs. gastroenterology/hepatology) on the quality of the CEUS has not been discussed in meta-analyses but could be important.
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