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Liver Metastases Liver Metastases Roland Hustinx, MD, PhDa,*, NancyWitvrouw, MDa, TinoTancredi, MDb KEYWORDS FDG PET PET/CT Liver metastases Gastrointestinal cancers MR imaging CT The liver is the most frequent site of hematoge- become all patients in whom all the lesions can be nous metastatic spread, and metastases removed, including those outside of the liver, and represent the most frequent liver malignancy in in whom the hepatic reserve is adequate. Such the United States and Europe. Tumors of the gas- approach obviously requires multidisciplinary and trointestinal tract, in particular colorectal cancer, multimodality collaboration to appropriately select are the primary source of metastatic liver involve- an ever-increasing number of patients. New treat- ment but other tumors such as breast and lung ment modalities also involve nuclear medicine cancers and melanomas also present a high likeli- physicians, with the development of techniques hood of hepatic dissemination.1 Close to 50% of such as selective internal irradiation of glass or the patients with colorectal cancer develop liver resin microspheres labeled with 90Y.3,4 Surgical metastases, either at initial presentation or during resection of liver metastases from noncolorectal the course of the disease, and the liver is the malignancies is also increasingly proposed, only site of distant spread in 30% to 50% of these although with more limited clinical results and in patients. This represents a population that is likely a smaller number of patients.5 to benefit from local therapy, in particular surgery. Indeed, surgical resection of liver metastases with curative intent can be performed with acceptable CONVENTIONAL IMAGING MODALITIES morbidity and leads to long-term survival rates of Ultrasonography up to 58%. The classical criteria for selecting Transabdominal ultrasonography (US) presents patients for surgery include the number and size several advantages, including low cost, absence of lesions as well as the necessity to achieve re- of irradiation, wide availability, and portability. section with a 1-cm free margin. In addition, the The sensitivity is very low, however, as half of the disease has typically to be limited to the liver. lesions are missed and the specificity is not very Recently, a trend has emerged to expand the in- high either.6 More recently, developments in the clusion criteria. This can be achieved through technique such as Power Doppler or contrast en- combining resection with radiofrequency ablation hancement with microbubbles have been reported or neoadjuvant chemotherapy, which aims at to significantly improve the diagnostic accuracy, reducing the tumor volume to be resected, or which may reach values close to those obtained through portal vein embolization or two-stage hep- with CT. For instance, a multicenter study was atectomy, which aims at increasing the hepatic re- recently performed in 102 patients with various pri- serve. As thoroughly discussed in a recent review maries.7 Contrast-enhanced US (ceUS) identified by Pawlik and colleagues,2 a new paradigm 55 lesions classified as metastases, compared consists of focusing the surgical decision on with 61 with triple-phase spiral CT and 53 with what would remain after resection, instead of MR imaging. These results and others8,9 are en- what is to be removed. Basically, eligibility criteria couraging but it should be kept in mind that a Division of Nuclear Medicine, University Hospital of Lie` ge, Campus Universitaire du Sart Tilman B35, 4000 Lie` ge, Belgium b Department of Medical Imaging, University Hospital of Lie` ge, Campus Universitaire du Sart Tilman B35, 4000 Lie` ge, Belgium * Corresponding author. E-mail address: [email protected] (R. Hustinx). PET Clin 3 (2008) 187–195 doi:10.1016/j.cpet.2008.09.004 1556-8598/08/$ – see front matter ª 2008 Elsevier Inc. All rights reserved. pet.theclinics.com 188 Hustinx et al ceUS highly depends on the operator’s skills and reticuloendothelial system (Kupffer cells in the experience. Currently, US is not recommended liver) and causes a signal loss on T2-weighted im- as a screening or surveillance method for ages, therefore darkening the normal liver back- evaluating liver metastases. ground on these images. Few systematic studies were performed comparing these tissue-specific CT contrast agents. In two Korean series from differ- ent investigators, the detection rate was similar CT technology has benefited from major techno- for both mangafodipir and SPIO MR imaging.16,17 logical improvements over the past decade. Multi- MnDPDP-MR imaging appears to be more sensi- detector scanners allow very fast imaging, thus tive than both unenhanced MR imaging and spiral eliminating any respiratory artifacts and allowing CT for detecting individual lesions.18 Similarly, precise timing of the various tissue enhancement both Gd-enhanced and SPIO-enhanced MR imag- after intravenous contrast injection, while achiev- ing are more accurate than CT, and SPIO tends to ing exquisite spatial resolution in all three planes. perform better than Gd for detecting subcentimet- The CT appearance of liver metastases varies ric lesions.19 Another series, however, reports according to the pathologic type of the primary similar results for CT and SPIO-enhanced MR im- tumor. Metastases from melanomas, sarcomas, aging.14 Currently, gadolinium remains the most neuroendocrine tumors, and renal cell carcinomas widely used contrast agent when performing liver are hypervascular and therefore better visualized MR imaging in the clinical setting, but the precise during the hepatic arterial phase. Metastases clinical indication as well as the local experience from colorectal cancer are hypovascular and of the radiology team contribute to guiding the therefore better visualized during the portal ve- choice of the technique, acquisition sequences, nous phase.10 Although breast cancer metastases and contrast agent. In particular, MR imaging may show early arterial enhancement, adding the with liver-specific contrast agents is increasingly early phase to the portal phase CT did not improve recommended in preoperative patients.20 the sensitivity of the technique.11 Therefore, triple- phase CT may not be mandatory in most patients being screened for liver metastases. PET As may be expected and in spite of a very high Considering that 2-[18F]fluoro-20-deoxyglucose spatial resolution, the detection rate of liver metas- (FDG) is avidly taken up by most cancer types tases by CT shows a negative correlation with the and given the high prevalence of metastatic size of the lesions.12 In lesion-per-lesion analyses, spread to the liver, it seems only logical to propose sensitivities ranging from 49% to 89% have been FDG-PET as a diagnostic and staging tool for liver reported.12–14 The specificity is usually high, involvement. The feasibility of the technique was although the study that showed the highest sensi- suggested by Yonekura and colleagues21 more tivity (89%) also showed a rather poor specificity than 25 years ago. Further studies, including those (67%).14 performed without attenuation correction, re- ported in the late 1990s diagnostic performances MR Imaging that compared favorably with the imaging Similar to CT, MR imaging technology has methods routinely used at that time.22–25 A first witnessed important developments, in the hard- meta-analysis comparing US, CT, MR imaging, ware, image acquisition protocols, and contrast and PET for detecting liver metastases from can- agents. On non–contrast-enhanced MR imaging, cers of the gastrointestinal tract was published in most metastases appear as hypo- to isointense 2002.26 The authors analyzed 54 studies, including on T1-weighted images and iso- to hyperintense 9 for US, 25 for CT, 11 for MR imaging, and on T2-weighted images.15 Dynamic imaging after 9 for PET. The most recent articles were published enhancement with gadolinium (Gd)-based agents in 1996 for US and in 2000 for the other tech- provides information regarding the vascularity of niques. The total number of patients was the lesions and therefore increases the perfor- 509 (US), 1371 (CT), 401 (MR imaging), and mance of MR imaging for differentiating benign 423 (PET). The primaries were colorectal cancers from malignant lesions. Tissue-specific contrast in all cases for PET and MR imaging, and in agents have been introduced to increase the 74% and 78% for US and CT, respectively. The tumor-to-liver contrast. Mangafodipir trisodium other primaries were gastric or esophageal can- (MnDPDP, Teslascan) is taken up by the hepato- cers. The prevalence of hepatic metastases in cytes, therefore increasing the signal from the the population samples ranged from 33% normal liver on T1-weighted images. Superpara- (US studies) to 58% (PET studies). The mean magnetic iron oxide (SPIO) is taken up by the weighted sensitivity was 66% for US, 70% for Liver Metastases 189 CT, 71% for MR imaging, and 90% for PET. The remained very high, at 92.3%. CT had a sensitivity authors further analyzed the data by stratifying of 85.8% and a specificity of 88.3%. These results subsets according to specificity. They considered further illustrate that the diagnostic performances that for any technique to be clinically useful and of PET and CT may be considered very similar relevant, its specificity should be superior or equal for detecting individual liver lesions. Worth men- to 85%. With such a cutoff for specificity, the sen- tioning is the excellent specificity of PET, as sitivity values became 55% for US, 72% for CT, most of the focal lesions that can be mistaken as 76% for MR imaging, and 90% for PET. The sensi- metastases with CT, such as angiomas or adeno- tivity was significantly higher for PET than for US mas, do not take up FDG. PET modified the clinical and CT, and marginally higher when compared management in 30.8% of the patients in the stud- with MR imaging (P 5 .055). There were statisti- ies that ranked above the mean regarding the cally significant differences among the sensitivity methodological quality and in 25.4% of the pa- of all three radiological techniques.
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