A non-smooth tumor margin on preoperative imaging assesses microvascular invasion of hepatocellular carcinoma: A systematic review and meta-analysis

Scientific Reports, Nov 2017

Microvascular invasion (MVI) is rarely diagnosed preoperatively in hepatocellular carcinoma (HCC). The aim of this meta-analysis is to assess the diagnostic power of a non-smooth tumor margin on preoperative imaging for MVI. We performed a literature search using the PubMed, Embase and Cochrane Library databases, and 11 studies were included involving 618 MVI-positive cases and 1030 MVI-negative cases. Considerable heterogeneity was found, and was indicated to be attributable to the mean patient ages in the included studies. In subgroups of studies with a mean patient age older than 60 years and studies with computed tomography (CT) as the imaging method (as opposed to magnetic resonance imaging (MRI)), heterogeneity was low, and the diagnostic odds ratio (DOR) of the single two-dimensional imaging feature for MVI was 21.30 (95% CI [12.52, 36.23]) and 28.78 (95% CI [13.92, 59.36]), respectively; this power was equivalent to or greater than that of certain multivariable-based scoring systems. In conclusion, a non-smooth tumor margin on preoperative imaging is of great value for MVI assessment and should be considered for inclusion in future scoring systems.

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A non-smooth tumor margin on preoperative imaging assesses microvascular invasion of hepatocellular carcinoma: A systematic review and meta-analysis

Abstract Microvascular invasion (MVI) is rarely diagnosed preoperatively in hepatocellular carcinoma (HCC). The aim of this meta-analysis is to assess the diagnostic power of a non-smooth tumor margin on preoperative imaging for MVI. We performed a literature search using the PubMed, Embase and Cochrane Library databases, and 11 studies were included involving 618 MVI-positive cases and 1030 MVI-negative cases. Considerable heterogeneity was found, and was indicated to be attributable to the mean patient ages in the included studies. In subgroups of studies with a mean patient age older than 60 years and studies with computed tomography (CT) as the imaging method (as opposed to magnetic resonance imaging (MRI)), heterogeneity was low, and the diagnostic odds ratio (DOR) of the single two-dimensional imaging feature for MVI was 21.30 (95% CI [12.52, 36.23]) and 28.78 (95% CI [13.92, 59.36]), respectively; this power was equivalent to or greater than that of certain multivariable-based scoring systems. In conclusion, a non-smooth tumor margin on preoperative imaging is of great value for MVI assessment and should be considered for inclusion in future scoring systems. Introduction Hepatocellular carcinoma (HCC) is the third-leading cause of cancer-related deaths worldwide1; even with treatment with potentially curative therapies, HCC has a 5-year recurrence rate of approximately 35–70%2. Vascular invasion is direct evidence of the biological aggressiveness of a tumor. Microvascular invasion (MVI), which is defined as tumor invasion of a portal vein radicle, the large capsule vessel or a vascular space lined by endothelial cells, is detectable only by microscopy3. Relative to other HCC patients, patients with MVI have a markedly higher risk of early recurrence and poor postsurgical survival3,4, even in cases involving small, solitary HCC tumors5,6. Moreover, patients who do not satisfy the Milan criteria can nonetheless exhibit excellent outcomes if they are confirmed to be negative for MVI7. The gold standard for diagnosing MVI is a histological examination, which requires extensive sampling. A noninvasive evaluation system capable of preoperatively identifying MVI would be of great clinical value for better determining optimal therapeutic strategies. If MVI is detected, an adjuvant therapy such as sorafenib treatment8 or trans-arterial chemoembolization (TACE)9 could be used, given that these approaches have been reported to improve survival for HCC patients with MVI. Several promising markers of MVI have been identified, although assessments of such markers involve technically demanding methods, including genetic testing, protein analysis and radiographic examination. A non-smooth tumor margin, which manifests as a lobulated or irregularly shaped tumor with the focal/multifocal outgrowth of nodules protruding into the non-tumor parenchyma10,11, is a two-dimensional imaging feature observable via even the simplest imaging methods, including ultrasonography. Moreover, this feature has been reported to be strongly related to elevated MVI risk and has even been identified as the only significant factor in a multivariable analysis10,12,13,14. To better understand this topic, we performed a review of the diagnostic performance of a non-smooth tumor margin for preoperative MVI assessment. Results Study selection We identified a total of 1101 studies using our search strategy (Fig. 1). Studies as duplicated reports, reviews, case reports, editorials or conference abstracts were excluded (351 studies). After titles and abstracts were reviewed, 685 studies were excluded for examining non-primary HCC, being in vitro experiments or unrelated to MVI estimation. The remaining 65 studies were subjected to full-text review, and 59 of these studies were excluded for overlapping population (3 studies), sample size smaller than 30 (1 study), involving gross analyses of non-smooth tumor margins (7 studies), or containing no valid extractable data for our meta-analysis (48 studies). Six studies were selected for inclusion, and 5 additional studies were included after reviewing citations of the retrieved articles. Figure 1 Flow chart diagram presenting the selection of eligible studies. Full size image Study characteristics Characteristics of the 11 studies are presented in Table 1, and additional information is presented in Table 1 of the Supplementary materials. The included studies were published between 2009 and 2016. In total, 618 pathologically diagnosed MVI-positive patients and 1030 MVI-negative patients were included in this meta-analysis. Two15,16 of the included studies were performed in European populations, and the remaining nine studies were performed in Asian populations. One study17 assessed HCC patients treated via liver transplantation, 8 studies assessed HCC patients treated via liver resection, and two10,16 studies included HCC patients treated via either modality. Tumor margins were eval (...truncated)


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HangTong Hu, Qiao Zheng, Yang Huang, Xiao Wen Huang, Zhi Cheng Lai, JingYa Liu, XiaoYan Xie, Shi Ting Feng, Wei Wang, Ming De Lu. A non-smooth tumor margin on preoperative imaging assesses microvascular invasion of hepatocellular carcinoma: A systematic review and meta-analysis, Scientific Reports, 2017, Issue: 7, DOI: 10.1038/s41598-017-15491-6