This study aimed to identify hub genes involved in regulatory T cell (Treg) function and migration, offering insights into potential therapeutic targets for cancer immunotherapy. We performed a comprehensive bioinformatics analysis using three gene expression microarray datasets from the GEO database. Differentially expressed genes (DEGs) were identified to pathway enrichment analysis to explore their functional roles and potential pathways. A protein-protein interaction network was constructed to identify hub genes critical for Treg activity. We further evaluated the co-expression of these hub genes with immune checkpoint proteins (PD-1, PD-L1, CTLA4) and assessed their prognostic significance. Through this comprehensive analysis, we identified CCR8 as a key player in Treg migration and explored its potential synergistic effects with ICIs. Our findings suggest that CCR8-targeted therapies could enhance cancer immunotherapy outcomes, with breast invasive carcinoma (BRCA) emerging as a promising indication for combination therapy. This study highlights the potential of CCR8 as a biomarker and therapeutic target, contributing to the development of targeted cancer treatment strategies.

The expression of the placental growth factor (PGF) in cancer cells and the tumor microenvironment can contribute to the induction of angiogenesis, supporting cancer cell metabolism by ensuring an adequate blood supply. Angiogenesis is a key component of cancer metabolism as it facilitates the delivery of nutrients and oxygen to rapidly growing tumor cells. PGF is recognized as a novel target for anti-cancer treatment due to its ability to overcome resistance to existing angiogenesis inhibitors and its impact on the tumor microenvironment. We aimed to integrate bioinformatics evidence using various data sources and analytic tools for target-indication identification of the PGF target and prioritize the indication across various cancer types as an initial step of drug development. The data analysis included PGF gene function, molecular pathway, protein interaction, gene expression and mutation across cancer type, survival prognosis and tumor immune infiltration association with PGF. The overall evaluation was conducted given the totality of evidence, to target the PGF gene to treat the cancer where the PGF level was highly expressed in a certain tumor type with poor survival prognosis as well as possibly associated with poor tumor infiltration level. PGF showed a significant impact on overall survival in several cancers through univariate or multivariate survival analysis. The cancers considered as target diseases for PGF inhibitors, due to their potential effects on PGF, are adrenocortical carcinoma, kidney cancers, liver hepatocellular carcinoma, stomach adenocarcinoma, and uveal melanoma.

We aimed to uncover genetic factors affecting resistance to the cancer drug olaparib. To do this, we utilized multiomics matrix factorization (MOFA), a multiomics approach, to explore omic-based features that might become biomarker candidates. Our results showed that 17 damaging mutations, 6 gene expression signatures, 17 DNA methylations, and 26 transcription-factor activities can impact the refractory response to olaparib. To verify the potential utility of the identified biomarker candidates, we generated a predictive model to differentiate between olaparib responding and nonresponding cell lines using machine learning techniques, including support vector machine algorithms, random forest algorithms, and Siamese neural networks. The model was centered around six gene-expression biomarker candidates and validated using the Genomics of Drug Sensitivity in Cancer database. Our findings suggest that using a multiomics approach with machine learning methods can lead to a better understanding of the mechanism of drug resistance and identify biomarkers, which will ultimately facilitate the appropriate administration of drugs to patients. The source codes can be found at https://github.com/wjlim/DrugResistance .

Target identification is a crucial process in drug development, aiming to identify key proteins, genes, and signal pathways involved in disease progression and their relevance in potential therapeutic interventions. While C-C chemokine receptor 8 (CCR8) has been investigated as a candidate anti-cancer target, comprehensive multi-omics analyzes across various indications are limited. In this study, we conducted an extensive bioinformatics analysis integrating genomics, proteomics, and transcriptomics data to establish CCR8 as a promising anti-cancer drug target. Our approach encompassed data collection from diverse knowledge resources, gene function analysis, differential gene expression profiling, immune cell infiltration assessment, and strategic prioritization of target indications. Our findings revealed strong correlations between CCR8 and specific cancers, notably Breast Invasive Carcinoma (BRCA), Colon Adenocarcinoma (COAD), Head and Neck Squamous Cell Carcinoma (HNSC), Rectum adenocarcinoma (READ), Stomach adenocarcinoma (STAD), and Thyroid carcinoma (THCA). This research advances our understanding of CCR8 as a potential target for anti-cancer drug development, bridging the gap between molecular insights and creating opportunities for personalized treatment of solid tumors.

PDF file - 144K, Supplementary Table S1. Sensitivity analysis for pooled HR of PET- and CT-based response criteria. Supplementary Table S2. Sensitivity analysis for pooled CR rates and Discordance rates of PET- and CT-based response criteria.

BackgroundChimeric antigen receptor (CAR) T-cell therapy is a promising treatment option for patients with refractory hematological malignancies. However, its efficacy in glioblastoma remains unclear. Here, we performed a systematic review to summarize the safety and efficacy of CAR T-cell therapy in glioblastoma.MethodsThe PubMed, EMBASE, and Cochrane databases were searched to identify articles published before June 30, 2021 describing the use of CAR T-cell therapy in glioblastoma. Information on the toxicity of CAR T-cell therapy was summarized. The pooled objective response rate (ORR) and overall survival (OS) of patients who underwent CAR T-cell therapy were estimated using a random-effects model with an inverse-variance weighting model and quantile estimation method, respectively.ResultsOf 397 articles identified, eight studies including 63 patients with recurrent glioblastoma treated with various CAR T-cell regimens were included in the analysis. Six (9.5%) patients developed cytokine release syndrome (grade ≤2), and 16 (25.4%) experienced non-critical neurological events. The pooled ORR was 5.1% (95% confidence interval [CI], 0.0–10.4; I2 = 0.05%), and the pooled median OS was 8.1 months (95% CI, 6.7–9.5; I2 = 0.00%).ConclusionAlthough CAR T-cell therapy is a relatively safe therapeutic option in patients with glioblastoma, it shows marginal efficacy, suggesting that further research is necessary for its translation into clinical practice for the treatment of recurrent glioblastoma.

Immunotherapy has revolutionized and opened a new paradigm for cancer treatment. In the era of immunotherapy and molecular targeted therapy, precision medicine has gained emphasis, and an early response assessment is a key element of this approach. Treatment response assessment for immunotherapy is challenging for radiologists because of the rapid development of immunotherapeutic agents, from immune checkpoint inhibitors to chimeric antigen receptor-T cells, with which many radiologists may not be familiar, and the atypical responses to therapy, such as pseudoprogression and hyperprogression. Therefore, new response assessment methods such as immune response assessment, functional/molecular imaging biomarkers, and artificial intelligence (including radiomics and machine learning approaches) have been developed and investigated. Radiologists should be aware of recent trends in immunotherapy development and new response assessment methods.

The treatment efficacy of immune checkpoint inhibitors (ICIs) in colorectal cancer (CRC) has been reported heterogeneously across clinical trials. We conducted a systematic review and meta-analysis to evaluate the efficacy of ICIs in patients with advanced/metastatic CRC. Ovid-Medline was searched to identify clinical trials providing the efficacy outcomes of overall response rate (ORR) or disease control rate (DCR). The pooled ORR and DCR were estimated across all studies and subgroups. Meta-regression was performed to find the influencing factors for treatment efficacy. A total of thirty studies (1870 patients) were eligible. The overall ORR and DCR were 20.1% and 58.5%, respectively, but these results were heterogeneous across studies. Multivariate meta-regression revealed that microsatellite phenotype (odds ratio of MSI-H/dMMR versus MSS/pMMR: 1.67, p < 0.001) and drug regimen (odds ratio of monotherapy versus combination therapy: 1.07, p = 0.019) were the source of heterogeneity and also significantly influenced factors for the efficacy of the treatment. Although the efficacy of ICIs as a first-line therapy was higher than that of ICIs as the second- or more-line therapy (ORR: 51.5% vs. 13.4%, DCR: 85% vs. 49.5%), multivariate regression showed that the line of therapy was not a significant factor for the treatment efficacy. Our study suggests that the microsatellite phenotype and drug regimen, rather than the line of treatment, are the primary factors influencing the treatment response among advanced/metastatic CRC patients treated with an ICI-based regimen.

BackgroundImmune checkpoint inhibitors (ICIs) have been increasingly used in cancer treatment, and a subset of patients undergo pseudoprogression. Recognizing the incidence of pseudoprogression is critical for clinical practice.PurposeTo evaluate by systematic review and meta-analysis the incidence of pseudoprogression in cancer treatment with ICIs, and compare the incidence according to response criteria, tumor types, and immunotherapeutic agents.Materials and MethodsMedline and Embase were searched to identify relevant studies published before December 31, 2018. Clinical trials, post hoc analysis of clinical trials, and prospective studies on ICI treatment in patients with malignant solid tumors were included. Pooled incidence of pseudoprogression for all included studies, per definition of pseudoprogression, cancer type, and drug type, was obtained by random-effects models with inverse variance weighting model.ResultsSeventeen studies with 3402 patients were analyzed. The pooled incidence of pseudoprogression was 6.0% (95% confidence interval: 5.0%, 7.0%). The definition of pseudoprogression were divided into four categories: progressive disease followed by partial response (PR) or complete response (CR) but not stable disease (SD) with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (six studies); progressive disease followed by SD or PR or CR with RECIST 1.1 (five studies); progressive disease followed by SD or PR or CR with RECIST 1.0 (three studies); and progressive disease followed by SD or PR or CR with immune-related response criteria (irRC) (three studies). Incidence of pseudoprogression varied from 4.5% to 8.0% per definition, ranged from 5.0% to 7.0% per cancer type, and was 5.6% with the monotherapy of programmed cell death-1 inhibitor.ConclusionThe overall incidence of pseudoprogression was 6.0% and was less than 10% in subgroup analyses according to the definitions of pseudoprogression, cancer type, and immune checkpoint inhibitor type. Varying definitions across trials and studies indicates the need for uniform criteria of pseudoprogression for solid tumors.© RSNA, 2020Online supplemental material is available for this article.See also the article by Dodd and MacDermott in this issue.

Background and Aim Patients with chronic hepatitis C (CHC) treated with direct-acting antivirals (DAAs) are still at risk for developing hepatocellular carcinoma (HCC) even after achieving sustained virologic response (SVR). Liver-stiffness measurement (LSM) on imaging has been investigated as a predictor of HCC occurrence. Objectives To provide systematic summary of the predictive value of LSM in predicting HCC occurrence in HCV patients treated with DAA. Methods A comprehensive literature search of the PubMed-MEDLINE and EMBASE databases was performed to identify studies that evaluated the predictive value of LSM in CHC patients treated with DAAs. Pooled hazard ratio (HR) comparing HCC occurrence between patients with positive and negative results on LSM was calculated for all studies and various subgroups. Subgroup analyses and meta-regression were performed. Results A review of 135 candidate articles identified eight eligible articles with a total of 3398patients for qualitative review and meta-analysis. The pooled HR for HCC occurrence determined by LSM was 3.43 (95% confidence interval [CI], 1.63-7.19) with heterogeneity (I-2 = 81.87%,P < 0.001), thus indicating that LSM might be helpful for predicting HCC occurrence. In subgroup analyses, pooled HRs were different according to the study design (2.29; [95% CI, 0.96-5.45] for retrospective studies; 4.61 [95% CI, 2.44-8.71] for prospective studies), study population (4.00 [95% CI, 2.00-7.99] for CHC; 2.64 [0.99-7.00] for CHC with liver cirrhosis) and LSM parameter (3.17 [95% CI, 1.35-7.41] for baseline LSM; 4.19 [95% CI, 1.89-9.29] for others). In multivariate meta-regression, study design was the only influencing factor for pooled HR for HCC occurrence (P < 0.05). Conclusions Consistent evidence demonstrated the predictive value of LSM for HCC occurrence in CHC patients treated with DAA. The significant influencing factor for risk of HCC occurrence indicated by LSM was study design.

Background Immune checkpoint inhibitors (ICI) have become an important treatment option for non-small cell lung cancer (NSCLC). We aimed to evaluate the clinical impact of pseudoprogression (PsP) and treatment beyond RECIST1.1-defined progressive disease (TBP) on outcome in NSCLC patients treated with ICI. Methods NSCLC patients treated with ICI between Mar 2016 and July 2018 were recruited in a consecutive manner. Response was assessed every 8-12 weeks using RECIST1.1 and iRECIST. Based on iRECIST, PsP was defined as progressive disease (PD) on RECIST1.1 subsequently reset to non-PD categories. Using log-rank test, progression-free survival (PFS) was compared between patients with and without PsP, and overall survival (OS) was compared between patients treated with and without TBP. The impact of TBP on OS was evaluated through multivariate Cox proportional hazard models. Results Of the 189 patients, seven (3.7%) experienced PsP which mostly occurred approximately 3 months after baseline. The median PFS was significantly longer in patients with PsP (not reached) than those without PsP (3.8 months,P = .02). Among patients who demonstrated PD according to RECIST1.1, median OS was significantly longer in patients with TBP (17.2 months) than those without TBP (7.4 months,P< .001). On multivariate analysis adjusting other covariates, TBP (HR, 0.4; 95% CI, 0.2-0.7) remained as a significant protective factor for mortality. Conclusion PsP occurred in 3.7% of NSCLC patients under ICI treatment. Based on iRECIST scheme, PsP and TBP may be associated with survival benefit.

Objective To assess the technical performance of two-dimensional shear wave elastography (2D-SWE) for measuring liver stiffness. Materials and Methods The Ovid-MEDLINE and EMBASE databases were searched for studies reporting the technical performance of 2D-SWE, including concerns with technical failures, unreliable measurements, interobserver reliability, and/or intraobserver reliability, published until June 30, 2018. The pooled proportion of technical failure and unreliable measurements was calculated using meta-analytic pooling via the random-effects model and inverse variance method for calculating weights. Subgroup analyses were performed to explore potential causes of heterogeneity. The pooled intraclass correlation coefficients (ICCs) for interobserver and intraobserver reliability were calculated using the Hedges-Olkin method with Fisher's Z transformation of the correlation coefficient. Results The search yielded 34 articles. From 20 2D-SWE studies including 6196 patients, the pooled proportion of technical failure was 2.3% (95% confidence interval [CI], 1.3–3.9%). The pooled proportion of unreliable measurements from 20 studies including 6961 patients was 7.5% (95% CI, 4.7–11.7%). In the subgroup analyses, studies conducting more than three measurements showed fewer unreliable measurements than did those with three measurements or less, but no intergroup difference was found in technical failure. The pooled ICCs for interobserver reliability (from 10 studies including 517 patients) and intraobserver reliability (from 7 studies including 679 patients) were 0.87 (95% CI, 0.82–0.90) and 0.93 (95% CI, 0.89–0.95), respectively, suggesting good to excellent reliability. Conclusion 2D-SWE shows good technical performance for assessing liver stiffness, with high technical success and reliability. Future studies should establish the quality criteria and optimal number of measurements.

INTRODUCTION:We evaluated the incidence of pneumonitis in clinical trials of anaplastic lymphoma kinase (ALK) inhibitors in patients with advanced non-small cell lung cancer (NSCLC) and compared the incidence among different cohorts, in order to identify possible predisposing factors for ALK inhibitor-related pneumonitis. METHODS:MEDLINE and EMBASE search up to 1/30/18 using the keywords, "alectinib", "ceritinib", "crizotinib", "brigatinib", and "lung cancer", resulting in a total of 20 eligible cohorts with 2261 patients treated with ALK inhibitor monotherapy for advanced NSCLC. The pooled incidences of all-grade, high-grade, and grade 5 pneumonitis were calculated. Subgroup analyses were conducted with meta-regression using study-level covariates. RESULTS:The overall pooled incidence of pneumonitis was 2.14% (95% CI: 1.37-3.34) for all grade, 1.33% (95% CI: 0.80-2.21) for high grade, and 0.22% (95% CI: 0.09-0.52) for grade 5 pneumonitis. The incidence was significantly higher in studies from Japan compared to studies of non-Japan origin, for all-grade (6.25% vs 1.14%, p < 0.001) and high-grade pneumonitis (3.31% vs 0.39%, p < 0.001). Multivariate meta-regression demonstrated the cohorts from Japanese studies had significantly higher odds of pneumonitis for all-grade (odds ratio [OR]: 4.329 [95% CI: 1.918, 9.770], p < 0.001) compared to those of non-Japan origin, after adjusting for types of ALK inhibitors. CONCLUSIONS:The overall incidence of ALK inhibitor pneumonitis was 2.14% in patients with advanced NSCLS. The patients from Japanese cohorts had a higher incidence of ALK-inhibitor pneumonitis, which indicates the need for increased awareness and caution for pneumonitis in Japanese patients treated with ALK inhibitors.

OBJECTIVE To qualify shear wave elastography (SWE) as a biomarker for clinically significant portal hypertension (CSPH) beyond proof of concept, we aimed to accumulate and summarize the current evidence through systematic review and meta-analysis. MATERIALS AND METHODS A computerized literature search was performed to identify studies from MEDLINE and EMBASE up to February 9, 2017. Studies on the diagnostic performance of liver stiffness measurements using SWE for CSPH with hepatic venous pressure gradient (HVPG) as the reference standard were included. Various aspects of SWE were comprehensively assessed. The summary diagnostic performance of SWE for the diagnosis of CSPH and the summary correlation coefficient between liver stiffness measured using SWE and HVPG were evaluated through a meta-analysis. RESULTS Nine articles (including 746 patients) were retrieved. The diagnostic performance of SWE for the diagnosis of CSPH was fairly good, with a summary sensitivity of 85% (95% CI, 75-91%; I2 = 78.56%) and summary specificity of 85% (95% CI, 77-90%; I2 = 0%); the area under the ROC curve was 0.88 (95% CI, 0.85-0.91). The summary correlation coefficient between liver stiffness and HVPG measurements was 0.741 (95% CI, 0.658-0.825; I2 = 0%). These results support the value of SWE as a diagnostic biomarker for CSPH. However, there was significant heterogeneity in the imaging devices, protocols, liver stiffness measurement methods, and cutoff values used, which suggests that standardization is required. CONCLUSION The consistent evidence favoring SWE as a biomarker for CSPH should be considered in the biomarker qualification process and management of patients with CSPH.

The objective was to outline differences in orphan medicine utilization, by timing and availability of market sales across OECDs, and to investigate factors associated with the access speed. We extracted a list of orphan designated medicines approved by FDA (2006-2015) and global pharmaceutical sales data of IQVIA MIDAS (2006-2016). For each drug and country, drug characteristics, demographic and economic information were collected. A descriptive summary provided characteristics of included medicines, availability of drugs with actual sales, and timing from FDA approval to initial sales occurrence. We analyzed the time to initial sales using Kaplan-Meier survival analysis with log rank test and Cox proportional hazard model to examine the access speed depending on drug and country level covariates. 165 unique orphan medicines were included. The orphan medicine approvals increased over time and the anti-neoplastic takes highest proportion (35%), followed by blood related medicines (13%) including anti-hemorrhagic. The timing to initial sales have shown a wide distribution across countries which the average duration varies from 198 days of US to 1628 days in Greece with 765 days as median duration (SD:306 days). The availability of drugs varies from 12.1% in Estonia to 90% in US with 38% of median availability among 165 drugs. Using KM log rank test, we found a statistically significant quicker access in timing of the initial sales by cancer indication, upper 50 percentile of GDP per capita, total pharmaceutical expenditure per capita, and population number, and recent FDA approval year (all; p<0.0001). In Cox PH model, GDP per capita(HR: 1.77 [1.56, 2.01]), cancer indication(HR: 1.26 [1.13, 1.41]) and recent approved medicines(HR: 1.18 [1.15, 1.21]) were independent predictors adjusting all covariates. Our study suggests a huge gap exists in the availability and access speed across OECDs which are modified by GDP per capita, cancer indication and recent FDA approvals.

Vertebral Fracture Assessment (VFA) is a useful tool to detect the vertebral fracture (VF) with low cost and radiation exposure. We aimed to compare screening strategies including VFA and spine radiography (X-ray) for detecting VF in terms of clinical effectiveness, cost and radiation exposure.

Purpose: Pneumonitis is a significant toxicity of EGFR tyrosine kinase inhibitors (EGFR-TKI) in non-small-cell lung cancer (NSCLC) patients. We studied the incidence of pneumonitis in clinical trials of EGFR-TKI published in 2003-2017, and performed subgroups analyses to identity predisposing factors. Methods: Ovid-MEDLINE and EMBASE search up to 4/17/17 using the keywords, "erlotinib", "gefitinib", "afatinib", "osimertinib", and "lung cancer", resulted in a total of 153 eligible trial cohorts with 15,713 advanced NSCLC patients treated with EGFR-TKI. The pooled incidence of all-grade, high-grade, and grade 5 pneumonitis was obtained. Subgroup analyses were performed with meta-regression using study-level covariates. Results: Among the patients without prior exposure to EGFR-TKI, the overall incidence was 1.12% (95% CI:0.79-1.58%) for all-grade, 0.61% (95% CI:0.40-0.93%) for high-grade, and 0.20% (95% CI:0.11-0.38%) for grade 5 pneumonitis. The incidence was significantly higher in Japanese studies compared to studies of non Japan origin, for all-grade (4.77% vs. 0.55%, p < 0.001), high grade (2.49% vs. 0.37%, p < 0.001), and grade 5 pneumonitis (1.00% vs. 0.18%, p < 0.001). Multivariate analyses demonstrated higher odds of pneumonitis in Japanese studies for all-grade (odds ratio [OR]: 5.04; 95% p < 0.001), high-grade (OR: 4.45; 95% p < 0.001), and grade 5 pneumonitis (OR: 4.55; 95% CI:2.20-9.44, p < 0.001) compared to others, after adjusting for types of EGFR-TKI and lines of therapy. In patients with EGFR retreatment analyzed separately, the pooled incidence was 1.13% (95% CI:0.40-3.15%) for all-grade, 0.49% (95% CI:0.21-1.11%) for high-grade, and 0.16% (95% CI:0.04-0.65%) for grade 5 pneumonitis. Conclusions: The overall incidence of EGFR-TKI pneumonitis was 1.12% in patients without prior exposure to EGFR-TKI, and 1.13% in EGFR-TKI retreatment group. The cohorts from Japan had significantly higher incidence of pneumonitis, providing insights for further mechanistic studies.

OBJECTIVE. We determined the cost-effectiveness of two different diagnostic imaging strategies in guiding curative treatment of early-stage hepatocellular carcinoma (HCC). MATERIALS AND METHODS. We developed a decision analytic model using as its starting point a cohort of patients aged 55 years with early-stage HCC detected at dynamic multiphasic CT and with Child-Pugh class A cirrhosis. The model compared two strategies on the initial workup: conventional CT strategy using dynamic multiphasic CT only and gadoxetic acid-enhanced MRI strategy using additional gadoxetic acid-enhanced MRI after initial CT. A Markov cohort model simulated a cohort of patients after curative or adjuvant treatment, with follow-up over the remaining life expectancy. We analyzed mean life-years gain, quality-adjusted life-years (QALYs), costs per person, and incremental cost-effectiveness ratio (ICER). To evaluate results, we performed one-way, two-way, and probabilistic sensitivity analyses. RESULTS. The life expectancies and QALY were 7.22 years and 5.08 for the conventional CT strategy and 7.79 years and 5.52 for the gadoxetic acid-enhanced MRI strategy, respectively. The expected costs were $99,770 for conventional CT and $105,025 for gadoxetic acid-enhanced MRI in the United States. The ICER with gadoxetic acid-enhanced MRI was $11,957, as opposed to that with conventional CT, which was lower than the cost-effectiveness threshold of $50,000/QALY. One-way, two-way, and probabilistic sensitivity analyses showed unchanged results over an acceptable range. CONCLUSION. Gadoxetic acid-enhanced MRI after CT is cost-effective for detecting additional HCC in patients with early-stage HCC who can undergo curative treatment (besides liver transplantation). The cost-effectiveness of gadoxetic acid-enhanced MRI may be considered in the management of patients with early-stage HCC during staging.

OBJECTIVE The purpose of this study is to evaluate the outcomes of hypovascular hypointense nodules in the hepatobiliary phase of gadoxetic acid-enhanced MRI and the risk factors for the hypervascular transformation of the nodules through a systematic review and meta-analysis. MATERIALS AND METHODS We searched the Ovid-MEDLINE and EMBASE databases for published studies of hypovascular hypointense nodules in patients with chronic liver disease. The pooled proportions of the overall and cumulative incidence rates at 1, 2, and 3 years for the transformation of hypovascular hypointense nodules into hypervascular hepatocellular carcinomas (HCCs) were assessed by using random-effects modeling. Metaregression analysis was performed. RESULTS Sixteen eligible studies with 944 patients and 1819 hypovascular hypointense nodules in total were included. The pooled overall rate of hypervascular transformation was 28.2% (95% CI, 22.7-33.6%; I2 = 87.46%). The pooled 1-, 2-, and 3-year cumulative incidence rates were 18.3% (95% CI, 9.2-27.4%), 25.2% (95% CI, 12.2-38.2%), and 30.3% (95% CI, 18.8-41.9%), respectively. The metaregression analysis revealed that the mean initial nodule size (cutoff value, 9 mm) was a significant factor affecting the heterogeneity of malignant transformation. CONCLUSION Hypovascular hypointense nodules detected in the hepatobiliary phase of gadoxetic acid-enhanced MRI carry a significant potential of transforming into hypervascular HCCs. The size of nodules is a significant risk factor for hypervascular transformation.

We aimed to evaluate the correlation between liver stiffness measurement using transient elastography (TE-LSM) and hepatic venous pressure gradient and the diagnostic performance of TE-LSM in assessing clinically significant portal hypertension through meta-analysis. Eleven studies were included from thorough literature research and selection processes. The summary correlation coefficient was 0.783 (95% confidence interval [CI], 0.737-0.823). Summary sensitivity, specificity and area under the hierarchical summary receiver operating characteristic curve (AUC) were 87.5% (95% CI, 75.8-93.9%), 85.3%(95% CI, 76.9-90.9%) and 0.9, respectively. The subgroup with low cut-off values of 13.6-18 kPa had better summary estimates (sensitivity 91.2%, specificity 81.3% and partial AUC 0.921) than the subgroup with high cut-off values of 21-25 kPa (sensitivity 71.2%, specificity 90.9% and partial AUC 0.769). In summary, TE-LSM correlated well with hepatic venous pressure gradient and represented good diagnostic performance in diagnosing clinically significant portal hypertension. For use as a sensitive screening tool, we propose using low cut-off values of 13.6-18 kPa in TE-LSM. (E-mail:medimash@gmail.com) (C) 2016 World Federation for Ultrasound in Medicine & Biology.