Contrast-enhanced US with Sulfur Hexafluoride and Perfluorobutane: LI-RADS for Diagnosing Hepatocellular Carcinoma.

Background Liver Imaging Reporting and Data System (LI-RADS) was designed for contrast-enhanced US (CEUS) with pure blood pool agents to diagnose hepatocellularfcarcinoma (HCC), such as sulfur hexafluoride (SHF), but Kupffer-cell agents, such as perfluorobutane (PFB), allow additional lesion characterization in the Kupffer phase yet remain unaddressed. Purpose To compare the diagnostic performance of three algorithms for HCC diagnosis: two algorithms based on CEUS LI-RADS version 2017 for both SHF and PFB and a modified algorithm incorporating Kupffer-phase findings for PFB. Materials and Methods This multicenter prospective study enrolled high-risk patients for HCC from June 2021 to December 2021. Each participant underwent same-day SHF-enhanced US followed by PFB-enhanced US. Each liver observation was assigned three LI-RADS categories according to each algorithm: LI-RADS SHF, LI-RADS PFB, and modified PFB. For modified PFB, observations at least 10 mm with nonrim arterial phase hyperenhancement were upgraded LR-4 to LR-5 if there was no washout with a Kupffer defect and were reassigned LR-M to LR-5 if there was early washout with mild Kupffer defect. The reference standard was pathologic confirmation or composite (typical CT or MRI features, or 1-year size stability and/or reduction). Diagnostic metrics of LR-5 for HCC using the three algorithms were calculated and compared using the McNemar test. Results Overall, 375 patients (mean age, 56 years ± 11 [SD]; 318 male patients, 57 female patients) with 424 observations (345 HCCs, 40 non-HCC malignancies, 39 benign lesions) were enrolled. PFB and SHF both using LI-RADS showed no significant difference in sensitivity (60% vs 58%; P = .41) and specificity (96% vs 95%; P > .99). The modified algorithm with PFB had increased sensitivity (80% vs 58%; P < .001) and a nonsignificant decrease in specificity (92% vs 95%; P = .73) compared with LI-RADS SHF. Conclusion Based on CEUS LI-RADS version 2017, both SHF and PFB achieved high specificity and relatively low sensitivity for HCC diagnosis. When incorporating Kupffer-phase findings, PFB had higher sensitivity without loss of specificity. Chinese Clinical Trial Registry no. ChiCTR2100047035 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Kim in this issue.

Nomogram to differentiate benign and malignant thyroid nodules in the American College of Radiology Thyroid Imaging Reporting and Data System level 5.

OBJECTIVES: To develop and validate a nomogram for differentiating benign and malignant thyroid nodules of American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) level 5 (TR5) and improving the performance of the guideline. METHODS: From May 2018 to December 2019, 640 patients with TR5 nodules were retrospectively included in the primary cohort. Univariate and multivariable analyses were performed to determine the risk factors for thyroid cancer. A nomogram was established on the basis of multivariable analyses; the performance of the nomogram was evaluated with respect to discrimination, calibration, and clinical usefulness. The nomogram model was also compared to the ACR score model. External validation was performed and the independent validation cohort contained 201 patients from April 2021 to January 2022. RESULTS: Multivariable analyses showed that age, tumour location, multifocality, concomitant Hashimoto's disease, neck lymph node status reported by ultrasound (US) and ACR score were the independent risk factors for thyroid cancer (all p < .05). The nomogram showed good discrimination, with an area under the curve (AUC) of 0.786 (95% confidence interval [CI]: 0.742-0.830) and 0.712 (95% CI: 0.615-0.809) in the primary cohort and external validation cohort, respectively. Decision curve analysis demonstrated the clinical usefulness of the model. Compared to the ACR score model, the nomogram showed higher AUC (0.786 vs. 0.626, p < .001) and specificity (0.783 vs. 0.391). CONCLUSIONS: The presented nomogram model, based on age, tumour features and ACR score, can differentiate benign and malignant thyroid nodules in TR5 and had a high specificity.

Head and neck MRI-based T stage and [18F]FDG PET/CT-based N/M stage improved prognostic stratification in primary nasopharyngeal carcinoma.

OBJECTIVES: To evaluate whether MRI-based T stage (TMRI), [18F]FDG PET/CT-based N (NPET/CT), and M stage (MPET/CT) are superior in NPC patients' prognostic stratification based on long-term survival evidences, and whether TNM staging method involving TMRI + NPET/CT + MPET/CT could improve NPC patients' prognostic stratification. METHODS: From April 2007 to December 2013, 1013 consecutive untreated NPC patients with complete imaging data were enrolled. All patients' initial stages were repeated based on (1) the NCCN guideline recommended "TMRI + NMRI + MPET/CT" ("MMP") staging method; (2) the traditional "TMRI + NMRI + Mconventional work-up (CWU)" ("MMC") staging method; (3) the single-step "TPET/CT + NPET/CT + MPET/CT" ("PPP") staging method; or (4) the "TMRI + NPET/CT + MPET/CT" ("MPP") staging method recommended in present research. Survival curve, ROC curve, and net reclassification improvement (NRI) analysis were used to evaluate the prognosis predicting ability of different staging methods. RESULTS: [18F]FDG PET/CT performed worse on T stage (NRI = - 0.174, p < 0.001) but better on N (NRI = 0.135, p = 0.004) and M stage (NRI = 0.126, p = 0.001). The patients whose N stage upgraded by [18F]FDG PET/CT had worse survival (p = 0.011). The "TMRI + NPET/CT + MPET/CT" ("MPP") method performed better on survival prediction when compared with "MMP" (NRI = 0.079, p = 0.007), "MMC" (NRI = 0.190, p < 0.001), or "PPP" method (NRI = 0.107, p < 0.001). The "TMRI + NPET/CT + MPET/CT" ("MPP") method could reclassify patients' TNM stage to a more appropriate stage. The improvement is significant in patients with more than 2.5-years follow-up according to the time-dependent NRI values. CONCLUSIONS: The MRI is superior to [18F]FDG PET/CT in T stage, and [18F]FDG PET/CT is superior to CWU in N/M stage. The "TMRI + NPET/CT + MPET/CT" ("MPP") staging method could significantly improve NPC patients' long-term prognostic stratification. CLINICAL RELEVANCE STATEMENT: The present research provided long-term follow-up evidence for benefits of MRI and [18F]FDG PET/CT in TNM staging for nasopharyngeal carcinoma, and proposes a new imaging procedure for TNM staging incorporating MRI-based T stage and [18F]FDG PET/CT-based N and M stage, which significantly improves long-term prognostic stratification for patients with NPC. KEY POINTS: • The long-term follow-up evidence of a large-scale cohort was provided to evaluate the advantages of MRI, [18F]FDG PET/CT, and CWU in the TNM staging of nasopharyngeal carcinoma. • A new imaging procedure for TNM stage of nasopharyngeal carcinoma was proposed.

Thyroid nodule recognition using a joint convolutional neural network with information fusion of ultrasound images and radiofrequency data.

OBJECTIVE: To develop a deep learning-based method with information fusion of US images and RF signals for better classification of thyroid nodules (TNs). METHODS: One hundred sixty-three pairs of US images and RF signals of TNs from a cohort of adult patients were used for analysis. We developed an information fusion-based joint convolutional neural network (IF-JCNN) for the differential diagnosis of malignant and benign TNs. The IF-JCNN contains two branched CNNs for deep feature extraction: one for US images and the other one for RF signals. The extracted features are fused at the backend of IF-JCNN for TN classification. RESULTS: Across 5-fold cross-validation, the accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) obtained by using the IF-JCNN with both US images and RF signals as inputs for TN classification were respectively 0.896 (95% CI 0.838-0.938), 0.885 (95% CI 0.804-0.941), 0.910 (95% CI 0.815-0.966), and 0.956 (95% CI 0.926-0.987), which were better than those obtained by using only US images: 0.822 (0.755-0.878; p = 0.0044), 0.792 (0.679-0.868, p = 0.0091), 0.866 (0.760-0.937, p = 0.197), and 0.901 (0.855-0.948, p = .0398), or RF signals: 0.767 (0.694-0.829, p < 0.001), 0.781 (0.685-0.859, p = 0.0037), 0.746 (0.625-0.845, p < 0.001), 0.845 (0.786-0.903, p < 0.001). CONCLUSIONS: The proposed IF-JCNN model filled the gap of just using US images in CNNs to characterize TNs, and it may serve as a promising tool for assisting the diagnosis of thyroid cancer. KEY POINTS: • Raw radiofrequency signals before ultrasound imaging of thyroid nodules provide useful information that is not carried by ultrasound images. • The information carried by raw radiofrequency signals and ultrasound images for thyroid nodules is complementary. • The performance of deep convolutional neural network for diagnosing thyroid nodules can be significantly improved by fusing US images and RF signals in the model as compared with just using US images.

Long-term outcome for colorectal liver metastases: combining hepatectomy with intraoperative ultrasound guided open microwave ablation versus hepatectomy alone.

OBJECTIVE: To compare the long-term outcome of combining hepatectomy with intraoperative ultrasound (IOUS)-guided open microwave ablation (MWA) versus hepatectomy alone in patients with colorectal cancer liver metastases (CRLM). METHOD: A retrospective analysis of patients with CRLM who underwent hepatectomy alone (HT group; 380 patients) or hepatectomy combined with IOUS-guided open MWA (HT + MWA group; 57 patients) from April 2002 to September 2018 was conducted at our center. A propensity score-matched (PSM) analysis was used to reduce data bias between the two groups. RESULTS: The overall survival (OS) and disease-free survival (DFS) were not significantly different between the two groups after matching. Although intrahepatic recurrence was more frequent in the HT + MWA group in both the whole and matched cohort, the two groups exhibited similar rates of extrahepatic recurrence as well as concomitant intra- and extrahepatic recurrence. A higher number of CRLM (>3), larger maximum-size and absence of response to induction chemotherapy were independent risk factors for OS. CONCLUSION: The oncological outcomes of hepatectomy combined with intraoperative open ablation was not significantly different to hepatectomy alone and should be considered as a safe and fair option for patients with difficultly resectable CRLM.

Comparison of the prognostic value of inflammation-based scores in early recurrent hepatocellular carcinoma after hepatectomy.

BACKGROUND & AIMS: Inflammation-based prognostic scores, such as the Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), Prognostic Index (PI), Prognostic Nutritional Index (PNI), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR) and systemic immune-inflammation index (SII), are correlated with the survival of hepatocellular carcinoma (HCC) patients, while remain unclear for recurrent HCC. This study aimed to compare the prognostic value of inflammation-based prognostic scores for post-recurrence survival (PRS) in patients with early recurrent HCC (ErHCC, within 2 years after hepatectomy). METHODS: A total of 580 patients with ErHCC were enrolled retrospectively. The association between the independent baseline and the time-dependent variables and PRS was evaluated by cox regression. The prediction accuracy of the inflammation-based prognostic scores was assessed by time-dependent receiver operating characteristic (ROC) and Harrell's concordance index (C-index) analyses. RESULTS: The GPS, mGPS, PI, PNI, NLR, PLR, LMR and SII were all related to the PRS of ErHCC patients, while only the SII (P < .001) remained an independent predictor for PRS in multivariate analysis (hazard ratio: 1.92, 95% confidence interval: 1.33-2.79). Both the C-index of the SII (0.65) and the areas under the ROC curves showed that the SII score was superior to the other inflammation-based prognostic scores for predicting the PRS of ErHCC patients. CONCLUSIONS: The SII is a useful prognostic indicator for PRS in patients with ErHCC after hepatectomy and is superior to the other inflammation-based prognostic scores in terms of prognostic ability.

Lymph-node Epstein-Barr virus concentration in diagnosing cervical lymph-node metastasis in nasopharyngeal carcinoma.

PURPOSE: Cervical lymph-node (CLN) metastasis commonly occurs in patients with nasopharyngeal carcinoma (NPC) metastasis. The presence of Epstein-Barr virus (EBV) genomes in neck lymph nodes may diagnose CLN. This research was designed to appraise the diagnostic value of EBV concentration for cervical lymph nodes in NPC. METHODS: Two hundred and fifty-three NPC patients with 276 CLNs were enrolled. MRI was performed to detect CLN metastasis, and plasma EBV concentration was measured by quantitative PCR before treatment. Ultrasonography (US) and US-FNA were subsequently performed in the suspicious lymph nodes. Fifteen patients (22 lymph nodes) underwent fine-needle aspiration cytology (FNAC), and the remaining 242 patients (254 lymph nodes) underwent core needle biopsy (CNB) for CLNs at the clinician's demand. The aspiration needle was rinsed with 1 ml of normal saline for EBV detection. The method of lymph-node EBV measurement was consistent with that for plasma. The MRI results and EBV concentrations in plasma and lymph nodes were recorded and analyzed. Plasma EBV concentrations ≥ 4000 copies/ml were regarded as positive. RESULTS: CLN-EBV concentrations ≥ 787.5 copies/ml were regarded as positive according to receiver-operating characteristic curve analysis. The AUC of the EBV (0.925) concentration in CLN metastasis was significantly larger than the AUC of MRI (0.714) (P < 0.001). The sensitivity and specificity were 94.09% and 48.72% for MRI in lymph-node metastasis and 95.36% (P > 0.05) and 84.62% (P < 0.01) for EBV DNA in CLN metastasis, respectively. The sensitivity and specificity of EBV in plasma were 77.2% and 71.8%, respectively. The diagnostic specificity and AUC of EBV in CLNs were higher than those of MRI and plasma EBV (P < 0.005). CONCLUSIONS: Ultrasound-guided CLN FNA to obtain EBV concentrations may provide a new method to diagnose CLN metastasis with high sensitivity and specificity.

Pretreatment anti-Mullerian hormone-based nomogram predicts menstruation status after chemotherapy for premenopausal women with hormone receptor-positive early breast cancer.

PURPOSE: Ovarian function is important for optimizing endocrine treatment in patients with hormone receptor-positive (HR+) early breast cancer (eBC). The aim of the study was to determine whether patients' pretreatment levels of anti-Mullerian hormone (AMH) were associated with menses status after chemotherapy and to build a predictive nomogram model for amenorrhea in women with HR+ eBC. METHODS: Between August 2013 and December 2014, 120 premenopausal patients with HR+ eBC were included retrospectively. The associations among age, prechemotherapy levels of AMH, follicle-stimulating hormone (FSH),and estradiol (E2) and the 2-year postchemotherapy menses status were analyzed. We determined the cutoff values of hormone levels by using the biostatistical tool (Cutoff Finder). A novel nomogram was established to predict the 2-year amenorrhea status based on the logistic analysis. Concordance index (C-index) was used to validate the capacity. RESULTS: One hundred nine women (90.8%) experienced amenorrhea after chemotherapy. AMH < 0.965 ng/ml predicted amenorrhea at 2 years (AUC 0.84, sensitivity 74% and specificity 81.8%), independent of age. The predictive nomogram based on age and pretreatment AMH and FSH levels was developed to predict the probability of 2-year postchemotherapy amenorrhea with a C-index of 0.88 (95% CI 0.84-0.91). CONCLUSIONS: In premenopausal patients with HR+ eBC, prechemotherapy AMH concentration was associated with the patient's 2-year amenorrhea status, independent of age. The nomogram model based on age and pretreatment AMH and FSH levels accurately predicted the 2-year amenorrhea status.

Lipiodol deposition in portal vein tumour thrombus predicts treatment outcome in HCC patients after transarterial chemoembolisation.

OBJECTIVE: To study lipiodol deposition in portal vein tumour thrombus (PVTT) in predicting the treatment outcome of hepatocellular carcinoma (HCC) patients after transarterial chemoembolisation (TACE). METHODS: We retrospectively reviewed data from 379 HCC patients with PVTT who underwent TACE as the initial treatment at Sun Yat-Sen University Cancer Center from January 2008 to December 2015. Patients were grouped by positive and negative lipiodol deposition based on the extent of lipiodol deposition in PVTT. The overall survival (OS) and progression-free survival (PFS) were compared between negative and positive lipiodol deposition groups; furthermore, the value of the combinatorial evaluation of tumour responses and lipiodol deposition in PVTT in predicting prognosis was analysed in subgroup patients with stable disease (SD) after TACE. RESULTS: Of the 379 patients, 264 (69.7%) had negative and 115 (30.3%) had positive lipiodol deposition in PVTT after TACE. Multivariate analysis identified positive lipiodol deposition in PVTT as an independent prognostic factor for favourable OS (p = 0.001). The median OS and PFS of negative and positive lipiodol deposition groups were 4.70 vs. 8.97 months (p = 0.001) and 3.1 months vs. 5.8 months (p < 0.001). In subgroup patients, the median OS and PFS of negative and positive lipiodol deposition groups were 4.7 months vs. 10.5 months (p < 0.001) and 3.5 months vs. 7.0 months (p < 0.001), respectively. CONCLUSIONS: The patients with positive lipiodol deposition in PVTT had a longer OS than those with negative lipiodol deposition. Furthermore, the positive lipiodol deposition in PVTT can further differentiate HCC patients with favourable prognosis from SD patients. KEY POINTS: • Lipiodol deposition in PVTT is a prognostic indicator for HCC patients after TACE treatment. • Positive lipiodol deposition in PVTT is associated with a better prognosis.

Nomogram to Predict Survival of Patients With Recurrence of Hepatocellular Carcinoma After Surgery.

BACKGROUND & AIMS: We aimed to establish and validate a nomogram to predict survival at 2 and 5 years after recurrence of hepatocellular carcinoma (HCC) in patients who have undergone curative resection. METHODS: We developed a nomogram using data from a training cohort of 638 patients (most with hepatitis B virus infection) with recurrence of HCC after curative resection at Sun Yat-sen University Cancer Center, in Guangzhou, China from 2007 through 2013. The median follow-up time was 39.7 months. Patients were evaluated every 3-4 months for the first 2 years after resection and every 3-6 months thereafter. The nomogram was based on variables independently associated with survival after HCC recurrence, including antiviral treatment; albumin-bilirubin grade and alpha-fetoprotein level at recurrence; time from primary resection to recurrence; size, site, number of recurrences; and treatment for recurrence. We validated the nomogram using data from an independent internal cohort of 213 patients treated at the same institution and an external cohort of 127 patients treated at 2 other centers in China, from 2002 through 2009. The predictive accuracy of the nomogram was measured using Harrell's concordance index (C index) and compared with the Barcelona Clinic Liver Cancer staging system of recurrence. RESULTS: Our nomogram predicted survival of patients in the training cohort with a C-index of 0.797 (95% CI, 0.765-0.830)-greater than that of the Barcelona Clinic Liver Cancer staging system for recurrence (C-index score, 0.713; 95% CI, 0.680-0.745) (P < .001). This nomogram accurately stratified patients into subgroups with predicted long, medium, and short survival times: the proportions of patients in each group who survived 2 years after HCC recurrence were 91.2%, 67.6%, and 23.8%; the proportions of patients in each group who survived 5 years after HCC recurrence were 74.9%, 53.3%, and 9.1%. Our nomogram predicted patient survival times with C-index scores of 0.756 (95% CI, 0.703-0.808) in the internal validation cohort and 0.747 (95% CI, 0.701-0.794) in the external validation cohorts. CONCLUSIONS: We developed a nomogram to determine the probability of survival, at different time points, of patients with recurrence of HCC (most with hepatitis B virus infection), after curative resection and validated it internally and externally.

Impact of follow-up interval on patients with hepatocellular carcinoma after curative ablation.

BACKGROUND: The optimal follow-up strategy after curative thermal ablation of hepatocellular carcinoma (HCC) remains unclear. METHODS: We retrospectively analyzed a prospective series of 616 patients who underwent curative thermal ablation for HCC within the Milan criteria. Multivariate Cox model was used to identify independent predictive factors for recurrence; accordingly, patients were stratified into 2 groups with different relapse risks: a low-risk group (solitary tumor ≤3 cm) and a high-risk group (multiple tumors ≤3 cm or solitary tumor between 3 and 5 cm). Then, patients were classified into short- (< 4 months) or long-interval (4-6 months) surveillance groups according to follow-up intensity within the first 2 years after ablation. The overall survival (OS) of patients were compared between short- and long-interval groups in low- or high-risk groups, as well as the stage of recurrent tumors and the proportion of patients who received curative-intent retreatments. RESULTS: In the low-risk group, 54 (83.0%) and 18 (72.0%) of patients exhibited early relapse at the Barcelona Clinic Liver Cancer (BCLC) 0/A stage in the short- and long-interval groups, respectively (P = 0.172); accordingly, 44 (77.2%) and 18 (81.8%) of patients received curative-intent retreatment (P = 0.086) after recurrence. Hence, 5-year OS was similar between short- and long-interval groups (80.4% vs. 77.5%, P = 0.400) in low-risk patients. However, in the high-risk group, patients with a short interval exhibited early relapse more frequently at the BCLC 0/A stage (83% vs. 72%, P = 0.028), with a trend showing that the corresponding proportion of patients who received curative-intent retreatment greater than that in the long-interval group (64.2% vs. 37.5%, P = 0.087). Moreover, the short-interval group showed better 5-year OS than the long-interval group in high-risk patients (69.9% vs. 42.7%, P = 0.020). CONCLUSIONS: Compared to a short surveillance interval, a long surveillance interval does not reduce OS in low-risk patients; however, a long surveillance interval compromises OS in high-risk patients.

Efficacy of ultrasound-guided core needle biopsy in cervical lymphadenopathy: A retrospective study of 6,695 cases.

OBJECTIVES: To determine the diagnostic yield of ultrasound-guided core needle biopsy (US-CNB) in cervical lymphadenopathy and identify the factors influencing the diagnostic accuracy of US-CNB. METHODS: We retrospectively reviewed the records of 6,603 patients with cervical lymphadenopathy who underwent 6695 US-CNB procedures between 2004 and 2017. RESULTS: Adequate specimens were obtained in 92.19 % (6,172/6,695) of cases. Most lymph nodes (67.65 %) were malignant (metastatic carcinoma 4,131; lymphoma 398). The overall accuracy of US-CNB for differentiating benign from malignant lesions was 91.70 % (6,139/6,695). Among biopsies in which adequate material was obtained, the sensitivity, specificity and accuracy of US-CNB were 99.70 %, 100 % and 99.46 %, respectively. The success or failure of US-CNB for the diagnosis of lymphadenopathy was significantly correlated with node size, nature (malignant vs. benign), and location as well as penetration depth, but not with needle size (p = 0.665), number of core tissues obtained (p = 0.324), or history of malignancy (p = 0.060). There were no major procedure-related complications. CONCLUSIONS: US-CNB is a safe and effective method of diagnosing cervical lymphadenopathy, and our findings may help optimise the sampling procedure by maximising its diagnostic accuracy and preserving its minimally invasive nature. KEY POINTS: • US-CNB is useful for the diagnosis of cervical lymphadenopathy. • US-CNB is safe to perform on lymph nodes located near vital structures. • Larger, malignant, level IV lymph nodes yield sufficient tissue samples more easily.

Comparison of Stable and Unstable Ethiodized Oil Emulsions for Transarterial Chemoembolization of Hepatocellular Carcinoma: Results of a Single-Center Double-Blind Prospective Randomized Controlled Trial.

PURPOSE: To compare the stability of stable and unstable water-in-oil emulsions and the efficacy and safety of these emulsions in a single-center, prospective double-blind trial of transarterial chemoembolization for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 812 patients with inoperable HCC were randomized (stable emulsion, n = 402; unstable emulsion, n = 410). The 2 emulsions were prepared by using the same protocol except that different solvents were used for chemotherapy agents, including epirubicin, lobaplatin, and mitomycin C. The solvent in the stable emulsion arm was contrast medium and distilled water, and the solvent in the unstable emulsion arm was distilled water. The primary endpoint was overall survival (OS), and secondary endpoints were time to progression (TTP), tumor response, adverse events (AEs), and plasma epirubicin concentrations. RESULTS: In vitro, stable emulsions did not occur until 1 day, and unstable emulsions, with a lower peak plasma concentration (P = .001) in vivo, exhibited rapid separation of the oil and aqueous phases after 10 minutes. Median OS times in the stable and unstable emulsion arms were 17.7 and 19.2 months, respectively (P = .81). No differences were found in TTP, tumor response, and AEs except for myelosuppression (anemia, 3.5% vs 7.6%; thrombocytopenia, 11.5% vs 17.7%), which was significantly more severe and frequent in the unstable emulsion arm (P = .013). CONCLUSIONS: Chemoembolization is equally effective with the use of stable and unstable emulsions, but the use of a stable emulsion has the advantage of less myelosuppression and a favorable pharmacokinetic profile.

MEP1A contributes to tumor progression and predicts poor clinical outcome in human hepatocellular carcinoma.

UNLABELLED: Although many staging classifications have been proposed for hepatocellular carcinoma (HCC), determining a patient's prognosis in clinical practice is a challenge due to the molecular diversity of HCC. We investigated the relationship between MEP1A, a candidate oncogene, and clinical outcomes of HCC patients; furthermore, we explored the role of MEP1A in HCC. In this report, it was demonstrated by quantitative real-time polymerase chain reaction that MEP1A messenger RNA levels were significantly elevated in HCC tumor tissues compared with matched adjacent nonneoplastic tissues and nonmalignant liver disease tissues. Immunohistochemical analyses of tissue samples from two independent groups of 394 HCC patients showed that positive expression of MEP1A in tumor cells was an independent and significant risk factor affecting survival after curative resection in both cohort 1 (hazard ratio = 2.05, 95% confidence interval 1.427-2.946; P < 0.001) and cohort 2 (hazard ratio = 1.89, 95% confidence interval 1.260-2.833; P = 0.002). Analysis of Barcelona Clinic Liver Cancer stage 0-A subgroup further showed that patients with positive MEP1A expression in tumor cells had poorer surgical prognoses than those with negative MEP1A expression in tumor cells (cohort 1 P = 0.001, cohort 2 P < 0.001). Both in vitro and in vivo assays showed that MEP1A promoted HCC cell proliferation, migration, and invasion. Further analyses found that MEP1A played an important role in regulating cytoskeletal events and induced epithelial-mesenchymal transition in HCC cells. CONCLUSION: MEP1A is a novel prognostic predictor in HCC and plays an important role in the development and progression of HCC.

Intermediate-stage hepatocellular carcinoma treated with hepatic resection: the NSP score as an aid to decision-making.

BACKGROUND: The subgroups of patients with intermediate-stage (BCLC-B) hepatocellular carcinoma (HCC) who would truly benefit from hepatic resection (HR) are unknown. An objective point score was established to guide the selection of these patients for HR. METHODS: In all, 255 consecutive patients with intermediate-stage HCC treated with HR were evaluated retrospectively and included in this study (the training cohort). The variables on overall survival (OS, log-rank test) were investigated and a point score (the NSP score) was developed by using a Cox-regression model and validated in an independent external cohort from another institution (n=169). RESULTS: The NSP score differentiated two groups of patients (⩽1, >1 point) with distinct prognoses (median OS, 61.3 vs 19.3 months; P<0.001). A high NSP score was associated with increased major adverse events after HR (5.6 vs 13.8%, P=0.027). Its predictive accuracy as determined by the area under the receiver operating characteristic curve (AUC) at 1, 3, and 5 years (AUCs 0.688, 0.739, and 0.732) was greater than the other six staging systems for HCC (0.513-0.677). The findings were supported by the validation cohort. CONCLUSIONS: The NSP scoring system is more accurate in selecting patients with intermediate-stage HCC for HR.

Resection vs. ablation for alpha-fetoprotein positive hepatocellular carcinoma within the Milan criteria: a propensity score analysis.

BACKGROUND & AIMS: The lack of histopathological confirmation of hepatocellular carcinoma (HCC) diagnosis for patients receiving ablation may result in misdiagnosis of benign liver nodule as HCC occasionally, contributing to false treatment efficacy. This underestimated issue is one reason why the ablation efficacy remains undetermined compared with hepatic resection. Our aim is to compare the efficacy of ablation and resection for HCC within the Milan criteria after excluding the impact of misdiagnosis. METHODS: Alpha-fetoprotein > 200 ng/ml was introduced as an inclusion criterion to improve diagnosis accuracy. A total of 435 (resection, 310; ablation, 125) HCC patients within the Milan criteria and without portal hypertension were enrolled. Propensity score matching analysis identified 259 (resection, 150; ablation, 109) patients to compare treatment efficacy. RESULTS: Before matching, the survival of resection group were superior to ablation group with 5-year overall survival (OS) rate of 77.6% vs. 53.8% (P < 0.001), respectively, and 5-year recurrence-free survival (RFS) rate of 57.2% vs. 29.1% (P < 0.001) respectively. After matching, the baseline was well-balanced between the two groups. The 5-year OS rates were 71.5% vs. 51.3% (P < 0.001), and 5-year RFS rates were 56.1% vs. 25.6% (P < 0.001) for the resection and ablation groups respectively. Cox regression analysis identified ablation as an independent predictor for mortality and tumour recurrence (HR: 2.123 and 2.308, respectively; both P < 0.01). CONCLUSIONS: Hepatic resection provides better OS and RFS than ablation for alpha-fetoprotein positive HCC patients within the Milan criteria and without portal hypertension.

Efficacy and safety of preoperative chemoembolization for resectable hepatocellular carcinoma with portal vein invasion: a prospective comparative study.

OBJECTIVES: To evaluate the outcomes of preoperative transarterial chemoembolization (TACE) for resectable hepatocellular carcinoma (HCC) with portal vein invasion. METHODS: From February 2006 to July 2011, 320 patients initially diagnosed with resectable HCC and portal vein invasion were prospectively non-randomized into two arms. In the immediate resection arm (Arm 1, n = 205) patients received immediate surgical resection. 115 patients were included in the preoperative TACE arm (Arm 2), and eventually 85 patients underwent TACE followed by surgical resection. RESULTS: The 1-, 3- and 5-year overall survival rates were 48.3 %, 18.7 % and 13.9 % for Arm 1 and 61.2 %, 31.7 % and 25.3 % for Arm 2 (P = 0.001), respectively. In the subgroup analysis of types I and II portal vein tumour thrombus (PVTT), the preoperative TACE arm demonstrated significantly better survival rates than the immediate resection arm (P I = 0.001, P II = 0.036). However, no significant difference was found for patients with type III PVTT (P III = 0.684). No significant difference was found between the two arms in terms of complications and mortality. CONCLUSIONS: Preoperative TACE seems to confer a survival benefit for resectable HCC with PVTT, especially for types I and II PVTT, and preoperative TACE should therefore be recommended as a routine procedure. KEY POINTS: • Preoperative TACE improves the clinical outcomes for patients with PVTT • Preoperative TACE could significantly improve the rate of en bloc thrombectomy • Preoperative TACE does not increase the related adverse events.

The role of clinically significant portal hypertension in hepatic resection for hepatocellular carcinoma patients: a propensity score matching analysis.

BACKGROUND: Whether portal hypertension (PHT) is an appropriate contraindication for hepatic resection (HR) in hepatocellular carcinoma (HCC) patient is still under debate. AIMS: Our aim was to assess the impact of clinically significant PHT on postoperative complication and prognosis in HCC patients who undergo HR. METHODS: Two hundred and nine HCC patients who underwent HR as the initial treatment were divided into two groups according to the presence (n = 102) or absence (n = 107) of clinically significant PHT. Propensity score matching (PSM) analysis was used to compare postoperative outcomes and survival. RESULTS: Before PSM, PHT patients had higher rates of postoperative complication (43.1% vs. 23.4%; P = 0.002) and liver decompensation (37.3% vs. 17.8%; P = 0.002) with similar rates of recurrence-free survival (RFS; P = 0.369) and overall survival (OS; P = 0.205) compared with that of non-PHT patients. However, repeat analysis following PSM revealed similar rates of postoperative complication (32.2% vs. 39.0%; P = 0.442), liver decompensation (25.4% vs. 32.2%; P = 0.416), RFS (P = 0.481) and OS (P = 0.417; 59 patients in each group). Presence of PHT was not associated with complication by logistic regression analysis, or with overall survival by Cox regression analysis. CONCLUSIONS: The presence of clinically significant PHT had no impact on postoperative complication and prognosis, and should not be regarded as a contraindication for HR in HCC patients.

Hepatectomy Versus Hepatectomy With Lymphadenectomy in Hepatocellular Carcinoma: A Prospective, Randomized Controlled Clinical Trial.

GOALS AND BACKGROUND: The role of preventive lymphadenectomy has not yet been determined for hepatocellular carcinoma (HCC) patients. We designed a study to evaluate the effect of hepatectomy combined with preventive lymphadenectomy on HCC patients. STUDY: Patients were randomly divided into group A (treated with hepatectomy alone) and group B (underwent hepatectomy combined with lymphadenectomy). The postoperative complications and oncologic prognoses were analyzed. RESULTS: Of the 85 patients enrolled into this study, 79 cases (38 in group A and 41 in group B) were pathologically confirmed to have HCC and received curative resection. One hundred and sixteen lymph nodes were dissected and evaluated as negative by the pathologist. The 12-, 36-, and 60-month disease-free survival rates of group A were 81.6%, 68.4%, and 63.2%, respectively, whereas they were 78.0%, 65.9%, and 63.4%, respectively, for group B. The 12-, 36-, and 60-month overall survival rates in group A were 94.7%, 78.9%, and 65.8%, respectively, whereas they were 87.8%, 78.0%, and 70.7%, respectively, in group B. The differences in the disease-free survival and overall survival between the 2 groups were not statistically significant according to the log-rank test (P=0.811 and P=0.881, respectively). The difference in the surgical complication rate between groups A and B was not statistically significant (47.4% vs. 36.6%, P=0.332). CONCLUSIONS: Although hepatectomy combined with regional lymphadenectomy is a safe procedure, preventive lymphadenectomy may not decrease the rate of tumor recurrence nor improve the prognosis in early-stage HCC patients.