Background: Despite the Barcelona Clinic Liver Cancer system discouraging hepatectomy for intermediate/advanced hepatocellular carcinoma, the procedure is still performed worldwide, particularly in Asia. This study aimed to develop and validate nomograms for predicting survival and recurrence for these patients. Methods: We analyzed patients who underwent curative -intent hepatectomy for intermediate/advanced hepatocellular carcinoma between 2010 and 2020 across 3 Chinese hospitals. The Eastern Hepatobiliary Surgery Hospital cohort was used as the training cohort for the nomogram construction, and the Jilin First Hospital and Fujian Mengchao Hepatobiliary Hospital cohorts served as the external validation cohorts. Independent preoperative predictors for survival and recurrence were identi fied through univariable and multivariable Cox regression analyses. Predictive accuracy was measured using the concordance index and calibration curves. The predictive performance between nomograms and conventional hepatocellular carcinoma staging systems was compared. Results: A total of 1,328 patients met the inclusion criteria. The nomograms for predicting survival and recurrence were developed using 10 and 6 independent variables, respectively. Nomograms ' concordance indices in the training cohort were 0.777 (95% con fidence interval 0.759-0.80 0) and 0.719 (95% con fidence interval 0.697-0.742) for survival and recurrence, outperforming 4 conventional staging systems ( P < .001). Nomograms accurately strati fied risk into low, intermediate, and high subgroups. These results were validated well by 2 external validation cohorts. Conclusion: We developed and validated nomograms predicting survival and recurrence for patients with intermediate/advanced hepatocellular carcinoma, contradicting Barcelona Clinic Liver Cancer surgical guidelines. These nomograms may facilitate clinicians to formulate personalized surgical decisions, estimate long-term prognosis, and strategize neoadjuvant/adjuvant anti -recurrence therapy. (c) 2024 Elsevier Inc. All rights reserved.

Background FOXP3, as a tumour suppressor gene, has a vital function in inhibiting the metastasis of breast cancer cells, but the mechanisms by which it inhibits metastasis have not been fully elucidated. This study intended to explore a new mechanism by which FOXP3 inhibits breast cancer metastasis. Methods Bioinformatic analysis was performed to identify potential downstream molecules of FOXP3. The function of FOXP3 in inhibiting MTA1 expression at the mRNA and protein levels was verified by real-time PCR and Western blot analysis. The interaction between FOXP3 and the MTA1 promoter was verified by transcriptomic experiments. In vitro and in vivo experiments were used to determine whether the regulation of MTA1 by FOXP3 affected the invasion and migration of breast cancer cells. Immunohistochemistry was adopted to explore the correlation between the expression levels of FOXP3 and MTA1 in breast cancer samples. Results Bioinformatics-based sequencing suggested that MTA1 is a potential downstream molecule of FOXP3. FOXP3 downregulated the expression of MTA1 in breast cancer cells by directly inhibiting MTA1 promoter activity. Importantly, FOXP3's regulation of MTA1 affected the ability of breast cancer cells to invade and metastasize in vitro and in vivo. Moreover, analysis of clinical specimens showed a significant negative correlation between the expression levels of FOXP3 and MTA1 in breast cancer. Conclusion We systematically explored a new mechanism by which FOXP3 inhibits breast cancer metastasis via the FOXP3-MTA1 pathway.

More than two-thirds of patients with hepatocellular carcinoma (HCC) cannot receive curative therapy and have poor survival due to late diagnosis and few prognostic directions. In our study, nontargeted and targeted metabolomics analyses were conducted by liquid chromatography-mass spectrometry to characterize metabolic features of HCC and identify diagnostic and prognostic biomarker candidate incorporating liver tissue and serum metabolites. A total of 552 subjects, including 432 with liver tissue and 120 with serum specimens, were recruited in China. In the discovery cohort, a series of 138 metabolites were identified to discriminate HCC tissues from matched nontumor tissues. Retinol presented with the highest area under the curve (AUC) of 0.991 and associated with Edmondson grade. In the validation cohort, all metabolites in retinol metabolism pathway were examined and the levels of retinol and retinal in tumor tissue and serum decreased in the order of normal to cirrhosis to HCC of Edmondson Grades I to IV. Retinol and retinal levels could also differentiate between HCC and cirrhosis, with AUCs of 0.996 and 0.994, respectively, in tissue and 0.812 and 0.744, respectively, in serum. The AUC of the combined retinol and retinal panel in serum was 0.852. Univariate and multivariate Cox regression identified this panel as an independent predictor for HCC and showed that low expression of retinol and retinal correlated with decreased survival time. In conclusion, the retinol metabolic signature had considerable diagnostic and prognostic value for identifying HCC patients who would benefit from prompt therapy and optimal prognostic direction.

目的 探讨FOXP3对乳腺癌转移的影响及分子机制.方法 在乳腺癌细胞系MCF7中转染FOXP3质粒,进行高通量转录组测序以及基因差异表达分析.在T47D和MCF7中均过表达和敲低FOXP3,RT-qPCR检测NCKAP1的表达.利用Jaspar数据库分析NCKAP1基因的启动子,ChIP实验检测FOXP3与NCKAP1基因启动子的结合活性,报告基因实验检测不同FOXP3的表达水平对NCKAP1启动子转录活性的影响.单独si-FOXP3、si-FOXP3和si-NCKAP1、control siRNA分别转染T47D细胞,划痕实验和Transwell实验检测细胞的迁移和侵袭能力.在GEPIA数据库中分析乳腺癌病人NCKAP1的表达水平以及生存期.在TCGA和GEPIA数据库中分析乳腺癌病人FOXP3和NCKAP1基因的表达相关性.结果 转录组测序结果表明,高表达FOXP3的MCF7细胞中NCKAP1表达下调.MCF7细胞和T47D细胞过表达FOXP3后,NCKAP1表达水平降低(P<0.05).沉默FOXP3后,MCF7细胞(P<0.01)和T47D细胞(P<0.001)内NCKAP1表达水平升高.NCKAP1基因的启动子上存在FOXP3的潜在结合位点,T47D细胞内FOXP3与NCKAP1基因的启动子结合(P<0.01).FOXP3抑制NCKAP1启动子的转录活性(P<0.001),且FOXP3表达水平越高抑制效果越明显(P<0.05).沉默FOXP3后,T47D细胞的迁移(P<0.01)和侵袭(P<0.001)能力增强,同时沉默FOXP3和NCKAP1后,T47D细胞的迁移和侵袭能力降低(P<0.001).NCKAP1高表达的乳腺癌患者预后较差(P<0.05).FOXP3和NCKAP1的表达量呈负相关(r=-0.1563,P<0.001).结论 FOXP3通过与NCKAP的启动子结合下调其表达,从而抑制乳腺癌的转移.

Chemoresistance is a major cause of recurrence and poor prognosis in triple-negative breast cancer (TNBC) patients. The essential oil of Rhizoma Curcumae has been recently reported to enhance the chemosensitivity of cancer cells. However, few reports have systematically illuminated the mechanism. Curcumol is the major component of the essential oil of Rhizoma Curcumae. Therefore, we wondered whether curcumol combined with chemotherapy could increase the anticancer effects. In the present study, we evaluated the anticancer effects of doxorubicin and curcumol alone or in combination by a series of growth proliferation and apoptosis assays in TNBC cells. Our results showed that curcumol enhanced the sensitivity of MDA-MB-231 cells to doxorubicin in vitro and in vivo. Through miRNA-seq, we found that miR-181b-2-3p was involved in the curcumol-mediated promotion of doxorubicin-sensitivity in both parental and doxorubicin-resistant MDA-MB-231 (MDA-MB-231/ADR) cells. Further study showed that miR-181b-2-3p suppressed ABCC3 expression by targeting its 3'UTR. More importantly, we identified that overexpression of miR-181b-2-3p sensitized MDA-MB-231/ADR cells to doxorubicin by inhibiting the drug efflux transporter ABCC3. Furthermore, we found that NFAT1 could be activated by curcumol. In addition, ChIP assay results revealed that NFAT1 could directly bind to the promoter region of miR-181b-2-3p. Finally, using PDX models, we identified that curcumol could enhance sensitivity to doxorubicin to suppress tumor growth by the miR-181b-2-3p-ABCC3 axis in vivo. Taken together, our study provides novel mechanistic evidence for curcumol-mediated sensitization to doxorubicin in TNBC, and it highlights the potential therapeutic usefulness of curcumol as an adjunct drug in TNBC patients with doxorubicin-resistance.

Forkhead box P3 (FOXP3), an X-linked tumor suppressor gene, plays an important role in breast cancer. However, the biological functions of FOXP3 in breast cancer apoptosis remain unclear. To investigate the underlying genes and networks regulated by FOXP3 in breast cancer, RNA sequencing was performed to compare FOXP3-overexpressing MDA-MB-231 cells and control MDA-MB-231 cells. Differentially expressed genes were identified, and functional enrichment analysis comparing the two groups was performed. The differentially expressed genes were mainly enriched in phagosomes, oxytocin, serotonergic synapses and the phospholipase D signaling pathway. Furthermore, gene set enrichment analysis revealed the enrichment of a gene signature associated with apoptosis in FOXP3-overexpressing MDA-MB-231 cells compared with wild-type cells. Further analysis showed that programmed cell death 4 (PDCD4), a key molecule involved in apoptosis, was overexpressed in FOXP3-MDA-MB-231 cells. Reverse transcription-quantitative PCR and western blotting showed that FOXP3 upregulated the expression of PDCD4 in breast cancer cells. Clinical sample analysis using a public database showed that the expression level of PDCD4 was associated with breast cancer clinical stages. Overall, the present study suggested that FOXP3 can promote the apoptosis of breast cancer cells by upregulating the expression of PDCD4, thus exerting a tumor suppressive function.

Introduction: Although curative resection is the optimal treatment for hepatocellular carcinoma (HCC), recurrence will develop in more than 60% HCC patients after resection. Thus, it is urgent to identify recurrence-related markers. The study aims to investigate the effectiveness of metabolic alternation in predicting recurrence for patients with HCC. Method: In total, 386 patients with HCC under curative resection in China were sorted and randomly divided in training and validation set. Paired HCC tissues and adjacent non-cancerous tissues were collected and analyzed in metabolomics. Least Absolute Shrinkage and Selection Operation (LASSO) was used to select differential expressed metabolites associated with recurrence and established metabolite expression-based signature. Independent factors for predicting recurrence were identified by univariable and multivariable Cox regression analyses and used for the nomogram construction. Result: After metabolomics analysis, a total of 18 differential expressed metabolites were identified between HCC tissues and adjacent non-cancerous tissues both in training and validation set. Three metabolites of glycerophosphocholine, glycocholic acid and 5-methyltetrahydrofolic acid were highlighted as biomarker candidate associated with HCC recurrence by LASSO regression in the training set. Based on the three metabolites, a metabolic signature was generated to classify patients into high-risk and low-risk groups. The 1-year and 3-year recurrence were 14.7% and 39.2% in low-risk group, and 71.3% and 96.5% in high-risk group, respectively. The prognostic accuracy of this metabolic signature was further confirmed in validation set. Furthermore, a nomogram comprising metabolic signature, cirrhosis, tumor number, tumor diameter, tumor differentiation, and microvascular invasion was generated to predict the 1-year and 3-year recurrence in training set and also performed well in the validation set (concordance index: 0.768 and 0.756). Conclusion: The metabolic signature is a reliable prognostic tool to predict recurrence for HCC patients and offer valuable guidance to plan recurrence surveillance and adjuvant therapy after curative resection.

Background and aims: Metabolomics serves as an important tool in distinguishing changes in metabolic pathway and the diagnosis of human disease. Hepatocellular carcinoma (HCC) is a malignance present of heterogeneous metabolic disorder and lack of effective biomarker for surveillance and diagnosis. In this study, we searched for potential metabolite biomarkers of HCC using tissue and serum metabolomics approach. Methods: A total of 30 pairs of matched liver tissue samples from HCC patients and 90 serum samples (30 HCC patients, 30 liver cirrhosis patients, and 30 healthy individuals) were assessed. Metabolomics was performer through ultra performance liquid chromatography-mass spectrometry in conjunction with multivariate and univariate statistical analyses. Results: A total of six differential metabolites including chenodeoxycholic acid (CDCA), glycocholic acid (GCA) LPC20:5, LPE18:0, succinyladenosine and uridine were present in HCC tissue and serum samples. CDCA LPC20:5, succinyladenosine and uridine were used to construct a diagnostic model based on logistic regression The four-metabolite panel discriminated HCC from liver cirrhosis with an AUC score of 0.938, sensitivity of 93.3% and specificity of 86.7%. For all HCC and cirrhosis patients, the diagnostic accuracy increased to 96.7% and 90.0%, respectively. Conclusion: The combination of CDCA, LPC20:5, succinyladenosine and uridine can be used as a biomarker panel to improve HCC sensitivity and specificity. This panel significantly benefits HCC diagnostics and reveal new insight into HCC pathogenesis.

BACKGROUND:Postoperative complications have a great impact on the postoperative course and oncological outcomes following major cancer surgery. Among them, infective complications play an important role. The aim of this study was to evaluate whether postoperative infective complications influence long-term survival after liver resection for hepatocellular carcinoma (HCC).METHODS:Patients who underwent resection with curative intent for HCC between July 2003 and June 2016 were identified from a multicentre database (8 institutions) and analysed retrospectively. Independent risk factors for postoperative infective complications were identified. After excluding patients who died 90 days or less after surgery, overall survival (OS) and recurrence-free survival (RFS) were compared between patients with and without postoperative infective complications within 30 days after resection.RESULTS:Among 2442 patients identified, 332 (13·6 per cent) had postoperative infective complications. Age over 60 years, diabetes mellitus, obesity, cirrhosis, intraoperative blood transfusion, duration of surgery exceeding 180 min and major hepatectomy were identified as independent risk factors for postoperative infective complications. Univariable analysis revealed that median OS and RFS were poorer among patients with postoperative infective complications than among patients without (54·3 versus 86·8 months, and 22·6 versus 43·2 months, respectively; both P < 0·001). After adjustment for other prognostic factors, multivariable Cox regression analyses identified postoperative infective complications as independently associated with decreased OS (hazard ratio (HR) 1·20, 95 per cent c.i. 1·02 to 1·41; P = 0·027) and RFS (HR 1·19, 1·03 to 1·37; P = 0·021).CONCLUSION:Postoperative infective complications decreased long-term OS and RFS in patients treated with liver resection for HCC.

To the Editor:We read with great interest the recent article by Chang et al.[1].By analyzing the data of 1350 cirrhotic patients,the authors concluded that statin significantly decreases the risk of decompensation of cirrhosis,mortality and hepatocellular carcinoma

BACKGROUND:The long-term prognosis after liver resection for multinodular (≥3 nodules) hepatocellular carcinoma (HCC) is generally considered to be unfavorable. However, the role of liver resection for binodular HCC is less investigated.SUBJECTS, MATERIALS, AND METHODS:From a multicenter database, consecutive patients who underwent curative-intent liver resection for binodular HCC and without macrovascular invasion between 2003 and 2015 were retrospectively reviewed. Patients' clinical variables as well as perioperative and long-term survival outcomes were analyzed. Univariable and multivariable analyses were performed to identify the risk factors associated with overall survival (OS) and recurrence-free survival (RFS) after curative resection.RESULTS:Of 263 enrolled patients, the perioperative 30-day mortality and morbidity rates were 1.5% and 28.5%. The 1-, 3-, and 5-year OS and RFS rates were 81.5%, 52.4%, and 39.1% and 57.1%, 35.8%, and 26.6%, respectively. Multivariable Cox-regression analyses identified preoperative alpha-fetoprotein level >400 μg/L, tumor size with a sum of two nodules >8 cm, tumor size ratio of large/small nodule >1.5 (asymmetrical proportion), unilateral hemiliver distribution of two nodules, distance of ≤3 cm between two nodules, and microvascular invasion in any nodule as independent risk factors associated with decreased OS and RFS.CONCLUSION:Liver resection was safe and feasible in patients with binodular HCC, with acceptable perioperative and long-term outcomes. Sum of two tumor sizes, size ratio and distribution, and distance between two nodules were independent risk factors associated with long-term survival outcomes after surgery. These results may guide clinicians to make individualized surgical decisions and estimate long-term prognosis for these patients.IMPLICATIONS FOR PRACTICE:Liver resection was safe and feasible in patients with binodular hepatocellular carcinoma, with acceptable perioperative and long-term outcomes. The sum of two tumor sizes, the size ratio and distribution of the two nodules, and the distance between two nodules were independent risk factors associated with long-term overall survival and recurrence-free survival after liver resection. The results of this study may guide clinicians to make individualized surgical decisions, estimate long-term prognosis, and plan recurrence surveillance and adjuvant therapy for these patients.

Clinical guidelines recommend surveillance in high-risk population to early detect hepatocellular carcinoma (HCC), when curative treatment such as liver resection can be applied. However, it is largely unknown whether surveillance would provide long-term survival benefits to these high-risk patients who have received curative liver resection for HCC. A prospectively maintained database on patients with chronic hepatitis B infection who underwent curative liver resection for HCC from 2003 to 2014 was reviewed. Patients’ overall survival and recurrence were compared between the groups of patients whose HCCs were diagnosed by surveillance or non-surveillance, as well as between the groups of patients operated in the first (2003–2008) and second (2009–2014) 6-year periods. Of 1075 chronic hepatitis B patients with HCC, 452 (42.0%) patients were diagnosed by preoperative surveillance. Compared with the non-surveillance group, the OS and RFS rates were significantly better in the surveillance group (both P < 0.001). Surveillance was associated with a 55% decrease in the overall survival risk and a 48% decrease in the recurrence risk (HR 0.45, 95% CI 0.38–0.53, and HR 0.52, 95% CI 0.44–0.61). Compared with the first period, a significant reduction of 12% and 19% in the overall death and recurrence risks, respectively, was observed in the second period (HR 0.88, 95% CI 0.78–0.97, and HR 0.81, 95% CI 0.70–0.95). Surveillance for HCC was associated with favorable long-term overall and recurrence-free survival rates after curative liver resection of HCC in patients with chronic hepatitis B.

Background: Serum prealbumin is a sensitive and stable marker for nutritional status and liver function. Whether preoperative prealbumin level is associated with long-term prognosis in patients undergoing liver resection for hepatocellular carcinoma (HCC) is unclear. Methods: Patients who underwent liver resection for HCC between 2001 and 2014 at six institutions were enrolled. These patients were divided into the low and normal prealbumin groups using a cut-off value of 170 mg/L for preoperative prealbumin level. The overall survival (OS) and recurrence-free survival (RFS) were compared between them. Results: In 1483 patients, 437 (29%) had a low prealbumin level. The 3- and 5-year OS and RFS rates of patients in the low-prealbumin group were 57 and 31%, and 40 and 20%, respectively, which were significantly poorer than those in the normal-prealbumin group (76 and 43%, and 56 and 28%, respectively, both p < 0.001). Multivariable Cox-regression analyses revealed that preoperative prealbumin level was an independent predictor of OS (HR, 1.45, 95% CI: 1.24-1.70, p < 0.001) and RFS (HR, 1.28, 95% CI: 1.10-1.48, p < 0.001). Conclusions: Preoperative prealbumin level could be used in predicting long-term prognosis for patients undergoing liver resection for HCC.

Background: The resection margin (RM) status and microscopic vascular invasion (MVI) are known prognostic factors for hepatocellular carcinoma (HCC). An enhanced understanding of their impact on long-term prognosis is required to improve oncological outcomes. Methods: Using multi-institutional data, the different impact of the RM status (narrow, <1 cm, or wide, >= 1 cm) and MVI (positive or negative) on overall survival (OS) and recurrence-free survival (RFS) after curative liver resection of solitary HCC without macrovascular invasion was analyzed. Results: In 801 patients, 306 (38%) had a narrow RM and 352 (44%) had positive MVI. The median OS and RFS were 109.8 and 74.8 months in patients with wide RM & negative MVI, 93.5 and 53.1 months with wide RM & positive MVI, 79.2 and 41.6 months with narrow RM & negative MVI, and 69.2 and 37.5 months with narrow RM & positive MVI (both P < 0.01). On multivariable analyses, narrow RM & positive MVI had the highest hazard ratio with reduced OS and RFS (HR 2.96, 95% CI 2.11-4.17, and HR 3.15, 95% CI, 2.09-4.67, respectively). Conclusions: Concomitant having narrow RM and positive MVI increases the risks of postoperative death and recurrence by about 2-fold in patients with solitary HCC.

Background Family history is a risk factor for the development of hepatocellular carcinoma (HCC). The aim of the current study was to investigate the association between family history of HCC and long-term oncologic prognosis among patients undergoing curative liver resection for hepatitis B virus (HBV)-related HCC. Methods Patients who underwent curative liver resection of HBV-related HCC between 2003 and 2013 were consecutively enrolled. Family history was defined as a self-reported history of HCC in a first-degree relative. Propensity score matching (PSM) and multivariable Cox-regression analyses were performed to compare overall survival (OS) and recurrence-free survival (RFS) among patients with and without a family history. Results Among 1,112 patients, 183 (16.5%) patients had a family history of HCC. Using PSM, 179 pairs of patients with and without a family history were created that had no differences in the baseline characteristics and operative variables. On matched analysis, family history was associated with decreased OS and RFS after curative-intent resection of HBV-related HCC in the propensity matching cohort (P=0.042 and 0.006, respectively). On multivariable Cox-regression analyses, a family history of HCC was associated with decreased OS (HR: 1.574; 95% CI: 1.171-2.116; P=0.003) and RFS (HR: 1.534; 95% CI: 1.176-2.002; P=0.002) after adjusting for other prognostic risk factors. Conclusions Family history was associated with decreased OS and RFS rates among patients undergoing curative liver resection of HBV-related HCC.

Introduction: Surgical resection is the only potentially curative treatment for patients with resectable perihilar cholangiocarcinoma (PHC). There is still no consensus on the value of lymphadenectomy despite evidence indicating lymph node (LN) status is an important prognostic indicator for postoperative long-term survival. We sought to perform a meta-analysis to summarize the current evidence on the value of lymphadenectomy among patients undergoing surgery for PHC. Method: The PubMed, Embase, Medline(OvidSP) and Cochrane Library were systematically searched for studies published before December 2018 that reported on lymphadenectomy at the time of surgery for PHC after curative surgery. According to the updating Cochrane handbook, random-effects model was chosen as a priority for all analyses, and 95% confidence interval (95% CI) of the pooled ratio was provided for analysis of statistically significant, as well as the effect range estimate. Result: 7,748 patients from 28 studies were included in the meta-analysis. No survival benefit was identified with increased number of LN resected (all P > 0.05). Meanwhile, LN status was an important prognostic factor. Patients with lymph node metastasis had a pooled estimate hazard ratio of death that was over two-fold higher than patients without lymph node metastasis (HR 2.07, 95% CI 1.65–2.59). The examination of 5 LNs on histology was associated with better staging of lymph node status and stratification of patients into positive or negative LN groups. Conclusion: While the extent of LN dissection was not associated with a survival benefit, examination of more than 5 LNs better staged patients into positive or negative LN groups with a lower risk of nodal understaging.

IMPORTANCE Late recurrence (more than 2 years) after liver resection for hepatocellular carcinoma (HCC) is generally considered as a multicentric tumor or a de novo cancer. OBJECTIVE To investigate the risk factors, patterns, and outcomes of late recurrence after curative liver resection for HCC. DESIGN, SETTING, AND PARTICIPANTS This study was a multicenter retrospective analysis of patients who underwent curative liver resection for HCC at 6 hospitals in China from January 2001 to December 2015. Among 734 patients who were alive and free of recurrence at 2 years after resection, 303 patients developed late recurrence. Data were analyzed from June 2017 to February 2018. INTERVENTIONS Liver resection for HCC. MAIN OUTCOMES AND MEASURES Risk factors of late recurrence as well as patterns, treatments, and long-term outcomes of patients with late recurrence. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors of late recurrence. RESULTS Of the included 734 patients, 652 (88.8%) were male, and the mean (SD) age was 51.0 (10.3) years. At a median (interquartile range) follow-up of 78.0 (52.8-112.5) months, 303 patients (41.3%) developed late recurrence. Multivariate analysis revealed that male sex, cirrhosis, multiple tumors, satellite nodules, tumor size greater than 5 cm, and macroscopic and microscopic vascular invasion were independent risk factors of late recurrence. Of the 303 patients with late recurrence, 273 (90.1%) had only intrahepatic recurrence, 30 (9.9%) had both intrahepatic and extrahepatic recurrence, and none had only extrahepatic recurrence. Potentially curative treatments were given to 165 of 303 patients (54.5%) with late recurrence, which included reresection, transplant, and local ablation. Multivariate Cox regression analysis showed that regular surveillance for postoperative recurrence (hazard ratio [HR], 0.470; 95% CI, 0.310-0.713; P = .001), cirrhosis (HR, 1.381; 95% CI, 1.049-1.854; P = .02), portal hypertension (HR, 2.424; 95% CI, 1.644-3.574; P < .001), Child-Pugh grade of B or C (HR, 1.376; 95% CI, 1.153-1.674; P < .001), Barcelona Clinic Liver Cancer stage B (HR, 1.304; 95% CI, 1.007-1.708; P = .04) and stage C (HR, 2.037; 95% CI, 1.583-2.842; P < .001), and potentially curative treatment (HR, 0.443; 95% CI, 0.297-0.661; P < .001) were independent predictors of overall survival for patients with late recurrence. CONCLUSIONS AND RELEVANCE Late recurrence after HCC resection was associated with sex, cirrhosis, and several aggressive tumor characteristics of the initial HCC. The patterns of late recurrence suggested surveillance for recurrence after 2 years of surgery should be targeted to the liver. Postoperative surveillance improved the chance of potentially curative treatments, with improved survival outcomes in patients with late recurrence.

Aim: To evaluate the diagnostic performance of serumAFUfor early stage hepatocellular carcinoma (HCC). Methods: Concentration of AFU and AFP were measured in 512 patients. The performance was compared for AFU and AFP alone or in combination. Results: The area under the curve (AUC) for AFU was 0.68, with a sensitivity of 56.1% and specificity of 69.2% at the cut-off value of 24U/l; whereasthe AUC for AFP was 0.83, with a sensitivity of 58.2% and specificity of 85.2% at cut-off value of 20ng/ml. The AUC of AFU alone or the combination with AFP were lower than that of AFP alone. Conclusion: AFU is a suboptimal biomarker for early detection of HCC.

Surgical resection for hepatocellular carcinoma (HCC) is potentially curative, but long-term survival remains unsatisfactory. There is currently no effective neoadjuvant or adjuvant therapy for HCC. We sought to evaluate the impact of preoperative transcatheter arterial chemoembolization (TACE) on long-term prognosis after surgical resection of huge HCCs (≥ 10 cm). Using a multicenter database, consecutive patients who underwent curative-intent resection for huge HCC without macrovascular invasion between 2004 and 2014 were identified. The association between preoperative TACE with perioperative outcomes, long-term overall survival (OS), and recurrence-free survival (RFS) was assessed before and after propensity score matching (PSM). Among the 377 enrolled patients, 88 patients (23.3%) received preoperative TACE. The incidence of perioperative mortality and morbidity was comparable among patients who did and did not undergo preoperative TACE (3.4% vs. 2.4%, p= 0.704, and 33.0% vs. 31.1%, p= 0.749, respectively). PSM analysis created 84 matched pairs of patients. In examining the entire cohort as well as the PSM cohort, median OS (overall cohort: 32.8 vs. 22.3 months, p= 0.035, and PSM only: 32.8 vs. 18.1 months, p= 0.023, respectively) and RFS (12.9 vs. 6.4 months, p= 0.016, and 12.9 vs. 4.1 months, p= 0.009, respectively) were better among patients who underwent preoperative TACE vs. patients who did not. After adjustment for other confounding factors on multivariable analyses, preoperative TACE remained independently associated with a favorable OS and RFS after the resection of huge HCC. Preoperative TACE did not increase perioperative morbidity or mortality, yet was associated with an improved OS and RFS after liver resection of huge HCC (≥ 10 cm).