Microwave ablation versus laparoscopic resection as first-line therapy for solitary 3-5-cm HCC.

BACKGROUND AND AIMS: The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3-5-cm HCC over time. APPROACH AND RESULTS: From 2008 to 2019, 1289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching was used to balance all baseline variables between the two groups in 2008-2019 (n = 335 in each group) and 2014-2019 (n = 257 in each group) cohorts, respectively. For cohort 2008-2019, during a median follow-up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (HR: 0.88, 95% CI 0.65-1.19, p = 0.420), and MWA was inferior to LLR regarding disease-free survival (DFS) (HR 1.36, 95% CI 1.05-1.75, p = 0.017). For cohort 2014-2019, there was comparable OS (HR 0.85, 95% CI 0.56-1.30, p = 0.460) and approached statistical significance for DFS (HR 1.33, 95% CI 0.98-1.82, p = 0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1-4.0-cm HCCs (HR 0.88, 95% CI 0.53-1.47, p = 0.630) and 4.1-5.0-cm HCCs (HR 0.77, 95% CI 0.37-1.60, p = 0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both p > 0.05), shorter hospitalization, and lower cost to LLR (all p < 0.001). CONCLUSIONS: MWA might be a first-line alternative to LLR for solitary 3-5-cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.

Lenvatinib with or without immune checkpoint inhibitors for patients with unresectable hepatocellular carcinoma in real-world clinical practice.

BACKGROUND: Lenvatinib is regarded as the first-line therapy for patients with unresectable hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of lenvatinib with or without immune checkpoint inhibitors (ICIs) in patients with unresectable HCC. METHODS: In this multicentric retrospective study, patients with unresectable HCC who treated with lenvatinib with or without ICIs would be enrolled. Overall survival, progression-free survival, objective response rate, and disease control rate were calculated to assess the antitumor response. RESULTS: Between January 2019 and August 2020, 65 patients received lenvatinib plus ICIs while other 45 patients received lenvatinib. The baseline characteristics were comparable between the two groups. Lenvatinib plus ICIs provided significantly higher overall survival (hazard ratio = 0.47, 95% CI 0.26-0.85; p = 0.013) and progression-free survival (hazard ratio = 0.35, 95% CI 0.20-0.63; p < 0.001) than lenvatinib monotherapy. Moreover, patients with lenvatinib plus ICIs had significantly higher objective response rate (41.5% vs 20.0%, p = 0.023) and disease control rate (72.3% vs 46.7%, p = 0.009) per RECIST v1.1 than those with lenvatinib. No treatment-related deaths were observed. Grade 3 or greater adverse events occurring in 10% or more of patients in either treatment group were hypertension [13 (20.0%) of 65 patients treated with lenvatinib plus ICIs vs 8 (17.8%) of 45 patients treated with lenvatinib], and palmar-plantar erythrodysesthesia [seven (10.8%) vs two (4.4%)]. CONCLUSIONS: In this real-world study, lenvatinib combined with ICIs showed significantly promising efficacy and manageable safety than lenvatinib alone in patients with unresectable HCC.

Clinical Features of Recurrence After Hepatic Resection for Early-Stage Hepatocellular Carcinoma and Long-Term Survival Outcomes of Patients with Recurrence: A Multi-institutional Analysis.

BACKGROUND: A potentially curative hepatic resection is the optimal treatment for hepatocellular carcinoma (HCC), but most HCCs, even at an early stage, eventually recur after resection. This study investigates clinical features of initial recurrence and long-term prognosis of patients with recurrence after curative resection for early-stage HCC. PATIENTS AND METHODS: From a multicenter database, patients who underwent curative hepatic resection for early-stage HCC [Barcelona Clinic Liver Cancer (BCLC) stage 0/A] were extracted. Time to initial recurrence, patterns of initial recurrence, and treatment modalities for recurrent tumors were investigated. Univariate and multivariate analysis were used to identify independent risks associated with postoperative recurrence, as well as post-recurrence survival (PRS) for patients with recurrence. RESULTS: Among 1424 patients, 679 (47.7%) developed recurrence at a median follow-up of 54.8 months, including 408 (60.1%) early recurrence (≤ 2 years after surgery) and 271 (39.9%) late recurrence (> 2 years). Independent risks of postoperative recurrence included cirrhosis, preoperative alpha-fetoprotein level > 400 ug/L, tumor size > 5 cm, multiple tumors, satellites, microvascular invasion, and intraoperative blood transfusion. Multivariate analysis revealed that receiving irregular recurrence surveillance, initial tumor beyond Milan criteria, early recurrence, BCLC stage B/C of the recurrent tumor, and noncurative treatments were independently associated with poorer PRS. CONCLUSIONS: Nearly half of patients with early-stage HCC experienced recurrence after resection. Understanding recurrence risks may help identify patients at high risk of recurrence who may benefit from future adjuvant therapies. Meaningful survival even after recurrence can still be achieved by postoperative regular surveillance and curative treatment.

Prognostic value of a nomogram based on peripheral blood immune parameters in unresectable hepatocellular carcinoma after intensity-modulated radiotherapy.

BACKGROUND: For patients with unresectable hepatocellular carcinoma (uHCC), intensity-modulated radiotherapy (IMRT) has become one of the options for clinical local treatment. Immune parameters, including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and systemic immune inflammatory (SII), predict survival in various cancers. This study aimed to determine whether peripheral immune parameters can predict survival in patients with uHCC undergoing IMRT and establish a clinically useful prognostic nomogram for survival prediction. METHODS: The clinical data of 309 HCC patients were retrospectively analyzed and randomly divided into training (n = 216) and validation (n = 93) cohorts. PLR, NLR and SII were collected before and after IMRT. Univariate and multivariate Cox analyses were performed to identify independent prognostic factors affecting survival, which were used to generate a nomogram. RESULTS: The median survival was 16.3 months, and significant increases in PLR, NLR, and SII were observed after IMRT (P < 0.001). High levels of immune parameters were associated with poor prognosis (P < 0.001); enlarged spleen, Barcelona clinic liver cancer stage (B and C), post-SII, and delta-NLR were independent risk factors for survival and were included in the nomogram, which accurately predicted 3- and 5-year survival. The nomogram was well verified in the validation cohort. CONCLUSIONS: High levels of immune parameters are associated with poor prognosis in uHCC patients receiving IMRT. Our nomogram accurately predicts the survival of patients with uHCC receiving IMRT.

Lower risk of hepatocellular carcinoma with tenofovir than entecavir treatment in subsets of chronic hepatitis B patients: an updated meta-analysis.

BACKGROUND AND AIM: Previous smaller meta-analyses comparing the incidence of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with tenofovir disoproxil fumarate (TDF) versus entecavir (ETV) provided controversial results. This updated meta-analysis aimed to reliably identify any difference in the HCC incidence between TDF-treated or ETV-treated CHB patients in general or in specific subgroups. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched for relevant studies with hazard ratios (HRs) for HCC between TDF-treated and ETV-treated CHB patients. Retrieved dates ranged from January 2009 to October 2021. HRs with or without adjustment were pooled with random-effects model. RESULTS: Twenty-four comparative studies involving 37 771 CHB patients treated with TDF and 72 094 treated with ETV were included. TDF was associated with lower risk of HCC compared with ETV, with pooled unadjusted HR of 0.76 (95% confidence interval [CI]: 0.67-0.86) (24 studies) and adjusted HR of 0.81 (95% CI: 0.72-0.91) (21 studies). In propensity score matching cohorts, the TDF superiority was confirmed for unadjusted HR 0.83 (95% CI: 0.71-0.97) (14 studies) and was close to significance for adjusted HR (0.78, 95% CI: 0.58-1.04) (8 studies). Subgroup analyses showed that TDF was associated with lower HCC risk than ETV treatment in CHB patients who were from Asia (adjusted HR: 0.76, 95% CI: 0.66-0.87; 15 studies) or nucleos(t)ide naïve (adjusted HR:0.74, 95% CI: 0.65-0.84; 18 studies). CONCLUSION: Current evidence from a sizable population suggests that TDF is associated with significantly lower HCC risk compared with ETV treatment in patients who are from Asia and/or nucleos(t)ide naïve.

Individual and joint influence of cytokeratin 19 and microvascular invasion on the prognosis of patients with hepatocellular carcinoma after hepatectomy.

BACKGROUND AND OBJECTIVES: To evaluate the individual and combined associations of cytokeratin 19 (CK19) and microvascular invasion (MVI) with prognosis of patients with hepatocellular carcinoma (HCC). METHODS: Clinicopathological data on 352 patients with HCC who underwent radical resection at our hospital between January 2013 and December 2015 were retrospectively analyzed. Patients were divided into four groups: CK19(-)/MVI(-), CK19(-)/MVI(+), CK19(+)/MVI(-), and CK19(+)/MVI(+). RESULTS: Of the 352 HCC patients, 154 (43.8%) were CK19(-)/MVI(-); 116 (33.0%), CK19(-)/MVI(+); 31 (8.8%), CK19(+)/MVI(-); and 51 (14.5%), CK19(+)/MVI(+). The disease-free survival of CK19(-)/MVI(-) patients was significantly higher than that of CK19(-)/MVI(+) patients and CK19(+)/MVI(+) patients. Similar results were observed for overall survival. CK19(+)/MVI(+) patients showed significantly lower overall survival than the other three groups. CONCLUSIONS: CK19 expression and MVI predict poor prognosis after radical resection of HCC, and the two markers jointly contribute to poor OS. Combining CK19 and MVI may predict post-resection prognosis better than using either factor on its own.

Prognostic significance of combined α-fetoprotein and CA19-9 for hepatocellular carcinoma after hepatectomy.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) varies considerably among patients with the same disease stage and characteristics, and only about two thirds show high levels of α-fetoprotein (AFP), a common prognostic indicator for HCC. Here, we assessed whether the combination of presurgical serum levels of AFP and carbohydrate antigen 19-9 (CA19-9) can predict the prognosis of HCC patients after hepatectomy. METHODS: The clinicopathological characteristics and post-hepatectomy outcomes of 711 HCC patients were retrospectively reviewed. The patients were classified into three groups based on whether their preoperative serum levels of both AFP and CA19-9 were higher than the respective cut-offs of 400 ng/ml and 37 U/ml [double positive (DP)], the level of only one marker was higher than the cut-off [single positive (SP)], or neither level was higher than the cut-off [negative (N)]. The overall survival (OS) and recurrence-free survival (RFS) rates were estimated using Kaplan-Meier curves. Univariate and multivariate survival analyses were performed to identify the clinicopathological factors significantly associated with HCC prognosis. RESULTS: The 1-year, 3-year, and 5-year RFS and OS rates in the N group were significantly higher than those in the SP group, while the DP group showed the lowest rates. Multivariate Cox regression analysis showed that large tumor size (> 5 cm), multiple tumors (≥ 2), incomplete tumor capsule, positive microvascular invasion, Barcelona Clinic Liver Cancer C stage, and CA19-9 level > 37 U/mL were independent risk factors for RFS and OS in HCC patients. Moreover, aspartate aminotransferase levels > 40 U/L proved to be an independent prognostic factor for OS. CONCLUSION: The combination of serum AFP and CA19-9 levels may be a useful prognostic marker for HCC patients after hepatectomy.

Development and Validation of a Nomogram to Preoperatively Estimate Post-hepatectomy Liver Dysfunction Risk and Long-term Survival in Patients With Hepatocellular Carcinoma.

OBJECTIVE: To develop a nomogram to estimate the risk of SPLD (International Study Group of Liver Surgery definition grade B or C) and long-term survival in patients with HCC before hepatectomy. BACKGROUND: SPLD is the leading cause of post-hepatectomy mortality. The decision to refer an HCC patient for hepatectomy is mainly based on the survival benefit and SPLD risk. Prediction of SPLD risk before hepatectomy is of great significance. METHODS: A total of 2071 consecutive patients undergoing hepatectomy for HCC were recruited and randomly divided into the development cohort (n = 1036) and internal validation cohort (n = 1035). Five hundred ninety patients from another center were enrolled as the external validation cohort. A nomogram was developed based on independent preoperative predictors of SPLD determined in multivariable logistic regression analysis. RESULTS: The SPLD incidences in the development, internal, and external validation cohorts were 10.1%, 9.5%, and 8.6%, respectively. Multivariable analysis identified total bilirubin, albumin, gamma-glutamyl transpeptidase, prothrombin time, clinically significant portal hypertension, and major resection as independent predictors for SPLD. Incorporating these variables, the nomogram showed good concordance statistics of 0.883, 0.851, and 0.856, respectively in predicting SPLD in the 3 cohorts. Its predictive performance in SPLD, 90-day mortality, and overall survival (OS) outperformed Child-Pugh, model for end-stage liver disease, albumin-bilirubin, and European Association for the Study of the Liver recommended algorithm. With a nomogram score of 137, patients were stratified into low and high risk of SPLD. High-risk patients also had decreased OS. CONCLUSIONS: The nomogram showed good performance in predicting both SPLD and OS. It could help surgeons select suitable HCC patients for hepatectomy.

Macrophage polarization-associated lnc-Ma301 interacts with caprin-1 to inhibit hepatocellular carcinoma metastasis through the Akt/Erk1 pathway.

BACKGROUND: Epithelial-mesenchymal transition (EMT) promotes migration, invasion, and metastasis of hepatocellular carcinoma (HCC) cells. The molecular mechanisms behind EMT and metastasis in HCC remain unclear. METHODS: Microarray analysis was used to identify lncRNAs expression during polarization of U937 macrophages from M2 to M1 phenotype. The expression of the identified lncRNA was compared between clinical samples of HCC tissues or adjacent normal tissues, as well as between HCC and normal liver cell lines. lnc-Ma301 was overexpressed or knocked-down in HCC cell lines, and the effects were assessed in vitro and in vivo. Interactions among lnc-Ma301 and its potential downstream targets caprin-1 were investigated in HCC cell lines. Effects of lnc-Ma301 over- and underexpression on the Akt/Erk1 signaling pathways were examined. RESULTS: Microarray analyses identified lnc-Ma301 as one of the most overexpressed long non-coding RNAs during polarization of U937 macrophages from M2 to M1 phenotype. Lnc-Ma301 showed lower expression in HCC tissues than in adjacent normal tissues, and lower expression was associated with worse prognosis. Activation of lnc-Ma301 inhibited cell proliferation, migration and EMT in HCC cell cultures, and it inhibited lung metastasis of HCC tumors in mice. Mechanistic studies suggested that lnc-Ma301 interacts with caprin-1 to inhibit HCC metastasis and EMT through Akt/Erk1 pathway. CONCLUSIONS: Lnc-Ma301 may help regulate onset and metastasis of HCC.

The lncRNA SNHG16 affects prognosis in hepatocellular carcinoma by regulating p62 expression.

Long noncoding RNAs (lncRNAs) regulate tumor development and progression by promoting proliferation, invasion, and metastasis. The oncogenic role of lncRNA SNHG16 in hepatocellular carcinoma (HCC) has not been revealed. LncRNA SNHG16 is upregulated in HCC and correlates with poorer prognosis. Patients with high SNHG16 expression showed lower rates of overall and disease-free survival than patients with low SNHG16 expression. Multivariate Cox regression revealed that SNHG16 expression was an independent predictor of poor overall and disease-free survival. In vitro, SNHG16 promoted HCC cell proliferation, migration, and invasion while inhibiting apoptosis; in vivo, it accelerated tumor development. Altering SNHG16 expression altered levels of miR-17-5p, which in turn modified expression of p62, which has been shown to regulate the mTOR and NF-κB pathways. Indeed, altering SNHG16 expression in HCC cells activated mTOR and NF-κB signaling. These results reveal a potential mechanism for the oncogenic role of SNHG16 in HCC. SNHG16 may therefore be a promising diagnostic marker as well as therapeutic target in HCC.

Correlation between serum prealbumin and prognosis of patients with hepatocellular carcinoma after hepatectomy.

OBJECTIVE: To determine whether serum prealbumin levels are associated with long-term survival after hepatectomy in patients with primary hepatocellular carcinoma(HCC). METHODS: A consecutive sample of 526 patients with HCC who underwent potentially curative hepatectomy from August 2007 to August 2010 was retrospectively analyzed. Patients were classified as having normal or reduced serum prealbumin based on cut-off values of 200 or 182 mg/L. RESULTS: Multivariate analysis identified the preoperative level of serum prealbumin as an independent prognostic factor of long-term survival (P < 0.05): Survival was significantly better for those with normal levels than for those with reduced levels, based on either cut-off value. Similar results were observed in subgroup analyses based on the degree of cirrhosis, level of ɑ-fetoprotein and Barcelona Clinic Liver Cancer stage. CONCLUSIONS: Preoperative level of serum prealbumin may be useful for predicting long-term survival in patients with HCC after hepatectomy.

MiR-141-3p suppresses gastric cancer induced transition of normal fibroblast and BMSC to cancer-associated fibroblasts via targeting STAT4.

BACKGROUND: Cancer associated fibroblasts (CAFs) are known to be crucial constituents of cancer microenvironment (CME) and play an important role in initiation, progression and metastasis of various types of cancer, such as oral cancer, pancreatic cancer, and gastric cancer. CAFs are usually derived from normal fibroblasts (NFs), but the mechanism of the transition in gastric cancer has not yet been fully elucidated. METHODS: qRT-PCR and western blot were employed to investigate differences of miR-141 and STAT4 expression respectively. The CAF-like features and wnt/ß-catenin pathway related proteins in NF or BMSC were assessed by qRT-PCR or western blot after treated with the conditioned medium from different indicated groups of gastric cancer cells. The invasion and migration ability of AGS cells after transfection were analyzed by Transwell assay and wound healing assay. Dual-luciferase report assay was employed to determine the direct binding of miR-141 to STAT4 3' UTR. RESULTS: For the first time, the present study found that STAT4 over-expression in gastric cancer cells induced NFs to obtain CAF-like features via activating wnt/ß-catenin pathway. Further gain-of-function and loss-of-function analysis revealed that miR-141 not only limited the migration and invasion of the gastric cancer cells, but also inhibited the transition of NFs and BMSC to CAFs. The luciferase assay indicated that miR-141 directly targeted the 3'-UTR predictive sequence of STAT4. CONCLUSION: Our data showed that miR-141 inhibited migration and invasion of gastric cancer cells and inhibited transition from NFs to CAFs via targeting STAT4/wnt/ß-catenin pathway.

Improving patient selection for selective internal radiation therapy of intra-hepatic cholangiocarcinoma: A meta-regression study.

BACKGROUND & AIMS: Selective internal radiation therapy (SIRT) is emerging as a potential therapy for unresectable intra-hepatic cholangiocarcinoma (iCCA) able to prolong life-expectancy. Aim of this study was to collect available literature meta-analyse data and results and investigate sources of heterogeneity through a meta-regression approach before suggesting SIRT as a valuable option. METHODS: A systematic review of studies published until 1 September 2016 in PubMed and Scopus databases was performed. Patient survival was the primary outcome measure. Meta-analysis was performed using a random-effects model. Meta-regression was applied to investigate relationships existing between clinical and tumour features and the primary outcome. RESULTS: Nine observational studies were included in the analysis involving 224 patients. The 1-, 2- and 3-year pooled survival estimates were 55.7%, 33.1% and 20.2%. Clinical and tumour characteristics showed medium-to-considerable heterogeneity (I2 >50%). Meta-regression analysis showed that determinants of best survivals were the presence of mass-forming iCCA type (median survival=19.9 months vs 8.1 months for the infiltrative type; P=.002) that also accounted for most of the heterogeneity between included studies (residual I2 =0); SIRT as first-line therapy (median survival=24 months vs 11.5 months for non-naïve patients; P=.048) and the adoption of concomitant chemotherapy (median survival 19.5 months vs 5.5 months in patients not receiving chemotherapy; P=.042). CONCLUSIONS: There is considerable heterogeneity between studies highlighting that indications for SIRT are extremely varied. To ameliorate SIRT results naïve patients with mass-forming iCCA should be selected as the best candidates with the possibility of adding concomitant standard chemotherapy.

Pre- and post-operative HBsAg levels may predict recurrence and survival after curative resection in patients with HBV-associated hepatocellular carcinoma.

PURPOSE: To investigate pre- and post-operative levels of HBsAg influence prognosis of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative resection. METHODS: Medical records were retrospectively analyzed for 881 patients with HBV-related HCC treated by curative resection. Patients were classified as having high or low serum HBsAg levels (≥200 or <200 ng/mL) pre- or post-operatively. RESULTS: OS and RFS were better for patients with low pre-operative serum levels of HBsAg than for those with high levels. Similarly, OS was better among patients with low post-operative serum levels of HBsAg than among those with high levels. RFS, in contrast, was similar between these two groups. After generating propensity score-matched pairs of patients, OS was higher in patients with falling post-operative HBsAg levels than in those with rising levels. In contrast, RFS was similar between these two groups. Antiviral nucleoside analog therapy prolonged OS in patients with high pre-operative HBsAg levels. CONCLUSIONS: Low pre- and post-operative levels of HBsAg may be associated with better long-term survival in patients with HBV-related HCC. Pre-operative serum levels of HBsAg ≥200 ng/mL may identify patients more likely to benefit from antiviral treatment.

Effect of neoadjuvant chemoradiotherapy on perioperative immune function of patients with locally advanced esophageal cancer.

This study aims to evaluate the effect of neoadjuvant chemoradiotherapy (NCRT) on perioperative immune function during surgery to treat resectable locally advanced esophageal cancer. Records were retrospectively analyzed for 220 patients with locally advanced esophageal cancer, of whom 112 received surgery alone and 98 received neoadjuvant NCRT plus surgery. The two groups were compared in terms of proportions of CD3+, CD4+, CD8+, and natural kill (NK) cells, as well as the ratio of CD4+ to CD8+ cells. These measurements were made using flow cytometry on preoperative day 1 and on postoperative days 1 and 7. Subgroup analysis were performed in terms of degrees of pathological response of NCRT. When the entire NCRT and no-NCRT (surgery alone) cohorts were compared, no significant differences in propocrtions of CD3+, CD4+, CD8+, or NK cells or in the CD4+/CD8+ ratio occurred at any of the three time points. Similar results were obtained using the subgroup of NCRT patients who were NCRT-sensitive, but the subgroup of NCRT-insensitive patients showed significantly lower CD4+ and NK proportions and lower CD4+/CD8+ ratio than the no-NCRT group. Our findings suggest that NCRT does not affect perioperative immune function in patients who are NCRT-sensitive, but it does significantly reduce such function in patients who are NCRT-insensitive.

Hepatectomy for liver metastases from gastric cancer: a systematic review.

BACKGROUND: Official guidelines recommend palliative treatments for patients with liver metastases from gastric cancer. However, many case series reported that hepatectomy for such cases is safe and effective. This systematic review compares the overall survival between hepatectomy and palliative therapy in patients with liver metastases from gastric cancer. METHODS: Two independent reviewers performed a systematic search of literature in EMBASE and PubMed, updated until 26 October 2016. The Newcastle-Ottawa score for cohort studies was used for quality assessment of included studies. RESULTS: A total of eight cohort studies involving 196 patients in the hepatectomy arm and 481 in the palliative arm were included. Median overall survival of patients in the two arms was 23.7 (range, 13.0 to 48.0) and 7.6 (range, 5.5 to 15.2), respectively. Median rates of overall survival of the two arms were 69, 40, 33 and 27, 8, 4% at 1, 2, and 3 years, respectively. Comparing with palliative therapy, hepatectomy was associated with significantly lower mortality at 1 year (odds ratio 0.17, P < 0.001) and 2 years (odds ratio 0.15, P < 0.001). Among the patients who underwent hepatectomy, Asian cohorts showed higher median rates of overall survival than Western cohorts at 1 year (76 vs. 60%), 2 years (47 vs. 30%) and 3 years (39 vs. 23%). CONCLUSIONS: Hepatectomy in the management of liver metastases from gastric cancer can be considered effective. In the elective setting, hepatectomy provides a potential alternative to palliative therapy.

Propensity score-based comparison of hepatic resection and transarterial chemoembolization for patients with advanced hepatocellular carcinoma.

For patients with advanced hepatocellular carcinoma (HCC), official guidelines recommend palliative treatments such as transarterial chemoembolization (TACE) but not hepatic resection (HR). This study compared short- and long-term outcomes in patients with advanced HCC treated by either HR or TACE. A retrospective analysis was performed for a consecutive series of 444 patients with advanced HCC who underwent HR (n = 339) or TACE (n = 205). Analyses were performed over all participants as well as for propensity score-matched patients to adjust for any baseline differences. When all patients were included in the analysis, the HR and TACE groups showed similar postoperative complication rate and mortality at 30 and 90 days (all P > 0.05). However, median survival time was significantly higher in the HR group (16.4 months) than in the TACE group (11.8 months; P = 0.012). Overall survival at 1, 3, 5, and 7 years was 58, 26, 18, and 18 % in the HR group, higher than the corresponding rates of 49, 14, 12, and 7 % in the TACE group. Similar results were obtained in the analysis of propensity score-matched patients. Therefore, HR can be safe and effective for patients with advanced HCC. Randomized controlled trials are warranted to confirm this finding.

Clinicopathological characteristics and liver stem cell marker expression in hepatocellular carcinoma involving bile duct tumor thrombi.

The aim of this study was to analyze the clinicopathological characteristics and expression of liver stem cell markers of hepatocellular carcinoma (HCC) involving bile duct tumor thrombi (BDTT). A total of 35 patients with HCC and BDTT in a consecutive series of HCC patients who underwent surgical treatment were studied retrospectively and compared with 916 patients without BDTT from the same series. Clinicopathological characteristics, overall survival (OS), and tumor expression of liver stem cell markers CD133, CD90, EpCAM, CK19, VEGF, and C-kit were compared between the two patient groups. Analysis was performed for the entire patient groups as well as for 35 pairs of patients with or without BDTT matched by propensity score. HCC patients with BDTT tended to have smaller tumors than those without BDTT, as well as a higher probability of having poorly differentiated tumor, Child-Pugh class B, liver cirrhosis, and microvascular invasion. Tumor tissue in patients with BDTT showed significantly higher expression rates of all liver stem cell markers examined. OS was significantly lower for patients with BDTT at 1 year (69 vs 84 %), 3 years (37 vs 64 %), and 5 years (20 vs 55 %) (P < 0.001). Patients with HCC and BDTT show lower OS than patients without BDTT. The higher frequency of liver stem cell marker expression in the presence of BDTT suggests that such stem cells may play a role in the pathogenesis of this form of HCC.