Endoplasmic reticulum stress induced LOX-1+ CD15+ polymorphonuclear myeloid-derived suppressor cells in hepatocellular carcinoma.

A recent study indicated that Lectin-type oxidized LDL receptor-1 (LOX-1) was a distinct surface marker for human polymorphisms myeloid-derived suppressor cells (PMN-MDSC). The present study was aimed to investigate the existence LOX-1 PMN-MDSC in hepatocellular carcinoma (HCC) patients. One hundred and twenty-seven HCC patients, 10 patients with mild active chronic hepatitis B, 10 liver cirrhosis due to hepatitis B, 10 liver dysplastic node with hepatitis B and 50 health control were included. LOX-1+  CD15+ PMN-MDSC were significantly elevated in HCC patients compared with healthy control and patients with benign diseases. LOX-1+  CD15+ PMN-MDSC in circulation were positively associated with those in HCC tissues. LOX-1+  CD15+ PMN-MDSCs significantly reduced proliferation and IFN-γ production of T cells with a dosage dependent manner with LOX-1-  CD15+ PMNs reached negative results. The suppression on T cell proliferation and IFN-γ production was reversed by ROS inhibitor and Arginase inhibitor. ROS level and activity of arginase of LOX-1 + CD15+ PMN were higher in LOX-1+  CD15+ PMN-MDSCs than LOX-1-  CD15+ PMNs, as well as the expression of the NADPH oxidase NOX2 and arginase I. RNA sequence revealed that LOX-1+ CD15+ PMN-MDSCs displayed significantly higher expression of spliced X-box -binding protein 1 (sXBP1), an endoplasmic reticulum (ER) stress marker. ER stress inducer induced LOX-1 expression and suppressive function for CD15+ PMN from health donor. For HCC patients, LOX-1+  CD15+ PMN-MDSCs were positively related to overall survival. Above all, LOX-1+  CD15+ PMN-MDSC were elevated in HCC patients and suppressed T cell proliferation through ROS/Arg I pathway induced by ER stress. They presented positive association with the prognosis of HCC patients.

Comparison of five models for end-stage liver disease in predicting the survival rate of patients with advanced hepatocellular carcinoma.

Prognosis of patients with advanced hepatocellular carcinoma (HCC) is under expectation. Life expectancy more than 3 months is one inclusion criteria for molecular targeted drugs in clinical trials. The main purpose of this research is to compare Model for End-Stage Liver Disease (MELD) and four MELD-based prognostic models in predicting the survival rate of advanced HCC patients. One hundred eighty-three patients with advanced HCC who were not amendable to standard anti-tumor therapy were retrospectively analyzed. Data were collected to classify patients according to MELD, Model for End-Stage Liver Disease with the incorporation of serum sodium (MELD-NA), Model for End-Stage Liver Disease to ascites and sodium (MELD-AS), integrated Model for End-Stage Liver Disease (iMELD), and Model for End-Stage Liver Disease to sodium (MESO) scores at diagnosis. 1-, 3-, and 6-month survivals were the end points used in the analysis. When predicting 1-month survival, MELD-AS, MELD, and MESO were the top 3 ranking staging systems. When predicting 3-month survival, area under the receiver operating characteristic curve (AUC) of MELD-AS is significantly higher than that of the other models (P < 0.05). When predicting 6-month survival, AUCs of MELD-AS and MELD-NA are significantly higher than those of the other models (P < 0.05). Cutoff point of MELD-AS is 23.11 with 40.5 % sensitivity and 93.8 % specificity at 1 month, 9.5 with 76.9 % sensitivity and 59.5 % specificity at 3 months, and 18.5 with 27.0 % sensitivity and 89.1 % specificity at 6 months. MELD-based scores of death group are significantly higher than those of survivors within 1 and 3 months (P < 0.001). Independent prognostic factors identified by multivariate analysis included persistent ascites, serum sodium, and thrombosis. MELD-AS is the best model in the prediction of short and intermediate survival among the five models for end-stage liver disease analyzed for Chinese advanced HCC patients.

Alanine aminotransferase to hemoglobin ratio is an indicator for disease progression for hepatocellular carcinoma patients receiving transcatheter arterial chemoembolization.

The prognosis of hepatocellular carcinoma (HCC) patients receiving transcatheter arterial chemoembolization (TACE) is far from being identified. The present study aimed to assess the role of blood cell counts, routine liver function tests, and alanine aminotransferase to hemoglobin ratio (AHR) in predicting the progression-free survival (PFS) of these patients. A total of 243 HCC patients receiving TACE were analyzed retrospectively. Cancer of the Liver Italian Program (CLIP) score system was indentified to be the best score system for this patient subgroup according to the Akaike information criterion (AIC) index and linear trend χ (2). Then, prognostic value of parameters was determined by integration into the CLIP score system. As a result, AHR was confirmed to be an independent predictor for the PFS of HCC patients receiving TACE (p = 0.001) with the other parameters failing to reach statistical significance. Moreover, AHR improved the performance of CLIP by adjusting into it, thus improving its discriminatory ability. AHR defined ≤0.4583 as low level and >0.4583 as high level. And, patients were also dichotomized into two groups accordingly. HCC patients receiving TACE with low AHR presented higher 1 year DCR (41.9 vs 18.1 %) compared with patients with high AHR levels. Furthermore, AHR level was associated with prognostic factors such as lower ALP, total bilirubin, and portal vein thrombosis. In summary, the present study firstly indentified AHR as an independent prognostic factor in HCC patients receiving TACE. The subgroup of HCC patients with lower AHR presented preferable disease control and were the idealistic candidates for TACE.

Platelet-to-lymphocyte ratio acts as a prognostic factor for patients with advanced hepatocellular carcinoma.

The platelet count, as an inflammation marker, is involved in the progress of tumor invasion. However, the prognostic value of platelet counts and the platelet-to-lymphocyte ratio (PLR) has not been investigated in patients with advanced hepatocellular carcinoma (HCC). This study aimed to determine the prognostic value of platelet counts and PLR in HCC patients. A total of 243 ethnic Chinese advanced HCC patients from two major hospitals, not receiving systemic sorafenib, were analyzed retrospectively. The prognostic value of differential blood cell counts and PLR for overall survival (OS) was determined by integrating the Cancer of the Liver Italian Program (CLIP) score system and model for end-stage liver disease by using a stepwise model of multivariate Cox regression. The Kaplan-Meier method and receiver operating characteristic (ROC) curves were utilized accordingly. PLR was confirmed to be an independent predictor for OS (p < 0.01), while the remaining parameters had no predictive value. Then, advanced HCC patients were dichotomized into two groups based on the PLR value (≤111.23 or >111.23), according to ROC analysis. Patients with a high PLR had a lower 3-month survival rate (37.6 vs. 57.6%) compared with patients with a low PLR. PLR was associated with aggressive malignant behavior, characterized by distant metastasis and portal vein thrombosis. Additionally, PLR was not associated with the CLIP score and Child-Pugh grade. PLR was identified as an independent prognostic factor for advanced HCC patients not receiving systemic sorafenib; the predictive ability of PLR partially relies on its association with the aggressive nature of HCC.

Autophagic LC3B overexpression correlates with malignant progression and predicts a poor prognosis in hepatocellular carcinoma.

Autophagy is a process that involves lysosomal degradations of cellular organelles and closely related to tumor occurrence and progression. However, its importance in hepatocellular carcinoma (HCC) was still controversial. Therefore, this study is aimed to address the clinicopathologic effect of microtubule-associated protein 1 light chain 3B (LC3B) and Beclin-1, as autophagic markers, in HCC patients. Tissue microarray-based immunohistochemistry was used to examine the expression of LC3B and another autophagy key regulator (Beclin-1) in 156 operable HCC patients. Kaplan-Meier analysis, chi-square test, and Spearman's correlation analysis were used to analyze correlation of LC3B and Beclin-1 and their influence on clinical characteristics and prognosis. We found that the expression level of LC3B was significantly associated with vascular invasion (P = 0.008), lymph node metastasis (P < 0.001), and Beclin-1 expression level (P < 0.001). However, LC3B was not related to other clinicopathological features, including hepatitis B virus infection, liver cirrhosis, tumor number, tumor size, pathology grade, and tumor-node-metastasis (TNM) stage. Besides, correlation between the expression of Beclin-1 and clinicopathological features were not identified. Survival analysis showed that patients with high LC3B expression had a poorer 5-year overall survival (OS) rate than those with low LC3B expression (high vs. low: 79.5 % vs. 20.5 %, P = 0.026). And high LC3B expression tended to be related with shorter progression-free survival (PFS) (P = 0.074), whereas the expression level of Beclin-1 did not show statistically significant association with OS or PFS. Further multivariate analysis revealed that lymph node metastasis (P = 0.047) and LC3B expression level (P = 0.047) were independent factors to predict the prognosis of OS in all patients. Our study demonstrated that high expression of LC3B, correlated with vascular invasion and lymph node metastasis, might be a novel prognostic biomarker and would be a potential therapy target for HCC, especially in operable patients.

Neutrophil-to-lymphocyte ratio acts as a prognostic factor for patients with advanced hepatocellular carcinoma.

Few studies investigated the prognosis of patients with advanced hepatocellular carcinoma (aHCC). This study was aimed to determine the prognostic value of differential blood cell counts including blood white cells, neutrophil, lymphocyte, neutrophil-lymphocyte ratio (NLR), and platelet in patients with aHCC. A total of 205 ethnic Chinese aHCC patients receiving non-systematic sorafenib were analyzed retrospectively. The prognostic value of differential blood cell counts and NLR for overall survival (OS) was determined by integration into Cancer of the Liver Italian Program (CLIP) score system using backward elimination model of multivariate Cox regression. As a result, NLR was confirmed to be an independent predictor for OS (p = 0.001) with the rest parameters presented negative results. Then, aHCC patients were dichotomized into two groups according to NLR values ≤ 2.43 or >2.43. Patients with low NLR presented lower CLIP score and higher 6-month survival rate (56.1 vs 25.9%) compared with patients with high NLR level. Besides, low NLR level was associated with favorable prognostic factors such as lower α-fetoprotein, alkaline phosphatase, and total bilirubin, as well as decreased incidence of ascites, portal vein thrombosis, and metastasis. Besides, low NLR level was associated less white cells and neutrophil granulocytes, as well as more lymphocyte. In summary, the present study firstly indentified NLR as an independent prognostic factor in aHCC patients receiving no systematic sorafenib.

An optimized antiviral modification strategy for prevention of hepatitis B reactivation in patients undergoing prophylactic lamivudine and chemotherapy: a pilot study.

In patients receiving prophylactic lamivudine (LAM) and chemotherapy, hepatitis B virus (HBV) reactivation cannot be eliminated without knowing the latent causes and optimal management. In our previous study, virus breakthrough and relapse were highly suspected as potential virologic causes for HBV reactivation. Therefore, we reviewed 24 previous studies and 447 patients who underwent chemotherapy and prophylactic LAM, with an incidence of 7.2 % HBV reactivation. Virus breakthrough and relapse were seldom investigated in these studies. In addition, 72 patients that underwent prophylactic LAM and chemotherapy at our centers were also analyzed. Among them, eight patients developed virus breakthrough, with another nine developing virus relapse after discontinuation of LAM. Eight patients received antiviral modification, which included administration of adefovir for patients with virus breakthrough or resumption of LAM for patients with virus relapse and none of them developed HBV reactivation. In contrast, of the nine patients who did not receive antiviral modification, six developed HBV reactivation and two died. In conclusion, this study demonstrated that virus breakthrough and relapse were the critical causative factors of HBV reactivation in patients receiving chemotherapy and prophylactic LAM. An optimized antiviral modification strategy could effectively prevent HBV reactivation in patients with virus breakthrough or relapse.

Comparison of five staging systems in predicting the survival rate of patients with hepatocellular carcinoma undergoing trans-arterial chemoembolization therapy.

The majority of patients with unresectable hepatocellular carcinoma (HCC) undergo trans-arterial chemoembolization (TACE). However, the prognosis of HCC remains poor. In the present study, five staging systems were compared to predict the survival rate of patients with HCC undergoing TACE treatment. A total of 220 patients with HCC were examined according to the model to estimate survival for hepatocellular carcinoma (MESH), hepatoma arterial embolization prognostic score (HAP), modified HAP (mHAP), performance status combined Japan Integrated Staging system (PSJIS) and tumor-node-metastasis (TNM) staging systems. The endpoints of the study were 3-month survival, 6-month survival, 1-year survival and overall survival (OS) rates. Receiver operating characteristic curve analysis indicated that the area under the curve of MESH, HAP, mHAP, PSJIS and TNM was 0.858, 0.728, 0.690, 0.688 and 0.699, respectively, in predicting 3-month survival rates; 0.822, 0.747, 0.720, 0.722 and 0.715, respectively, in predicting 6-month survival rates and 0.725, 0.664, 0.672, 0.645 and 0.654, respectively, in predicting 1-year survival rates. Discriminatory ability, homogeneity, monotonicity and prognostic stratification ability was evaluated using a likelihood ratio test and Akaike information criterion values among the five staging systems, and revealed that the MESH system was the optimal prognostic staging system for HCC. In conclusion, the results of the present study suggest that the MESH system is the most accurate prognostic staging system of 3-month survival, 6-month survival, 1-year survival and OS rates among the five systems analyzed in patients with HCC who have received TACE treatment.

Serum Golgi protein 73 is a prognostic rather than diagnostic marker in hepatocellular carcinoma.

Serum Golgi protein 73 (sGP73) is a candidate diagnostic biomarker for hepatocellular carcinoma (HCC). However, current evidence of its diagnostic value is conflicting, primarily due to the small sample sizes of previous studies, and its prognostic role in HCC also remains unclear. In the present study, sGP73 levels in 462 patients with HCC, 186 patients with liver cirrhosis, and 83 healthy controls were evaluated using ELISA, and it was identified that the median sGP73 levels were significantly higher in the HCC (18.7 ng/ml) and liver cirrhosis (18.5 ng/ml) patients than in the healthy controls (0 ng/ml; both P<0.001); however, the levels did not significantly differ between the HCC and liver cirrhosis groups (P=0.632). sGP73 had an inferior sensitivity and specificity for HCC diagnosis (27.79 and 77.96%, respectively) compared with α-fetoprotein (57.36 and 90.96%, respectively; P<0.001). In the HCC group, a high level of sGP73 was associated with aggressive clinicopathological features and independently predicted poor overall survival (OS) time (P<0.001). Additionally, in patients with resectable HCC, a high level of sGP73 was associated with significantly decreased disease-free survival (P<0.001) and OS (P=0.039) times compared with a low level of sGP73. This study demonstrated that sGP73 is unsuitable as a diagnostic marker for the early detection of HCC; however, it is an independent negative prognostic marker, providing a novel risk stratification factor and a potential therapeutic molecular target for HCC.

Validation and ranking of seven staging systems of hepatocellular carcinoma.

The aim of the present study was to evaluate the ability of seven staging systems to predict 3- and 6-month and cumulative survival rates of patients with advanced hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Data were collected from 220 patients with HBV-associated HCC who did not receive any standard anticancer treatment. Participants were patients at The Third Affiliated Hospital of Sun Yat-sen University from September 2008 to June 2010. The participants were classified according to the Chinese University Prognostic Index (CUPI), the Cancer of the Liver Italian Program (CLIP), Japan Integrated Staging (JIS), China Integrated Score (CIS) systems, Barcelona Clinic Liver Cancer (BCLC), Okuda and tumor-node-metastasis (TNM) staging systems at the time of diagnosis and during patient follow-up. The sensitivity and specificity of the predictive value of each staging system for 3- and 6-month mortality were analyzed by relative operating characteristic (ROC) curve analysis with a non-parametric test being used to compare the area under curve (AUC) of the ROC curves. In addition, log-rank tests and Kaplan-Meier estimator survival curves were applied to compare the overall survival rates of the patients with HCC defined as advanced using the various staging systems, and the Akaike information criterion (AIC) and likelihood ratio tests (LRTs) were used to evaluate the predictive value for overall survival in patients with advanced HCC. Using univariate and multivariate Cox's model analyses, the factors predictive of survival were also identified. A total of 220 patients with HBV-associated HCC were analyzed. Independent prognostic factors identified by multivariate analyses included tumor size, α-fetoprotein levels, blood urea nitrogen levels, the presence or absence of portal vein thrombus, Child-Pugh score and neutrophil count. When predicting 3-month survival, the AUCs of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 0.806, 0.772, 0.751, 0.731, 0.643, 0.754 and 0.622, respectively. When predicting 6-month survival, the AUCs of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 0.828, 0.729, 0.717, 0.692, 0.664, 0.746 and 0.575, respectively. For 3-month mortality, the prognostic value of CLIP ranked highest, followed by CIS; for 6-month mortality, the prognostic value of CLIP also ranked highest, followed by JIS. No significant difference between the AUCs of CLIP and CIS (P>0.05) in their predictive value for 3-month mortality was observed. The AUC of CLIP was significantly higher compared with that of the other staging systems (P<0.05) for predicting 6-month mortality. The χ2 values from the LRTs of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 75.6, 48.4, 46.7, 36.0, 21.0, 46.8 and 7.24, respectively. The AIC values of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 1601.5, 1632.3, 1629.9, 1641.1, 1654.8, 1627.4 and 1671.1, respectively. CLIP exhibited the highest χ2 value and lowest AIC value, indicating that CLIP has the highest predictive value of cumulative survival rate. In the selected patients of the present study, CLIP was the staging system best able to predict 3- and 6-month and overall survival rates. CIS ranked second in predicting 3-month mortality.

Identification of the prognostic value of lymphocyte-to-monocyte ratio in patients with HBV-associated advanced hepatocellular carcinoma.

The inflammatory microenvironment serves an important function in the progression of hepatocellular carcinoma (HCC). Peripheral blood lymphocyte-to-monocyte ratio (LMR), as a novel inflammatory biomarker combining an estimate of host immune homeostasis with the tumor microenvironment, has been identified to be a predictor of clinical outcomes in a number of malignancies. The present study aimed at investigating the prognostic value of LMR in patients with hepatitis B virus (HBV)-associated advanced HCC. A total of 174 patients with HBV-associated advanced HCC, without fever or signs of infections, were analyzed. Clinicopathological parameters, including LMR, were evaluated to identify predictors of overall survival time. Univariate and multivariate analysis was performed using Cox's proportional hazards model. A threshold value was determined using a time-dependent receiver operating characteristic curve. Univariate and multivariate analysis identified LMR as an independent prognostic factor in overall survival (OS) time in patients with HBV-associated advanced HCC (P<0.05). The threshold value of LMR was 2.22. All patients were divided into either a low LMR group (≤2.22) or a high LMR group (>2.22). The OS time of the high LMR group was significantly longer compared with the low LMR group (P<0.001). Patients in the high LMR group exhibited a significantly increased 3-month and 6-month OS rate, compared with that of the patients within the low LMR group (P<0.001). An increased level of LMR was significantly associated with the presence of metastasis, ascites and increased tumor size (P<0.01). LMR is an independent prognostic factor of HBV-associated advanced HCC patients and an increased baseline LMR level indicates an improved prognosis.

Nomogram for preoperative estimation of long-term survival of patients who underwent curative resection with hepatocellular carcinoma beyond Barcelona clinic liver cancer stage A1.

BACKGROUND AND AIMS: This retrospective cohort study developed a prognostic nomogram to predict the survival of hepatocellular carcinoma (HCC) patients diagnosed as beyond Barcelona clinic liver cancer stage A1 after resection and evaluated the possibility of using the nomogram as a treatment algorithm reference. RESULTS: The predictors included in the nomogram were total tumour volume, Child-Turcotte-Pugh class, plasma fibrinogen and portal vein tumour thrombus. Patients diagnosed as beyond A1 were stratified into low-, medium- and high-risk groups using nomogram scores of 0 and 51 with the total points of 225. Patients within A1 exhibited similar recurrence-free survival (RFS) and overall survival (OS) rates compared with the low-risk group. Patients in the medium-risk group exhibited a similar OS but a worse RFS rates compared with patients within A1. The high-risk group was associated with worse RFS and OS rates compared with the patients within A1 (3-year RFS rates, 27.0% vs. 60.3%, P < 0.001; 3-year OS rates, 49.2% vs. 83.1%, P < 0.001). METHODS: A total of 352 HCC patients undergoing curative resection from September 2003 to December 2012 were included to develop a nomogram to predict overall survival after resection. Univariate and multivariate survival analysis were used to identify prognostic factors. A visually orientated nomogram was constructed using a Cox proportional hazards model. CONCLUSIONS: This user-friendly nomogram offers an individualized preoperative recurrence risk estimation and stratification for HCC patients beyond A1 undergoing resection. Resection should be considered the first-line treatment for low-risk patients.

Poor oncologic outcomes of hepatocellular carcinoma patients with intra-abdominal infection after hepatectomy.

AIM: To evaluate the impact of postoperative infectious complications on hepatocellular carcinoma following curative hepatectomy. METHODS: We performed a retrospective analysis of 200 hepatocellular carcinoma patients who underwent hepatectomy at our institution between September 2003 and June 2011. The patients' demographics, clinicopathological characteristics and postoperative infectious complications were analyzed. The Clavien-Dindo classification was adopted to assess the severity of complications. The dynamic change in the neutrophil-to-lymphocyte ratio, defined as the absolute neutrophil count divided by the absolute lymphocyte count, after surgery was also investigated. The observation endpoints for this study were recurrence-free survival and overall survival of the patients. Statistical analysis of the survival curves was performed using the Kaplan-Meier method and the log-rank test. The prognostic value of each variable for predicting prognosis was assessed via multivariate Cox proportional hazards regression analysis. The cutoff score for each variable was selected based on receiver operating characteristic curve analysis. All statistical tests were two-sided, and significance was set at P < 0.05. RESULTS: The median age of the patients was 49 years, and the majority of patients were male (86%) and had been infected with hepatitis B virus (86%). The 30-d postoperative infectious complication rate was 34.0% (n = 68). Kaplan-Meier survival analysis revealed that postoperative infection was significantly correlated with tumor recurrence (P < 0.001). The postoperative intra-abdominal infection group exhibited a worse prognosis than the non-intra-abdominal infection group (P < 0.001). A significantly increased incidence of postoperative intra-abdominal infection was observed in the patients with hepatic cirrhosis (P = 0.028), concomitant splenectomy (P = 0.007) or vascular invasion (P = 0.026). The patients who had an elevated postoperative neutrophil-to-lymphocyte ratio change (> 1.643) clearly exhibited poorer recurrence-free survival than those who did not (P = 0.009), although no significant correlation was observed between overall survival and the change in the postoperative neutrophil-to-lymphocyte ratio. Based on multivariate analysis, hepatitis B surface antigen positivity, Child-Turcotte-Pugh class B, an elevated postoperative neutrophil-to-lymphocyte ratio change and intra-abdominal infection were significant predictors of poor recurrence-free survival. Hepatic cirrhosis, the maximal tumor diameter and intra-abdominal infection were significant predictors of overall survival. CONCLUSION: Postoperative intra-abdominal infection adversely affected oncologic outcomes, and the change in postoperative neutrophil-to-lymphocyte ratio was a good indicator of tumor recurrence in hepatocellular carcinoma patients after curative hepatectomy.

Lymphocyte-to-monocyte ratio predicts survival of patients with hepatocellular carcinoma after curative resection.

AIM: To investigate the prognostic value of preoperative lymphocyte-to-monocyte ratio (LMR) in patients with hepatocellular carcinoma (HCC) undergoing curative hepatectomy. METHODS: Clinicopathological data of 210 hepatitis B virus (HBV)-associated HCC patients who were treated by radical hepatic resection between 2003 and 2010 were retrospectively analyzed. None of the patients received any preoperative anticancer therapy or intraoperative radiofrequency ablation. The diagnosis was confirmed by pathological examination after surgery. Absolute peripheral blood lymphocyte and monocyte counts were derived from serum complete blood cell count before surgery, and LMR was calculated by dividing lymphocyte count by monocyte count. The best cutoff was determined by receiver operating characteristics (ROC) curve analysis. Correlations between LMR levels and clinicopathological features were assessed using the χ(2) test. Survival outcomes were estimated using the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate analyses were performed to evaluate the prognostic impact of LMR and other clinicopathological factors on overall survival (OS) and recurrence-free survival (RFS), using the Cox proportional hazards model. RESULTS: The optimal cutoff value of LMR for survival analysis was 3.23, which resulted in the most appropriate sensitivity of 55.3% and specificity of 74.7%, with the area under the curve (AUC) of 0.66 (95%CI: 0.593-0.725). All patients were dichotomized into either a low (≤ 3.23) LMR group (n = 66) or a high (> 3.23) LMR group (n = 144). A low preoperative LMR level was significantly correlated with the presence of cirrhosis, elevated levels of total bilirubin and larger tumor size. Patients with a low LMR level had significantly reduced 5-year OS (61.9% vs 83.2%, P < 0.001) and RFS (27.8% vs 47.6%, P = 0.009) compared to those with a high LMR level. Multivariate analyses indicated that a lower LMR level was a significantly independent predictor of inferior OS (P = 0.003) and RFS (P = 0.006). Subgroup analysis indicated that survival outcome was significantly more favorable in cirrhotic patients with LMR > 3.23. However, there were no differences between low and high LMR groups for OS and RFS in non-cirrhotic patients. CONCLUSION: Preoperative LMR was demonstrated for the first time to serve as an independent prognostic factor in HBV-associated HCC patients after curative resection. Prospective studies with larger cohorts for validation are warranted.

Efficacy of Prophylactic Entecavir for Hepatitis B Virus-Related Hepatocellular Carcinoma Receiving Transcatheter Arterial Chemoembolization.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) reactivation was reported to be induced by transcatheter arterial chemoembolization (TACE) in HBV-related hepatocellular carcinonma (HCC) patients with a high incidence. The effective strategy to reduce hepatitis flares due to HBV reactivation in this specific group of patients was limited to lamivudine. This retrospective study was aimed to investigate the efficacy of prophylactic entecavir in HCC patients receiving TACE. METHODS: A consecutive series of 191 HBV-related HCC patients receiving TACE were analyzed including 44 patients received prophylactic entecavir. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log10 copies/ml higher than nadir the level, and hepatitis flares due to HBV reactivation were the main endpoints. RESULTS: Patients with or without prophylactic were similar in host factors and the majorities of characteristics regarding to tumor factors, HBV status, liver function and LMR. Notably, cycles of TACE were parallel between the groups. Ten (22.7%) patients receiving prophylactic entecavir reached virologic response. The patients receiving prophylactic entecavir presented significantly reduced virologic events (6.8% vs 54.4%, p=0.000) and hepatitis flares due to HBV reactivation (0.0% vs 11.6%, p=0.039) compared with patients without prophylaxis. Kaplan-Meier analysis illustrated that the patients in the entecavir group presented significantly improved virologic events free survival (p=0.000) and hepatitis flare free survival (p=0.017). Female and Eastern Cooperative Oncology Group (ECOG) performance status 2 was the only significant predictors for virological events in patients without prophylactic antiviral. Rescue antiviral therapy did not reduce the incidence of hepatitis flares due to HBV reactivation. CONCLUSION: Prophylactic entecavir presented promising efficacy in HBV-related cancer patients receiving TACE. Lower performance status and female gender might be the predictors for HBV reactivation in these patients.

Staged Improvement in Awareness of Disease for Elderly Cancer Patients in Southern China.

BACKGROUND: In mainland China, awareness of disease of elderly cancer patients largely relies on the patients' families. We developed a staged procedure to improve their awareness of disease. MATERIALS AND METHODS: Participants were 224 elderly cancer patients from 9 leading hospitals across Southern China. A questionnaire was given to the oncologists in charge of each patient to evaluate the interaction between family and patients, patient awareness of their disease and participation in medical decision-making. After first cycles of treatment, increased information of disease was given to patients with cooperation of the family. Then patient awareness of their disease and participation in medical decision-making was documented. RESULTS: Among the 224 cancer elderly patients, 26 (11.6%) made decisions by themselves and 125 (55.8%) delegated their rights of decision- making to their family. Subordinate family members tended to play a passive role in decision-making significantly. Patients participating more in medical decision-making tended to know more about their disease. However, in contrast to the awareness of disease, patient awareness of violation of medical recommendations was reversely associated with their participation in medical decision-making. Improvement in awareness of diagnosis, stages and prognosis was achieved in about 20% elderly cancer patients. About 5% participated more actively in medical decision-making. CONCLUSIONS: Chinese elderly cancer patient awareness of disease and participation in medical decision-making is limited and relies on their family status. The staged procedure we developed to improve patient awareness of disease proved effective.

MicroRNA-34a-5p enhances sensitivity to chemotherapy by targeting AXL in hepatocellular carcinoma MHCC-97L cells.

Mature microRNA (miRNA) 34a-5p, which is a well-known tumor suppressor in hepatitis virus-associated hepatocellular carcinoma (HCC), plays an important role in cell processes, such as cell proliferation and apoptosis, and is therefore an optimal biomarker for future clinical use. However, the role of miRNA-34a-5p in chemoresistance has yet to be identified. In the present study, the expression of miRNA-34a-5p was assessed by an in situ hybridization assay in HCC tissues and was found to be significantly decreased compared with the pericarcinomatous areas of the tissue specimens, which consisted of samples obtained from 114 patients with HCC. High expression of miRNA-34a-5p was found to be associated with a favorable overall survival time in HCC patients. Functional tests performed by transfecting miRNA-34a-5p mimics or inhibitors into MHCC-97L cells illustrated that miRNA-34a-5p inhibited proliferation, elevated apoptosis and decreased chemoresistance to cisplatin in HCC cells. AXL is the direct target of miRNA-34a-5p, as confirmed by sequence analysis and luciferase assay. Transfection of the cells with small interfering RNA for AXL (siAXL) increased the apoptosis ratio of the MHCC-97L cell line. Transfection with siAXL led to similar biological behaviors in the MHCC-97L cells to those induced by ectopic expression of miRNA-34a-5p. Thus, it was concluded that miRNA-34a-5p enhanced the sensitivity of the cells to chemotherapy by targeting AXL in hepatocellular carcinoma. In addition, low expression of miRNA-34a-5p in HCC tissues yielded an unfavorable prognosis for patients with HCC that received radical surgery, due to the promotion of proliferation and an increase in chemoresistance in HCC cells.

Combination of low-dose gemcitabine in 6-hour infusion and carboplatin is a favorable option for patients in poor performance status with advanced non-small cell lung cancer.

This study sought to investigate the efficacy and tolerability of the regimen of low-dose gemcitabine combined with carboplatin in chemo-naïve patients with non-small cell lung cancer (NSCLC). The study involved 37 chemo-naive patients with unresectable stage IIIB or stage IV NSCLC. The predominant histological type was squamous carcinoma (22/37), and the performance status (PS) was 2 in 23 patients (62%). All received gemcitabine, 250 mg/m(2) in 6-hour infusion on days 1 and 8 plus carboplatin area under the curve (AUC)  =  5 on day 1, every 28 days. The overall response rate (ORR) was 62·2% and disease stabilization was achieved in 21·6% of the patients. After a median follow-up duration of 13 months, the median overall survival (OS) time was 14·0 months (95% CI 13·3-16·6 months), and the median progression-free survival (PFS) time was 7·0 months (95% CI 6·1-8·9 months). Hematological toxicities were well-tolerated with the development of grade 3/4 neutropenia and thrombocytopenia in 10·3 and 10·3% of patients respectively, and the gastrointestinal toxicities were mild.

Hepatitis B virus DNA negativity acts as a favorable prognostic factor in hepatocellular carcinoma patients.

BACKGROUND: This retrospective study was aimed to investigate the efficacy of prophylactic agents in hepatocellular carcinoma (HCC) patients receiving TACE and compare the difference between lamivudine and entecavir. MATERIALS AND METHODS: A consecutive series of 203 HBV-related HCC patients receiving TACE were analyzed including 91 patients given prophylactic agents. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log10 IU/ml higher than the nadir level, hepatitis flares due to HBV reactivation and progression free survival (PFS) were the main endpoints. RESULTS: Some 48 (69.6%) reached virologic response. Prophylaxis significantly reduced virologic events (8.8% vs 58.0%, p=0.000) and hepatitis flares (1.1% vs 13.4%, p=0.001). Patients presenting undetectable HBV DNA levels displayed a significantly improved PFS as compared to those who never achieved undetectable HBV DNA. Prophylaxis and e-antigen positivity were the only significant variables associated with virologic events. In addition, prophylaxis was the only independent protective factor for hepatitis flares. Liver cirrhosis, more cycles of TACE, HBV DNA negativity, a lower Cancer of the Liver Italian Program score, non-metastasis and no hepatitis flares were protective factors for PFS. Prophylactic lamivudine demonstrated similar efficacy as entecavir. CONCLUSIONS: Prophylactic agents are efficacious for prevention of HBV reactivation in HCC patients receiving TACE. Achievement of undetectable HBV DNA levels displayed a significant capability in improving PFS. Moreover, persistent tumor residual lesions, positive HBV DNA and hepatitis B flares might be causes of tumor progression in these patients.