Xiao-Kun Ma

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 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.

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.

Comparison of current staging systems for advanced hepatocellular carcinoma not amendable to locoregional therapy as inclusion criteria for clinical trials.

The prognosis of patients with advanced hepatocellular carcinoma (HCC) is poor and testing drug efficacy in clinical trials is hazardous. This study was aimed to evaluate different prognostic scoring systems for HCC in estimating prognosis (3‐month survival and overall survival (OS)).

Efficacy and Tolerance of Pegaspargase-Based Chemotherapy in Patients with Nasal-Type Extranodal NK/T-Cell Lymphoma: a Pilot Study

Nasal-type extranodal natural killer (NK)/T-cell lymphoma (ENKL) is a highly invasive cancer with a poor prognosis. More effective and safer treatment regimens for ENKL are needed. Pegaspargase (PEG-Asp) has a similar mechanism of action to L-asparaginase (L-Asp), but presents lower antigenicity. The aim of the present research was to evaluate the safety profile and the latent efficacy of a PEG-Asp-based treatment regimen in patients with ENKL. Data collected from 20 patients with histologically confirmed ENKL, admitted to the Third Affiliated Hospital of Sun Yat-Sen University from January 2009 to August 2013, were included in the study. All patients received 2500 IU/m2/IM PEG-Asp on day 1 of every 21-day treatment cycle. Patients received combination chemotherapy with CHOP (n=5), EPOCH (n=7), GEMOX (n=7) or CHOP with bleomycin (n=1). After 2-5 treatment cycles (median, 4 cycles) of PEG-Asp-based chemotherapy, five patients (25%) showed a complete response (CR), and the overall response rate (ORR) was 60%. Grade 3/4 neutropenia occurred in fourteen patients (70%). Grade 3 alanine aminotransferase (ALT) elevation was observed in two. Grade 1-2 non-hematological toxicity consisted of activated partial thromboplastin time (APTT) elongation (n=9), hypofibrinogenemia (n=6), hypoproteinemia (n=17), hyperglycemia (n=3), and nausea (n=6). No allergic reactions were detected. No treatment related death was reported. Our results suggested that PEG-Asp-based chemotherapy presented an acceptable tolerance and a potential short-term outcome in patients with nasal-type ENKL.

Prognostic analysis of acute exacerbations of hepatitis-B after chemotherapy in combination with rituximab in 19 patients with lymphoma

The prognosis and management of acute exacerbations of hepatitis-B in patients with lymphoma after chemotherapy in combination with rituximab remain unclear. Here, we describe 19 Chinese patients with lymphoma who suffered this complication, in order to analyze their clinical characteristics. Receiver operating characteristic analysis and Kaplan–Meier survival analysis were utilized to determine potential prognostic factors. We found that key prognostic factors included the peak prothrombin time (PT), international normalized ratio (INR), and total bilirubin (TB), as well as the PT and INR on admission and the interval between acute exacerbation of hepatitis-B and the last cycle of chemotherapy. Moreover, our data suggested that shorter interval between the last cycle of rituximab and acute exacerbation of hepatitis-B might be another prognostic indicator of inferior survival. Our results revealed that the severity of hepatic damage and the interval between the last cycle of chemotherapy and hepatitis flare were the major prognostic factors of an acute exacerbation of hepatitis-B induced by immunochemotherapy. Prophylactic antiviral and rescue antiviral therapy remain to be further characterized.

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.

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.

Advance directives: cancer patients’ preferences and family-based decision making

Background Advance directives are a sensitive issue among traditional Chinese people, who usually refrain from mentioning this topic until it is imperative. Medical decisions for cancer patients are made by their families, and these decisions might violate patients’ personal will. Objectives This study aimed to examine the acceptance of advance directives among Chinese cancer patients and their families and patient participation in this procedure and, finally, to analyze the moral risk involved. Results While 246 patients and their family members refused official discussion of an advance directive, the remaining 166 patients and their families accepted the concept of an advance directive and signed a document agreeing to give up invasive treatment when the anti-cancer treatment was terminated. Of these, only 24 patients participated in the decision making. For 101 patients, anti-cancer therapy was ended prematurely with as many as 37 patients not told about their potential loss of health interests. Materials and Methods Participants were 412 adult cancer patients from 9 leading hospitals across China. An advance directive was introduced to the main decision makers for each patient; if they wished to sign it, the advance directive would be systematically discussed. A questionnaire was given to the oncologists in charge of each patient to evaluate the interaction between families and patients, patients’ awareness of their disease, and participation in an advance directive. Conclusions Advance directives were not widely accepted among Chinese cancer patients unless anti-cancer therapy was terminated. Most cancer patients were excluded from the discussion of an advance directive.

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.

A comparison of dioctahedral smectite and iodine glycerin cream with topical mouth rinse in treatment of chemotherapy induced oral mucositis: A pilot study

PURPOSE OF THE RESEARCH To compare the efficacy of dioctahedral smectite and iodine glycerin (DSIG) cream with topical mouth rinse (composed of saline, gentamicin and Vitamin B12) in treatment of chemotherapy induced oral mucositis (OM). METHODS AND SAMPLE A total of 130 intensive chemotherapy or stem cells transplantation induced OM patients were recruited. Among these patients, 67 patients received topical mouth rinse and 63 patients received DSIG cream treatment. The OM would be treated on the OM appearance and sustained for 5 days. OM severity was measured daily using The American Oncology Nursing Society recommended Oral Assessment Guideline (OAG) score system. KEY RESULTS Compared with topical mouth rinse treatment, a significant lower OAG score was observed in DSIG cream treated patients. Specifically, the OAG scores were respectively 12.1 ± 1.1, 12.0 ± 1.2, 11.3 ± 1.3 and 10.4 ± 1.3 from day 2 to day 5 in topical mouth rinse treatment subgroup. Correspondingly, the OAG scores were respectively 10.2 ± 1.0, 9.3 ± 0.9, 8.5 ± 0.6 and 8.0 ± 0.2 for DSIG cream treatment subset (all P < 0.05). Importantly, compared with topical mouth rinse treatment, the DSIG cream significantly shortened OM repair time (4.68 ± 0.98 vs. 8.76 ± 1.80 days, P < 0.001). After 5 days treatment, 54 patients (85.7%) obtained complete regression with an OAG score ≤8, and 7 patients (11.1%) had partial regression with an OAG score of 9-10 in DSIG cream treatment subgroup. However, only 2 patients (3.0%) obtained completed regression and 32 patients (47.8%) had partial regression in topical mouth rinse treatment cohort. Moreover, no serious side-effect was observed in both cohorts. CONCLUSIONS Compared with topical mouth rinse, DSIG cream significantly lowered the OAG score and shortened OM duration.