Yan-Fang Xing

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.

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)).

Palliative care in urban areas of China

1 in The Lancet Oncology, which set a good example for local comprehensive palliative care. The Chinese medical system in urban areas is similar to the system in Japan to some extent, with free access to all medical institutions, 60-80% of patients covered by national insurance, and an under- developed system exists for primary care and organisation of palliative care resources. 2,3

Neutrophil count is associated with myeloid derived suppressor cell level and presents prognostic value for hepatocellular carcinoma patients

Myeloid Derived Suppressor Cell (MDSC) has been raised to be a novel target for multiple cancers. However, target agents on MDSC have not display promising efficacy. One of the critical reasons shall be less optimal patient selection. In the present study, we aimed to identify clinical parameters relevant to MDSC level in hepatocellular carcinoma (HCC) patients for future MDSC targeted therapy. In the present study, a series of 55 HCC patients (testing group) and 20 healthy donors were analyzed investigating frequencies of MDSC in peripheral blood mononuclear cells (PBMC). As a result, we found that MDSC level was increased in HCC patients compared to healthy donors (10.33% vs 1.54%, p < 0.0001). The monocytes (r2 = 0.2875, p < 0.0001), neutrophils (r2 = 0.3630, p < 0.0001) and platelet counts (r2 = 0.0828, p = 0.0331) in circulation was positively associated with MDSC level. Then, the prognostic value of the above predictors was determined in a retrospective database of 255 HCC patients (validation group). The baseline characteristics of testing and validation group were similar. Multivariate analysis by Cox regression revealed that neutrophil count was an independent predictor for overall survival (OS) (p = 0.000, HR 1.065, 95% CI 1.028–1.103), with the rest parameters failed to reach a significant result. In summary, the present study firstly identified blood neutrophil counts was a predictor of MDSC level in PBMC for HCC patients. And, patients with higher neutrophil count level might be the optimal patient subgroup for MDSC targeted therapy.

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 multidisciplinary team approach for nutritional interventions conducted by specialist nurses in patients with advanced colorectal cancer undergoing chemotherapy: A clinical trial

Background & aims: Nutritional interventions for malnutrition in cancer patients can be helpful. However, concise intervention recommendations remain controversial. Thus, the aim of this study was to report on a nutrition intervention conducted by a multidisciplinary team of specialist nurses and to explore the effect of nutritional intervention on cancer patients. Methods: This prospective clinical trial study enrolled 110 colorectal cancer patients undergoing chemotherapy. The patients were evaluated upon admission using the 2002 Nutritional Risk Screening system (NRS-2002). The patients were randomly divided into intervention and control groups including 55 patients each. Patients in the control group were administered a normal diet, while those in the intervention group received individual recipes developed by a team of professional nurses, clinical doctors, dietitian, family caregivers, and the patients themselves. Patient weight and serum albumin and prealbumin levels were compared between the 2 groups at different time points. Results: There was a significant difference in patient weight and serum albumin and prealbumin levels before and after nutrition intervention in the intervention group (P < .05). In the control group, weight did not change during ordinary diet guidance. Serum albumin level was slightly improved after 12 cycles of chemotherapy, similar to the prealbumin results. There were statistically significant differences in serum albumin and prealbumin levels between the intervention and control groups after nutrition intervention (P < .05). However, there was no statistically significant difference in weight between the groups after nutrition intervention (P > .05). Conclusion: A multidisciplinary team approach for nutrition intervention conducted by specialist nurses improved prealbumin levels in colorectal cancer patients undergoing chemotherapy, with no weight change.

Selection of glucocorticoid-sensitive patients in interstitial lung disease secondary to connective tissue diseases population by radiomics

Purpose The effect of glucocorticoid(s) on connective tissue disease (CTD)-related interstitial lung disease (ILD) is controversial. This multicenter study aimed to identify glucocorticoid-sensitive patients using a radiomics approach. Methods A total of 416 CTD-ILD patients who began glucocorticoid treatment at the discretion of the attending physician, with or without cyclophosphamide, were included in this study. High doses were defined as pulsed intravenous methylprednisolone, an initial dose of 1 mg/kg/day of prednisolone or 0.8 mg/kg/day of methylprednisolone. Low doses were defined as those less than high doses. Radiomics features were manually extracted from primary lung lesions delineated on computed tomography images, and selected by variance, univariate feature selection, and least absolute shrinkage and selection operator regression model. The prediction models were developed using data from 309 patients from two centers and externally validated in 107 patients from four other hospitals. Results Treatment response in the training and validation groups was 38.5% and 36.4%, respectively. Eleven radiomics features were selected from 1,029 features with predictive value. Random forest models built for radiomics features to predict treatment response yielded a sensitivity of 0.897. The calibration curve of a nomogram demonstrated good agreement between prediction and observation. Decision curve analysis indicated that glucocorticoid was beneficial if the predicted response rate was 50%–60% for an individual. High doses of glucocorticoids and cyclophosphamide yielded superior efficacy. Conclusion Radiomics-based predictive models reliably identified glucocorticoid-sensitive CTD-ILD patients. Short-term, high-dose glucocorticoid with cyclophosphamide yielded promising results as a potential therapy.