Jiaping Li

Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Predictors of Survival and Metastasis for Recurrent Hepatocellular Carcinoma after Transarterial Chemoembolization

Purpose To evaluate whether neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) predict survival and metastasis in patients after transarterial chemoembolization (TACE) for recurrent hepatocellular carcinoma (RHCC). Materials and Methods Clinical and laboratory data from 132 RHCC patients treated with TACE from January 2003 to December 2012 were retrospectively reviewed. Prognostic factors were assessed by multivariate analysis, and the predictive values of NLR and PLR for overall survival (OS) and extrahepatic metastases were compared. Results Pretreatment mean NLR and PLR were 3.1 and 137, respectively. The 0.5-, 1-, and 2-year OS rates were 93.7%, 67.1%, and 10.1% in the low NLR group and 81.1%, 18.9%, and 3.8% in the high NLR group, respectively (P = 0.017). The corresponding OS rates in the low and high PLR groups were 92.5%, 58.1%, and 9.7% and 84.6%, 23.1%, and 2.6%, respectively (P = 0.030). The discriminatory performance predicting 1-year survival probability was significantly poorer for NLR (area under the curve [AUC] = 0.685, 95% confidence interval [CI] 0.598–0.763) than for PLR (AUC = 0.792, 95% CI 0.712–0.857; P = 0.0295), but was good for both ratios for predicting post-TACE extrahepatic metastasis. Multivariate analysis indicated that high PLR (hazard ratio [HR] = 0.373, 95% CI = 0.216-0.644, P < 0.001, vascular invasion (HR = 0.507, 95% CI = 0.310–0.832, P = 0.007), and multiple tumors (HR= 0.553, 95% CI = 0.333–0.919, P = 0.022) were independent prognostic factors for OS. Conclusions High NLR and PLR were both associated with poor prognosis and metastasis in RHCC patients treated with TACE, but high PLR was a better predictor of 1-year OS. High PLR, vascular invasion, and multiple tumors were independent, unfavorable prognostic factors.

OPN and αvβ3 expression are predictors of disease severity and worse prognosis in hepatocellular carcinoma.

Expressions of OPN and αvβ3 are associated with a poor prognosis in many malignancies. However, their relationship in hepatocellular carcinoma remains unclear. We systematically collected hepatocellular carcinoma tissue samples from 305 patients over 3 years, and analyzed the status of OPN and αvβ3 in hepatocellular carcinoma and correlate expression with patient disease status and survival outcome. Our study results indicated that OPN and αvβ3 are expressed at significantly higher rates in hepatocellular carcinoma compared with adjacent non-tumorous tissue (69.5% vs 18.4%, p<0.01 and 77.4% vs 21.6%, p<0.01, respectively). Both OPN and αvβ3 expression levels are associated with poor prognostic factors, including tumor size, capsular invasion, tumor thrombus of the portal vein, metastasis of the lymph node and clinical staging. Patients expressing OPN and αvβ3 had significantly shorter survival compared with patients negative for protein expression (p<0.01). Multivariate analysis also showed that both OPN and αvβ3 expression are independent prognostic factors for poorer survival in hepatocellular carcinoma. By this study, we conclude that OPN and αvβ3 are negative prognostic predictors in patients with hepatocellular carcinoma. The expressions of both OPN and αvβ3 are associated with worse survival outcome.

Decreased WWOX expression promotes angiogenesis in osteosarcoma

WWOX (WW domain-containing oxidoreductase) is known to be an important tumor suppressor in cancer. In this study, we used samples from 201 osteosarcoma patients to investigate the effects of WWOX on angiogenesis and invasion. WWOX levels were negatively correlated with RUNX2 and VEGF levels, but were not correlated with OPN levels. Among the clinicopathological characteristics examined, WWOX was associated only with response to neoadjuvant chemotherapy, and its expression in osteosarcoma tissues was a predictor of disease-free survival. WWOX promoted apoptosis and inhibited invasion and expression of bcl-2, OPN, RUNX2, and VEGF in osteosarcoma cells in vitro. In MG-63 cells, bcl-2 increased VEGF expression, while RUNX2 increased VEGF and OPN expression. Administration of DNA methylation inhibitors increased WWOX expression in MG-63 cells and methylation of WWOX gene promoter CpG island in the osteosarcoma of patients was associated with suppression of WWOX expression. Overexpression of WWOX in osteosarcoma cells inhibited tube formation in co-cultured HUVEC cells, and high WWOX expression was associated with decreased microvessel density (MVD). These results suggest that reduced WWOX expression in osteosarcoma inhibits apoptosis, promotes invasion and increases MVD.WWOX (WW domain-containing oxidoreductase) is known to be an important tumor suppressor in cancer. In this study, we used samples from 201 osteosarcoma patients to investigate the effects of WWOX on angiogenesis and invasion. WWOX levels were negatively correlated with RUNX2 and VEGF levels, but were not correlated with OPN levels. Among the clinicopathological characteristics examined, WWOX was associated only with response to neoadjuvant chemotherapy, and its expression in osteosarcoma tissues was a predictor of disease-free survival. WWOX promoted apoptosis and inhibited invasion and expression of bcl-2, OPN, RUNX2, and VEGF in osteosarcoma cells in vitro. In MG-63 cells, bcl-2 increased VEGF expression, while RUNX2 increased VEGF and OPN expression. Administration of DNA methylation inhibitors increased WWOX expression in MG-63 cells and methylation of WWOX gene promoter CpG island in the osteosarcoma of patients was associated with suppression of WWOX expression. Overexpression of WWOX in osteosarcoma cells inhibited tube formation in co-cultured HUVEC cells, and high WWOX expression was associated with decreased microvessel density (MVD). These results suggest that reduced WWOX expression in osteosarcoma inhibits apoptosis, promotes invasion and increases MVD.

Vascular Endothelial Growth Factor Accelerates Establishment of a Model of Hepatic Metastasis in Walker-256 Tumor-Bearing Rats

Background:Animal models of secondary liver cancer are limited by the time required for the development of hepatic metastases. The authors administered vascular endothelial growth factor (VEGF) to stimulate tumor growth in a model of hepatic metastasis. Methods:A 0.5 to 1.0 mm3 Walker-256 carcinosarcoma tumor tissue was implanted into the livers of 45 Sprague-Dawley rats, randomly assigned to 3 equal groups to receive daily injections (0.1 mL), for 1 week, of either normal saline (control group), 20 mg/L VEGF (VEGF-20 group) or 40 mg/L VEGF (VEGF-40 group). Tumor growth was assessed by magnetic resonance imaging after 3, 7 and 14 days, and overall survival was recorded. Results:Three days after implantation, no tumors were detected by magnetic resonance imaging in the control group. In contrast, tumors were observed in 50% of rats in the VEGF-20 group and 66.7% of rats in the VEGF-40 group (P < 0.05). By day 7, tumors were detected in 92.8% of rats in the VEGF-20 group, 86.7% of rats in the VEGF-40 group, but only 21.4% of rats in the control group (P < 0.05). Tumor size increased progressively, reaching 1.81 ± 0.08, 2.51 ± 0.12 and 2.67 ± 0.10 cm3 in the control, VEGF-20 and VEGF-40 groups, respectively, 14 days after implantation of tumor tissue. Median survival times were significantly shorter in the VEGF-40 group (15 days) than in the control and VEGF-20 groups (27 and 25, respectively) (both P < 0.05). Conclusions:Daily VEGF injection (20 mg/L, 1 week) accelerates tumorigenesis without compromising survival, potentially extending the period in which experiments can be conducted in this model.

Comparison of intraluminal radiofrequency ablation and stents vs. stents alone in the management of malignant biliary obstruction.

Abstract Purpose: To retrospectively evaluate the added benefit of adding intraluminal radiofrequency ablation (RFA) to biliary metal stent placement for patients with malignant biliary obstruction (MBO). Methods: From November 2013 to December 2015, 89 patients with MBO who had undergone percutaneous intraluminal RFA and stent placement (RFA-stent group, n = 50) or stent placement only (stent group, n = 39) were included. Outcomes were compared according to the type of tumour: cholangiocarcinoma or non-cholangiocarcinoma. Results: Primary and secondary stent patency (PSP, SSP) were significantly higher for the RFA-stent group than the stent group (PSP: 7.0 months vs. 5.0 months, p = 0.006; SSP: 10.0 months vs. 5.6 months, p < 0.001), with overall survival being comparable (5.0 months vs. 4.7 months, p = 0.068). In subgroup analysis, RFA-stent showed significant PSP benefits compared to stent alone in patients with cholangiocarcinoma (7.4 months vs. 4.3 months; p = 0.009), but with comparable outcomes in patients with non-cholangiocarcinoma (6.3 months vs. 5.2 months; p = 0.266). The SSP was improved in both subgroups (cholangiocarcinoma, 12.6 months vs. 5.0 months, p < 0.001; non-cholangiocarcinoma, 10.3 months vs. 5.5 months, p = 0.013). Technical success and clinical success were not significantly different between the two groups. The rate of complication was higher for the RFA-stent group, but tolerable when compared to the stent group. Conclusions: Although survival was comparable between the groups, RFA-stent confers therapeutic benefits to patients with MBO in terms of stent patency compared to stent placement alone, especially in those with cholangiocarcinoma.

Percutaneous computed tomography-guided cryoablation for recurrent retroperitoneal soft tissue sarcoma: a study of safety and efficacy

Aims To evaluate the use of computed tomography image-guided percutaneous cryoablation for recurrent retroperitoneal soft tissue sarcomas (RPSs). Results Adverse events were limited to grades 1 and 2, included fever (n = 19), local pain (n = 11), emesis (n = 10), frostbite (n = 6), and nerve injury (n = 1). Fever was more frequent in the large tumor group (15.8%) than in small tumor group (1.9%) (P = 0.008). Median PFS and OS were 37.0 ± 7.7 months (range, 4–39 months) and 43.0 ± 5.9 months (range, 6–54 months), respectively. PFS and OS were significantly longer in the small tumor group than in the large tumor group (P = 0.011 and P = 0.015, respectively), but the response rate (82.7% vs. 72.8%, P = 0.240) did not differ significantly. On univariate analysis, tumor size, tumor invasion grade, and distant metastasis were significant prognostic factors for PFS and OS. On multivariate analysis, a tumor size ≥10 cm was an independent negative prognostic factor for PFS and OS after cryoablation (HR: 3.98, 95% CI: 1.27–12.50, P = 0.018 and HR: 4.33, 95% CI: 1.41–13.26, P = 0.010, respectively). Materials and Methods Data from 72 patients with recurrent RPSs who underwent percutaneous cryoablation were reviewed retrospectively. The prognostic factors for progression-free survival (PFS), overall survival (OS), and efficacy based on mRECIST criteria were analysis. Adverse events were compared according to tumor size (<10 and ≥10 cm). Conclusion Minimally invasive percutaneous cryoablation was safe and efficacious for recurrent RPSs.

Initial Experience: Alleviation of Pain with Percutaneous CT–Guided Cryoablation for Recurrent Retroperitoneal Soft-Tissue Sarcoma

PURPOSE To evaluate the pain-alleviating effect of computed tomography (CT)-guided percutaneous cryoablation for recurrent retroperitoneal soft-tissue sarcomas (RPSs). MATERIALS AND METHODS Data from 19 men and 20 women (median age, 50.3 y) with recurrent malignant RPS who underwent percutaneous cryoablation were reviewed retrospectively. A total of 50 tumors were treated by cryoablation, including a single tumor in 29 patients, 2 tumors in 9, and 3 tumors in 1. Adverse events and analgesic outcomes were compared as a function of tumor size (< 10 cm and ≥ 10 cm). Efficacy was assessed based on modified Response Evaluation Criteria In Solid Tumors and progression-free survival (PFS). RESULTS Grade 1/2 adverse events included fever (n = 17), emesis (n = 7), frostbite (n = 5), and local pain (n = 4). The median follow-up period and PFS were 18.5 months (range, 12-42 mo) and 13.4 months ± 6.2, respectively. At the end of follow-up, 13 patients had died and 26 were living. The mean severe local pain scores on pretreatment day 1 and posttreatment days 1, 5, 10, 15, 20, and 25 were 7.49, 7.40, 6.51, 5.81, 5.35, 5.04, and 5.44, respectively, and significant differences versus pretreatment (P < .001) were reported for posttreatment days 5-25. Immediate relief occurred more frequently in the small-tumor group (4 of 7; 57.1%; P = .018), whereas delayed relief occurred more frequently in the large-tumor group (17 of 22; 77.3%; P = .030). CONCLUSIONS Minimally invasive percutaneous cryoablation improves local pain and is a feasible treatment for recurrent RPSs.

Genetic epidemiology of porcine epidemic diarrhoea virus circulating in China in 2012-2017 based on spike gene

Summary A porcine epidemic diarrhoea outbreak first occurred in southern China at the end of 2010 and afterwards the disease spread throughout the country. Spike gene is divergent and important for understanding the genetic relations of porcine epidemic diarrhoea virus field strains, the epidemiological status of the virus and vaccine development. In this study, S1 regions of spike gene of 1,235 selected strains collected from 2012 to 2017 in China were clustered along with 25 references of spike sequences mainly from China. The phylogenetic analysis demonstrates that these sequences of S1 regions were genetically more diverse with time. In all strains, G1a, G1b, G2a and G2b clusters accounted for 1.9%, 9.6%, 32.2% and 56.3%, respectively, namely G2a and G2b were the two most prevalent clusters in China. Furthermore, we made a more detailed classification for G2 group based on phylogenetic tree, in which G2a was divided into two subgroups, and G2b was separated into four subgroups.

Raltitrexed based Transcatheter Arterial Chemoembolization (TACE) forUnresectable Hepatocellular Carcinoma: A Single-center Randomized ControlledStudy

Background: We aimed to evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE), a combination of raltitrexed, oxaliplatin, and epirubicin, for unresectable hepatocellular carcinoma (HCC). Methods: We enrolled 163 patients in this single-center, randomized, controlled trial comparing TACE with epirubicin and oxaliplatin (control group; 83 patients) to TACE with raltitrexed, epirubicin, and oxaliplatin (raltitrexed group; 80 patients).The primary endpoint was overall survival(OS);secondary endpoints included progression-free survival(PFS),tumor response and adverse events. Results: The median progression-free survival (mPFS) and overall survival (mOS) were similar (mPFS: 4.3 vs. 4.6 months, P = 0.201; mOS: 9.6 vs. 9.8 months, P = 0.698, respectively). The disease control rates for the control and raltitrexed groups were 57.8% and 63.8%, respectively, and did not reach statistical significance (P = 0.439). Adverse events were also similar in both the groups (P > 0.05). Conclusion: Although the study did not meet its primary endpoint, the treatment induced a high response rate and promising PFS and OS rates in patients, suggests that the use of raltitrexed as an alternative for TACE may confer some benefit to patients with unresectable HCC.

Sorafenib Continuation after First Disease Progression Could Reduce Disease Flares and Provide Survival Benefits in Patients with Hepatocellular Carcinoma: a Pilot Retrospective Study

BACKGROUND Sorafenib is a promising drug for advanced hepatocellular carcinoma (HCC); however, treatment may be discontinued for multiple reasons, such as progressive disease, adverse events, or the cost of treatment. The consequences of sorafenib discontinuation and continuation are uncertain. MATERIALS AND METHODS We retrospectively analyzed 88 HCC patients treated with sorafenib from July 2007 to January 2013. Overall survival (OS), post-disease progression overall survival (pOS), and time to disease progression (TTP) were compared for survival analysis. Cox proportional hazard regression was performed to assess the effect of important factors on OS in the overall patient population and on pOS in patients who continued sorafenib treatment. RESULTS Sorafenib was discontinued and continued in 24 and 64 patients, respectively. The median OS (355 vs 517 days respectively; p=0.015) and median post-PD OS (260 vs 317 days, respectively; p=0.020) were statistically different between the discontinuation and continuation groups. Neither the median time to first PD nor the time to second PD were significantly different between the 2 groups. In the discontinuation group, 3 of the 24 patients (12.5%) suffered disease outbreaks. In Cox proportional hazard regression analysis after correction for confounding factors, BCLC stage (p=0.002) and PD site (p=0.024) were significantly correlated with pOS in patients who continued sorafenib treatment. CONCLUSIONS Sorafenib discontinuation may cause HCC flares or outbreaks. It is advisable to continue sorafenib treatment after first PD, particularly in patients with Barcelona Clinic Liver Cancer stage B disease or only intrahepatic PD.