Prognostic sub-classification of intermediate-stage hepatocellular carcinoma: a multicenter cohort study with propensity score analysis

There is significant heterogeneity in the clini- copathological characteristics of intermediate hepatocellu- lar carcinoma (IHCC). This also translates to treatment as transarterial chemoembolization (TACE) is used as first- line therapy for patients with IHCC; however, in Asia liver resection (LR) is preferred. Prognostic tools are required to help guide clinicians in deciding treatment options. This study evaluates the prognostic impact of the Intermediate Stage Score (ISS) on overall survival (OS) in a large, multicenter cohort study of patients with IHCC treated with TACE or surgery LR. Consecutive patients from centers in Japan, Korea, Italy and the United Kingdom who under- went TACE or LR between 2001 and 2015 were enrolled. Propensity score (PS) adjustment was used to remove residual confounding and applied to LR (n=162) and TACE ( n = 449) to determine the prognostic significance of ISS. Among 611 patients, 75 % were men and 25 % women, with a mean age of 70 years. ISS is a valid prognostic tool in the BCLC-B population with a median OS ISS 1–51, 2–38.3, 3–24.3, 4–15.6, 5–16 months ( p \ 0.0001). ISS was analyzed within each treatment modality, and this was a valid prognostic score among those treated with TACE and LR ( p \ 0.001 vs. p = 0.008). In the PS-adjusted model, ISS retained its prognostic utility in TACE and LR groups (p\0.001 vs.p=0.007). ISS optimizes prognostic prediction in IHCC, reducing clinical heterogeneity, and is a useful tool for patients treated for TACE or LR

Combined sequential use of HAP and ART scores to predict survival outcome and treatment failure following chemoembolization in hepatocellular carcinoma: a multi-center comparative study.

BACKGROUND: The prognosis of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is variable, despite a myriad of prognostic markers. We compared and integrated the established prognostic models, HAP and ART scores, for their accuracy of overall survival (OS) prediction. RESULTS: In both training and validation sets, HAP and ART scores emerged as independent predictors of OS (p<0.01) with HAP achieving better prognostic accuracy (c-index: 0.68) over ART (0.57). We tested both scores in combination to evaluate their combined ability to predict OS. Subgroup analysis of BCLC-C patients revealed favorable HAP stage (p<0.001) and radiological response after initial TACE (p<0.001) as positive prognostic factors. PATIENTS AND METHODS: Prognostic scores were studied using multivariable Cox regression and c-index analysis in 83 subjects with Barcelona Clinic Liver Cancer (BCLC) A/B stage from UK and Italy (training set), and 660 from Korea and Japan (validation set), all treated with conventional TACE. Scores were further validated in an separate analysis of patients with BCLC-C stage disease (n=63) receiving initial TACE. CONCLUSION: ART and HAP scores are validated indices in patients with intermediate stage HCC undergoing TACE. The HAP score is best suited for screening patients prior to initial TACE, whilst sequential ART assessment improves early detection of chemoembolization failure. BCLC-C patients with low HAP stage may be a subgroup where TACE should be explored in clinical studies

Photodeposition as a facile route to tunable Pt photocatalysts for hydrogen production:on the role of methanol

Photodeposition of H2PtCl6 in the presence of methanol promotes the formation of highly dispersed, metallic Pt nanoparticles over titania, likely via capture of photogenerated holes by the alcohol to produce an excess of surface electrons for substrate-mediated transfer to Pt complexes, resulting in a high density of surface nucleation sites for Pt reduction. Photocatalytic hydrogen production from water is proportional to the surface density of Pt metal co-catalyst, and hence photodeposition in the presence of high methanol concentrations affords a facile route to optimising photocatalyst design and highlights the importance of tuning co-catalyst properties in photocatalysis

The ALBI grade provides objective hepatic reserve phenotyping across each BCLC stage of hepatocellular carcinoma

BACKGROUND & AIMS: Overall survival (OS) is a composite clinical endpoint in hepatocellular carcinoma (HCC) due to the mutual influence of cirrhosis and active malignancy in dictating patient's mortality. The ALBI grade is a recently described index of liver dysfunction in hepatocellular carcinoma, based solely on albumin and bilirubin levels. Whilst accurate, this score lacks cross-validation, especially in intermediate stage HCC, where OS is highly heterogeneous. METHODS: We evaluated the prognostic accuracy of the ALBI grade in estimating OS in a large, multi-centre study of 2426 patients, including a large proportion of intermediate stage patients treated with chemoembolization (n=1461) accrued from Europe, the United States and Asia. RESULTS: Analysis of survival by primary treatment modality confirmed the ALBI grade as a significant predictor of patient OS after surgical resection (p<0.001), transarterial chemoembolization (p<0.001) and sorafenib (p<0.001). Stratification by Barcelona Clinic Liver Cancer stage confirmed the independent prognostic value of the ALBI across the diverse stages of the disease, geographical regions of origin and time of recruitment to the study (p<0.001). CONCLUSIONS: In this large, multi-centre retrospective study, the ALBI grade satisfied the criteria for accuracy and reproducibility following statistical validation in Eastern and Western HCC patients, including those treated with chemoembolization. Consideration should be given to the ALBI grade as a stratifying biomarker of liver reserve in routine clinical practice. LAY SUMMARY: Liver failure is a key determinant influencing the natural history of hepatocellular carcinoma (HCC). In this large multi-centre study we externally validate a novel biomarker of liver functional reserve, the ALBI grade, across all the stages of HCC

Identification of a novel angiogenic peptide from periostin

Angiogenic peptides have therapeutic potential for the treatment of chronic ischemic diseases. Periostin, an extracellular matrix protein expressed in injured tissues, promotes angiogenesis and tissue repair. We previously reported that in vivo administration of both recombinant full-length protein and the first FAS I domain of periostin alleviated peripheral artery occlusive disease by stimulating the migration of humane endothelial colony forming cells (ECFCs) and subsequent angiogenesis. In the present study, we ascertained the peptide sequence responsible for the periostin-induced angiogenesis. By serial deletion mapping of the first FAS I domain, we identified a peptide sequence (amino acids 142-151) of periostin for stimulation of chemotactic migration, adhesion, proliferation and endothelial tube formation of human ECFCs in vitro. Chemotactic migration of ECFCs induced by the periostin peptide was blocked by pre-incubation with an anti-??5 integrin neutralizing antibody. Treatment of ECFCs with the periostin peptide led to phosphorylation of both AKT and ERK, and pretreatment of ECFCs with the MEK-ERK pathway inhibitor U0126 or the PI3K-AKT pathway inhibitors, LY294002 or Wortmannin, blocked the periostin peptide-stimulated migration of ECFCs. These results suggest that the synthetic periostin peptide can be applied for stimulating angiogenic and therapeutic potentials of ECFCs