ObjectiveBleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is a frequent adverse event after ESD. We aimed to develop and externally validate a clinically useful prediction model (BEST-J score: Bleeding after ESD Trend from Japan) for bleeding after ESD for EGC.DesignThis retrospective study enrolled patients who underwent ESD for EGC. Patients in the derivation cohort (n=8291) were recruited from 25 institutions, and patients in the external validation cohort (n=2029) were recruited from eight institutions in other areas. In the derivation cohort, weighted points were assigned to predictors of bleeding determined in the multivariate logistic regression analysis and a prediction model was established. External validation of the model was conducted to analyse discrimination and calibration.ResultsA prediction model comprised 10 variables (warfarin, direct oral anticoagulant, chronic kidney disease with haemodialysis, P2Y12 receptor antagonist, aspirin, cilostazol, tumour size >30 mm, lower-third in tumour location, presence of multiple tumours and interruption of each kind of antithrombotic agents). The rates of bleeding after ESD at low-risk (0 to 1 points), intermediate-risk (2 points), high-risk (3 to 4 points) and very high-risk (≥5 points) were 2.8%, 6.1%, 11.4% and 29.7%, respectively. In the external validation cohort, the model showed moderately good discrimination, with a c-statistic of 0.70 (95% CI, 0.64 to 0.76), and good calibration (calibration-in-the-large, 0.05; calibration slope, 1.01).ConclusionsIn this nationwide multicentre study, we derived and externally validated a prediction model for bleeding after ESD. This model may be a good clinical decision-making support tool for ESD in patients with EGC.

JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org. . International Association for Plant Taxonomy (IAPT) is collaborating with JSTOR to digitize, preserve and extend access to Taxon. This first bibliography of Irish lichenology, handsomely executed in a privately printed edition, contains the enumeration in alphabetical order of 422 literature references followed by an analytical index referring to 12 special subjects (ecology, exsiccatae, floras, etc.) including vice-comital distribution (broken down in 40 sub-entries). The 1727 entry which is the chronological starting point of the bibliography is C. Threlkeld's Synopsis stirpium Hibernicarum alphabetice dispositarum; another interesting early item is J. K'Eogh, Botanologia universalis Hibernica, Corke 1737. The author represented by the highest number of entries (20) is W. Nylander, the middle nineteenth century author who stood at the beginning of the expansion of European lichenology. PLANT LIPID BIOCHEMISTRY C. HITCHCOCK and B. W. NICHOLS, Plant lipid Biochemistry. The biochemistry of fatty acids and acyl lipids with particular reference to higher plants and algae. I97I. Academic Press, London and New York, [24-28 Oval Road, London NWI 7DU], 387 pp., 141/2 X 23 cm., buckram, price ? 6.5o.

Cancer stem cells (CSCs) are a pivotal target for eradicating hepatocellular carcinoma (HCC).While considered monoclonal in origin, cancer is a heterogeneous disease in terms of morphology, biological behavior, chemo/radiation resistance, and prognosis. Traditionally, this heterogeneity has been attributed to the clonal evolution of tumor cells with the stochastic accumulation of genetic/epigenetic/genomic changes 1 . However, recent studies have suggested that cancer cell heterogeneity can also be explained by the hierarchical organization of the tumor mediated by a subset of cells with stem/progenitor cell features called cancer stem cells (CSCs) 2 . As normal stem cells can repopulate the cell lineages of the corresponding organ, CSCs can divide symmetrically (self-renewal capacity) and asymmetrically (differentiation capacity) to repopulate the tumor 3 . CSCs generally express normal stem/progenitor cell markers, are highly tumorigenic/metastatic, and show chemo/ radiation resistance. Therefore, the eradication of CSCs is considered pivotal in the treatment of cancer.

BackgroundSorafenib is a multiple receptor tyrosine kinase inhibitor known to prolong overall survival in patients with advanced hepatocellular carcinoma (HCC). Predicting this drug’s survival benefits is challenging because clinical responses are rarely measurable during treatment. In this study, we hypothesized that serum cytokines levels could predict the survival of advanced HCC patients, as sorafenib targets signaling pathways activated in the tumor stromal microenvironment and potentially affects serum cytokine profiles.MethodsOf 143 patients with advanced-stage HCC, 104 who were recruited between 2003 and 2007 received hepatic arterial infusion chemotherapy (HAIC) that mainly targets tumor epithelial cells at S-phase (cohort 1); additionally, 39 recruited between 2010 and 2012 received sorafenib, which primarily targets the stromal vascular endothelial cells. Serum samples were collected and aliquoted prior to the treatment. Serum EGF, bFGF, HGF, IFN-γ, IL-10, IL-12, IL-2, IL-4, IL-5, IL-6, IL-8, IP-10, MIG, PDGF-BB, SCF, SDF1, TGF-β, TGF-α, TNF-α, and VEGF-A were measured via enzyme-linked immunosorbent assays. The Modified Response Evaluation Criteria in Solid Tumors were used to assess tumor responses.ResultsThe median survival time of HCC patients in cohorts 1 (HAIC-treated) and 2 (sorafenib-treated) were 12.0 and 12.4 months, respectively. Kaplan-Meier analysis revealed no significant survival differences between the 2 groups. Patients who survived more than 2 years after sorafenib treatment exhibited higher serum levels of IL-10, IL-12, TNF-a, IL-8, SDF-1, EGF, PDGF-BB, SCF, and TGF-α. Furthermore, cohort 2 patients with higher serum IL-5 (>12 pg/mL), IL-8 (>10 pg/mL), PDGF-BB (>300 pg/mL), and VEGF-A (>50 pg/mL) levels achieved longer survival; cohort 1 patients did not. Hierarchical cluster analysis of 6 cytokines robustly enriched for comparison analysis between cohorts 1 and 2 (IL-5, IL-8, TGF-α, PDGF-BB, CXCL9, and VEGF-A) revealed that elevation of these cytokines correlated with better survival when treated with sorafenib but not with HAIC.ConclusionsPatients who exhibited survival benefits owing to sorafenib treatment tended to present higher serum cytokines levels, potentially reflecting the activation of stromal signaling in the tumor microenvironment. Our study thus introduces novel biomarkers that may identify advanced HCC patients who may experience survival benefits with sorafenib treatment.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3889-x) contains supplementary material, which is available to authorized users.

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