Quantitative assessment of HCC wash-out on CT is a predictor of early complete response to TACE

OBJECTIVES: To investigate the predictive value of four-phase contrast-enhanced CT (CECT) for early complete response (CR) to drug-eluting-bead transarterial chemoembolization (DEB-TACE), with a particular focus on the quantitatively assessed wash-in and wash-out. METHODS: A retrospective analysis of preprocedural CECTs was performed for 129 HCC nodules consecutively subjected to DEB-TACE as first-line therapy. Lesion size, location, and margins were recorded. For the quantitative analysis, the following parameters were computed: contrast enhancement ratio (CER) and lesion-to-liver contrast ratio (LLC) as estimates of wash-in; absolute and relative wash-out (WO(abs) and WO(rel)) and delayed percentage attenuation ratio (DPAR) as estimates of wash-out. The early radiological response of each lesion was assessed by the mRECIST criteria and dichotomized in CR versus others (partial response, stable disease, and progressive disease). RESULTS: All quantitatively assessed wash-out variables had significantly higher rates for CR lesions (WO(abs) p = 0.01, WO(rel) p = 0.01, and DPAR p = 0.00002). However, only DPAR demonstrated an acceptable discriminating ability, quantified by AUC = 0.80 (95% CI0.73–0.88). In particular, nodules with DPAR ≥ 120 showed an odds ratio of 3.3(1.5–7.2) for CR (p = 0.0026). When accompanied by smooth lesion margins, DPAR ≥ 120 lesions showed a 78% CR rate at first follow-up imaging. No significative association with CR was found for quantitative wash-in estimates (CER and LLC). CONCLUSIONS: Based on preprocedural CECT, the quantitative assessment of HCC wash-out is useful in predicting early CR after DEB-TACE. Among the different formulas for wash-out quantification, DPAR has the best discriminating ability. When associated, DPAR ≥ 120 and smooth lesion margins are related to relatively high CR rates. KEY POINTS: • A high wash-out rate, quantitatively assessed during preprocedural four-phase contrast-enhanced CT (CECT), is a favorable predictor for early radiological complete response of HCC to drug-eluting-bead chemoembolization (DEB-TACE). • The arterial phase of CECT shows great dispersion of attenuation values among different lesions, even when a standardized protocol is used, limiting its usefulness for quantitative analyses. • Among the different formulas used to quantify the wash-out rate (absolute wash-out, relative wash-out, and delayed percentage attenuation ratio), the latter (DPAR), based only on the delayed phase, is the most predictive (AUC = 0.80), showing a significant association with complete response for values above 120

Consensus conference: il trattamento dell’epatocarcinoma

Riassunto: Il percorso di stadiazione e l’indicazione al trattamento dell’epatocarcinoma devono essere scelti poiché ritenuti i più omogenei ed efficaci rispetto alle condizioni generali del paziente. Numerose linee guida sono applicate dai maggiori centri di riferimento Europei, Asiatici e Nordamericani e, nel nostro paese, di recente sono state emanate le raccomandazioni dell’AISF (Associazione Italiana per lo Studio del Fegato) per la gestione integrata del paziente con Epatocarcinoma. La presente revisione riassume la posizione assunta dalla comunità di esperti Nazionali riunitasi in occasione del Congresso Gargano 2012 in merito alla stadiazione ed al trattamento dell’HCC nei diversi stadi, alla luce delle linee guida e delle raccomandazioni vigenti

CK2β Regulates Hematopoietic Stem Cell Biology and Erythropoiesis

The Ser-Thr kinase CK2 plays important roles in sustaining cell survival and resistance to stress and these functions are exploited by different types of blood tumors. Yet, the physiological involvement of CK2 in normal blood cell development is poorly known. Here, we discovered that the β regulatory subunit of CK2 is critical for normal hematopoiesis in the mouse. Fetal livers of conditional CK2β knockout embryos showed increased numbers of hematopoietic stem cells associated to a higher proliferation rate compared to control animals. Both hematopoietic stem and progenitor cells (HSPCs) displayed alterations in the expression of transcription factors involved in cell quiescence, self-renewal, and lineage commitment. HSPCs lacking CK2β were functionally impaired in supporting both in vitro and in vivo hematopoiesis as demonstrated by transplantation assays. Furthermore, KO mice developed anemia due to a reduced number of mature erythroid cells. This compartment was characterized by dysplasia, proliferative defects at early precursor stage, and apoptosis at late-stage erythroblasts. Erythroid cells exhibited a marked compromise of signaling cascades downstream of the cKit and erythropoietin receptor, with a defective activation of ERK/JNK, JAK/STAT5, and PI3K/AKT pathways and perturbations of several transcriptional programs as demonstrated by RNA-Seq analysis. Moreover, we unraveled an unforeseen molecular mechanism whereby CK2 sustains GATA1 stability and transcriptional proficiency. Thus, our work demonstrates new and crucial functions of CK2 in HSPC biology and in erythropoiesis