Intermediate hepatocellular carcinoma: current treatments and future perspectives

Current guidelines recommend transarterial chemoembolization (TACE) as the standard treatment of Barcelona-Clinic Liver Cancer (BCLC)-B patients. However, the long-term survival outcomes of patients managed with this technique do not appear fully satisfactory; in addition, intermediate-stage hepatocellular carcinoma (HCC) includes a heterogeneous population of patients with varying tumour burdens, liver function and disease aetiology. Therefore, not all patients with intermediate-stage HCC may derive similar benefit from TACE, and some patients may benefit from other treatment options, which are currently approved or being explored. These include different TACE modalities, such as selective TACE or drug-eluting beads TACE and radioembolization. The introduction of sorafenib in the therapeutic armamentarium for HCC has provided a new therapeutic option for the treatment of BCLC-B patients who are unsuitable to TACE or in whom TACE resulted in unacceptable toxicity. In addition, clinical trials aimed at investigating the potential role of this molecule in the treatment of patients with intermediate-stage HCC within combination therapeutic regimens are ongoing. This narrative review will present and discuss the most recent evidence on the locoregional or medical treatment with sorafenib in patients with intermediate-stage HCC.

Quaternary radiolarian counts from Site 181-1123

In the present work Quaternary radiolarian assemblages from the Southwest Pacific were investigated due to their importance for correlation and identification of climatic changes. The studied Ocean Drilling Program (ODP) Site 1123 (Leg 181) is situated on the northern flanks of the Chatham Rise, 1100 kilometres offshore eastern New Zealand and in a water depth o f 3290 metres. It is situated just north of the Subtropical Convergence (STC) in temperate climatic conditions, influenced by the cold deep Deep Western Boundary Current (DWBC) and by the subtropical East Cape Current (ECC) in shallow water depths. A continuous record of 79 sediment samples from this site with a temporal resolution of ~15,000 years provided a medium-resolution record of radiolarian assemblages through the Quaternary. This allowed investigations on how radiolarian assemblages are influenced by climatic variations at obliquity and eccentricity bandwidth, with periodic variations of 40,000, 100,000 and 400,000 years, respectively. Emphasis was given to changes in radiolarian assemblages through the Mid-Pleistocene climate transition (MPT) that marks a fundamental reorganisation in Earth's climate system by change from 40,000 to 100,000 year cycles. Glacial and interglacial variations in oceanography were investigated. Especially the influence of the DWBC was examined due to its input of deep and cold waters to the Pacific Ocean, which plays an important role in Earth's climate system. 167 radiolarian counting groups were examined concerning variations in radiolarian abundance, preservation, diversity, the relative abundance of orders, families, and selected species in order to detect influences of past climatic variations in the Southwest Pacific. No significant changes in radiolarian assemblages were found in coincidence with the onset of the MPT. Investigations led to the recognition of four characteristic phases within the last 1.2 million years. Within one of these phases (Phase Ill), about 160,000 years after the onset of the MPT, fundamental changes in radiolarian assemblages occurred. Investigations yielded highest diversity and highest numbers of nassellarians in abundant samples, whereas sparse samples were mostly poorly preserved and were dominated by spumellarians. Abundance of certain radiolarian families in interglacials or glacials indicated their usefulness as indicators for climatic conditions at Site 1123. Trends o f selected taxa within these families supported the significance of warm- or cool-water preference of these families. Use of 67 radiolarian species as climate indicators showed abundance of warm-water assemblages within interglacials, whereas abundance of cool-water species was increased within glacials. Depth distributional patterns of 52 radiolarian species indicated a strong influence of shallow waters, possibly the EEC, within interglacials and increased influence of deep and intermediate waters, possibly of southern-sourced character and the DWBC in glacial stages.