Elevated expression of c-kit in small venous malformations of blue rubber bleb nevus syndrome

The blue rubber bleb nevus syndrome (BRBNS, syn. bean syndrome) is a rare disease characterized by multiple cutaneous and gastrointestinal venous malformations associated with severe bleeding. However, the underlying molecular mechanisms are unknown and no targeted therapeutic approach exists to date. Here we report the case of a 19-year-old male patient with severe BRBNS in whom we analyzed the expression of tyrosine kinases frequently involved in tumor development by immunohistochemistry (vascular endothelial growth factor receptor-2, stem cell growth factor receptor (c-kit), platelet-derived growth factor receptor-β, and stem cell tyrosine kinase-1). A prominent expression of c-kit was detectable in smaller blood vessels, which also showed a moderate expression of the proliferation marker MIB1. Surprisingly, other growth factor receptors stained negatively. We therefore conclude that pharmacological inhibition of the c-kit signaling pathway in cavernous hemangiomas by selective kinase inhibitors may offer options in the treatment of BRBNS patients

A phase I trial of S-1 with concurrent radiotherapy for locally advanced pancreatic cancer

This study investigated the maximum tolerated dose of S-1 based on the frequency of its dose-limiting toxicities (DLT) with concurrent radiotherapy in patients with locally advanced pancreatic cancer. S-1 was administered orally at escalating doses from 50 to 80 mg m−2 b.i.d. on the day of irradiation during radiotherapy. Radiation therapy was delivered through four fields as a total dose of 50.4 Gy in 28 fractions over 5.5 weeks, and no prophylactic nodal irradiation was given. Twenty-one patients (50 three; 60 five; 70 six; 80 mg m−2 seven patients) were enrolled in this trial. At a dose of 70 mg m−2 S-1, two of six patients demonstrated DLT involving grade 3 nausea and vomiting and grade 3 haemorrhagic gastritis, whereas no patients at doses other than 70 mg m−2 demonstrated any sign of DLT. Among the 21 enrolled patients, four (19.0%) showed a partial response. The median progression-free survival time and median survival time for the patients overall were 8.9 and 11.0 months, respectively. The recommended dose of S-1 therapy with concurrent radiotherapy is 80 mg m−2 day−1. A multi-institutional phase II trial of this regimen in patients with locally advanced pancreatic cancer is now underway

Historical shoreline trend analysis and drivers of coastal change along the Ravenna coast, NE Adriatic

One of the most important aspects of coastal zone management is the analysis of shoreline dynamics. Over the last years, beaches of the Ravenna coast (NE Italy) experienced large modifications, in some places narrowing or even being completely lost, thus threatening tourism, coastal assets and nature. Coastal erosion has direct consequences for Ravenna tourist-based economy, which largely depends on the attraction provided by sandy beaches. In this study, long-term (> 50 years) coastal analysis was used to identify the sectors along the coast where the shoreline position has changed, either advancing or retreating. Shoreline changes were measured on GIS environment by means of Digital Shoreline Analysis System (DSAS) extension. Net Shoreline Movement (NSM) and Linear Regression Rate (LRR) strategies were employed to examine shoreline variability and reveal erosional/accretional trends. The results show that significant shoreline changes affected the entire coastal region, with most of the study area under retreat, mainly in the most valuable tourist assets of the littoral. The effects were found to be worsened by impacts of land subsidence, presence of harbor infrastructure and deficit in sediment budget. A simple shoreline classification was performed over the DSAS results and cross-checked with local knowledge of the area. The measurement of erosion or accretion rates in each studied segment is found to be useful for land use planning and coastal management plans, especially regarding the prediction of future shoreline positions. Especially important is the potential of the classification to identify areas of significant position change, with current and future implications for the design of sustainable shoreline management and mitigation measures