9%).[19, 20] Hence, as a regimen using more powerful chemotherapy is developed in one of the multidisciplinary treatments for CRLM, hepatic BIBW2992 cost toxicity is likely to be exacerbated,

such as sinusoidal obstructive syndrome (SOS), steatosis (non-alcoholic fatty liver disease), steatohepatitis (non-alcoholic steatohepatitis) and biliary sclerosis (Table 1). Especially, L-OHP-based chemotherapy with molecular targeting agents, such as bevacizumab, cetuximab or panitumumab, plays a central role of initial chemotherapy for unresectable colorectal cancer in Japanese Society for Cancer of the Colon and Rectum guidelines[21] and it was well known that L-OHP-based chemotherapy appears to be primarily associated with SOS. In this review, we attempt to summarize the current experience with hepatic injury induced by L-OHP-based chemotherapy focusing on SOS. VENO-OCCLUSIVE DISEASE INDUCED by a lethal poisoning of pyrrolizine alkaloids in humans was first reported in 1920, and the abnormalities of the central vein and the centrilobular localization of the damage were recognized.[22] In 1999, De Leve et al. established the rat hepatic veno-occlusive disease model induced by monocrotaline.[23]

Epigenetics inhibitor In this article, congestion and dilatation of the hepatic sinusoids, discontinuity in the sinusoidal membrane and collagen deposits in the perisinusoidal spaces were proven as histopathological features. This pathophysiology, which has an impressive macroscopic character “blue liver”, has been well known in SOS (Fig. 1). Recently, the induction of L-OHP-based chemotherapy for advanced

colorectal cancer has developed the frequent 上海皓元医药股份有限公司 onset of SOS. SOS is defined as a disruption of the sinusoidal membrane, collagenization of the perisinusoidal space and sinusoidal dilatation. A part of the molecular pathophysiology of SOS involves the depolymerization of F-actin in sinusoidal endothelial cells, which leads to the increased expression of matrix metalloproteinase (MMP)-9 and MMP-2 by sinusoidal endothelial cells.[24] As morphological change, it was microscopically revealed that red blood cells penetrated under the sinusoidal endothelial cell barrier and dissected the endothelium off the extracellular matrix in the Disse space. At the same time, anticancer agents (L-OHP or Taxan with 5-FU) made it possible to induce oxidative stress.[25, 26] These SOS can be associated with fibrosis and consequent portal hypertension and liver dysfunction. In 2004, Rubbia-Brandt et al. published the first clinical series of SOS in non-tumorous liver induced by L-OHP administration as preoperative chemotherapy.