Existence of early markers of development of portosinusoidal vascular disease after exposure to oxaliplatin

2 de January de 2020

Digestive, Pathological Anatomy and Oncology Units of the Marques de Valdecilla University Hospital have published in MPDI, open access journal, a review of the porto-sinusoidal vascular disease associated with oxaliplatin.

The article “Porto-Sinusoidal Vascular Disease Associated to Oxaliplatin: An Entity to Think about It” is a review of the literature of a rare entity such as the porto-sinusoidal vascular disease associated with oxaliplatin. It is a hepatic vascular disease, in which, patients with a history of exposure to oxaliplatin (mostly in the context of stage III and IV colon cancer) develop presinusoidal portal hypertension (i.e., without an underlying cirrhosis) years after end of chemotherapy treatment. In most cases, the disease is asymptomatic in the form of platelet and splenomegaly, but in a small percentage, patients can develop the typical complications of portal hypertension such as bleeding from esophageal / peristomal varicose veins, ascites or encephalopathy.

This review is the prelude to a multicenter study, led by the Digestive Service in collaboration with the HUMV Oncology Service, which has been carried out in 8 Spanish hospitals and whose preliminary results confirm that there are early markers of disease development vascular portosinusoidal after exposure to oxaliplatin, such as the persistence of plaquetopenia and splenomegaly after the end of chemotherapeutic treatment, so this subgroup of patients would benefit from a specific follow-up in Hepatology units.



There are three mechanisms through which oxaliplatin can cause sinusoidal damage:

1. Oxaliplatin can potentially cause liver sinusoid endothelial cell damage and stimulate both free radical release, glutathione transferase depletion, and decrease extracellular matrix metalloproteinase expression (MMP-2 and MMP -9) thereby altering the integrity of the sinusoidal wall. The damage to the sinusoidal wall, favors the passage of erythrocytes to the space of Dissé and formation of perisinusoidal fibrosis.

2. Said vascular damage causes the obstruction of the sinusoidal capillaries and the appearance of areas of parenchymal extinction, thus interrupting the portal circulation, and can generate an increase in presinusodal pressure.

3. The appearance of regenerative nodular hyperplasia is favored by chronic hypoxia of the centrolobular areas.

Ref. Porto-Sinusoidal Vascular Disease Associated to Oxaliplatin: An Entity to Think about It. Puente A, Fortea J, Del Pozo C, Huelin P, Cagigal ML, Serrano M, Cabezas J, Arias Loste MT, Iruzubieta P, Cuadrado A, Llerena S, Lopez C, Fábrega E, Crespo J. PMID: 31771307 DOI: 10.3390/cells8121506