Porto-Sinusoidal Vascular Disease Associated to Oxaliplatin: An Entity to Think about It

Abstract

Portal sinusoidal vascular disease is a presinusoidal cause of portal hypertension (PHT) of unknown etiology, characterized by typical manifestations of PHT (esophageal varices, ascites, portosystemic collaterals), plaquetopenia and splenomegaly with a gradient of portal pressure slightly increased, according to the presinusoidal nature of the PHT. A few cases in the literature have shown a relationship between oxaliplatin and the development of presinusoidal portal hypertension, years after the chemotherapy for colorectal cancer (therefore, different to sinusoidal obstruction syndrome). There are three mechanisms through which oxaliplatin can cause sinusoidal damage: (1) damage at the level of endothelial cells and stimulates the release of free radicals and depletion of glutathione transferase, with altering the integrity of the sinusoidal cells. The damage in the endothelial sinusoidal cells allows to erythrocytes to across into the Dissé space and formation of perisinusoidal fibrosis, (2) the appearance of nodular regenerative hyperplasia is favored by the chronic hypoxia of the centrilobular areas and, finally, (3) oxaliplatin can generate an obliteration of the blood capillaries and zones of parenchymal extinction. These three facts can develop, in a minority of cases, the appearance of a presinusoidal increase of portal pressure, which typically appears years after the completion of chemotherapy and sometimes is underdiagnosed until variceal bleeding, ascites or encephalopathy appear. The knowledge of this pathology is essential to be able to perform an early diagnostic and consult to the hepatologist.

Surgical intervention for portal hypertension caused by oxaliplatin-based chemotherapy: a case report and a review of literature regarding radiological and/or surgical interventions for oxaliplatin-associated portal hypertension

“…As abovementioned, the hepatotoxicity of the OBC is not caused by the hepatocyte injury itself but caused by the SOS [15]. Therefore, hyperammonemia rarely occurs in the OBC-associated portal-hypertension [3][4][5][6][7][8][9][10][11][12][13][14][15]. Thus, the portosystemic shunt is considered reasonable for the treatment of the OBC-associated portal-hypertension.…”

“…The hepatotoxicity of the OBC became notorious because the morbidity after hepatectomy for CRLM was more likely to occur in patients who received the OBC before hepatectomy than in those who did not [2,3,8,9,[13][14][15]. The hepatotoxicity of the OBC is considered attributable to the SOS, i.e.…”

“…the sinusoidal endothelial injury [2,[13][14][15]. In other words, the OBC-associated hepatotoxicity originates not directly from the parenchymal injury but indirectly from the sinusoid-circulatory disturbance caused by the SOS [2,15]. In early 2000s, the OBC-associated hepatotoxicity was considered problematic only when performing hepatectomy [1-3, 5, 6, 8, 9].…”

“…In early 2000s, the OBC-associated hepatotoxicity was considered problematic only when performing hepatectomy [1-3, 5, 6, 8, 9]. However, the portal-hypertension has been reported as the significant clinical manifestation of the SOS from the late 2000s [4][5][6][7][10][11][12][13][14][15]. Thereafter, the treatment of the OBC-associated portal-hypertension itself has been often reported [4,7,[9][10][11][12][13][14].…”

“…Although the sinusoidal obstruction syndrome (SOS) has been reportedly observed in 20-50% of the patients receiving the OBC [2], the OBC-associated portal-hypertension due to SOS is considered relatively rare [3][4][5][6][7][8][9][10][11][12][13][14][15]. However, it can cause potentially life-threatening complications, such as massive ascites, pancytopenia, and gastrointestinal variceal bleeding [3][4][5][6][7][8][9][10][11][12][13][14][15]. To prevent and/or treat these complications, the radiological and/or surgical interventions are sometimes required, such as partial splenic embolization (PSE) [10], splenic arterial ligation [9], or transjugular intrahepatic portosystemic shunt (TIPS) [7].…”