Atorvastatin does not protect against ischemia-reperfusion damage in cholestatic rat livers.

BACKGROUND: Extrahepatic cholestasis sensitizes the liver to ischemia/reperfusion (I/R) injury during surgery for perihilar cholangiocarcinoma. It is associated with pre-existent sterile inflammation, microvascular perfusion defects, and impaired energy status. Statins have been shown to protect against I/R injury in normal and steatotic mouse livers. Therefore, the hepatoprotective properties of atorvastatin were evaluated in a rat model of cholestatic I/R injury. METHODS: Male Wistar rats were subjected to 70% hepatic ischemia (during 30 min) at 7 days after bile duct ligation. Rats were randomized to atorvastatin treatment or vehicle-control in three test arms: (1) oral treatment with 5 mg/kg during 7 days after bile duct ligation; (2) intravenous treatment with 2.5, 5, or 7.5 mg/kg at 24 h before ischemia; and (3) intravenous treatment with 5 mg/kg at 30 min before ischemia. Hepatocellular damage was assessed by plasma alanine aminotransferase (ALT) and histological necrosis. RESULTS: I/R induced severe hepatocellular injury in the cholestatic rat livers (~10-fold increase in ALT at 6 h after I/R and ~30% necrotic areas at 24 h after I/R). Both oral and intravenous atorvastatin treatment decreased ALT levels before ischemia. Intravenous atorvastatin treatment at 5 mg/kg at 24 h before ischemia was the only regimen that reduced ALT levels at 6 h after reperfusion, but not at 24 h after reperfusion. None of the tested regimens were able to reduce histological necrosis at 24 h after reperfusion. CONCLUSION: Pre-treatment with atorvastatin did not protect cholestatic livers from hepatocellular damage after I/R. Clinical studies investigating the role of statins in the protection against hepatic I/R injury should not include cholestatic patients with perihilar cholangiocarcinoma. These patients require (pharmacological) interventions that specifically target the cholestasis-associated hepatopathology.

Perioperative blood transfusion is not associated with overall survival or time to recurrence after resection of perihilar cholangiocarcinoma.

BACKGROUND: Perioperative blood transfusions have been associated with worse oncological outcome in several types of cancer. The objective of this study was to assess the effect of perioperative blood transfusions on time to recurrence and overall survival (OS) in patients who underwent curative-intent resection of perihilar cholangiocarcinoma (PHC). METHODS: This retrospective cohort study included consecutive patients with resected PHC between 1992 and 2013 in a specialized center. Patients with 90-day mortality after surgery were excluded. Patients who did and did not receive perioperative blood transfusions were compared using univariable Kaplan-Meier analysis and multivariable Cox regression. RESULTS: Of 145 included patients, 80 (55.2%) received perioperative blood transfusions. The median OS was 49 months for patients without and 41 months for patients with blood transfusions (P = 0.46). In risk-adjusted multivariable Cox regression analysis, blood transfusion was not associated with OS (HR 1.00, 95% CI 0.59-1.68, P = 0.99) or time to recurrence (HR 1.00, 95% CI 0.57-1.78, P = 0.99). In addition, no differences in effect were found between different types of blood products transfused. CONCLUSION: Blood transfusion was not associated with survival or time to recurrence after curative resection of PHC in this series. The alleged association is presumably related to the circumstances necessitating blood transfusions.