Ramucirumab-Induced Hepatocellular Carcinoma Rupture and Gastrointestinal Perforation

BACKGROUND Hepatocellular carcinoma (HCC) is a primary liver malignant tumor that typically but not always develops in the setting of chronic liver disease, particularly in patients with cirrhosis or chronic hepatitis B virus infection. Advanced HCC portends a poor prognosis; however, recent advances in first-line and second-line treatment options yield significant survival improvements. Ruptured HCC is an uncommon presentation that occurs in approximately 3-26% of patients. CASE REPORT We present a case of a patient with HCC who was undergoing treatment with the antiangiogenic monoclonal antibody ramucirumab. Subsequently, he presented with signs and symptoms of acute abdomen. The abdominal imaging revealed pneumoperitoneum with multiple abdominal and pelvic collections. The patient underwent exploratory laparotomy and was found to have necrotic liver parenchyma, which appeared to be perforated. Also, a microperforation was noted in the proximal duodenum. The pathology report from liver specimens showed fragments of hepatocellular cancer with extensive necrosis. CONCLUSIONS The mechanism of tumor rupture in HCC is poorly understood. The so-called vascular injury hypothesis states that collagen expansion and elastin proliferation in the arterial wall supplying the tumor could be the leading cause of HCC rupture. We believe that the process mentioned above was accelerated in our patient using the antiangiogenic factor ramucirumab. A similar antiangiogenic mechanism is also implicated in gastrointestinal hemorrhage and perforation related to this drug.