Adjuvant Radiation Therapy for Gastric Cancer Causing Focal Sinusoidal Obstructive Syndrome Masquerading as Metastatic Disease

Abstract

Purpose: A 48 year old white male, with no history of liver disease, was referred for evaluation of ascites and jaundice and a possible mass in the liver. 6 months previously, he underwent partial gastrectomy for an 8 centimeter stage IIIB signet ring gastric cancer. Pathology demonstrated invasion to the gastric serosa and perigastric adipose tissue with 3/9 lymph nodes positive for adenocarcinoma. At the time of surgery, there was no evidence of hepatic or peritoneal spread with normal intra-operative liver biopsy. He received two uneventful rounds of chemotherapy with 5-fluorouracil and leucovorin. After the third cycle of chemotherapy plus localized adjuvant radiation therapy, he developed jaundice, ascites, and mild right upper quadrant pain with TB of 7 mg/dL, alk phos of 399 U/L, and ALT of 120 U/L. Ascitic fluid analysis demonstrated high SAAG with negative cytology. Doppler ultrasound of the liver demonstrated normal hepatic vasculature. CT and MRI demonstrated a centralized heterogenous 8.2 x 9.3 cm lesion in the liver with peripheral sparing. No biliary abnormalities were seen on ERCP. Biopsy at the outside hospital demonstrated perivenular hepatocyte necrosis, marked congestion and some signs of sinusoidal dilation; there was no evidence of malignancy. Porto-systemic gradient measurements were 19. At presentation his jaundice had improved, and his ascites was managed on diuretics. He denied any history of heavy alcohol use, of herbal medications or any family history of liver disease. Physical exam findings included mild scleral icterus, no appreciable ascites, and an enlarged, firm, nontender liver. Lab findings include platelets of 355,000, INR 1.23, bilirubin of 2.7 mg/dl, alkaline phosphatase 355 U/L, AST 59 U/L, ALT 54 U/L, albumin of 2.5 g/dL, total protein of 7.2 g/DL, CEA 2.3 ng/mL and AFP 4.3 ng/mL. MRI at our institution again demonstrated a centralized abnormality pre and post contrast on T1 and T2 weighted images. However, no abnormality was visualized on one hour delayed T2 weighted images, consistent with focal fatty infiltration. Given the history of gastric cancer, US guided liver biopsy demonstrated marked central congestion with features of sinusoidal obstruction syndrome. Given the geographic distribution, the locations of the radiation therapy ports were reviewed, and were found to have inadvertently targeted the liver. We report here a case of focal sinusoidal obstruction syndrome induced by the additive effects of radiation therapy to the liver in combination with 5-fluorouracil. Although not common, consideration of iatrogenic liver damage during chemoradiation should be part of the differential of a new liver lesion.