Fatal Acute Liver Failure in a Child with Metastatic ...

Journal of Pediatric Gastroenterology and Nutrition 43:116 Y 118 Ó July 2006 by Lippincott Williams & Wilkins

Case Report

Fatal Acute Liver Failure in a Child with Metastatic Gastric Adenocarcinoma *Sunny Zaheed Hussain, *Arti Jaiswal, *Ali Amjed Bader, *Parvathi Mohan, †Bruce M. Markle, ‡Caterina Minnitti, §Ronald Przygodzki, *Benny Kerzner, and *ÝStuart S. Kaufman *Department of Gastroenterology and Nutrition, ÞDepartment of Radiology, þDivision of Hematology and Oncology, §Department of Pathology, Children’s National Medical Center, and ¬ The Georgetown University Transplant Institute, Washington, DC

Within 48 hours of admission, ALT rose to 693 U/L, AST to 1727 U/L, bilirubin to 4.8 mg/dL (conjugated 3.2), and prothrombin time to 19.4 seconds (INR 3.3). Computerized tomography showed a large liver with near-complete replacement of parenchyma by nodular masses. There was minimal ascites (Fig. 1). Transjugular liver biopsy demonstrated poorly differentiated adenocarcinoma with widespread necrosis. Subsequently, the patient experienced hematemesis. Upper endoscopy revealed a small, ulcerated, and hemorrhagic mass on the greater curve of the gastric antrum with partial gastric outlet obstruction (Fig. 2). Grasp biopsies of the mass demonstrated ulcerated gastric epithelium without Helicobacter pylori. Despite supportive care that included transfusions of packed red cells, platelets, and fresh frozen plasma, hepatic function deteriorated in the next 96 hours with mental status changes consistent with hepatic encephalopathy (plasma ammonia 254 Kg/dL; normal 29 Y 54). After respiratory failure requiring mechanical ventilation and anuria developed, support was withdrawn in consultation with the patient’s family. Autopsy confirmed that the antral mass contained sheets of malignant cells with rare intracytoplasmic vacuoles (signet ring cells) identical with those seen in the liver. The cells invaded the submucosa and muscularis propria (Figs. 3 and 4). Local tumor extension was present without evidence of primary tumor elsewhere.

CASE REPORT A 17-year-old white male presented with a 2 month history of burning epigastric pain initially relieved by proton pump inhibitors. Anorexia, fatigue, and recurring low-grade fever began 1 month before presentation. For several days before presentation, he experienced repeated episodes of nonbilious, nonbloody emesis. He had lost 10 pounds in 2 months. He had no previous history of abdominal pain or gastroesophageal reflux. The maternal grandfather had had a brain tumor, and the paternal grandmother had had breast cancer. On physical examination, the patient was afebrile. He was pale. He was in no respiratory distress. There were enlarged lymph nodes in the right supraclavicular, right submandibular, and bilateral inguinal areas. The right hepatic lobe was enlarged, projecting 10 cm below the right costal margin. The spleen was not enlarged. Laboratory test results included an aspartate aminotransferase (AST) of 282 (normal 10 Y41) U/L, alanine transaminase (ALT) 138 (normal 24 Y 54) U/L, total bilirubin 0.6 (normal G 0.8) mg/dL, prothrombin time 17.3 (normal 10.3 Y12.3) seconds, International Normalized Ratio (INR) 2.45 (normal 0.8Y 1.4), and partial thromboplastin time 51.9 (normal 24.5Y 40.3) seconds. Alpha-fetoprotein was 2.6 (normal 0.6Y3.9) ng/mL, lactic dehydrogenase 555 (normal 117 Y 217) U/L, and carcinoma embryonic antigen 96.9 (normal 0 Y2.4) ng/mL. Hemoglobin was 9.0 (normal 11 Y14.5) g/dL, white cells 10,100/KL (normal 3.84Y 9.84), and platelets 83,000/KL (normal 175 Y330). Blood urea nitrogen and creatinine were normal. Serologic testing for hepatitis A, B, C, and E viruses and HIV was negative. Polymerase chain reaction testing for cytomegalovirus and Epstein-Barr virus was negative.

DISCUSSION This is the first report of fulminant hepatic failure resulting from metastatic gastric adenocarcinoma before adulthood. Metastatic malignancy, specifically acute leukemia, is a rare cause of acute liver failure in children (1). Acute liver failure secondary to hepatic tumor infiltration is more frequent in adults. As with children, hematologic malignancies in adults are the most common metastatic malignancies responsible for liver failure. These include non-Hodgkin and Hodgkin

Received September 7, 2005; accepted December 17, 2005. Address correspondence and reprint requests to Dr. Stuart S. Kaufman, Children’s National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010. (e-mail: [email protected]).

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LIVER FAILURE FROM GASTRIC ADENOCARCINOMA

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FIG. 3. Autopsy sections of gastric antrum demonstrating sheets of poorly differentiated malignant cells with rare intracytoplasmic vacuoles (arrow), (hematoxylin-eosin, magnification 400).

FIG. 1. Computed tomographic scan of abdomen showing multiple irregular hypodensities diffusely distributed throughout the liver consistent with infiltrative liver disease.

lymphoma (2), acute and chronic leukemia (3,4), and rarely multiple myeloma (5). A Medline review of the medical literature to 1966 reveals only one unambiguous case of fulminant liver failure secondary to gastric adenocarcinoma in a 59-year-old Asian male (6). In

FIG. 2. Endoscopy of stomach showing ulcerated, hemorrhagic antral mass of adenocarcinoma.

contrast with our patient, liver failure occurred several months after diagnosis and palliative gastrectomy. Extensive sinusoidal infiltration with malignant cells and progressive portal vein obstruction by tumor thrombus are the two pathways by which solid organ metastases cause ischemic necrosis of the liver (7). Other nonhematologic malignancies that may present in this manner include adenocarcinoma of the breast (8), prostate cancer (9), small-cell carcinoma of lung (10), carcinoma of the urinary bladder (11), and malignant melanoma (12). Less than 10% of gastric adenocarcinomas occur before age 40 years, and of these, most occur between 35 and 40 years (13). Although gastric adenocarcinoma occurs in children, it accounts for only 0.05% of all pediatric gastrointestinal malignancies (14). The youngest reported patient appears to have been 7 years old

FIG. 4. Autopsy sections of metastatic adenocarcinoma in liver: adenocarcinoma (*) is sharply delineated from surrounding, focally autolytic hepatic liver trabeculae (arrow) (hematoxylineosin, magnification 100). J Pediatr Gastroenterol Nutr, Vol. 43, No. 1, July 2006


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(15). Molecular genetic profiles of early tumors appear to differ from those occurring later in life (16). A positive family history is not unusual with early-onset gastric adenocarcinoma, which may arise in any area of the stomach. The antrum and region of the cardioesophageal junction together account for approximately one half (13). Metastasis to the liver occurs in approximately 35% of cases (7). Tumors in patients less than age 40 are more likely to be undifferentiated with signet ring cells, are more biologically aggressive, and have a worse prognosis than those in older individuals (13,17). Our experience emphasizes that malignancy must be included in the differential diagnosis of upper gastrointestinal tract symptoms that do not respond to empiric therapy. Our experience also emphasizes that nonhematologic as well as hematologic tumor metastasis must be included in the differential diagnosis of fulminant liver failure in the pediatric age group, particularly when usual viral, toxic, and metabolic causes have been excluded. Although not without risk in patients with coagulopathy (18), transjugular liver biopsy may be necessary to confirm the diagnosis and verify the futility of liver transplantation in a child with fulminant hepatic failure. REFERENCES 1. Kader A, Vara R, Egberongbe Y, et al. Leukaemia presenting with fulminant hepatic failure in a child. Eur J Pediatr 2004;163:628 Y 9. 2. Rowbotham D, Wendon J, Williams R. Acute liver failure secondary to hepatic infiltration: a single centre experience of 18 cases. Gut 1998;42:576 Y 80. 3. Anderson SH, Richardson P, Wendon J, et al. Acute liver failure as the initial manifestation of acute leukaemia. Liver 2001;21:287Y 92. 4. Hasuike S, Hayashi K, Abe H, et al. Acute hepatic failure due to hepatic involvement by chronic lymphocytic leukemic cells in a patient with chronic hepatitis B. J Gastroenterol 2004;39:499 Y 500.

5. Berrios M, Armas-Merino R, Franco C, et al. Acute liver failure in patient with liver amyloidosis associated to multiple myeloma. Rev Med Chil 2003;131:1301 Y 4. 6. Sawabe M, Kato Y, Ohashi I, et al. Diffuse intrasinusoidal metastasis of gastric carcinoma to the liver leading to fulminant hepatic failure. A case report. Cancer 1990;65:169 Y 73. 7. Tanaka A, Takeda R, Mukaihara S, et al. Tumor thrombi in the portal vein system originating from gastrointestinal tract cancer. J Gastroenterol 2002;37:220 Y 8. 8. Agarwal K, Jones DE, Burt AD, et al. Metastatic breast carcinoma presenting as acute liver failure and portal hypertension. Am J Gastroenterol 2002;97:750 Y 1. 9. Boyiadzis M, Nam M, Dahut W. Fulminant hepatic failure secondary to metastatic prostate cancer. Urol Int 2005;74:185 Y 7. 10. McGuire BM, Cherwitz DL, Rabe KM, et al. Small-cell carcinoma of the lung manifesting as acute hepatic failure. Mayo Clin Proc 1997;72:133 Y 9. 11. Alcalde M, Garcia-Diaz M, Pecellin J, et al. Acute liver failure due to diffuse intrasinusoidal metastases of urothelial carcinoma. Acta Gastroenterol Belg 1996;59:163 Y 5. 12. Tanaka M, Watanabe S, Masaki T, et al. Fulminant hepatic failure caused by malignant melanoma of unknown primary origin. J Gastroenterol 2004;39:804 Y 6. 13. Koea JB, Karpeh MS, Brennan MF. Gastric cancer in young patients: demographic, clinicopathological, and prognostic factors in 92 patients. Ann Surg Oncol 2000;7:346 Y 51. 14. Katz S, Berernheim J, Kaufman Z, et al. Pernicious anemia and adenocarcinoma of the stomach in an adolescent: clinical presentation and histopathology. J Pediatr Surg 1997;32:1384 Y 5. 15. Goto S, Ikeda K, Ishii E, et al. Carcinoma of the stomach in a 7-year-old boy Y a case report and a review of the literature on children under 10 years of age. Z Kinderchir 1984;39:137 Y 40. 16. Carvalho R, Milne AN, van Rees BP, et al. Early-onset gastric carcinomas display molecular characteristics distinct from gastric carcinomas occurring at a later age. J Pathol 2004;204: 75 Y 83. 17. Theuer CP, Kurosaki T, Taylor TH, et al. Unique features of gastric carcinoma in the young: a population-based analysis. Cancer 1998;83:25 Y 33. 18. MacQuillan GC, Mutimer D. Fulminant liver failure due to severe veno-occlusive disease after haematopoietic cell transplantation: a depressing experience. QJ Med 2004;97:581 Y 9.

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