Surgical Pancreatic Complications Induced by L-Asparaginase By John Sadoff, Shelley Hwang, David Rosenfeld, Lawrence Ettinger, and Nitsana Spigland New Brunswick, New Jersey and New York, New York l Pancreatitis has been noted to be a potential complica- tion in 2% to 16% of patients undergoing treatment with L-asparaginase for a variety of pediatric neoplasms, but rarely has surgical intervention been necessary. The authors present two fulminant cases of L-asparaginase-induced pan- creatitis and review the current literature. The first patient is a 15-year-old boy who underwent induction chemotherapy with L-asparaginase for non-Hodgkin’s lymphoma with bone marrow involvement. He presented with diffuse patchy necrosis of the pancreas as well as a large infected pancre- atic pseudocyst. He subsequently required operative debride- ment of the pancreas and external drainage of the pseudo- cyst. He is currently doing well. The second patient is a 5-year-old boy who was treated with L-asparaginase for a diagnosis of acute lymphocytic leukemia. Within 3 weeks of initiation of therapy,fulminant pancreatitis developed, which progressed to multisystem organ failure. Computed tomog- raphy scan demonstrated extensive pancreatic necrosis in- volving 90% of the gland. He underwent surgical debride- ment of his necrotic pancreas and wide drainage of the lesser sac. Postoperatively he improved but subsequently multiple complications developed including erosion of his gastroduo- denal artery with significant intraabdominal bleeding, which was controlled with angiographic embolization. Subse- quently erosion of his endotracheal tube into the innominate vein developed, and he died. L-asparaginase-induced pancre- atitis has been described after therapy for various pediatric neoplasms. and the reported cases have usually been self- limiting. However, our cases demonstrate potentially fatal sequelae of this complication and mandate early diagnosis with appropriate surgical intervention in this setting. Copyright Q 1997 by W.B. Saunders Company INDEX WORDS: Surgery, pancreatitis, L-asparaginase. -ASPARAGINASE is an aminohydrolase enzyme de- L rived from Escherichia coli. L* It is a useful chemo- therapeutic agent for the treatment of a variety of lymphoproliferative disorders including acute lympho- cytic leukemia and lymphoma. It acts by inhibiting protein synthesis in cells that depend on exogenous asparagine. Normal cells synthesize their own asparagine and are less affected by the depletion of asparagine by From the Departments of Surgety~ Radiology, and Pediatrics, VMDNJ- Robert Wood Johnson Medical School, New Brunswick, NJ, and the Department of Surgery, The New York Hospital-Cornell Medical Centen New York, NY Presented at the 28th Annual Meeting of the Canadian Association of Paediutric Surgeons, Halijkx, Nova Scotia, August 18-20, 1996. Address reprint requests to Nitsana Spigland, MD, Division of Pediatric Surgery, The New York Hospital-Cornell Medical Centen 525 East 68th St, New York, NY 10021. Copyright 0 1997 by WB. Saunders Company 0022-3468/97/3206-0014$03.00/O 860 L-asparaginase.3 When L-asparaginase is used in conjunc- tion with vincristine and prednisone for acute lympho- cytic leukemia in children, the combination has been effective in producing first induction remissions in 83% to 95% of patients.4-7 Asparaginase toxicity is varied and ranges from acute hypersensitivity and hyperglycemia to hepatocellular dysfunction and acute pancreatitis8 In patients with preexisting pancreatic disorders, L-asparaginase is contra- indicated because of its well-known pancreatic toxicity. The incidence of pancreatic toxicity varies between 2% and 16%9-11; however, pseudocyst formation and se- quelae requiring surgical intervention are quite rare and require diligent management to avert morbidity and mortality. There have been only seven previously re- ported cases of pancreatic pseudocysts associated with L-asparaginase treatment. 7~12-16 We report two additional cases that presented with varying degrees of pancreatic necrosis and pseudocysts and subsequently required surgical intervention. CASE REPORTS Case 1 A 15-year-old white boy was in good health untrl April 1995 when he experienced enlarged bilateral axillary lymph nodes. He was subse- quently diagnosed with non-Hodgkin’s lymphoma (T-cell lymphoblas- tic lymphoma) with leukemic involvement of the bone marrow and immediately began on an L-asparaginase-based chemotherapeutic regi- men. He received PEG-asparaginase (2,500 U/m2 intramuscularly) once every 2 weeks for a total of four doses. Maintenance therapy included daily 6mercaptopurine and weekly methotrexate. He had periodic reinduction therapy including L-asparagmase. Five weeks after the last dose of L-asparaginase, the patient experienced diffuse abdominal pain, nausea and vomiting, as well as an ileus pattern noted on abdominal x-ray. An initial serum amylase of 348 IU (normal, 44 to 124) and serum lipase of 1.120 IU (normal, 10 to 58) prompted an abdominal computed tomography (CT) scan, which showed drffuse enlargement of the pancreas consistent with acute pancreatitis. The patient was initially treated conservatively with parenteral nutrition and nasogastric decompression. Despite gradual amelioration of his symptoms as well as amylase and lipase values that returned to normal, he continued to have persistent nausea and vomiting. A follow-up CT scan of the abdomen showed a large retrogastric pancreatic pseudocyst with focal areas of necrosis in the body and head of the pancreas (Fig 1). He continued to have persistent fevers and gastrointestinal obstructive symptoms. Follow-up CT scan showed progressive organization of the pseudocyst, and he subsequently underwent CT-guided percutaneous drainage of the cyst. After the drainage procedure, high output from the drain was treated with octreotide. This resulted in initial reduction of drainage from the pancreatic fistula. however, a persistent fluid collection in the lesser sac Journal ofPediarric Surgery, Vol 32, No 6 (June), 1997: pp 860-863