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Case Reports

Indian Pediatrics 2003; 40:670-672 

Pancreatic Pseudocyst Complicating Treatment of Acute Lymphoblastic Leukemia


Sanjay Tomar
Sameer Bakhshi
S.K. Kabra
L.S. Arya
 

From the Department of Pediatrics (Pediatric Oncology), All India Institute of Medical Sciences, New Delhi, India.

Correspondence to: Professor L.S. Arya, Head, Division of Pediatric Oncology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110 029, India.
E-mail: [email protected]

Manuscript received: November 21, 2001; Initial review completed: January 31, 2002;Revision accepted: January 13, 2003.

Acute pancreatitis is recognized with increasing frequency in the pediatric population as a result of trauma, biliary tract disease, viral illness, states of intracranial hypertension and steroids(1). Children with acute lymphoblastic leukemia(ALL) treated with L-asparaginase represent an additional group at risk to develop pancreatitis(1,2). L-asparaginase induced pancreatitis is a relatively benign disease with few complications in 80-90% of cases. Several cases of L-asparaginase related pancreatitis have been reported in literature, but there are only seven reports of L-asparaginase related pancreatic pseudocyts(3-7). L-asparaginase induced pancreatitis has a mortality as high as 12%(7). The principal toxicites of the drug, besides pancreatitis, include: hypersensitivity reactions, central nervous system and liver dysfunction, coagulopathy and hyper-glycemia. The incidence of pancreatitis has been reported to range between 2-16%(2). We report a case of pancreatic pseudocyst developing in a child undergoing treatment for ALL.

Case Report

A 12-year-old female child was diagnosed as acute lymphoblastic leukemia based on an initial complete blood count (CBC), which demonstrated hemoglobin 7 g/dL, WBC 2,68,000/mm3 with 95% lymphoblasts (L2 morphology), and platelet count 32,000/mm3. The child was put on the Indo-US multi-centric protocol 841 for ALL, which included a 4-drug induction (prednisolone, vincristine, L-asparaginase and daunorubicin) followed by consolidation and 6 maintenance cycles of 90 days each subsequently. Each maintenance cycle consisted of an initial 7-day period of prednisolone with vincristine and 4 injections of L-asparaginase on alternate days, followed by weekly oral methotrexate and daily 6-mercaptopurine. With the above treatment protocol, the child was in state of hemato-logical remission and had reached the 5th maintenance cycle.

Soon after receiving four injections of L-asparaginase in the initial week of the 5th maintenance cycle, she was admitted in hospital with severe epigastric pain and bilious vomiting. Pain was radiating to the back, aggravated by food intake and relieved by sitting or leaning forward. On examination, she was febrile and tachypneic and abdominal guarding and reduced bowel sounds. Her serum amylase was 450 somogyi units (normal 60-200 SU). Based on the clinical presentation and high serum amylase, a diagnosis of L-asparaginase induced acute pancreatitis was made. She inproved on conservative treatment with intravenous fluids, nasogastric decompression and broad spectrum antibiotics, and was discharged after 7 days. She returned three weeks later with fever and abdominal lump of 2 days duration. On physical examination, her abdomen was diffusely tender with absent bowel sounds. CBC revealed: Hb 5g/dL, WBC 5,300/mm3, platelets 65,000/mm3. Serum amylase was 106 somogyi units and serum calcium was normal. Chest X-ray was normal. Ultrasound examination of the abdomen showed a bulky hypoechoic pancreas with ill defined outline and a large pseudocyst in left hypochondrium anterior to the left kidney measuring 13.4 × 10.7 cm in size consistent with a pseudo-pancreatic cyst.

The pseudopancreatic cyst was managed conservatively with continuous nasogastric suction, intravenous fluids and antibiotics. Her temperature returned to normal, oral feedings were resumed and was discharged after 1 week. Subsequent ultrasound studies showed disappearance of the pseudocyst. Maintenance chemotherapy without L-asparaginase was started again. The child is presently in complete remission since the past 2 years following completion of therapy.

Discussion

L-asparaginase, an enzyme extracted from Escherichia coli, is one of the most imporant drugs in the current multiagent protocols used for treating ALL. Among a total of 1,403 patients, studied for L-asparaginase induced toxicities in several series, only 34 cases (2.5%) were reported to have developed clinically apparent pancreatitis(2). Pancreatitis, which is usually mild and self limited, may begin any time during treatment or even upto 16 weeks after discontinuation of treatment with L-asparaginase(6). Serum amylase and lipase levels may remain normal during clinically apparent pancreatitis since L-asparaginase is known to interfere with the synthesis of these enzymes(8). Of the seven previously reported pseudocyst cases(3-7), 4 cases occurred within two weeks of administration of L-asparaginase; 2 cases occurred 7 and 16 weeks after administration respectively and 1 case occurred after 3 days of L-asparaginase administration. In our patient, the interval between the last dose of L-asparaginase and development of the pseudocyst was 24 days.

Corticosteroids are capable of inducing acute pancreatitis in children and the incidence of clinical pancreatitis seems much higher in patients receiving combination chemotherapy comprising L-asparaginase, corticosteroids and other agents(2,3). Since our patient had received corticostroids, she was at increased risk of developing acute pancreatitis and pseudocyst formation. Pancreatic pseudocyst is known to resolve spontaneously and thus an initial period of observation is indicated in a stable patient(9). However, in cases of progressive enlargement of pseudocyst, signs of gastric outlet obstruction or rupture/hemorrhage of the cyst, prompt surgical intervention is indicated. Internal drainage of the pseudocyst by cystogastrostomy or roux-en-Y-cystojejuno-stomy is the procedure of choice(9). External drainage has been less satisfactory and is often complicated by formation of a persistent pancreatic cutaneous fistula. Recently octreotide, a synthetic somatostatin analogue in the dose of 5 microgram/kg/day in divided doses has been suggested for use in the management of pancreatitis(7). Samatostatin is a naturally occurring oligopeptide produced primarily in the gastrointestinal tract. The rationale for use of octreotide is that by inhibiting pancreatic exocrine function, autodigestion of the pancreas along with damage to the surrounding tissue will be prevented(7). It has seen found to have few side effects with soreness at the injection site being the most common.

In summary, acute pancreatitis is an uncommon but potentially lethal complication of L-asparaginase therapy. A high index of suspicion and careful periodic physical examination are crucial to the diagnosis. Serum amylase determination must not be relied upon to rule out evolving acute pancreatitis(8). Abdominal sonography at regular intervals has been suggested as a noninvasive and accurate means of detecting early pancreatitis(10). Skillful management of pancreatitis as well as alertness in identifying its attendant complications such as necrosis, abscess and pseudocyst formation can minimize morbidity and death in children undergoing multiagent chemotherapy for ALL.

Contributors: LSA conceptualized the report and will act the guarantor of the paper. ST was the resident involved in the management of the patient and helped in drafting of the manuscript. SN and SB drafted the final manuscript. SKK helped to co-ordinate the study as well as helped in drafting of the manuscript.

Funding: None.

Competing interests: None stated.

 

 References


 

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7. Garrington T, Bensard D, Ingram D, Christopher C, Silliman CC. Successful management with octreotide of a child with L-asparaginase induced hemorrhagive pancreatitis. Med Pediatr Oncol 1998; 30: 106-109.

8. Cooney DA, Handschumacher RE. L-aspara-ginase and L-asparagine metabolism. Annu Rev Pharmac

9. Warren KW, Athanassiades S, Frederick P, Kune GA. Surgical treatment of pancreatic cyst. Review of 183 cases. Ann Surg 1966; 163: 886-891.

10. Samuels BI, Culbert SJ, Okamura J, Sullivan MP. Early detection of chemotherapy - related pancreatic enlargement in children using abdominal sonography: a preliminary report. Cancer 1976; 38: 1515-1523.

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