Anticancer treatment for acute lymphoblastic leukemia (ALL) is based on drugs such as methotrexate, 6-mercaptopurine, vincristine, and asparaginase [1]. Side effects related to asparaginase include hypersensitivity reactions, hepatotoxicity, hypertrigly ceridemia, hyperglycemia, pancreatitis, encephalopathy, thrombosis, or hemorrhagic complications, with the risk increasing with age and dose [2]. Asparaginase-related pancreatitis has an incidence of up to 18% and is a major cause of discontinuation of anticancer treatment for leukemia attributed to its acute onset and chronic complications [3]. Caution is advised, as recurrence of pancreatitis has been reported in up to 63% of patients following re-exposure to asparaginase [4]. Additionally, asparaginase-related pancreatitis is reported to cause peripancreatic fluid retention and pseudocysts more frequently than other causes [5].

Treatment for pancreatic pseudocyst is typically conservative or interventional, including percutaneous external drainage, endoscopic drainage, or surgical treatment. Various cases of peripancreatic fluid retention caused by anticancer drugs in patients with leukemia have been reported. Recently, lumen-apposing metal stents (LAMS) have exhibited good effects for endoscopic drainage. The electrocautery-enhanced LAMS is a fully covered, self-expanding stent preloaded with the Hot Delivery System. This is a through-the-scope, electrocautery-enhanced delivery system designed for use with therapeutic echoendoscopes. The delivery system provides endoscopic control and uses a locked, two-step release system to prevent unintended deployment of the proximal flange. The stent is equipped with bilateral anchor flanges for lumen-to-lumen anchoring. These features reduce the risk of stent migration and leakage along the stent, prevent tissue growth, and enable easy removal. By creating an electrocautery function at the tip of the LAMS delivery device, stent placement is possible in a one-step procedure. This system reduces the overall procedure complexity and risk of side effects by avoiding the use of additional accessories (e.g., needles, guidewires, or extension devices) [6]. However, few cases have reported the use of hot-system LAMS to treat pancreatic complications following chemotherapy in patients with leukemia. In this case report, we present a case where hot-system LAMS was employed to manage L-asparaginase-induced acute pancreatitis and pancreatic pseudocyst in an adult patient with ALL.

A 23-year-old male patient was admitted to the outpatient clinic due to abdominal pain, nausea, and vomiting that began a few days before admission. The patient had been diagnosed with ALL 7 months earlier and was undergoing chemotherapy with drugs including daunorubicin, vincristine, and prednisolone, as well as L-asparaginase for the management of leukemia. He was hospitalized due to epigastric discomfort that persisted for several days following the 6th round of chemotherapy. The patient had no significant medical history other than ALL, no history of drinking or smoking, and no unusual family history. On admission, he was hemodynamically stable. Laboratory testing revealed low white blood cell count of 2.21×10³ /uL (normal range, 4.0-10.0×10³ /uL) with a differential of 44.8% neutrophils (36.0-75.0%); low hemoglobin of 9.8 g/dL (12.0-16 g/dL); normal platelet count of 300×10³ /uL (150-450×10³ /uL and slightly elevated amylase and normal lipase: 87 U/L (30-11 U/L) and 7 U/L (23-300 U/L), respectively. Despite stopping chemotherapy and receiving conservative treatment, including intravenous fluids and painkillers, his nausea, vomiting, and abdominal pain persisted. Therefore, an abdominal computed tomography (CT) scan was performed 1-2 weeks after hospitalization. The CT scan revealed multifocal fluid collection in the peripancreatic area, with more prominent ill-defined low density along the body to the tail of the pancreas, suggestive of acute necrotic pancreatitis with walled-off necrosis (WON). The patient was referred to our department (Fig. 1). Pancreatic fluid collection (PFC), including WON, is commonly described as a sequela of pancreatitis. Endoscopic ultrasound-guided PFC drainage can be performed using plastic stents (PS), fully covered self-expanding metallic stents (FCSEMS), or LAMS. Especially for WON, the smaller diameter of the plastic stent increases the risk of passage obstruction due to necrotic debris. FCSEMS overcomes these limitations, but lack of fixation is reported to increase the risk of migration. LAMS is an all-in-one device with an electrocautery-enhanced tip designed to overcome these limitations in addition to reducing procedure time [7]. After explaining these various treatments and discussing them with the patient, we decided to proceed with LAMS. We performed an endoscopic ultrasound-guided transmural puncture using a 19-gauge needle (Echotip-19; Cook Medical, Winston-Salem, NC, USA) (Fig. 2A). Afterward, a guidewire was introduced through the needle and coiled within the cyst (Fig. 2B, C). The LAMS utilized in this case was a Hot Spaxus (Taewoong Medical, Gimpo, Korea) device with a diameter of 23 mm and a length of 2 cm. Additionally, the pus-like cystic contents were confirmed to be draining into the stomach through the stent (Fig. 2D).

Following the stent insertion, the patient’s symptoms improved, and he was able to start eating. He was discharged on the 4th day after the procedure. Three weeks later, the patient was readmitted for stent removal (Fig. 3A). Follow-up endoscopy confirmed that the size of the pseudocyst had decreased, and after irrigating the remaining pus as much as possible through a balloon catheter, the LAMS was removed using rat-tooth forceps (Fig. 3B). After confirming the absence of complications following the procedure, the patient was discharged the next day. Four months after stent removal, a follow-up abdominal CT scan was performed again to evaluate the progress. The CT demonstrated that the previous WON in the peripancreatic area was nearly completely resolved. Furthermore, no evidence of acute pancreatitis or pseudocyst was observed (Fig. 4A). A gastroscopy confirmed that the stent removal site was almost completely healed (Fig. 4B). The patient has been receiving maintenance treatment with 6-mercaptopurine for leukemia and is now 5 months post-LAMS procedure. He is being followed up in an outpatient setting in stable condition, with no recurrence of pancreatitis. The patient is in complete hematologic remission of ALL and remains transplant-free 14 months after diagnosis.

Chemotherapy for ALL in adults is based on a combination of various drugs. The regimen consists of remission induction treatment, central nervous system preventive treatment, and post-remission treatment such as consolidation and maintenance therapies. Remission induction treatment typically takes 4 to 6 weeks, and in most cases, remission is achieved within about 4 weeks. Treatments include vincristine, steroids, and anthracyclines, and may also include drugs such as asparaginase, cyclophosphamide, and cytarabine [1]. Among these, asparaginase depletes intracellular levels of asparagine, which is essential for protein synthesis in leukemic cells. The agents used were Escherichia coli, polyethylene glycolated, and Erwinia asparaginases [6]. The exact etiology of asparaginase-related pancreatitis is unknown, but it is believed to involve reduced protein synthesis due to asparagine depletion by asparaginase [8,9].

In clinical trials, pancreatitis has been reported in 2 to 18% of patients receiving asparaginase therapy for ALL, with grade 3/4 pancreatitis occurring in 5 to 10% of patients. The incidence in pediatric patients can reach up to 18%, and in adults, up to 14% [10]. Previous studies have reported old age, high disease-risk stratification, peg-asparaginase, and dosage as potential risk factors. Additionally, studies have shown that genetic associations known to be linked with alcohol-induced or idiopathic pancreatitis may also be potential factors [9]. If acute pancreatitis occurs during chemotherapy for ALL, asparaginase should be withheld until the pancreatitis improves, and the drug should be permanently discontinued in cases of grade 3 or higher toxicity [11]. In this case, the patient was diagnosed with leukemia and subsequently developed pancreatitis during chemotherapy which included asparaginase. Considering that pancreatitis did not recur while the patient was receiving maintenance treatment based on 6-mercaptopurine without asparaginase, the most likely cause was drug-induced pancreatitis related to asparaginase. The prophylactic use of octreotide may be beneficial in pediatric and adult patients at risk for asparaginase-associated pancreatitis, though octreotide is not widely used at present [12].

In patients with acute pancreatitis, the development of fluid retention around the pancreas is a frequently observed complication and can present as pancreatic necrosis, pancreatic pseudocyst, or WON [13]. A pancreatic pseudocyst is a collection of clear fluid surrounded by an inflammatory wall that typically appears about 4 weeks after the onset of acute interstitial edematous pancreatitis. The pseudocyst is primarily located outside the pancreas and is not associated with necrosis. On CT, the pseudocyst appears as a distinct circular or oval shape with uniform density, contains no solid components, and is surrounded by a single wall [13]. When pseudocysts or WON exhibit symptoms or are accompanied by infection, drainage is strongly recommended rather than conservative treatment. Endoscopic, percutaneous, or surgical methods may be considered for the procedure. If the lesion is adjacent to the stomach or duodenum, endoscopic treatment may be performed.

Both plastic and metal stents can be used for endoscopic drainage [14]. PS have been widely used as they are inexpensive and can be easily removed even after prolonged periods. However, metal stents have the advantage of a large diameter, enabling efficient drainage and reducing stent blockage. Currently, LAMS is widely used as it simplifies the procedure, shortens procedure time, and yields favorable results [15]. Although most reported cases of pancreatitis complications during chemotherapy in patients with leukemia have been managed with general symptomatic treatment or percutaneous/endoscopic drainage using plastic tubes, this case is significant for its use of endoscopic treatment with LAMS. In this case, the pseudocyst was drained using Hot-SPAXUS. In endoscopic pseudocyst drainage, HOT AXIOS and HOT SPAXUS stents are devices equipped with an electrocautery tip at the distal end of the delivery system. This allows them to deliver cutting current, creating a safe and immediate drainage path between the gastrointestinal tract and the pseudocyst. This “Hot-System” refers to the electrocautery tip, which allows direct puncture without a separate needle puncture or guide wire placement, facilitating a faster and more efficient procedure, meanwhile, reducing the risk of complications. Although meta-analyses and studies have addressed acute leukemia and its complications in both children and adults, patients with leukemia require more careful consideration before undergoing endoscopic treatment compared to typical adult patients with pancreatitis.

The treatment approach should be determined by considering not only radiological evaluation but also the patient’s immune status, presence of concomitant infections, and stage of chemotherapy. Further research and development are required to enhance the safety of endoscopic procedures in specialized conditions such as leukemia.