Elevated Lipase Research Articles

S3175 Elevated Lipase in a Newly Diagnosed IBD. Is It “Pancreatically” Relevant?

S3175 Elevated Lipase in a Newly Diagnosed IBD. Is It “Pancreatically” Relevant?

Choledochocele Presenting as Recurrent Pancreatitis: A Case Report

Introduction: Choledococele is a rare congenital abnormality involving the intramural segment of the common bile duct. We report the case of a patient presenting with acute pancreatitis who was diagnosed with choledochocele. Case report: A 17-year-old boy, with a history of hospitalization 2 years ago for acute pancreatitis stage E, admitted for acute epigastralgia radiating to the back with notion of vomiting. Abdominal examination revealed epigastric tenderness without other abnormalities. Laboratory data reported leukocystosis (WBC: 16000/ul); elevated CRP at 111 mg/l; elevated Lipase at 412 IU/L. Abdominal CT scan shows stage D pancreatitis with an intra duodenal cystic formation in front of the ampulla of Vater suggesting a choledochocele. Abdominal MRI demonstrated a cystic dilatation of the lower bile duct classified as Todani type III. Echo endoscopy was performed indicating an ampullary cystic formation measuring 22,8x15,3mm which continues with the CBD evoking a choledocal cyst with presence of stones in intra-cystic. As a result of these findings, the patient was diagnosed with acute pancreatitis secondary to intraduodenal choledochocele. He had surgery with resection of the choledochocele. Conclusion: Choledococele is extremely rare. The diagnosis is facilitated by advances in imaging. Management and therapeutic choice are not yet consensual regarding radical surgical treatment or conservative endoscopic treatment.

Acute pancreatitis after cesarean section

The prevalence of acute pancreatitis in pregnancy is low; similarly to the non-pregnant population, the outcome varies from mild to fatal forms. Occurrence of the disease in pregnancy is mostly in the third trimester or the postpartum period. The most common cause of acute pancreatitis is cholelithiasis but hypertriglyceridemia, fatty diet, obesity and alcohol consumption are further predisposing factors. A 27-year-old twin-pregnant woman developed acute severe pain 2 days after a cesarean section. Labor tests showed elevated amylase (1080 U/L) and lipase (2670 U/L) serum levels. For the purpose of pain relief, we inserted an epidural catheter and indicated an abdominal computer tomography examination. The abdominal imaging did not show morphological disorder of the pancreas or cholangial obstruction. We performed conservative therapy, early per os feeding, pain relief and fluid resuscitation. On the postpartum 7. day, the serum pancreas enzyme levels decreased to normal and the patient - with her babies - was discharged home. Though acute pancreatitis is a rare event in pregnancy, we should consider it in cases with acute, typical or non-typical pain. It is challenging to differentiate the disease from the acute syndromes of pregnancy. Orv Hetil. 2023; 164(31): 1231-1234.

Pancreatitis and Hyperlipasemia in the Setting of Immune Checkpoint Inhibitor Therapy.

Immune checkpoint inhibitor-induced pancreatic injury (ICI-PI) ranges from asymptomatic hyperlipasemia to symptomatic acute pancreatitis (AP). The proportion of pancreatic injury while receiving ICIs that is attributable to therapy remains unclear. We evaluated the etiology of hyperlipasemia in patients receiving ICIs, and the clinical characteristics, management, and outcomes of ICI-PI. We assessed 6,450 consecutive adult patients with cancer who received ICI doses between 2011 and 2019, 364 of whom had at least 1 instance of elevated serum lipase after ICI initiation and were included in our trial. Primary outcomes were the development of ICI-PI and ICI-induced acute pancreatitis (ICI-AP). Pancreatic injury was attributable to ICI use in 105 individuals (29% of those with hyperlipasemia; 1.6% overall). Of 27 patients with ICI-AP, 4 (15%) presented asymptomatically with hyperlipasemia and pancreatic inflammation on imaging. In multivariable regression, the presence of other immune-related adverse events was positively associated with ICI-AP (≥2 events: odds ratio, 5.43; 95% CI, 1.47-26.03). Compared with patients with other ICI-PI, those with ICI-AP more frequently required steroids (74% vs 4%), intravenous fluids (85% vs 10%), hospitalization (89% vs 9%), and permanent cessation of ICIs due to pancreatic injury (70% vs 3%), and less frequently continued therapy uninterrupted (0% vs 40%) (P<.01 for all). Of the 105 patients, 3 (3%) developed exocrine insufficiency and 9 (9%) developed endocrine insufficiency, which were concentrated among those with ICI-AP. A minority of occurrences of pancreatitis and hyperlipasemia in patients receiving ICIs are due to these therapies, supporting NCCN recommendations to exclude alternative etiologies. Because a notable proportion of patients with ICI-AP were asymptomatic but warranted treatment per current guidelines, abdominal imaging is diagnostically valuable in those with significant hyperlipasemia. Patients with ICI-AP should be monitored for exocrine pancreatic insufficiency. Many with hyperlipasemia who do not meet the criteria for AP can continue therapy uninterrupted.

1431-P: Exocrine Pancreatic Insufficiency Is Both a Risk Factor for and Comorbidity of Diabetes Mellitus

Introduction: Exocrine Pancreatic Insufficiency (EPI) is an uncommon but important disease of the exocrine pancreas. Its relationship to endocrine pancreas function and diabetes (DM) remains poorly characterized. To better understand this relationship, a retrospective chart review was performed in a large statewide multispecialty practice. Methods: A retrospective review of the entire 1.3 million patient-practice of Ochsner Health system in Louisiana was performed to cover the period of January 2017 to January 2020. All cases of documented EPI and patients on pancreatic enzyme replacement therapy (PERT) were identified and underwent individual chart review to identify etiologic factors and cardiometabolic, demographic, vital sign data, and clinical course information. Results: 677 EPI patients were identified with DM being the most prevalent etiologic risk factor (44.6% T2DM, 9.6% T1DM and 11.5% secondary DM). EPI patients without DM had a 10.9% prevalence of pre-DM, and 127 new DM cases developed over the observation period among EPI patients initially without DM with an 18.7% incidence rate. EPI patients, compared to the general DM population, were significantly younger with more diverse DM etiology. They also had greater LFT and serum lipase elevations. EPI patients had lower BMIs; 25.6 ± 7.5 vs 32.8 ± 46.9 kg/m2 with greater alcohol use. EPI patients also had better glycemic control (HBAC 6.83 ± 2.1 vs 7.2 ± 1.9) and triglycerides (125.7 ± 104.7 vs 140.6 ± 118.9) though other lipids were similar. Discussion and Conclusions: EPI, though uncommon, is both an important risk factor for onset of DM and comorbidity of diabetes. DM patients with EPI have distinctive etiologic, metabolic, and anthropometric features from DM patients in the general population. Further study of EPI patients to better understand predictors of onset of EPI in DM patients and DM onset in non-DM EPI patients are needed to guide evidence based screening. This would in turn enable early EPI recognition and management. Disclosure K.G.Romo: None. S.Shu: None. A.A.Noor: None. W.A.West: None. S.Bhamre: None. G.I.Uwaifo: None.

Pancreatic adverse events of immune checkpoint inhibitors therapy for solid cancer patients: a systematic review and meta-analysis.

This review aims to determine the incidence and risk of pancreatic adverse events (AEs) associated with immune checkpoint inhibitors (ICIs) therapy for solid tumors. We conducted a comprehensive systematic literature search in PubMed, Embase, and Cochrane Library up to March 15, 2023, to identify all randomized controlled trials comparing ICIs with standard treatment in solid tumors. We included studies that reported immune-related pancreatitis or elevation of serum amylase or lipase levels. Following protocol registration in PROSPERO, we conducted a systematic review and meta-analysis. 59 unique randomized controlled trials with at least one ICI-containing arm (41 757 patients) were retrieved. The incidences for all-grade pancreatitis, amylase elevation and lipase elevation were 0.93% (95% CI 0.77-1.13), 2.57% (95% CI 1.83-3.60) and 2.78% (95% CI 1.83-4.19), respectively. The incidences for grade ≥3 pancreatitis, amylase elevation and lipase elevation were 0.68% (95% CI 0.54-0.85), 1.17% (95% CI 0.83-1.64) and 1.71% (95% CI 1.18-2.49), respectively. The use of ICIs was associated with an increased risk of all-grade pancreatic immune-related AEs (irAEs) including pancreatitis (OR=2.04, 95% CI 1.42-2.94, P =0.0001), amylase elevation (OR=1.91, 95% CI 1.47-2.49, P < 0.0001) and lipase elevation (OR=1.77, 95% CI 1.37-2.29, P < 0.0001). In addition to these, the post-hoc analysis found that PD-1 inhibitors had a significant higher risk of pancreatic AEs compared with PD-L1 inhibitors and the patients undergoing dual ICI therapy were at a significantly higher risk of pancreatic AEs than the patients receiving single ICI therapy. Our study provides an overview of the incidence and risk of ICI-associated pancreatitis and pancreatic enzyme elevations in the treatment of solid tumors. Our findings may help raise awareness among clinicians of the potential for ICI-associated pancreatic AEs in clinical practice. https://www.crd.york.ac.uk/PROSPERO, identifier 345350.

Subgroup analysis from a phase II trial of ponatinib and blinatumomab in relapsed/refractory (R/R) Philadelphia chromosome-positive acute lymphoblastic leukemia or chronic myeloid leukemia in lymphoid blast phase.

e19038 Background: The chemotherapy-free combination of ponatinib and blinatumomab improved outcomes in patients (pts) with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). This regimen may also induce deeper responses and prolong remissions in patients (pts) with R/R Ph+ ALL and chronic myeloid leukemia in lymphoid blast phase (CML-LBP). Methods: In this phase II trial, pts with R/R Ph+ ALL or CML-LBP received up to 5 cycles of blinatumomab. Pts received ponatinib 30mg daily in Cycle 1, with dose reduction to 15mg daily once in complete molecular response (CMR). After completion of blinatumomab, ponatinib was continued for at least 5 years. 12 doses of prophylactic intrathecal chemotherapy were administered in all pts. Results: 21 pts were treated (14 R/R, 7 CML-LBP) between 2/2018 and 7/2022. The median age of the R/R Ph+ ALL and CML-LBP cohorts were 38 years (range, 24-61) and 67 years (range, 29-82), respectively. BCR:ABL1 transcripts were p190 in 93% of the R/R cohort. 43% of pts in the R/R Ph+ ALL cohort were in Salvage 2+. Among the CML-LBP pts, 4 were de novo and 3 were transformed from previously treated CML (1 of whom had received prior therapy for LBP). Among the 14 pts with R/R Ph+ ALL, the rate of CR/CRi was 92% (12 of 13 evaluable pts), with CR in 11 (85%) pts. MMR was achieved in 86% and CMR in 79%. Six of 7 (86%) pts with CML-LBP achieved CR/CRi. Rates of MMR and CMR were 57% and 43%, respectively. The median follow-up is 24 months (range, 19-57) in the R/R cohort, and 27 months (range, 7-46) in the CML-LBP cohort. Among the 14 pts in the R/R cohort, 1 did not respond, 6 proceeded to ASCT (1 of whom relapsed and died), 4 did not undergo ASCT and relapsed after a median of 6.4 months (range, 2.7-8.1), 1 died in CR, and 2 are in ongoing response without ASCT after a median CR duration of 34 months (range, 17-51). Of the 5 relapses, 2 were hematologic only, 2 were in the CNS with MRD positivity in the bone marrow, and 1 was CNS only. The estimated 2-year EFS and OS for the R/R cohort were 50% and 64%, respectively. Among the 6 responders in the CML-LBP cohort, 3 relapsed and 3 are in ongoing response without ASCT after a median CR duration of 34 months (range, 3-43). The 2-year EFS and OS for the CML-LBP cohort are 38% and 50%, respectively. Grade 3 adverse events were febrile neutropenia, cytokine release syndrome, elevation of lipase and alkaline phosphatase in 1 pt each. There were no Grade 4-5 events. 1 pt discontinued ponatinib due to grade 3 portal vein thrombosis. 1 pt discontinued blinatumomab due to persistent grade 2 tremor. Conclusions: The combination of ponatinib and blinatumomab is an effective and well-tolerated chemotherapy-free regimen for pts with R/R Ph+ ALL. The rate of deep molecular response was relatively low in CML-LBP, suggesting that chemotherapy might still be needed in these pts. Clinical trial information: NCT03263572 .

CABIOS trial: A phase Ib study of cabozantinib and nivolumab in combination with abiraterone in patients (pts) with metastatic hormone sensitive prostate cancer (mHSPC).

5084 Background: Androgen deprivation therapy (ADT) combined with novel hormonal agents +/- docetaxel is a standard of care treatment for mHSPC. The combination of tyrosine kinase inhibitors (TKI) and immune checkpoint blockade (ICB) is FDA approved in renal cell carcinoma, and shows promising efficacy in preclinical models of prostate cancer by favorably altering the tumor immune microenvironment. There are currently ongoing trials of TKI + ICB in metastatic castration resistant prostate cancer. Here we present interim safety results from an ongoing phase Ib single-arm trial of cabozantinib + nivolumab + abiraterone/prednisone (cabo, nivo, abi/pred) in pts with newly diagnosed mHSPC (NCT04477512). Methods: Eligible pts had de-novo or recurrent mHSPC with up to 12 weeks ADT prior to enrollment, ECOG 0-1, and adequate organ function. Prior abi and docetaxel were excluded. Pts received cabo 20 mg or 40 mg daily (3+3 dose escalation in 2 cohorts) combined with nivo 480mg IV q4 weeks, and abi/pred 1,000mg/5mg daily until progression or unacceptable toxicity. The primary endpoint is safety and tolerability. Secondary endpoints include overall response rate (ORR) by RECIST 1.1, overall survival (OS), progression free survival (PFS), and PSA response. Exploratory analyses include CyTOF of peripheral blood and serum cytokine ELISA. Results: As of 19DEC2022, 17 pts were enrolled, 3 at 20mg and 14 at 40mg cabo with no dose-limiting toxicity (DLTs) observed. Median age was 65 yrs, 4/17 pts are Black, 11 had de-novo and 6 recurrent disease, with median baseline PSA 78ng/mL. Most had bone (n=16), lymph node (6), or lung (1) mets, and 11 (64.7%) had high-volume disease. With median follow-up 12.8 months, 9 pts (53%) remain on study. 1 withdrew, 3 discontinued due to disease progression (with 1 death), and 4 stopped due to toxicity. Grade ≥ 3 adverse events (AEs) include encephalitis (n=1, grade 4 likely nivo-related after 1yr on therapy), diarrhea (n=2), elevated AST/ALT (n=4), wound infection/dehiscence, adrenal insufficiency, hypertension, elevated lipase, and proteinuria (grade 3, n=1 each). No other AEs were reported outside the current safety labels for the study agents. Of 15 response evaluable pts, 7 had RECIST-measurable lesions; 4 had partial response and 3 had stable disease as best response at data cutoff. 9/14 (64.3%) evaluable had PSA &lt;0.2ng/mL at 7 months. Immune correlative studies are ongoing. Conclusions: Here we present the initial safety and preliminary efficacy results of the first trial of cabo + nivo in mHSPC patients receiving SOC ADT + abi. To date, the combination has a safety profile consistent with known AEs for these agents, no DLTs, and evidence of clinical benefit. Further follow up will be required to fully assess clinical safety, efficacy and immune responses. Future, larger studies could compare this combination to SOC ADT + abi. Clinical trial information: NCT04477512 .

Nivolumab and ipilimumab in advanced non small cell lung cancer previously treated with PD1 axis inhibition.

9121 Background: Nivolumab combined with ipilimumab is currently one of many first line treatment options for patients with advanced non-small cell lung cancer (NSCLC). The benefit of this regimen in patients with NSCLC previously treated with a programmed death 1 (PD1) axis inhibitor is unclear. Methods: We conducted a phase II study (NCT03262779) of nivolumab and ipilimumab in patients with PDL1 unselected advanced NSCLC with either primary resistance (cohort 1) or acquired resistance (cohort 2) to prior PD1 axis inhibitor therapy. Nivolumab 3 mg/kg was administered intravenously every 2 weeks, and ipilimumab 1 mg/kg every 6 weeks, and continued until disease progression or treatment limiting toxicity. If &gt; 1 response or prolonged stability (&gt; 24 weeks) using immune related response criteria were observed in the first 10 patients treated on cohort 1, an additional 30 patients would be accrued (simon 2-stage). A total of 10 patients would be accrued to cohort 2 (exploratory cohort). The primary endpoint was objective response rate (ORR) by RECIST v1.1 in cohort 1. Secondary endpoints included, ORR in cohort 2, progression free survival (PFS) and overall survival (OS) in both cohorts. Results: Among 10 patients with primary resistance to PD1 axis inhibitor therapy, no objective responses were observed (8 patients had progressive disease (PD) and 2 patients had unconfirmed stable disease (SD) as best response). Among 10 patients with acquired resistance to PD-1 axis inhibitor therapy, ORR was 10% (1 patient with confirmed complete response, 5 patients with confirmed SD including 4 patients with SD lasting more than 9 months, 3 patients with unconfirmed SD, and 1 patient with PD). Durable clinical benefit (DCB, response or SD for at least 6 months) rate was 50%. Median duration of benefit in the 5 patients with DCB was 11.9 months. Nine of the 10 patients in cohort 2 developed initial resistance to PD-1 axis inhibitor monotherapy (rather than combination chemo-immunotherapy), all received immunotherapy as part of their last line of therapy. The remaining patient developed resistance while on maintenance chemoimmunotherapy after initial response to chemoimmunotherapy; best response to trial therapy in this patient was unconfirmed SD. Median PFS/ OS in cohort 1 were 1.8 months/ 6.8 months, and in cohort 2, 6.7 months/ 31.8 months. Grade 3 treatment-related adverse events (TRAEs) occurred in 4 patients across both cohorts, including colitis (2 pts), diabetes (1 pt), pneumonia (1 pt) and elevated lipase (1 pt). There were no grade 4/5 TRAEs. Two patients discontinued trial therapy due to toxicity (colitis), both in cohort 2. Conclusions: Combination immunotherapy with nivolumab and ipilimumab does not overcome primary resistance to PD1 axis inhibitor therapy; however, can overcome acquired resistance to PD1 axis inhibitor therapy. Translational studies from tumor and serial peripheral blood collections are ongoing. Clinical trial information: NCT03262779 .

Clinical and immune phenotypes associated with immune checkpoint inhibitor-induced autoimmune diabetes.

2509 Background: ICI-induced autoimmune diabetes (ICI-DM) is an immune-related adverse event (IrAE) that affects approximately 1% of patients who receive ICI. Most reports of ICI-DM suggest that it resembles fulminant type 1 diabetes, with low or absent endogenous insulin production at presentation. However, milder cases have recently been reported, suggesting a more heterogeneous disease. In this study, we identified distinct clinical phenotypes of ICI-DM that may improve individualized approaches to management. Methods: We performed a retrospective chart review of 16,582 patients treated with either anti-PD1, anti- PDL1, anti-CTLA4, or combination between 2010 and 2022 in a multi-centered academic hospital system. We identified patients with ICI-DM as those with a new diagnosis of type 1 diabetes or drug-induced diabetes and a prescription for medium- or long-acting insulin following ICI therapy; cases were confirmed by chart review by two board-certified endocrinologists. To phenotype ICI-DM based on endogenous insulin production, we reviewed all patients with ICI-DM who had a C-peptide level in our system, which allowed us to identify and subdivide 57 cases of ICI-DM. These patients were further characterized at both initial presentation and up to 30 months of follow-up. Results: We identified six distinct groups of ICI-DM based on the presence (A+) or absence (A-) of diabetes-specific autoantibodies, further divided by level of endogenous insulin production, preserved (B+), low (B+/-) or undetectable (B-). In our cohort, A+B- patients showed to have the lowest time to diagnosis (median 45 days) and high rates of both DKA and hospitalization (67%) at presentation. At the other end of the spectrum, A-B+ patients had a longer time to diagnosis (median 176 days) and no evidence of DKA or hospitalization at presentation. Surprisingly, all groups had similar insulin requirements without significant dosage variations at 30-month follow up. Elevated lipase levels varied widely across groups with the highest rate (66.7%) reported in the A+B- cohort. The prevalence of thyroiditis in our cohort was highest in the A-B- group but did not seem to follow any specific distribution. Conclusions: Our study examined the largest data set to date of deep clinical phenotyping of patients with ICI-DM. We define at least three distinct subsets of ICI-DM, with A+B- patients being most similar to the initially described cases of fulminant type 1 diabetes. Patients with negative antibodies seem to have a milder form of the disease. Our findings also suggest significant heterogeneity and distinct underlying mechanisms amongst cases of ICI-DM. Further studies will be needed to elucidate whether these findings could extrapolate to other individual IrAEs, which may also encompass distinct phenotypes with distinct mechanisms.

Acute pancreatitis: An unusual presentation of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a multi-system and chronic inflammatory autoimmune disease characterised by the presence of autoantibodies and the creation of immune complexes, coming up with protean manifestations. Its occurrence in children is rare and acute pancreatitis as the presenting manifestation of childhood SLE is exceptional. Diagnosis of lupus pancreatitis is clinical, biological and radiological. Here, we report an 8 year 8-month-old young girl who presented to our hospital with abdominal pain, nausea and vomiting. She also had a fever, alopecia, oral ulceration and glossitis. Her investigations showed elevated serum amylase and lipase levels, suggestive of acute pancreatitis. Other investigations revealed pancytopenia, low complement, microalbuminuria and high antinuclear antibodies level, indicative of SLE. As a result, the diagnosis of lupus pancreatitis was retained. Her clinical symptoms and signs markedly improved after a course of glucocorticoid and immunosuppressive therapy. The child is now being brought for regular follow-up and is doing well.

A Systematic Approach to Patients with Elevated Levels of Serum Amylase or Lipase

Serum amylase and lipase tests are routinely performed in patients presenting with abdominal pain or even during regular health screening. Elevated serum levels of these two enzymes are often encountered in clinical practice. The differential diagnosis is broad and includes acute pancreatitis, chronic pancreatitis, gastrointestinal tract obstruction, malignancies, and other disease conditions. In this article, we review the pathophysiology of elevated amylase and lipase, possible conditions that cause the increase, and diagnostic strategies for such patients. We conclude that a systematic approach to patients with elevated amylase and/or lipase is critical to making an accurate diagnosis and initiating appropriate treatment.

Factors affecting the recurrence of acute cholecystitis after treatment with percutaneous cholecystostomy

BackgroundThe aim of this study was to determine the recurrence rate of patients who did not have interval cholecystectomy after treatment with percutaneous cholecystostomy and to investigate the factors that may affect the recurrence.MethodsPatients who did not undergo interval cholecystectomy after percutaneous cholecystostomy treatment between 2015 and 2021 were retrospectively screened for recurrence.Results36.3% of the patients had recurrence. Recurrence was found more frequently in patients with fever symptoms at the time of admission to the emergency department (p = 0.003). Recurrence was found to be more frequent in those who had a previous cholecystitis attack (p = 0.016). It was determined that patients with high lipase and procalcitonin levels had statistically more frequent attacks (p = 0.043, p = 0.003). It was observed that the duration of catheter insertion was longer in patients who had relapses (p = 0.019). The cut-off value for lipase was calculated as 15.5, and the cut-off value for procalcitonin as 0.955, in order to identify patients at high risk for recurrence. In the multivariate analysis for the development of recurrence, presence of fever, a history of previous cholecystitis attack, lipase value higher than 15.5 and procalcitonin value higher than 0.955 were found to be risk factors.ConclusionsPercutaneous cholecystostomy is an effective treatment method in acute cholecystitis. Insertion of the catheter within the first 24 h may reduce the recurrence rate. Recurrence is more common in the first 3 months following removal of the cholecystostomy catheter. Having a previous history of cholecystitis attack, fever symptom at the time of admission, elevated lipase and procalcitonin are risk factors for recurrence.

The Case Files

The Case Files

O146 Natural history and clinical outcomes in patients with groove pancreatitis: an observational study

Abstract Introduction Groove pancreatitis (GP) is a rare and focal form of pancreatitis affecting the para-duodenal groove area. Diagnosis is usually made by radiological imaging or histological analysis. This study aimed to determine the disease pattern, treatment modalities and outcomes. Methods Data were retrospectively collected for patients diagnosed with GP radiologically and/or histologically at our tertiary hospital from 2010 to 2019. A search of our imaging database was conducted using the term groove pancreatitis totalling 1,040 patients. Duplicates (95) and reports mentioning only groove or only pancreatitis (945) were eliminated. All included patients were then re-assessed by two expert hepatopancreaticobiliary radiologists and a specialist histopathologist to confirm inclusion. Results Our cohort comprised of 54 patients, 39 males and 15 females. The mean age was 67 years (range 39-101 years). Of the 54 patients, 11 had pancreatic cancer (20%). Pain as a main presenting complaint occurred in 78% and jaundice in only 13%. 26% had elevated lipase and 37% had deranged LFTs. 69% were managed conservatively as first line. 11% of patients failed conservative management and proceeded to endoscopic treatment. Surgical intervention occurred in 24%. 11% of all patients had complete symptom relief, and 76% showed symptom improvement. Mortality at 2years of follow-up, was 45% and 28% in those with and without cancer. Conclusion GP is a benign disease with a non-specific natural history. It remains unclear if there is a transition between GP and GP-associated mass. This emphasises a high index of suspicion in diagnosis, using radiological, endoscopic, and cytological analysis.

The Frequency of Pancreatic Enzyme Elevations and Effect on Disease Severity in COVID-19

Aim: In this study, we aimed to evaluate the frequency of pancreatic enzyme elevations in COVID-19-infected patients and to examine the effect on disease severity.&#x0D; Material and Methods: A total of 1249 patients who hospitalized with COVID-19 infection were included. The frequency of pancreatic enzyme elevations and the effect on disease severity in patients infected with COVID-19 were investigated.&#x0D; Results: The pancreatic enzyme elevations (amylase/lipase or both) were detected in 32 of 1249 patients (incidence 2.96%). 32 cases with a mean age of 64.97±5.63 years were included in this study. 30 (93.75%) of the cases were men’s gender. 31 (96.87%) of them had elevated amylase levels, 26 (81.25%) had elevated lipase levels and 25 (78.12%) of them had elevated both amylase and lipase levels. Only 10 (31.25%) of them tested radiological for acute pancreatitis (AP) and there was no radiological finding compatible with AP in any of the limited numbers of abdominal computerized tomography scans performed. 18 (56.25%) of the patients were transferred to the intensive care unit due to clinical worsening and mortality developed in 13 (40.62%) patients. The mean age of the deceased cases was 66.4±6.6 years and there was no statistically significant difference between deceased and survived COVID-19 patients (&gt;0.05).&#x0D; Conclusion: The median lymphocyte count was lower, and the median AST, ALT, and lipase levels were higher in the deceased group. Perhaps close clinical follow-up of patients with pathological findings in these values and radiological imaging, if necessary, may be beneficial in the method of the disease.&#x0D; Keywords: COVID-19; disease severity; pancreatic enzyme elevations.

Abstract #1385190: Empagliflozin Induced Acute Pancreatitis

Acute pancreatitis is a rapid onset inflammatory process of the pancreas which may have local and systemic manifestations. The most common causes of acute pancreatitis are gallstones and alcohol use. Other causes include drug-induced. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a class of oral hypoglycemic agents which is approved by the FDA for treating diabetes and for heart failure. 56-year-old, female patient known to have uncontrolled type 2 diabetes. Presented with a complaint of acute epigastric pain radiating to the back and then become a generalized abdominal pain, moderate in severity, not relieved by analgesic, associated with nausea and vomiting. The patient denied any history of alcohol, smoking use. A review of her medication list included sitagliptin 100 mg, metformin 2g, gliclazide 60 mg and more recently, empagliflozin 10 mg which was started seven weeks prior to symptoms onset. Physical examination was significant for tenderness in epigastric area. Laboratory workup revealed an elevated serum lipase 3851 units/L, serum amylase 3755 units\L abdominal CT scan shows mild fatty atrophy and mild peri-pancreatic fat stranding and free fluid adjacent to the tale and body suggesting evidence of acute pancreatitis. Abdominal ultrasound shows the gall bladder was without stones. The patient was admitted with diagnosis of mild acute pancreatitis and underwent conservative management. Patient condition was improved and discharged on same pre-admission antidiabetic medication with OPD follow-up. 3 weeks later she presented to the emergency department complaining from acute epigastric pain radiating to the back and association of nausea and vomiting. With tenderness in epigastric area laboratory workup revealed an elevated serum lipase and amylase. Abdominal CT scan confirmed acute interstitial pancreatitis. After 3 days of conservative management she was improved and discharged but this time her diabetologist discontinue empagliflozin and she was started on insulin. She was following up with her diabetologist in outpatient clinic and there was no history of recurrence of pancreatitis. Drug induce pancreatitis are rare cause but must be considered. It is therefore important to determine the underlying etiology of acute pancreatitis to prevent occurrence, recurrence, and the complications of pancreatitis. FDA and Health Canada have identified a potential safety issue and possible association between SGLT-2 inhibitors and acute pancreatitis but Further studies are required to investigate this association. This case report emphasized the possible association between SGLT2 inhibitors and acute pancreatitis. Physicians must be aware about this side effect as a possible cause of acute pancreatitis after exclusion of most common etiologies. Also, physician should inform the patient about the side effects of SGLT2 and the symptoms of acute pancreatitis and advised them to stop SGLT-2 inhibitors use in case such symptoms occur. Further studies are required to investigate this association.

Abstract #1407180: Drug Induced Acute Pancreatitis Secondary to Ezetimibe

Drug induced acute pancreatitis (DIAP) is a rare clinical entity with incidence of <2% in general population. Most cases are typically mild and have excellent prognosis but prompt diagnosis and cessation of offending drug is important to avoid adverse outcomes. A 58-year-old female former smoker with history of COPD and hyperlipidemia presented to the hospital with sudden onset abdominal pain radiating to the back associated with nausea and vomiting for 12 hours. On arrival vitals were normal and physical examination showed epigastric tenderness with negative murphy’s sign. Labs showed normal CBC and CMP with elevated serum lipase (2469 U/L – Normal 16 - 61 U/L) concerning for acute pancreatitis. CT abdomen and pelvis showed normal biliary tract. US of the abdomen showed no evidence of gall stone or biliary sludge. Serum lipid panel showed total cholesterol of 193, HDL of 66, LDL of 111 and triglyceride of 87. Serum Calcium was normal. Detailed history revealed no alcohol but that patient recently started ezetimibe 10 mgs daily 8 weeks prior to present due to history of statin intolerance. Her only other medication was inhaled Albuterol taken as needed. Immune panel include IgG-4 was negative. Patient was diagnosed with drug induced acute pancreatitis secondary to ezetimibe, and was managed conservatively cessation of ezetimibe, pain meds and bowel rest. Her overall condition improved in 48 hours and diet was progressed. She was discharged with outpatient follow up. Serum lipase dropped to 74 U/L prior to discharge. Drug induced pancreatitis account for ∼ 5% of all cases of pancreatitis. There is limited data on the exact mechanism by which drugs can induce pancreatitis as most evidence is bases on case reports or meta-analysis. On the basis of these case reports drugs are classified from class I-IV depending on the probability to cause pancreatitis. Some proposed mechanisms include immunologic reactions, direct toxic effect, accumulation of a toxic metabolite, ischemia, intravascular thrombosis, and an increased viscosity of pancreatic juice. Though most cases are mild the identification of the offending drug is crucial to prevent ongoing damage and recurrence. However, in most instances the diagnosis of drug induced pancreatitis and identification of offending drug can be challenging due to the presence of multiple agents. Current proposed criteria for identification include: 1) Pancreatitis develops during treatment with the drug, 2) Other likely causes of pancreatitis are not present 3) Pancreatitis resolves upon discontinuation of the drug and 4) Pancreatitis usually recurs upon re-administration of the drug. Our patient fulfilled 3 of the above criteria which suggest Ezetimibe induced Pancreatitis. Prior to this case there is one more case reported cases of Ezetimibe induced Pancreatitis but in both the cases there is no re-challenge of Ezetimibe which makes it a Class IV drug to cause pancreatitis.

Treatment of Central Nervous System Post-Transplant Lymphoproliferative Disorder in Immunocompromised Patients with Pancreas Transplant– Between the Rock and a Hard Place (P2-13.002)

<h3>Objective:</h3> To describe the clinical presentation and management of two patients who developed pancreatic transplant rejection during treatment of post-transplant CNS lymphoma (PT-CNSL). <h3>Background:</h3> PT-CNSL is a rare neoplasm developing after immunosuppressive therapy following solid-organ transplantation. Treatment involves reducing immunosuppression, which risks graft rejection. In pancreas transplant recipients, this is associated with increased mortality rates with limited therapeutic alternatives. <h3>Design/Methods:</h3> NA <h3>Results:</h3> <h3>Case Description:</h3> <h3>Case 1:</h3> a 43-year-old female status post pancreas-kidney transplant was diagnosed with PT-CNSL in 2022, initially managed by withholding tacrolimus and initiating rituximab therapy at 375 mg/m2 IV (starting weekly for 3 months, then monthly). The lymphoma regressed with treatment until the patient experienced pancreatic graft rejection (lipase peak 1,124 U/L). This was treated by adding on low-dose tacrolimus which resulted in an improvement in graft rejection and allowed ongoing therapy with rituximab, yielding a complete response of the PT-CNSL. <h3>Case 2:</h3> A 55-year-old female status post pancreas-kidney transplant in 2010, was diagnosed with PT-CNSL in 2021. Treatment involved discontinuation of mycophenolate and tacrolimus and initiation of rituximab at 375 mg/m2 IV (starting weekly for six months, then monthly). Although the lymphoma regressed, the patient experienced acute epigastric pain with a lipase peak of 2,715 U/L with CT of the abdomen illustrating acute pancreatitis. Due to concern for transplant rejection, low-dose tacrolimus was initiated along with rituximab, resulting in resolution of elevated lipase. Continued serial neuroimaging studies demonstrated a complete response. <h3>Conclusions:</h3> PT-CNSL increases morbidity and mortality in pancreas transplant patients with limited treatment options. Treatment should balance maintaining CNS response with careful re-initiation of immunosuppression in the setting of graft rejection; however, there is limited knowledge regarding ideal doses of immunosuppression. We demonstrate that low-dose tacrolimus to prevent graft rejection was safe and effective in treating two patients with PT-CNSL, highlighting the need for further investigation into optimal management strategies. <b>Disclosure:</b> Mrs. Haque has nothing to disclose. Prof. ORLANDO has nothing to disclose. Glenn Lesser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cancer Expert Now. Glenn Lesser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for SDP Oncology. Glenn Lesser has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Agios. Glenn Lesser has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Incysus . Glenn Lesser has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ONO Pharma. Glenn Lesser has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer. The institution of Glenn Lesser has received research support from Denovo Biopharma. The institution of Glenn Lesser has received research support from Oblato . The institution of Glenn Lesser has received research support from Novocure. The institution of Glenn Lesser has received research support from GBM Agile - GCAR. Dr. Strowd has received personal compensation for serving as an employee of Kaplan. Dr. Strowd has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Monteris Medical, Inc. Dr. Strowd has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novocure. Dr. Strowd has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Academy of Neurology. The institution of Dr. Strowd has received research support from Southeastern Brain Tumor Foundation. The institution of Dr. Strowd has received research support from Jazz Pharmaceuticals. The institution of Dr. Strowd has received research support from National Institutes of Health. The institution of Dr. Strowd has received research support from Alpha Omega Alpha. The institution of Dr. Strowd has received research support from American Board of Psychiatry and Neurology. Dr. Strowd has received publishing royalties from a publication relating to health care. Dr. Strowd has received publishing royalties from a publication relating to health care.

Abstract CT227: Interim results of a phase 1b/2 study of ADG126 (a masked anti-CTLA-4 SAFEbody®) monotherapy and in combination with toripalimab (an anti-PD-1 antibody) in patients (pts) with advanced/metastatic solid tumors

Abstract Background: ADG126 is an anti-CTLA-4 fully human IgG1 SAFEbody® with a masking peptide blocking the antigen binding site. ADG126 is designed to be preferentially activated in the tumor microenvironment (TME), with the goal of limiting on-target off-tumor toxicities and promoting prolonged exposure to active drug in the TME. Activated ADG126 binds to a unique and conserved epitope of CTLA-4 with species cross-reactivity. Nonclinical studies have demonstrated that activated ADG126 potentiates T cell activation and depletes immunosuppressive Tregs through strong antibody-dependent cellular cytotoxicity (ADCC) specifically in the TME. We present interim results from our ongoing Phase 1b/2 study (ADG126-1001, NCT04645069) on dose escalation and expansion of ADG126 monotherapy as well as dose escalation of ADG126 + toripalimab (Tori). Method: Pts with advanced solid tumors received ADG126 monotherapy (0.1, 0.3, 1, 3, 10, and 20 mg/kg) Q3W IV or ADG126 (6 or 10 mg/kg) + Tori (240mg) Q3W IV. Primary endpoints are safety and tolerability. Secondary endpoints are PK, anti-drug antibody (ADA), as well as ORR, DCR, DOR and PFS per RECIST 1.1. Result: As of Dec. 26, 2022, 30 pts have received ADG126 monotherapy. The median number of treatment cycles was 2 (range: 1-24). The median age was 63.5 (39-84) years. 43% of pts had ≥ 3 prior lines of therapies, and 47% had been previously treated with anti-PD-(L)1 and/or anti-CTLA-4 therapies. ADG126 was well-tolerated with no dose-limiting toxicities (DLTs) observed, nor was the MTD reached. Only Grade (G) 1-2 TRAEs were reported; TRAEs ≥10% included diarrhea (17%), fatigue (17%), pruritus (13%), and rash (10%). Among 27 evaluable pts, DCR = 37%. One pt with ovarian serous carcinoma had a major CA125 response (90% reduction) and her disease was stable with ongoing treatment of ADG126 1 mg/kg at Cycle 24 (~16 months). In addition, 14 pts have received ADG126 + Tori in the dose escalation cohorts. The median age was 60 (36-85) years; 50% had ≥ 3 prior lines of therapies, and 43% received prior anti-PD-1 therapies. Both dose levels were well tolerated with no DLT. TRAEs (&amp;gt; 10%) included diarrhea (21%), fatigue (14%), pruritus (14%), rash (14%) and nausea (14%). After multiple cycles at 6 or 10 mg/kg Q3W, G3 TRAEs were observed in 21% (3/14) pts, including elevated liver function test/hepatitis, elevated lipase and diarrhea, which are immune-related, and sepsis. No G4/5 TRAEs have been reported. Among 12 evaluable pts, DCR = 58%, including 2 partial responses. Early efficacy signals were observed with continuous tumor shrinkage and stabilization in IO-resistant and cold tumors. Conclusion: The anti-CTLA-4 SAFEbody ADG126 shows favorable safety profiles in monotherapy up to 20 mg/kg and in combination with Tori up to 10 mg/kg. Furthermore, promising anti-tumor activity in heavily pre-treated patients was observed in the dose escalation phase. By enabling higher dose levels in combination with anti-PD-1 therapy, ADG126 may unleash the full therapeutic potential for proven and novel indications. Citation Format: Mihitha Ariyapperuma, John J. Park, Adnan Khattak, Gary Richardson, Anis Hamid, Michelle Morris, Anthony W. Tolcher, Boon Cher Goh, Justina Lam, Bartosz Chmielowski, Kristine She, Yanyan Zhang, Ai Li, Songmao Zheng, Guizhong Liu, Lvyu Zhu, Hongyan Wang, Xiaoxing Cui, Peter Luo, Jiping Zha. Interim results of a phase 1b/2 study of ADG126 (a masked anti-CTLA-4 SAFEbody®) monotherapy and in combination with toripalimab (an anti-PD-1 antibody) in patients (pts) with advanced/metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT227.