History Of Pancreatitis Research Articles

Assessment of pre and intra-operative predictors for difficult laparoscopic cholecystectomy

Background: Laparoscopic cholecystectomy from the day of its introduction has aimed at improving the results of traditional surgical treatment and is regarded as gold standard treatment in cholecystitis. Objective: To assess various operative predictors for difficult laparoscopic cholecystectomy. Material and methods: The present prospective study was conducted over 100 patients with diagnosis of cholelithiasis confirmed by abdominal ultrasonography (USG). Surgical procedure was categorized postoperatively into easy, difficult and very difficult surgical procedure on the basis of time taken in minutes, bile/stone spillage, injury to duct and conversion to open cholecystectomy. All patients were evaluated for risk factors preoperatively and intraoperative findings were noted. Data so obtained was analyzed us-ing SPSS-22 data analysis software. Chi square test was used for statistical analysis with p<005 as significant value. Results: The present study found that obesity, co-morbid diseases, previous history of acute cholecystitis or pancreatitis, delayed surgery after 72 hour of gall bladder inflammation, increased thickness of gallbladder, multiple stones, size of calculi more than 1 cm are significant factors that result in difficult and very difficult surgical procedures. Conversion to open cholecystectomy was seen in 25 (25%) patients.

Risk of cardiovascular disease and mortality in patients with diabetes and acute pancreatitis history: a nationwide cohort study

Patients with acute pancreatitis (AP) may have an increased risk of cardiovascular disease (CVD). Few studies have dealt with the association between AP and the risk of CVD in diabetic patients. This study aimed to investigate the risk of CVD and mortality in patients with diabetes and AP history by analyzing a large-scale national claims database in Korea. Data from the Korean National Health Insurance Service database was analyzed. A total of 2,746,988 participants with type 2 diabetes mellitus that underwent a general health examination between 2009 and 2012 were enrolled. The participants were divided into two groups according to AP history (yes or no) prior to the examination date, and follow-up data until 2018 was analyzed. The primary endpoint was the occurrence of stroke, myocardial infarction (MI), or death. The Cox proportional hazards regression analysis was used to evaluate the association between AP history and the risk of stroke, MI, and mortality. After exclusion, the included number of participants with and without AP history were 3,810 and 2,258,910, respectively. The presence of AP history showed a significantly higher incidence of stroke, MI, and mortality. The adjusted hazard ratios (95% confidence interval) for the risk of stroke, MI, and mortality were 1.534 (1.342–1.753), 1.998 (1.733–2.303), and 2.353 (2.200–2.515), respectively. Age < 65, male sex, current smoking, and drinking significantly increased the risk of death in the subgroup analyses. The risk of stroke, MI, and mortality was significantly higher in diabetic participants with AP history than those without AP history at 9-year follow-up. This suggests that active management of cardiovascular risk factors is necessary in diabetic patients with AP history.

RF28 | PSUN182 Risk of Pancreatitis After Glp-1 Receptor Agonist in Individuals With Known History of Pancreatitis

Abstract Introduction Randomized clinical trials identified a small increased risk of acute pancreatitis in patients using glucagon-like peptide-1 receptor agonist (GLP1- RA) therapy. As a result, GLP-1RA therapy is generally avoided in patients with a history of acute pancreatitis. The aim of this report was to evaluate the real-world experience of GLP-1RA therapy in patients with a history of acute pancreatitis. Methods A retrospective chart review was conducted (2010-2019) using the enterprise-wide electronic health record (EHR) system. Patients with a history of acute pancreatitis and a subsequent encounter diagnosis of acute pancreatitis (ICD-9/ ICD-10 codes), after exposure to GLP-1R, were identified. Exposure to GLP-1RA was defined as a documented prescription for GLP-1RA in the EHR. Patients were followed until the date of recurrent acute pancreatitis (RAP) or censoring. Categorical and continuous variables were summarized using N (%) and mean (SD), respectively. Results A total of 161 patients were identified, 50.9% were female, 56.6% Caucasian, with mean age (years) 54 (±13) and mean BMI 35 kg/m2 (±8). Type 2 diabetes, hypertension, and obesity were present in 92.5% (N=149), 86.3% (N=139), and 73.9% (N=119), respectively. The mean duration of follow-up for all patients was 28.2 months (±24.6). The etiologies of the first documented episode of pancreatitis prior to GLP-1RA exposure were gall stones (N=49, 30.4%), alcoholism (N=21, 13%), hypertriglyceridemia (N=9, 5.6%), medication-induced N=5 (3.1%), and the remaining cases (N=77, 47.8%) were classified as idiopathic. Among these 161 patients, N=16 (9.9%) had a second episode of pancreatitis after GLP1-RA exposure. The mean duration of exposure to GLP-1RA prior to RAP was 10.8 months (±7.2). RAP was attributed to GLP 1-RA exposure N=6 (37.5%), alcohol intake N=2 (12.5%), hypertriglyceridemia N=3 (18.8%), oral hypoglycemic agent N=1 (6.2%), ampulla stenosis N=1 (6.2%), and the remaining N=3 (18.8%) were considered idiopathic. Conclusions Among 161 patients with a history of acute pancreatitis exposed to GLP-1RA, a total of 16 (9.9%) cases of RAP were identified, but only N=6 (4%) of these were determined attributable to GLP-1RA exposure. The overall rate of RAP among our cohort of GLP-1RA exposed patients (9.9%) is similar to the overall rate of RAP reported in the literature (12.7%), regardless of the underlying etiology or drug exposure.1 Acute pancreatitis related to drug exposure is a diagnosis of exclusion; thus, it is certainly possible that some of the cases in our report considered idiopathic were actually related to GLP-1RA exposure. While caution needs to be exercised, our data would support the use of GLP-1RA in patients with a history of acute pancreatitis, on an individualized basis, where the benefits are considered to outweigh the risks. References 1) Mallick et al. Differences between the outcome of recurrent acute pancreatitis and acute pancreatitis. JGH Open. 2018 Jun 6;2(4): 134-138. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:30 p.m. - 12:35 p.m.

Associations Between Iron Homeostasis and Pancreatic Enzymes After an Attack of Pancreatitis.

Dysregulation of iron homeostasis and exocrine pancreatic dysfunction are linked but remain undefined in individuals with a history of pancreatitis. The objective is to investigate the relationship between iron homeostasis and pancreatic enzymes in individuals after a pancreatitis attack. This was a cross-sectional study of adults with a history of pancreatitis. Markers of iron metabolism (hepcidin and ferritin) and pancreatic enzymes (pancreatic amylase, pancreatic lipase, and chymotrypsin) were measured in venous blood. Habitual dietary iron intake data (total, heme, and nonheme iron) were collected. Multivariable linear regression analyses were performed while considering covariates. One hundred and one participants were studied at a median of 18 months after their last pancreatitis attack. Hepcidin was significantly associated with pancreatic amylase (β coefficient, -6.68; 95% confidence interval, -12.88 to -0.48; P = 0.035) and heme iron intake (β coefficient, 0.34; 95% confidence interval, 0.08 to 0.60; P = 0.012) in the adjusted model. Hepcidin was not significantly associated with pancreatic lipase or chymotrypsin. Ferritin was not significantly associated with pancreatic enzymes and dietary iron intake. An iron homeostasis-exocrine pancreas crosstalk exists in individuals after an attack of pancreatitis. The role of iron homeostasis in pancreatitis warrants high-quality purposely-designed studies.

PSUN63 Approach to hyperlipidemia management in Carnitine Palmitoyltransferase II deficiency

Abstract Background Carnitine Palmitoyltransferase II deficiency (CPT II) is a disorder of long-chain fatty-acid oxidation. Clinical presentations include a lethal neonatal form, severe infantile hepatocardiomuscular form, and myopathic form. The myopathic form is the most common disorder of lipid metabolism affecting skeletal muscle. Individuals with CPT II deficiency are unable to metabolize long-chain fatty acids and can have myalgia. The incidence of statin-induced muscle symptoms is 1.5% to 5%. Individuals with CPT II deficiency have been reported to have an increased incidence of statin-associated myopathy. Yet, it remains crucial to place patients with high ASCVD risk on the appropriate statin therapy. Case Presentation We present a 70-year-old male with medical history of CPT II deficiency (myopathic form), hyperlipidemia with significant hypertriglyceridemia, hypertension, type 2 diabetes mellitus, carotid artery stenosis, atrial fibrillation, and recurrent pancreatitis. Family history was positive for hyperlipidemia and premature coronary artery disease. After history of recurrent pancreatitis and severe myalgias, patient was diagnosed with CPT II deficiency at the age of 30 years. The myalgias were managed by increased carbohydrates intake for many years. Multiple low potency statins, and fenofibrate were attempted but he developed severe myalgia with elevated CPK levels. Eventually he was started on ezetimibe 10 mg daily with fish oil 2000 mg twice daily but his LDL-C continued to rise. CMP and TSH were within normal limits. Nuclear stress test was normal but his ASCVD risk score was 39%. Given the patient's CPT II deficiency and high risk for ASCVD score, statin was recommended for primary prevention. After a thorough discussion of risks and benefits of lipid-lowering therapy, the patient was started on pitavastatin 2 mg twice-weekly regimen and ezetimibe 10mg was continued. Eight weeks later, his LDL-C reduced from 132 mg/dl to 94 mg/dl (n &amp;lt;129mg/dl), TG from 449 mg/dl to 307 mg/dl (n 0-149 mg/dl). As he experienced no myalgias, an extra tablet of pitavastatin a week was added until he reached a daily regimen. He continued to tolerate this treatment and his LDL-C improved to 66 mg/dl with normal CPK levels. Clinical Lesson: We present a case of CPT II deficiency and significant hyperlipidemia successfully managed with pitavastatin and ezetimibe, which helped to achieve a desirable LDL-C. Pitavastatin is not metabolized by hepatic CYP3A4 isoenzyme as other statins and is minimally metabolized by CYP2C9. In addition, patients with CPT II deficiency may benefit from avoiding extended episodes of exertion and high-fat diet. When treating patients with CPT II deficiency and hyperlipidemia, close follow-up and laboratory monitoring will be needed. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

PSUN270 Magnified Risk of Pancreatitis by GLP-1: A Case of Necrotizing Pancreatitis in a Patient on Dulaglutide with Baseline Elevated Triglycerides

Abstract Introduction Glucagon-like peptide 1 receptor agonists (GLP-1 RA), used in the treatment of diabetes mellitus, have been associated with pancreatitis in both animal studies and clinical trials. Furthermore, GLP-1 RA are associated with increased levels of serum lipase and amylase, possibly indicating resultant pancreatic inflammation.1 While there is debate on the actual degree of risk of pancreatitis in patients on GLP-1 RA, there may be individuals who are at higher risk due to baseline comorbidities that may have their risk of pancreatitis further potentiated by treatment with GLP-1 RA. We present a case in which a patient with baseline moderately elevated triglycerides on long term GLP-1 RA develops necrotizing pancreatitis after minimal alcohol intake. Case A 46-year-old man with type 2 diabetes mellitus, hyperlipidemia, and depression presented with one day history of severe right upper quadrant abdominal pain, nausea, and non-bloody, non-bilious vomiting. He also endorsed subjective fevers and chills, shortness of breath, chest pain, and constipation. He reported that he had drank one bottle of sparkling wine the day prior but denied drinking regularly. Labs and imaging were consistent with acute necrotizing pancreatitis with elevated lipase (502 U/L), elevated triglycerides (TG) (3,480 mg/dL), and CT abdomen/pelvis showing focal hypoattenuation/edema of the pancreatic head with surrounding fat stranding. Subsequent MRI abdomen showed evolving necrotic pancreatitis with focal area of nonenhancement in the pancreatic head. He denied any history of gallstones, recent trauma, diarrhea, weight loss, or prior pancreatitis. Review of his medications was notable for dulaglutide for management of his diabetes. He also had a history of consistently elevated TG to the mid-300s mg/dL as far back as 3 years ago. Patient was ultimately managed conservatively with intravenous fluids with resolution of symptoms and downtrend of lipase and triglycerides. He was discharged on fenofibrate and icosapent ethyl for further triglyceride control. Discussion While several META analyses have not shown significant association between GLP-1 RA and pancreatitis, there still is a proportion of patients who have developed pancreatitis on GLP-1 RA.2 Our patient had baseline elevated triglycerides, but they were below the typical threshold for treatment. With minimal alcohol consumption, he still developed pancreatitis. We suspect that his risk for pancreatitis was magnified by his GLP-1 RA. We believe that in patients such as ours who have baseline independent risk factors for pancreatitis, GLP-1 RA should be carefully considered before initiation. 1. Trujillo J. Safety and tolerability of once-weekly GLP-1 receptor agonists in type 2 diabetes. J Clin Pharm Ther. 2020;45 Suppl 1(Suppl 1): 43-60. doi: 10.1111/jcpt.13225 2. Monami M, Dicembrini I, Nardini C, Fiordelli I, Mannucci E. Glucagon-like peptide-1 receptor agonists and pancreatitis: a meta-analysis of randomized clinical trials. Diabetes Res Clin Pract. 2014;103(2): 269-275. doi: 10.1016/j.diabres.2014.01.010 Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

RF24 | PSUN126 A Very-Low Calorie Diet Can Reduce Insulin Resistance and Cause Remission of Diabetes Mellitus and Hypertriglyceridemia in a Patient With Familial Partial Lipodystrophy Type 2

Abstract Background Lipodystrophy syndromes are associated with inadequate adipocyte capacity that results in an earlier threshold for ectopic deposition and metabolic dysfunction. We have previously reported that patients with familial partial lipodystrophy (FPLD) present with metabolic severity equivalent to what is observed at 8-12 BMI points higher in a population with common obesity. Currently, there is no strong evidence that any specific diet is the preferred treatment, but bariatric surgery has been reported to improve metabolic outcomes in a few patients. Here, we report the effect of an aggressive calorie-restricted diet in a patient with FPLD who showed remarkable benefit after 16 weeks of the intervention. Clinical Case This is a 38-year-old female diagnosed with FPLD type 2, with LMNA p. R482Q mutation who had a history of recurrent pancreatitis, NAFLD, impaired ovulation, and diabetes mellitus. She had a short-term goal of improving her metabolic state rapidly to achieve pregnancy by IVF. Upon presentation, body weight was 81.6kg, BMI 23.2kg/m2, HbA1c 7.7% and triglycerides 215mg/dL. She was started on very-low calorie diet (VLCD) (800 kcal/day) employing a formula total liquid diet meal replacement: 160 kcal per shake (18g total carbohydrates, 15g net carbohydrates, 3.5g fat, and 16g protein) with the goal to reduce body weight by 15% as has been described for patients in the University of Michigan Weight Management Program. After 1 week on diet, she discontinued glucose and lipid lowering therapies. After 12-weeks of VLCD followed by 4 weeks of transition to low-calorie diet (incorporating 3 meal replacements, one meal, and ad libitum non-starchy vegetables), we observed 12.3kg of body weight and a 1.4% decrease in HbA1c. Insulin resistance was reduced by 66.7 and 61.5% (HOMA-IR and ADIPO-IR, respectively). Fasting insulinemia was reduced by 64.2%. We also performed an OGTT with 75g of glucose for 180 min and observed a decrease in the area under the curve of insulin (-33.2%), triglycerides (-40.7%), and free fatty acids (-34%). DEXA scan showed a reduction in total body fat of 16%. Liver fat via the chemical shift MRI method was reduced from 10±2% to 2±1%. She did not experience any adverse events during the intervention. More importantly, her egg retrieval rate and egg quality during IVF were far superior to past attempts. Conclusion This case illustrates the strong effect and safety of a VLCD intervention in a patient with lipodystrophy. We observed rapid reduction in body weight, and in insulin resistance leading to the remission of diabetes mellitus, hypertriglyceridemia and fatty liver disease. Moreover, there was improved response to ovulation induction. Our data encourage the use of this medical approach for other patients with similar metabolic and reproductive abnormalities due to adipose tissue distribution abnormalities. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 12:36 p.m. - 12:41 p.m.

PSUN236 Previously Undiagnosed Hereditary Pancreatitis Presenting as New Onset Type 3c Diabetes Mellitus

Abstract Background Type 3c Diabetes Mellitus (DM3c) or Pancreatogenic Diabetes is defined as diabetes secondary to pancreatic disease. The most common cause of Type 3c Diabetes is chronic pancreatitis, accounting for 80% of cases.1 Hereditary pancreatitis, with mutations such as SPINK1, CFTR, CTRC, is an underdiagnosed cause of chronic pancreatitis leading to Type 3c Diabetes Mellitus.1 The typical disease course for hereditary pancreatitis is recurrent episodes of acute pancreatitis that leads to chronic pancreatitis.1 The average time between hereditary pancreatitis diagnosis and development of DM3c has been shown to be 80 +/- 24 months.1 We present a case of previously undiagnosed hereditary pancreatitis presenting as new onset Type 3c Diabetes Mellitus. Clinical Case A 33-year-old male presents with a two month history of diarrhea, epigastric pain, and weight loss. Vital signs on presentation were blood pressure 105/74, heart rate 59, BMI 13. Physical exam revealed a cachectic appearing male with epigastric tenderness. Lab-work showed blood glucose 819 mg/dL, SOsm 313 mOsm/kg, lipase 21 U/L, bicarbonate 33 mmol/L. A computed tomography (CT) of the abdomen revealed punctate pancreatic parenchymal calcifications, suggestive of chronic pancreatitis. He was admitted to general medicine for management of HHS, where he was treated with IV hydration and insulin therapy. Workup for new onset diabetes revealed a negative anti-GAD Ab &amp;lt;5.0 U/mL, and C peptide level 0.5 ng/mL which suggested β cell dysfunction and decreased endogenous insulin secretion. With these lab values, along with radiographic findings consistent with chronic pancreatitis, the likely driving factor for his diabetes was pancreatic disease and he was diagnosed with DM3c. Severe pancreatic disease was further shown by a reduced fecal elastase level of &amp;lt;50, suggesting exocrine pancreatic insufficiency. Investigating the etiology of his chronic pancreatitis, history revealed no prior episodes of acute pancreatitis or abdominal pain, and no family history of pancreatitis. Workup for common causes of pancreatitis, including alcohol use, hypertriglyceridemia, and gallstones was negative, and genetic workup was pursued. The patient was found to be heterozygous for a SPINK1 mutation, which is a known mutation in hereditary pancreatitis.1 Therefore, hereditary pancreatitis was determined to be the likely cause of his chronic pancreatitis which led to Type 3c Diabetes Mellitus. He was started on daily insulin therapy and pancreatic enzymes for his endocrine and exocrine pancreatic dysfunction respectively, with improvement in symptoms. Conclusion This is a unique case of hereditary pancreatitis presenting as new onset Type 3c Diabetes Mellitus with no prior episodes of acute pancreatitis or established diagnosis of chronic pancreatitis. References Ramalho, G. X., &amp; Dytz, M. G. (2020). Diabetes of the exocrine pancreas related to hereditary pancreatitis, an update. Current Diabetes Reports, 20(6). Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

PSUN241 A Case of Dulaglutide-Induced Acute Pancreatitis in a Diabetic Patient – A Case Report

Abstract Introduction Dulaglutide is a glucagon-like peptide-1 (GLP-1 RA) receptor agonist that was approved by the FDA as a pharmacological treatment of diabetes management over the last decade. It is available in an injectable form that is dosed weekly which increases patients’ adherence and improves outcomes. The mechanism of action of GLP-1 RA is through regulation of blood glucose levels through glucose-dependent stimulation of insulin secretion and inhibition of glucagon release. Also, their effect on GLP-1 receptors in the CNS and the gastrointestinal tract leads to delay in gastric emptying and induces satiety. Such mechanism of action decreases the risk of hypoglycemia and facilitates weight loss. All these features make GLP-1 RA of great interest among new diabetes pharmacological options.The most frequently reported adverse effects from GLP-1 RA are gastrointestinal symptoms and injection-site pruritus. Acute pancreatitis is a rare but serious complication of GLP-1 RA use. We present a case of Dulaglutide-induced acute pancreatitis in a diabetic patient. Case presentation 77-year-old type II diabetic male on Dulaglutide 1.5 mg weekly which was increased to 3 mg weekly 2 weeks prior to a presentation presented with epigastric pain, nausea, and vomiting for 2 days. The patient denied any previous episodes, history of gallstones or alcohol use or recent endoscopic retrograde cholangiogram. An abdominal exam revealed epigastric tenderness. Laboratory workup was remarkable for Lipase of 953, otherwise, Calcium, triglycerides, liver enzymes were within normal limit. Computed tomography scan of the abdomen confirmed pancreatitis. Right upper quadrant ultrasound showed no evidence of gallstones or biliary system dilation. Holding Dulaglutide with standard treatment for pancreatitis resulted in symptom resolution. Discussion GLP-1 RA-induced pancreatitis is a very serious adverse event, yet this association has not been well established in humans, especially that baseline rate of pancreatitis in diabetic patients (most population studied using GLP-1 agonist) is higher compared to the general population. Until now most available data are driven from studies on animals, case reports, and a few observed cases on studies.Pathophysiologyis not well understood. One theory is thought to be due to GLP-1 RA effect on decreasing gut motility including biliary and gallbladder, which increases the risk of gallstone formation. However, not all reported cases had history of gallstones. This leads us to the other suggested mechanism through effect of GLP-1 RA on exocrine pancreas through ductal proliferation and metaplasia which if severe, can lead to hemorrhagic pancreatitis.Hence, the GLP-1 RA use should be judicious in patients with high risk of pancreatitis, such as severe hypertriglyceridemia, alcohol intake, or prior pancreatitis history. Conclusion Diabetes and hypertriglyceridemia are independent risk factors of acute pancreatitis. Future studies are warranted to assess GLP-1 RA-induced pancreatitis in non-diabetic patients and to investigate its dose-dependence relationship. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Efficacy of pancreatic duct stenting to prevent postendoscopic retrograde cholangiopancreatography pancreatitis after covered self-expandable metal stentdeployment.

Although covered self-expandable metal stents (CSEMSs) are associated with the risk of postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis due to pancreatic duct (PD) orifice obstruction, they are often used for biliary drainage treatment in malignant biliary obstruction (MBO). This study aimed to investigate the efficacy of PD stenting in preventing post-ERCP pancreatitis after CSEMS implantation. This retrospective cohort study analyzed 554 patients with transpapillary CSEMS for MBO. Patients with noninitial deployment, benign disease, CSEMS deployment above the papilla, surgically altered anatomy, uncovered self-expandable metal stents, multiple thin self-expandable metal stents, and unavailable procedure videos were excluded. Logistic regression analysis estimated the association between PD stenting and post-ERCP pancreatitis incidence. We adjusted for age, sex, pancreatitis history, prophylactic rectal nonsteroidal anti-inflammatory drug use, naïve papilla, MBO etiology, and prolonged biliary cannulation time. Among 554 patients, 67 (12.1%) experienced post-ERCP pancreatitis. Post-ERCP pancreatitis was recorded in 13.7% of patients in the non-PD stenting and 4.3% in the PD stenting groups. Pancreatic duct stenting was associated with lower risks of post-ERCP pancreatitis (odds ratio [OR] 0.28; 95% confidence interval [CI] 0.099-0.79; P = 0.028). In multivariable analysis, the association between PD stenting and lower post-ERCP pancreatitis incidence was consistent (OR 0.19; 95% CI 0.062-0.58; P = 0.0034). Pancreatic duct stenting could reduce the risk of post-ERCP pancreatitis after CSEMSs.

Risk Factors Associated with Pancreatic Cancer in the UK Biobank Cohort.

Simple SummaryThe study explored pancreatic cancer (PaCa) risk factors in the UK Biobank cohort. The risk factors included non-modifiable risk factors: age, gender, and modifiable risk factors: cigarette smoking, overweight and obesity, increased waist circumstance, abdominal obesity, Diabetic Mellitus (DM), and pancreatitis history. The study findings suggested that stopping cigarette smoking, avoiding overweight or obesity, abdominal obesity, Diabetic Mellitus, and pancreatitis history could contribute to a significant reduction in future PaCa cases if these exposures are avoided.Evidence on pancreatic cancer (PaCa) risk factors from large population-based cohort studies is limited. This study investigated the PaCa risk factors and the population attributable fraction (PAF) of modifiable risk factors in the UK Biobank cohort. The UK Biobank is a prospective cohort consisting of 502,413 participants with a mean follow-up time of 8.2 years. A binomial generalized linear regression model was used to calculate relative risks for PaCa risk factors. PAF was calculated to estimate the proportional reduction in PaCa if modifiable risk factors were to be eliminated. A total of 728 (0.14%) PaCa incident cases and 412,922 (82.19%) non-PaCa controls were analyzed. The non-modifiable risk factors included age and gender. The modifiable risk factors were cigarette smoking, overweight and obesity, increased waist circumstance, abdominal obesity, Diabetic Mellitus (DM), and pancreatitis history. The PAF suggested that eliminating smoking and obesity can contribute around a 16% reduction in PaCa cases while avoiding abdominal obesity can eliminate PaCa cases by 22%. Preventing pancreatitis and DM could potentially reduce PaCa cases by 1% and 6%, respectively. This study has identified modifiable and non-modifiable PaCa risk factors in the UK population. The PAF of modifiable risk factors can be applied to inform PaCa prevention programs.

RARE CASE OF SEVERE NECROTIZING PNEUMONIA DUE TO STREPTOCOCCUS PYOGENES RESULTING IN REFRACTORY HYPOXEMIA

RARE CASE OF SEVERE NECROTIZING PNEUMONIA DUE TO STREPTOCOCCUS PYOGENES RESULTING IN REFRACTORY HYPOXEMIA

S1765 Management of Young Patients With Recurrent Episodes of Acute Pancreatitis

Introduction: Hereditary pancreatitis (HP) is a rare genetic condition, the evolution of which is marked by recurrent episodes of acute pancreatitis that begin in childhood or adolescence and lead to the early inception of chronic pancreatitis and a significant increase in the risk of pancreatic cancer in young adults. Case Description/Methods: We present the case of a 22-year-old patient, with repeated appearances in the gastroenterology department for episodes of acute pancreatitis (11 episodes), started at the age of 15, for which recent computed tomography scan (2022) showed changes suggestive for chronic pancreatitis. Anamnestic and laboratory tests have ruled out alcohol use, medications, dysmetabolic syndrome, as the most common causative factors involved in triggering episodes of acute pancreatitis. The echo-endoscopic investigation with biopsy was negative for specific markers of autoimmune pancreatitis. Given the positive history of acute pancreatitis (multiple episodes) of relatives (father and uncle), the presence of inherited genetic mutations was taken into account. The result of the genetic panel revealed the presence of a pathogenic variant probably heterozygous in the PRSS1 gene associated with hereditary pancreatitis (Figure). The case was included in an individualized management program with multidisciplinary involvement, with a focus on pain management, medical therapy for endocrine and exocrine insufficiency, and surveillance of the sequelae of chronic pancreatitis and pancreatic adenocarcinoma. Discussion: The recurrence of acute pancreatitis episodes at a young age, with negative results for the causes frequently involved in the onset of acute episodes (toxic, metabolic, autoimmune), but with a positive family history of acute pancreatitis, justifies the extension of genetic testing investigations to establish an early diagnosis on hereditary pancreatitis. Given that there are no clearly established methods for preventing the development or progression of the disease in the context of the presence of a genetic mutation associated with HP, the emphasis in case management will focus on avoiding the triggers that can exacerbate and aggravate pancreatitis and monitoring the progression toward adenocarcinoma pancreatic.Figure 1.: The result of the genetic panel.

S2659 Splenic Artery Pseudoaneurysm as a Rare Cause of Upper Gastrointestinal Bleeding

Introduction: Upper gastrointestinal bleeding (UGIB) is one of the most common causes for hospital admission in the US. Common etiologies for UGIB include peptic ulcer disease, erosive esophagitis, varices, and less commonly malignancies. Splenic artery pseudoaneurysm (PSA) is a known complication of pancreatitis. It may be asymptomatic or present with left upper quadrant or epigastric pain, and rarely as hemorrhagic shock. Splenic artery PSA presenting with UGIB is extremely unusual. Case Description/Methods: We present the case of a 57-year-old male with alcohol use disorder complicated by a prior episode of alcoholic pancreatitis, who presented with 3 days of hematemesis, melena, and recurrent syncopal episodes. In the ED his vitals and physical exam were notable for tachycardia, hypotension, and melena. Labs revealed a hemoglobin of 4.2. Non-contrast CT of the abdomen and pelvis showed evidence of blood in the antrum and a 2.0 x 1.6 cm out-pouching from the greater curvature of the stomach which was postulated to be a gastric diverticulum (image 1). Upper endoscopy revealed fresh blood in the antrum and duodenum, as well as a massive adherent clot in the fundus. Since no single site of active bleeding was identified, the patient was started on IV PPI with continued close monitoring in the ICU. He continued to have melena, and increased PRBC requirements. Repeat EGD was performed but was unchanged from prior. A CT angiogram of the abdomen and pelvis demonstrated a 1.5 cm actively bleeding PSA arising from a first divisional branch of the splenic artery communicating with the fundus of the stomach (images 2 & 3). The patient underwent successful coil embolization (image 4). Hemoglobin remained stable throughout the remainder of his admission with no further evidence of bleeding. Discussion: This case demonstrates PSA as a rare cause of UGIB. Lesions are most commonly caused by chronic pancreatitis, pancreaticobiliary surgery, and trauma. This patient’s PSA was likely secondary to his prior episode of alcoholic pancreatitis. Prompt diagnosis of PSA is essential given the high mortality rate associated with rupture. Clinicians should maintain a high index of suspicion for gastrointestinal PSA in patients with a history of pancreatitis who present with UGIB for whom no obvious source of bleeding can be identified on endoscopy.Figure 1.: CT Thx/Abd/Pel demonstrating a 2.0 x 1.6 cm out-pouching from the greater curvature of the stomach (arrow), postulated to be a gastric diverticulum, 2. CT Angiogram Abd/Pel demonstrating the splenic artery PSA (arrow), 3. Fluoroscopic imaging re-demonstrating the splenic artery PSA with extravasation of contrast into the gastric lumen, 4. Splenic Artery PSA after successful coil embolization.

S1708 Combination of Pancreatic and Hepatic Pseudocyst in a Patient With Pancreatitis: A Case Report

Introduction: Pancreatic pseudocysts are common occurrences after episodes of acute pancreatitis. Up to 20% of pseudocysts are extra-pancreatic throughout the abdomen including intrahepatic. There are only a few cases of hepatic pseudocysts reported in the literature. We report this unique case with both pancreatic and intrahepatic pseudocysts occurring at the same time in a patient with pancreatitis. Case Description/Methods: A 56-year-old White woman with history of alcoholism and chronic pancreatitis, presented with epigastric and left upper quadrant abdominal pain radiating to the left shoulder. Examination revealed tenderness in the epigastric and left upper quadrant of the abdomen. Labs showed an elevated lipase of 217 IU/L (13-60), normal total bilirubin and transaminases, hemoglobin of 9.1 g/dL(11.5-15), and slight leukocytosis 12.6 K/uL (3.7-10.4). She was admitted 3 times in the last 4 months. Prior computerized tomography (CT) scan showed pseudocysts in the head and tail of the pancreas. CT scan this admission showed a decreased size of pseudocyst in the pancreatic head from 2.5 cm to 2.2 cm and pancreatic tail from 4.2 cm to 3.7 cm (Figure). It also showed 2 subcapsular fluid collections in the left lobe of the liver measuring 9X5X2cm and 9X7X3 cm. Percutaneous drainage of the hepatic cysts with the placement of a drainage catheter was performed by interventional radiology. 50 mL of bilious appearing fluid was drained with negative gram stain and cultures with an elevated fluid amylase level of 1,765 U/L. The patient’s pain improved and a subsequent CT a few weeks after discharge showed a decrease in the size of the hepatic cysts. Discussion: This is the first documented case of combined pancreatic and intrahepatic pseudocyst formation. Elevated amylase level in the hepatic fluid analysis confirmed the diagnosis of a hepatic pseudocyst. The interesting fact is that the size of the pancreatic pseudocyst decreased as the hepatic pseudocyst increased because of fluid tracking likely in the pre-renal space or along the hepato-gastric ligament. The diagnosis of hepatic pseudocyst needs to be considered in a patient with new hepatic fluid collection with a recent history of pancreatitis and pancreatic pseudocyst.Figure 1.: A – Axial CT showing previous pancreatic pseudocyst prior to admission B – Axial CT showing new hepatic pseudocyst adjacent to falciform ligament during admission C – Axial CT showing drain in hepatic pseudocyst.

ALL-269 Safety and Pharmacokinetics of Calaspargase Pegol in Adults With Newly Diagnosed Philadelphia-Negative Acute Lymphoblastic Leukemia: A Phase 2/3 Study

Asparaginase remains an important component in many adult regimens for acute lymphoblastic leukemia (ALL). In pediatric patients (<21 years), calaspargase pegol (Cal-PEG) provides sustained asparagine depletion as compared to pegaspargase, with similar rates of complete remission (CR), minimal residual disease (MRD), event-free survival (EFS), and overall survival (OS), with a similar safety profile. To confirm the recommended dose of Cal-PEG in adults (age ≥22 years) and to establish safety and PK/PD analysis. Multicenter, phase 2/3 study (NCT04817761) assessing safety and anti-leukemic activity of Cal-PEG. Part 1 enrollment commenced in Q3 2021 and will establish the safety of Cal-PEG in four groups: patients aged 22-39, 40-54, and ≥55, and patients with an elevated BMI >35 kg/m2. A minimum of 4 (initial cohort) and ~8 patients will be enrolled per group. The study will be conducted in ≤25 investigational centers in the US. Part 2 will comprise expansion cohorts after verifying safety and PK/PD analysis. Newly diagnosed patients with Philadelphia-negative B- or T-cell ALL ≥22 years with ECOG performance status 0-2, no known history of pancreatitis, coagulopathy, CNS thrombosis, or severe hepatic impairment. Approximately 114-122 patients are expected to be enrolled in the study, including 16-32 patients in Part 1. Starting doses of Cal-PEG will be based on the patients' age and BMI, with older patient groups assigned to lower doses. Patients aged≥22-39 and 40-<55 will receive Cal-PEG 2000 and 1500 U/m2, respectively. Patients with BMI >35 kg/m2 and those aged ≥55 will receive 1000 U/m2. A total of 6 Cal-PEG doses will be administered during the treatment period as part of a multiagent chemotherapy regimen based on CALGB 10403, with an end-of-treatment visit 1 year after the induction dose, and an additional 2 years of survival follow-up. The primary endpoints in part 1 are the safety of Cal-PEG, the incidence of pre-defined unacceptable toxicities within 30 days after the induction dose and achieving plasma asparaginase activity ≥0.1 U/mL 21 days after the consolidation day 43 dose. Secondary endpoints include immunogenicity, CR, end-of-induction and consolidation MRD, 1-, 2- and 3-year EFS, disease-free survival, and OS.

S1920 A Rare Case of Small Cell Lung Cancer With Pancreatic Metastasis Presenting as Obstructive Jaundice

Introduction: Small cell lung cancer (SCLC) is an aggressive high grade neuroendocrine carcinoma that accounts for 15% of all lung cancers & usually presents with early distant metastatic spread typically to liver, bone, brain & lung on diagnosis. Pancreas is a very uncommon site of metastasis. We present a rare case of SCLC metastasis to the pancreas presenting as obstructive jaundice upon initial presentation. Case Description/Methods: A 62-year-old male with a past medical history of recurrent pancreatitis presented to the emergency department with abdominal pain, nausea, vomiting, & jaundice. Routine blood work on admission were notable for elevated total bilirubin of 16.4 mg/dL along with elevation in alkaline phosphatase at 547 IU/L & elevation in AST & ALT to 120 U/L & 144 U/L, respectively. Imaging with CT followed by MRI abdomen showed focal enlargement of the pancreatic head with dilatation of the common bile duct & the main pancreatic duct along with innumerable rim-enhancing lesions within the liver consistent with metastasis. CT Chest was also done that showed a large right suprahilar mass with mass effect on the right main bronchus. CT guided biopsy of liver lesion was performed which confirmed small cell carcinoma on pathology. Worsening jaundice prompted ERCP with EUS which showed a large mass at the major papilla site. Pancreatic duct was cannulated & sphincterotomy was performed; However, biliary cannulation could not be completed due to the size of the mass & prior history of chronic pancreatitis cannulation. Patient subsequently underwent IR guided PTC drain placement with appropriate decrease in bilirubin. Chemotherapy was initiated with carboplatin/ etoposide for metastatic small cell cancer with spread to the pancreas & liver (Figure). Discussion: SCLC metastasis to pancreas is rare & majority of patients with pancreatic metastasis are asymptomatic upon incidental diagnosis by abdominal CT. Pancreatitis & obstructive jaundice are seldom found on initial presentation, as seen in our patient. Jaundice can result from biliary ductal obstruction if SCLC spreads to lymph nodes in the porta hepatis or the pancreatic head. Endoscopic ultrasound (EUS) is more sensitive than CT or MRI in the diagnosis of pancreatic malignancy. Metastasis to pancreas typically indicates advanced disease & clinicians should consider palliative treatment with surgical biliary bypass & chemotherapy in select patient groups which has shown to lead to clinically significant increased mean survival time.Figure 1.: MRI Abdomen with contrast transverse image showing rim-enhancing lesions within the liver and focal enlargement of the pancreatic head with dilatation of the common bile duct and the main pancreatic duct (A). Endoscopic imaging showing a large fungating mass was found at the major papilla (B).

S1902 A Rare Case of Lipomatous Pseudohypertrophy of the Pancreas Diagnosed With EUS-FNA

Introduction: Lipomatous pseudohypertrophy (LPH) of the pancreas is a rare benign entity of undetermined pathogenesis characterized by the enlargement of the pancreas due to replacement of exocrine parenchyma with adipose tissue in patients without obesity, diabetes, or pancreatitis. Adipose infiltration may be local or diffuse and forms a pseudotumor that mimics pancreatic malignancies, which has led to unnecessary resections. Endoscopic ultrasound with biopsy (EUS- FNA) has improved the ability to diagnose LPH and rule out malignancy. LPH is typically asymptomatic, however, abdominal pain may be a presenting symptom with steatorrhea due to exocrine insufficiency or jaundice due to mass effect seen in late stages. Case Description/Methods: 48-year-old female with history of hypothyroidism and migraines presented with epigastric pain, poor oral intake due to postprandial vomiting, and non-bloody mucoid diarrhea. Prior to admission, she had been having chronic GI symptoms and recent MRI demonstrated near complete fatty replacement of an enlarged pancreas causing mass effect with only a small amount of normal parenchyma remaining. She had been diagnosed with exocrine pancreatic deficiency and started on replacement therapy. Surgery was consulted for potential resection of the body and tail of the pancreas due to compressive symptoms. Due to concern for other malignant process including liposarcoma, EUS-FNA was pursued (Figure). The body and tail of the pancreas appeared diffusely hyperechoic and homogeneous, consistent with fatty replacement. Biopsies showed bland pancreatic islets in a background of mature adipose tissue consistent with fatty replacement of the pancreas. These pathology findings in conjunction with pancreatic hypertrophy and compression on surrounding organs without a history of obesity, diabetes, or pancreatitis, supported the diagnosis of LPH of the pancreas. She was ultimately treated conservatively with monitoring and pancreatic enzyme replacement therapy with improvement in symptoms. Discussion: LPH is a rare, benign disorder typically managed with enzyme therapy when symptoms develop. The mass formed by LPH mimics that of malignant disease which has led to unnecessary resections. The use of EUS-FNA to observe histological features and confirm diagnosis has led to a decrease in resections and differentiation from other causes of pancreatic fat infiltration. The pathogenesis remains unknown but is distinct from pancreatic steatosis commonly seen in metabolic syndromes or inflammation.Figure 1.: EUS showing pancreatic parenchymal abnormalities consisting of diffuse echogenicity with homogenous appearance in the Neck (A), Body (B), and Tail (C) of the pancreas. These findings consistent with fatty replacement of the pancreas. There is no focal mass noted, the pancreatic duct was not visualized.

S2804 Refractory Bleeding From Nodular Gastric Antral Vascular Ectasia (GAVE): Is Combination Therapy of Sclerotherapy and Band Ligation the Solution?

Introduction: Gastric antral vascular ectasia (GAVE) is a rare condition that presents in the distal stomach as dilated longitudinal columns of blood vessels prone to bleeding. Nodular GAVE is an even rarer variant and is often refractory to standard therapy for GAVE. Endoscopic treatment options widely varies and include rubber band ligation, radiofrequency ablation (RFA), argon plasma coagulation (APC), and resection with hot snare. We present a case study of successful treatment of nodular GAVE of a patient who has been refractory to repeated APC with combination therapy of band ligation and sclerotherapy. Case Description/Methods: 63-year-old female with history of alcoholic cirrhosis and pancreatitis who has had persistent iron deficiency anemia thought secondary to chronic blood loss requiring constant transfusions. Initial EGD was performed at age of 60 with evidence of small grade I esophageal varices, portal hypertensive gastropathy, and innumerable gastric polyps in the gastric body and antrum that on biopsy was consistent with nodular GAVE. She then underwent 5 repeat EGDs over a span of 6 months with a combination RFA, APC, snare resection followed by hemostatic clipping, and banding, with continued recurrence of nodular GAVE and transfusion dependent anemia, with total of 17 units of packed red blood cell (pRBC) transfusions required over the same 6 month period. On her seventh EGD, she then underwent combination therapy of sclerotherapy (1% sodium tetradecyl sulfate (STS), 20mL total), which were injected at the base of the nodular areas, along with placement of 12 bands. Her transfusion requirements subsequently subsided after the initial sclerotherapy and band ligation combination session, and the patient received additional 6 EGD sessions with repeat combination therapy over the next 12 months, with notable visual improvement endoscopically subsequent to 2 sclerotherapy plus banding sessions. She only required a total of 3 units of pRBC transfusion over the same period. (Figure) Discussion: We described the first known case of combination sclerotherapy and band ligation therapy for treatment of refractory nodular GAVE. The treatment resulted in significant reduction in transfusion requirements with concomitant improvement of the appearance of nodular GAVE even after just 2 sessions, and may be particularly useful in patients who have failed more conventional treatments. Additional studies will need to be performed to determine the safety and efficacy of this combination treatment modality.Figure 1.: endoscopic images of nodular GAVE before and after serial treatments, along with a timeline of hemoglobin level, transfusions, and endoscopic sessions/therapies over the patient's follow up period of 1.5 years.

S1667 Isolated Intramural Gastric Metastasis of Pancreatic Ductal Adenocarcinoma (PDAC) Detected on Surveillance Esophagogastroduodenoscopy (EGD) Before Endoscopic Ultrasound (EUS) Guided Biopsy

Introduction: PDAC is an aggressive malignancy that requires prompt diagnosis and treatment to provide the patient with the best chance of long-term survival. Patients who have an imaging-confirmed solitary pancreatic mass generally undergo a EUS-guided biopsy for histological confirmation of the diagnosis. We describe a rare case of solitary intramural gastric metastases discovered on surveillance EGD prior to EUS-guided biopsy. Case Description/Methods: 63-year-old male with a past medical history of hypertension, chronic pancreatitis, and tobacco use presented with 2 months history of epigastric pain, and 5lbs weight loss. He denied jaundice, loss of appetite, pale-colored stools, or generalized itching. Initial CT abdomen showed a 2.7cm x2.6cm mass in the pancreas body with associated proximal pancreatic duct dilatation and atrophy, suspicious of pancreatic neoplasm. Ca19-9 was 111, and CEA was 1.1. No evidence of metastasis was found on the CT chest/abdomen. EUS-guided biopsy of the mass was scheduled. At the beginning of the procedure, a surveillance EGD was performed which showed a 2cm submucosal, non-circumferential mass in the gastric fundus (Figure a). EUS was performed next which confirmed a 2.1 cm intramural mass in the gastric fundus originating from the muscularis propria (Figure b), and a 3.9cm x 3.8cm mass in the pancreatic body with invasion into superior mesenteric vein, splenic vein, and splenoportal confluence with no noted arterial involvement (Figure c). EUS-guided fine needle biopsy of both lesions was obtained using separate needles. Histopathology from both biopsies demonstrated invasive adenocarcinoma, histomorphologically similar and suggestive of a pancreatic primary. This changed the staging of the patient from borderline resectable to metastatic and he was referred for palliative chemotherapy. Discussion: Isolated gastric metastasis of PDAC is extremely rare, and documented cases in the literature are from a prior diagnostic biopsy that created a seeding tract. Our case highlights 2 major points: 1) Though rare, isolated intramural gastric metastasis can occur and can be missed on cross-sectional imaging. 2) Currently there is no consensus or guideline that mandates an EGD prior to EUS. In this case, this significant finding which changed the staging, treatment, and prognosis of the patient could have been missed with an oblique viewing EUS scope. At our center, we routinely perform EGD prior to EUS. Prospective studies are needed to confirm the utility of this practice.Figure 1.: a: EGD demonstrating 2cm submucosal, non-circumferential mass in the gastric fundus. b: EUS demonstrating a 2.1 cm intramural mass in the gastric fundus originating from the muscularis propria. c: EUS demonstrating 3.9-cm x 3.8-cm mass in the pancreatic body with invasion into the superior mesenteric vein, splenic vein, and splenoportal confluence with no noted arterial involvement.