Recurrent Episodes Of Acute Pancreatitis Research Articles

Role of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 in hypertriglyceridemia and diabetes.

In diabetes, the impairment of insulin secretion and insulin resistance contribute to hypertriglyceridemia, as the enzymatic activity of lipoprotein lipase (LPL) depends on insulin action. The transport of LPL to endothelial cells and its enzymatic activity are maintained by the formation of lipolytic complex depending on the multiple positive (glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 [GPIHBP1], apolipoprotein C-II [APOC2], APOA5, heparan sulfate proteoglycan [HSPG], lipase maturation factor 1 [LFM1] and sel-1 suppressor of lin-12-like [SEL1L]) and negative regulators (APOC1, APOC3, angiopoietin-like proteins [ANGPTL]3, ANGPTL4 and ANGPTL8). Among the regulators, GPIHBP1 is a crucial molecule for the translocation of LPL from parenchymal cells to the luminal surface of capillary endothelial cells, and maintenance of lipolytic activity; that is, hydrolyzation of triglyceride into free fatty acids and monoglyceride, and conversion from chylomicron to chylomicron remnant in the exogenous pathway and from very low-density lipoprotein to low-density lipoprotein in the endogenous pathway. The null mutation of GPIHBP1 causes severe hypertriglyceridemia and pancreatitis, and GPIGBP1 autoantibody syndrome also causes severe hypertriglyceridemia and recurrent episodes of acute pancreatitis. In patients with type 2 diabetes, the elevated serum triglyceride levels negatively correlate with circulating LPL levels, and positively with circulating APOC1, APOC3, ANGPTL3, ANGPTL4 and ANGPTL8 levels. In contrast, circulating GPIHBP1 levels are not altered in type 2 diabetes patients with higher serum triglyceride levels, whereas they are elevated in type 2 diabetes patients with diabetic retinopathy and nephropathy. The circulating regulators of lipolytic complex might be new biomarkers for lipid and glucose metabolism, and diabetic vascular complications.

The Case Files

The Case Files

Autoimmune Pancreatitis: A Case Report

Abstract Autoimmune Pancreatitis is an uncommon form of chronic inflammation of the Pancreas. It is an autoimmune disease and so it can be associated with other autoimmune disorders. There are 2 types of Autoimmune Pancreatitis (AIP) with type 1 being the more common form. We reported a case of Autoimmune Pancreatitis where the patient presented with recurrent episodes of acute Pancreatitis managed conservatively until he was diagnosed with autoimmune pancreatitis type 2 based on clinical picture, lab investigations and radiological findings. Keywords: Autoimmune Pancreatitis, AIP, Acute Pancreatitis, Magnetic Resonance Imaging, MRI, Magnetic resonance cholangiopancreatography, MRCP, Computed Tomography, CT.

Recurrent acute pancreatitis: a diagnostic and a therapeutic dilemma

Although uncommon, surgeons and physicians are sometimes confronted with patients who presents with recurrent episodes of acute pancreatitis. When two or more episodes of acute pancreatitis occur without an identifiable cause, it is referred to as Recurrent Acute Pancreatitis (RAP). In such patients, selecting the most appropriate management strategy continue to pose a challenge due to multiple aetiological factors, associated conditions, microanatomical and pathological processes and complex immunological mechanisms of this condition. The identifiable causes of RAP such as bile duct stones, biliary sludge or crystals, Sphincter of Oddi Dysfunction (SOD), pancreatic duct obstructions due to benign and malignant neoplasms, genetic mutations, Pancreatic Divisum (PD), metabolic disorders, alcohol consumption and smoking may be identified in some patients. There are several other rare conditions which may be associated with RAP. However, in about 30%, no cause/s can be identified. Diagnosis is further complicated by the fact that, although the gland may appear morphologically normal following the initial episode of Acute Pancreatitis (AP), in some patients, evidence of Chronic Pancreatitis (CP) may manifest later. Furthermore, there is an ongoing debate as to whether, recurrent bouts of pancreatitis following the first; the Sentinel Acute Pancreatitis episode in patients who are 'immunologically' predisposed may lead to Chronic Pancreatitis. In such patients who subsequently develop acute episodes, i.e., Acute on Chronic Pancreatitis will further complicate recognition of aetiological factors of RAP. The recognition of possible causes, associated factors, and understanding of pathological progressions are therefore important in the management of such patients. Detailed clinical assessment and clinical reasoning, standard haematological and biochemical workup and basic and advanced imaging studies will help identify patients who can be selected for specific invasive and medical therapy to prevent acute episodes. This brief review is a clinical update to guide clinicians, the best way forward in the management of RAP.

Pancreatitis as a Potential Trigger for Severe Accelerated Cardiac Allograft Vasculopathy Early Post Heart Transplant: A Case Report

We present a case of severe accelerated cardiac allograft vasculopathy (CAV), an infrequent finding usually related to dismal prognosis, in a heart recipient with recurrent episodes of acute pancreatitis. A 38-year-old male was transplanted owing to advanced heart failure related to nonischemic dilated cardiomyopathy. On the fifth day after transplantation, a nonbiliary acute ischemic pancreatitis occurred. Recurrent relapses ensued within the following year requiring hospital readmissions for both supportive and pain management. The patient developed graft dysfunction by the 18th month post-transplant with severe multivessel CAV. A trial of bortezomib and percutaneous coronary interventions with drug-eluting stents at coronary arteries were attempted but the patient died suddenly, before the scheduled staged percutaneous coronary intervention for the coronary total occlusion was performed. The causal mechanisms of aggressive accelerated CAV are unclear, but it is suggested that important inflammatory and/or humoral responses may play a pivotal role in this life-threatening disease pathogenesis. Increased levels of biomarkers have been linked to advanced CAV, as well as pancreatitis pathogenesis, related to cytokine activation with remarkable systemic inflammatory response. Some of those inflammatory mediators have been reported as central in both pancreatitis and CAV, more specifically interleukin-6. A pro-inflammatory state due to recurrent acute pancreatitis early after transplantation may have contributed to severely accelerated CAV development in the presented case. Comprehensive evaluation of risk factors may assist in close surveillance and targeted therapies in the management of this challenging post-heart transplant scenario.

RF32 | PSUN67 Recurrent Acute Pancreatitis Secondary to Hypertriglyceridemia in an Adolescent With Type 2 Diabetes, Symptomatic Hypocalcemia, and COVID-19 Infection

Abstract Introduction Hypertriglyceridemia is the third most common cause of acute pancreatitis, leading to increased morbidity and mortality. Hypocalcemia is a frequent complication of pancreatitis, attributed to saponification of calcium by the release of pancreatic lipase. Free fatty acids are released by the breakdown of triglycerides, then react with extracellular calcium, forming fatty acid salts that deposit in the retroperitoneum and reduce calcium availability.1 We present a case of an adolescent female with recurrent episodes of acute pancreatitis, hypertriglyceridemia, and hypocalcemia. Her first presentation of pancreatitis coincided with new-onset type 2 diabetes, while this third episode with COVID-19. Case An 18-year-old morbidly obese female with type 2 diabetes, hypertriglyceridemia, hepatomegaly, and recurrent acute pancreatitis was admitted for a third episode of pancreatitis secondary to severe hypertriglyceridemia. On admission, triglycerides were 3213 mg/dL (reference 35-134mg/dL), lipase 12,721 units/L (145-226u/L), amylase 323 units/L (<106u/L), AST 90 units/L (10-26u/L), and ALT 109 units/L (19-49u/L). A1C was 7.5%, blood glucose 301 mg/dL, bicarbonate 25 mmol/L, and large urine ketones. Initial calcium was 8.7 mg/dL (9.0-10.7mg/dL) and albumin 4.0 gm/dL (3.8-5.6gm/dL). The next day, she developed hypocalcemia with numbness and tingling. Serum calcium was 5.3mg/dL, ionized calcium 0.74 mmol/L (1.12-1.37mmol/L), and albumin <0.6 gm/dL. 25-hydroxy vitamin D level was 16.5 ng/mL (30-100). QTc was 470 ms (350-440ms). She was transferred to pediatric intensive care and initiated on an insulin drip at 0.1 units/kg/hour for hypertriglyceridemia. She received four IV calcium gluconate boluses (1000-2000 mg each). Symptoms improved within one day. Triglycerides decreased to 642 mg/dL, calcium and albumin normalized, and subcutaneous insulin regimen was resumed. She started vitamin D 3000 IU daily and elemental calcium carbonate 26 mg/kg/day. During her hospitalization, she was found to be COVID-19 positive and had become hypoxemic requiring 2.5 liters of oxygen. Upon resolution, she was discharged with outpatient follow-up. Of note, there is a strong maternal family history of type 2 diabetes and hypertriglyceridemia. The mother had three strokes in her forties. The patient has not previously undergone pancreatitis genetic testing. Discussion To conclude, this case affirms the importance of detecting hypertriglyceridemia-induced pancreatitis early on and improved outcomes with insulin drips. It is important to determine triggers for recurrent pancreatitis in those with underlying genetic etiologies of hypertriglyceridemia. Additionally, it is crucial to monitor for secondary hypocalcemia, particularly given the risk for prolonged QT interval and ventricular arrhythmias. Lastly, the COVID-19 pandemic may be associated with more severe presentations of pancreatitis. 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.

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 <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 <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., & 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.

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.

S1888 A Curious Case of Recurrent Pancreatitis: A Case Report

Introduction: Annular pancreas, a congenital anomaly characterized by incomplete rotation of the ventral pancreatic bud, causes a ring of pancreatic tissue to encircle the duodenum. It is commonly accompanied by pancreatic divisum, which occurs when the main pancreatic duct and accessory duct fail to fuse. Patients often present with recurrent pancreatitis due to partial obstruction of the pancreatic duct caused by fibrosis. Case Description/Methods: A 72-year-old Caucasian male presented with recurrent episodes of acute pancreatitis. A CT abdomen (Figure A) revealed pancreatic tissue surrounding the second portion of the duodenum consistent with an annular pancreas. A pancreatic duct stone was also noted. An MRCP (Magnetic resonance cholangiopancreatography) was consistent with annular pancreas with persistent dilation of the main and accessory pancreatic ducts and a 6mm stone noted in the pancreatic duct (Figure B). On an initial ERCP (Endoscopic retrograde cholangiopancreatography), the pancreatic duct could not be cannulated through the major papilla and minor papilla could not be identified due to inflammation. An EUS (Endoscopic ultrasound) was performed, which was suggestive of pancreas divisum. The minor papilla was cannulated, and a stent was placed in the pancreatic duct. In a subsequent ERCP (Figure C), the patient had the pancreatic stone removed, with complete resolution of his symptoms. Discussion: Typically, patients with annular pancreas present with symptoms during childhood. While infrequent, some patients remain asymptomatic until 20-50 years of age. This case demonstrates the potential to remain asymptomatic until even 72 years of age. Thus, it is important for physicians to be aware of the clinical manifestations of annular pancreas, as they could arise at any stage in life. By increasing awareness surrounding annular pancreas and management of its complications, we hope to increase the rate of early intervention.Figure 1.: Image 1A. Contrast-enhanced axial CT of the abdomen at the level of the pancreatic head. The pancreas (white bracket) is seen surrounding the 2nd part of the duodenum (white asterisk), compatible with annular pancreas. A 6 mm calcification (circled) is present in the region of the minor papilla (arrows indicating pancreatic ducts). Image 1B. Coronal MRCP images. Annular pancreas, with only a thin rim of pancreatic tissue surrounding the duodenum. The dorsal duct is best shown to wrap completely around the duodenum on MRCP images (arrow). Image 1C. ERCP fluoro image showing the previously placed pancreatic duct stent (which does appear to have a loop-like configuration) and the pancreatic stone.

Unique Case of Management of Severe Hypertriglyceridemia Secondary to Familial Chylomicronemia Syndrome

<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> None. <h3>Background/Synopsis</h3> We review a case of a 61-year-old female diagnosed at age 21 with severe hypertriglyceridemia with debilitating, recurrent episodes of acute pancreatitis. <h3>Objective/Purpose</h3> To review a clinical scenario involving severe hypertriglyceridemia and the role of novel therapies in management. <h3>Methods</h3> Clinical management at tertiary care lipid program. <h3>Results</h3> A 61-year-old slightly overweight female with a history of congenital aplasia of the pancreas, coronary artery disease post stents, pre-diabetes, and non-alcoholic fatty liver disease was diagnosed with severe hypertriglyceridemia secondary to chylomicronemia syndrome at age 21. No secondary causes were identified. She was trialed on several cholesterol and triglyceride lowering medications including niacin, rosuvastatin, gemfibrozil, fenofibrate, fish oil supplements with minimal improvement in symptoms and/or reduction in recurrent hospitalizations for acute pancreatitis. Interestingly, she showed a dramatic ∼70% reduction in triglycerides on evinacumab based on compassionate use, resulting in significant improvement in quality of life with no episodes of acute pancreatitis while on therapy for 12 months. <h3>Conclusions</h3> Familial chylomicronemia syndrome (FCS) is an autosomal recessive disorder with a lack of lipoprotein lipase (LPL) functionality, thereby markedly impairing clearance of chylomicrons from the plasma. The primary reason for concern is an increased risk of acute pancreatitis with an estimated odds ratio of 360 in patients with FCS. Acute pancreatitis, in fact, is responsible for a significant economic burden in the United States with an estimated annual cost of care of over $2 billion, accounting for about 50% higher healthcare-related costs compared to patients without acute pancreatitis. Additionally, studies have shown that patients on statin with high residual cardiovascular risk as well as high triglycerides had higher risk for nonfatal myocardial infarction and nonfatal stroke compared to patients with normal triglycerides. Unfortunately, there are currently no FDA-approved treatments for FCS. For this reason, novel therapies are crucially needed to relieve the debilitating state of these patients. One such concept is the use of ANGPTL3 inhibitor, evinacumab, currently FDA approved for homozygous familial hypercholesterolemia. ANGPTL3 inhibition enhances the activities of endothelial lipase and lipoprotein lipase, thereby reducing levels of LDL-C independent of LDL receptor activity, HDL and triglycerides. Based on meta-analysis and a few Phase 1-2 trials, evinacumab is shown to reduce triglycerides from 50% to 80% in patients with severe hypertriglyceridemia. In our patient, with TG/TC ratio >8:1 and normal to low apoB, FCS is more likely the culprit for severe triglyceride burden, contributing to recurrent acute pancreatitis. Furthermore, our patient also suffers from mixed dyslipidemia and metabolic syndrome, which significantly raises her lifetime atherosclerotic cardiovascular risk. Thus, we propose the use of evinacumab in such patients to not only target high triglycerides to reduce risk of acute pancreatitis but also optimize overall cardiovascular risk.

Acute pancreatitis in children – morbidity and outcomes at 1 year

ObjectiveTo establish short-term and medium-term complications 1-year postdiagnosis, of acute pancreatitis (AP) in children aged 0–14 years.DesignOne-year follow-up of a prospective monthly surveillance of new cases of AP in children...

Hypertriglyceridemia induced acute pancreatitis: 4 years' experience from a tertiary care institute and quick literature review.

ABSTRACTHypertriglyceridemia (HTG) is infrequent but an established etiology that can trigger recurrent episodes of acute pancreatitis. The risk of acute pancreatitis is significant when serum triglycerides levels surpass >1000 mg/dL. Although the severity of HTG-induced acute pancreatitis (HTG-AP) may be correlated to higher HTG levels in the early stages, the overall clinical outcomes are similar to other aetiologies. The initial management also differs from the routine recommendations with additional diagnostic and therapeutic challenges. This retrospective case series includes a 4-year experience with HTG-AP at our facility and a brief literature review.

Lomitapide Effectively Reduces Triglyceride (TG) Levels in Familial Chylomicronemia Syndrome (FCS)

Lead Author's Financial Disclosures A.C. has received consulting fees from Amryt. Study Funding Amryt Pharma. Background/Synopsis FCS is a rare autosomal recessive disorder caused by impaired lipoprotein lipase (LPL) function, resulting in elevated TG levels, intense abdominal pain, hepatosplenomegaly, and recurrent episodes of acute pancreatitis. Treatment requires a strict, extremely low-fat diet (<10% fat/day) to control TG levels <750-1000mg/dL, which does not fully control the disease. Lomitapide is a microsomal triglyceride transfer protein (MTP) inhibitor that prevents assembly of triglycerides (TGs) into chylomicrons, in addition to very low-density lipoproteins and thereby reduces circulating levels of TGs. Objective/Purpose The LOCHNES study was designed to evaluate the efficacy and safety of lomitapide in FCS. Methods This open-label, single arm LOCHNES study of lomitapide in FCS, enrolled adult patients ≥18 years with genetically confirmed FCS, elevated fasting TG≥750mg/dL and a history of pancreatitis, across 3 Italian centres. Patients were administered escalating-doses of lomitapide to maximum tolerated dose (MTD) for 26 weeks. The primary endpoint was the percent change in TGs from baseline to week 26, with lomitapide in combination with other lipid lowering therapy. Results Eighteen patients were enrolled in the study (mean+/-SD: age 46.6+/-16.7y; body mass index 23.7+/-4.1kg/m2). Median baseline TG levels were 1804mg/dL (range 810-4151mg/dL). Lomitapide increased from standard starting dose 5mg/day at baseline to mean 32.8+/-17.8mg/day at week 26. Median TGs reduced to 305mg/dL (range 70-1818mg/dL) at week 26. This equates to a 70.5% reduction in median fasting triglyceride levels. At week 26, 13 patients achieved TGs ≤750mg/dL. Treatment with lomitapide was generally well tolerated with no patient discontinuations. Adverse events were mild to moderate and were mainly related to gastrointestinal tolerability (n=9) and ALT/AST enzyme elevations ≥3x upper limit of normal (n=4). Where available (n=13), liver MRI imaging revealed increases in hepatic fat in some patients (n=5/13), and three patients with a baseline hepatic fat >20% (range 22-30%), experienced increases to 30-50% hepatic fat at 26 weeks. No patient experienced an episode of acute pancreatitis or severe abdominal pain during lomitapide treatment. One patient who temporarily interrupted lomitapide treatment due to an episode of diarrhoea, experienced acute pancreatitis during the treatment interruption period. Conclusions Lomitapide is effective in reducing triglycerides in FCS and preventing the recurrence of acute pancreatitis in this pilot study. The extent of the benefit of lomitapide to patients with FCS should be further evaluated in a larger prospective clinical trial. A.C. has received consulting fees from Amryt.

Acute Pancreatitis in Henoch-Schonlein Purpura Complicated by Large Pseudocyst Formation Requiring Cystogastrotomy

Henoch-Schönlein purpura (HSP) is a small-vessel vasculitis that typically occurs in children and causes characteristic purpuric skin lesions occasionally associated with multisystemic involvement. Gastrointestinal symptoms appear in 70% of the patients varying from mild to severe abdominal pain resembling an acute abdomen but HSP rarely presents with acute pancreatitis. Here, we report the case of an 11-year-old girl admitted with HSP-associated recurrent episodes of acute pancreatitis complicated with large pseudocyst formation. She was treated with pulse methylprednisolone followed by oral prednisolone and a single cyclophosphamide pulse but finally required a cystogastrotomy.

198-LB: A Novel Heterozygous Mutation in Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) Gene in a Woman with Familial Partial Lipodystrophy

Background: The nuclear peroxisome proliferator-activated receptor gamma (PPAR-γ) plays a role in the regulation of glucose and lipid metabolism in adipocytes by regulating their differentiation, distribution and function. Heterogeneous mutations of PPAR-γ can cause loss of gene function or reduce its expression leading to a clinical variety of phenotypes that characterize type 3 familial partial lipodystrophy syndrome. The most common features of this syndrome are abnormal body fat accumulation, muscle hypertrophy, insulin resistance, hypertriglyceridemia, polycystic ovary syndrome and hepatic steatosis. Case report: A 32-year-old-woman was referred to the Endocrinology Division of PUC-SP for treatment of a severe hypertriglyceridemia diagnosed 4 years ago with recurrent episodes of acute pancreatitis and eruptive xanthomas since then. Also, diabetes mellitus (DM) was diagnosed 1 year ago with poor glycemic control. Her sister also had severe hypertriglyceridemia, recurrent episodes of acute pancreatitis and died in 2016. No DM was reported in her family. On physical examination, we found the presence of lipodystrophy, acanthosis nigricans on the neck and eruptive xanthomas on trunk, upper limbs, and thighs. BMI=24.9kg/m2; waist circumference=96cm. Abdominal CT scan revealed splenomegaly and fatty liver disease. Genetic sequencing showed a heterozygous (autosomal dominant inheritance) in the PPAR-γ of a Chr3 variant: 12.416.957 T&amp;gt; C (or alternatively c.1073T&amp;gt; C - ENST000002287820), promoting the substitution of leucine in codon 358 by proline (p.Leu358Pro). Conclusion: The substitution of the amino acid leucine in codon 358 for proline is highly conserved in several species, and computer programs for predicting in silico of pathogenicity, suggesting that this new heterozygous mutation in the PPAR-γ gene is probably related to the type 3 familial partial lipodystrophy syndrome. Disclosure P. V. Wanderley: None. J. C. Dias: None. M. W. Vieira: None. G. Garcia: None. I. T. Filho: None. R. F. Chamma: None. L. S. Gugoni: None. R. B. Giorgi: None. C. R. G. Barcellos: None.

Simvastatin in the Prevention of Recurrent Pancreatitis: Design and Rationale of a Multicenter Triple-Blind Randomized Controlled Trial, the SIMBA Trial.

Background: One in every four patients with a first episode of non-gallstone-related acute pancreatitis (AP) develops recurrent disease. Recurrent episodes of AP or acute flares of chronic pancreatitis (CP) are associated with decreased quality of life and progression of the disease. Besides removing the etiology of pancreatitis (which sometimes is not possible), there are no effective measures to prevent recurrence. Meta-analyses of randomized controlled trials, as well as epidemiological and cohort studies, suggest that statins may be protective against the development of index AP.Methods: The SIMBA study is a triple-blind randomized placebo-controlled, parallel-group multicenter trial. Patients with recurrent AP or with acute flares of CP (at least two episodes in the last 12 months) will be randomized to receive simvastatin 40 mg daily or placebo. During a 3-year study period, 144 patients (72 per arm of treatment) from 26 centers will be enrolled. The patients will receive the study treatment for 1 year. The primary aim is to compare the recurrence of AP or acute flares in CP. Secondary endpoints include the incidence of new-onset diabetes mellitus, new-onset exocrine pancreatic insufficiency (EPI), new-onset imaging signs of CP, frequency of all-cause hospital admissions, severity of AP, adherence to treatment, and frequency of adverse events.Discussion: The SIMBA trial will ascertain whether simvastatin, a safe, widely used and inexpensive drug, can change the natural course of recurrent pancreatitis.Trial Registration: ClinicalTrials.gov Identifier: NCT04021498

Large pancreatic myoepithelial hamartoma associated with familial insulin dependent diabetes mellitus

Presenter: Jeffrey Ord BS | Duke University Medical Center Background: Pancreatic myoepithelial hamartoma (PMEH) is a rare, benign solid and cystic lesion of the pancreas which can appear as a solid mass or solid-cystic lesion. Patients with pancreatic hamartomas may present with vague abdominal pain, pancreatitis, biliary obstruction or may be entirely asymptomatic. Histologic features of PMEH include small to medium-sized ductal structures lined by columnar epithelium and disarranged acini surrounded by smooth muscles and varying amounts of fibrous stroma. While several reports of pancreatic hamartomas exist, there are only 3 confirmed cases of PMEH in the literature, all of which presented as discrete pancreatic head masses. Two of these cases were associated with a single family, all originated in Eastern Asia. Methods: The first case of an adult with a giant myoepithelial hamartoma extending throughout the pancreatic gland associated with familial diabetes is described. Results: A 46-year-old male was referred to Duke University Hospital with recurrent acute pancreatitis. CT showed a 10.3x9.3x6.7cm heterogeneous calcified pancreatic head solid-cystic mass (figure 1). Pertinent medical history includes insulin dependent diabetes mellitus (IDDM) diagnosed at age 30 and family history of endocrine and exocrine pancreatic disease in paternal lineage. Paternal grandmother similarly had early adult onset IDDM and chronic pancreatitis which required a pancreaticoduodenectomy, revealing a 3x4x2cm necrotic pancreatic pseudocyst with hamartomatous characteristics. Endoscopic ultrasound (EUS) showed a large heterogenous, calcified, mixed solid and cystic mass extending from the pancreatic head through the pancreatic body. Fine-needle aspiration (FNA) returned benign pancreatic acinar tissue and smooth muscle without evidence of malignancy. Surgery was performed due to recurrent bouts of pancreatitis requiring multiple hospitalizations. Total pancreatectomy was performed due to the diffuse nature of the cystic disease and preexisting IDDM. On gross examination, the pancreas was diffusely enlarged, particularly in the head with replacement of normal parenchyma by pale tan to white whorled solid tissue with multiple cystic spaces up to 1.3x1cm filled with viscous fluid and calculi (figure 2). Microscopic hematoxylin-eosin staining showed disorganized bundles of smooth muscle with numerous embedded small ducts and cysts, with scattered pancreatic exocrine lobules exhibiting chronic inflammation and pancreatic calculi (figure 3). Immunohistochemical stain for desmin and caldesmon was strongly positive in smooth muscle cells. The histopathologic diagnosis was consistent with myoepithelial hamartoma. Conclusion: There are three published cases of PMEH, all originating from Eastern Asia. This is the first case of PMEH reported in the western literature and the first case of diffuse PMEH with near total replacement of the entire pancreatic parenchyma. This case draws several similarities to one case series of PMEH in mother, son and daughter—including possible familial inheritance, recurrent episodes of acute pancreatitis, honeycombed/microcystic appearance on MRI. However, uniquely, this case includes a strong family history of heritable IDDM. Improved identification and management of rare conditions including PMEH will heavily depend on increasing awareness, reporting and genetic study of future cases.

Recurrent acute pancreatitis induced by 5-ASA and azathioprine in ulcerative colitis

Drug-induced acute pancreatitis (DIAP) is an often-neglected entity where the disorder is the consequence of the toxic effects of various agents applied to treat potentially life-threatening conditions, such as inflammatory bowel disease. Here, we present the case of a male patient with ulcerative colitis with a history of two episodes of recurrent acute pancreatitis. After excluding other potential causes, we suspected DIAP since the patient received 5-aminosalycilate (5-ASA) prior to the first episode and, one year later, azathioprine (AZA) prior to the second episode. The causative effect of AZA was confirmed by performing a re-challenge with a reduced dose. While both episodes of DIAP had a mild disease course, they were associated with acute relapse of ulcerative colitis. Last seen, the patient was asymptomatic. With this case, we would like to highlight the importance and diagnostic difficulties of DIAP in the background of recurrent cases when common etiological factors of acute pancreatitis are excluded.

S1423 Lipoprotein Lipase Deficiency as a Rare Cause of Acute Pancreatitis

INTRODUCTION: Hypertriglyceridemia (HTG)-induced pancreatitis comprises 1 to 14 % of all cases of acute pancreatitis. Generally, primary HTG refers to a genetic disorder that includes type 1, 4 and 5 dyslipidemia. Familial lipoprotein lipase (LPL) deficiency is a rare condition of primary HTG with autosomal recessive transmission and a prevalence of 1-2:1,000,000. This case describes a patient with acute pancreatitis attributed secondary to LPL deficiency. CASE DESCRIPTION/METHODS: A 28 year old female with a history of type 1 diabetes mellitus complicated by diabetic gastroparesis s/p gastrojejunal bypass, HTN, HTG, recurrent pancreatitis presented to ED with abdominal pain. She had numerous admissions in the past due to recurrent pancreatitis secondary to HTG , one of which was complicated by necrotizing pancreatitis and wall off necrosis for which she underwent partial pancreatectomy. The patient also has an extensive family history of early onset type 1 diabetes and HTG. Despite the use of high intensity statin, fenofibrate, diet restriction and insulin pump, triglyceride levels has been very difficult to control. On physical examination, multiple red-yellowish bumps are noted on the arms consistent with xathomas. Labs were significant for elevated triglycerides and lipase (4500 and 400 respectively). Abdomen and pelvis CT scan showed evidence suggestive of acute pancreatitis, splenic vein thrombosis and hepatosplenomegaly. Due to high suspicion, molecular genetic testing for LPL deficiency was sent and came back positive. DISCUSSION: Patients with LPL are classically found to have high serum plasma triglycerides, low HDL-cholesterol, and presence of fasting chylomicrons in the plasma due to mutation of the enzyme that is responsible for hydrolysis and removal of triglycerides from the plasma. The most feared complication of the disease is recurrent and potentially life threatening acute pancreatitis. Although this is a very rare condition, it is an important differential diagnosis to consider due to refractoriness of conventional medical therapies including statins, fibrates and reduced fat intake(less than 20 g/day). There have been some studies that suggested high dose antioxidant therapy could potentially help lower the level of triglycerides and prevent recurrent episodes of acute pancreatitis in that particular group of patients. It is also critical to make the diagnosis as soon as possible for early medical interventions during childhood and genetic counseling and testing for family members.

Rising incidence of acute pancreatitis in Sweden: National estimates and trends between 1990 and 2013.

Recent reports from western countries have indicated an increased incidence and a decreased mortality in acute pancreatitis. However, the incidence assessment has often been hampered by the inclusion of both first-time and recurrent episodes of acute pancreatitis. In this retrospective cohort study, all Swedish residents hospitalized with a first-time episode of acute pancreatitis between 1990 and 2013 were identified using national registers. Sex- and age-standardized incidence rates per 100,000 individuals and year were calculated, as were annual percent changes (APC) from joinpoint regression models. Overall, between 1990 and 2013, 66,131 individuals had a first-time episode of acute pancreatitis in Sweden. Comparing the first five years (1990-1994) to the last four years (2010-2013) of the study period, the overall incidence of acute pancreatitis increased from 25.2 (95% confidence interval (CI): 24.1, 26.3) to 38.3 (95% CI: 37.0, 39.5) cases per 100,000 individuals and year. An increase in incidence was observed irrespective of the subtypes of acute pancreatitis as well as the sex and age of the patients. Although the incidence of complicated acute pancreatitis declined in both men and women between 1990 and 2004, it started to increase in both sexes (APC 3.0; 95% CI: 0.5, 5.5 in men; APC 5.4; 95% CI: 2.6, 8.2 in women) from 2005 onwards. Based on nationwide data, the incidence of first-time acute pancreatitis has increased in Sweden over a period of 24 years. The incidence of disease-related complications has also been on the rise during the past few years, after declining for more than 15 years before that.