Recurrent Pancreatitis Research Articles

A nomogram for predicting the transition from recurrent acute pancreatitis to chronic pancreatitis

Abstract Objectives: Acute pancreatitis, recurrent acute pancreatitis, and chronic pancreatitis are recognized as a continuum of pancreatic diseases. Recurrence increases the risk of progression to chronic pancreatitis. The aim of this study was to search for clinical features that may promote the progression of chronic pancreatitis in patients with recurrent acute pancreatitis. Methods: We retrospectively reviewed patients with recurrent acute pancreatitis from Medical Information Mart for Intensive Care-IV database. They were divided into a training cohort and a validation cohort. A nomogram was constructed based on clinical features during the second hospitalization. The discrimination and calibration of the nomogram were evaluated using the concordance index, area under the time-dependent receiver operating characteristic curve, and calibration plots. Results: A total of 432 recurrent acute pancreatitis patients were evaluated, of which 93 (21.53%) were diagnosed with chronic pancreatitis later. Age, biliary pancreatitis, admission interval, alcohol dependence, lipase, and platelet were selected. The concordance index was 0.717 (95% CI: 0.691-0.743) for the training cohort and 0.718 (95% CI: 0.662-0.774) for the validation cohort. The area under the time-dependent receiver operating characteristic curve was >0.7 over 1000 days. Conclusions: A nomogram was developed and validated to evaluate the transition from recurrent acute pancreatitis to chronic pancreatitis.

Pancreatic Duct Stenting: Does Interventional Radiology Have a Role?

AbstractPancreatic duct stenting involves the placement of a stent into the pancreatic duct to restore drainage and flow of pancreatic secretions. It relieves upstream duct dilation, facilitates drainage of pancreatic secretions, and alleviates associated symptoms like pain, nausea, malnutrition, and recurrent pancreatitis. Additionally, it is utilized to treat a variety of pancreatic duct pathologies, including obstructions from conditions like chronic pancreatitis, malignancy, and pancreatic leaks. Depending on the clinical scenario, different types of stents can be placed using endoscopic, percutaneous, or surgical approaches. Endoscopic approaches, such as endoscopic retrograde cholangiopancreatography and endoscopic ultrasound-guided stenting, are often considered first-line procedures for managing pancreatic duct pathologies. However, in cases where these procedures fail, interventional radiology (IR) becomes crucial in managing these conditions, providing a safe and minimally invasive alternative that effectively addresses the underlying issues. This review aims to discuss the clinical, radiological, and technical considerations for pancreatic duct stenting and specifically highlight the role of IR in managing various pancreatic duct pathologies.

Genomic and Bioinformatics Analysis of Familial Partial Lipodystrophy Type 3 Identified in a Patient with Novel PPARγ Mutation and Robust Response to Pioglitazone

Familial partial lipodystrophies (FPLDs) are very rare inherited disorders characterized by partial loss of adipose tissue from the upper and lower extremities. At least seven subtypes of FPLD have been identified and are mostly dominantly inherited. FPLD type 3 is caused by mutations in the PPARγ gene, which encodes for the protein peroxisome proliferator-activated receptor gamma (PPARγ). We identified a Saudi female with PFLD3 presented with partial lipoatrophy, uncontrolled diabetes, severe hypertriglyceridemia, and recurrent pancreatitis. The clinical and biochemical findings in this proband were described before and after treatment with Pioglitazone in addition to the conventional treatment. DNA extraction and whole exome sequencing (WES) were performed to detect the variant. The mutant gene was subjected to Sanger analysis to confirm the results. We applied five specific computational prediction tools to assess the pathogenicity of variation, namely the MT, DANN, CADD, BayesDel, and fitCons tools. We assessed protein modeling and stability with the AlphaFold-generated structures for both wild-type and mutant proteins. Finally, we conducted molecular docking using the AutoDock Vina virtual docking. Upon whole exome sequencing, a c.1024C>T p.(Gln342Ter) missense mutation was detected in the PPARγ gene associated with FPLD3. This variant is a novel mutation that has not been described in all genome databases. Sanger analysis confirmed the heterogenicity and pathogenicity of this variant. All five computational prediction tools indicate that this variant is considered highly pathogenic. Our patient showed a dramatic response to Pioglitazone, a synthetic PPARγ agonist. From structural modeling, we found that the enhanced binding affinity of the mutant PPARγ protein to Pioglitazone likely improves the activation of PPARγ, enhancing its transcriptional activity and resulting in better clinical outcomes. These findings extend the spectrum of PPARγ mutations responsible for FPLD3 and highlight the potential for personalized treatment strategies based on genetic mutations.

Endoscopic diagnosis and treatment of recurrent acute pancreatitis after pancreaticojejunostomy: A case report

Endoscopic diagnosis and treatment of recurrent acute pancreatitis after pancreaticojejunostomy: A case report

Liraglutide for the Treatment of Severe Hypoglycemia Following Total Pancreatectomy and Islet Autotransplantation

Abstract Total pancreatectomy and islet autotransplantation (TPIAT) is an effective treatment for chronic and recurrent acute pancreatitis, and it provides a significant potential additional benefit of insulin independence. Spontaneous hypoglycemia in the absence of insulin therapy following TPIAT is a recognized complication, which has been attributed to lack of protective glucagon responses to hypoglycemia, following intrahepatic islet autotransplantation. We describe the use of liraglutide to treat spontaneous hypoglycemia following TPIAT. Continuous glucose monitoring was used to identify timing of hypoglycemia in relation to meals and monitor treatment effect. Liraglutide has been used for management of hypoglycemia following bariatric surgery, but, to our knowledge, this is the first application of its effective use to treat spontaneous severe hypoglycemia following TPIAT.

12615 Extremely High-dose Insulin Requirement In A Child With Covid-19 Infection

Abstract Disclosure: R. Pratibha: None. T.R. Langner: None. Background: COVID-19 infection has been associated with new diagnosis of diabetes, worsening of hyperglycemia, and increased frequency and severity of diabetic ketoacidosis (DKA) in type 1 diabetes (DM) patients. Stress- related and steroid induced hyperglycemia are also well described during COVID infection with poor glycemic control being linked to more severe SARS-CoV-2 infection outcomes. While insulin needs increase during infection, extremely high insulin requirement is uncommon and not described in the pediatric population. We present here a case of mild COVID infection with transient markedly high insulin requirements. Clinical Case A 16-year-old-African-American- female with history of fairly well controlled type 2 diabetes mellitus on closed loop system insulin pump (Omnipod) with continuous glucose monitor (CGM), was admitted with COVID-19, aspiration pneumonia and hyperglycemia. She had been diagnosed 10 months prior with Hemoglobin A1c (HbA1c) of 11.4% and mild diabetic ketoacidosis (DKA). Diabetes antibodies were negative. Four months prior to admission her HbA1c was 7.8%. Upon this hospitalization she had no hypoxemia or respiratory failure and did not need steroids. Procalcitonin level 0.09 ng/mL was normal. Developmental delay, non-ambulatory and non-verbal status, an underlying mitochondrial neurological disease with G tube and ventilator dependence added to the medical complexity. HbA1c (8.1%) and Fructosamine 316 (n 200-285 mcmol/L) were not indicative of poor control. While her pneumonia resolved promptly, blood sugar (BG) elevation prolonged her hospitalization. She was not in DKA. Despite increasing her basal rate by 50% and an additional 20% higher temporary basal rate via her insulin pump there was little response. She was switched to Insulin drip by the 7th day. Her Insulin rate had increased to 26 units per hour (at 0.64 Units/Kg/hour) by day 8. This high insulin-dose need lasted for around 36 hours, before gradually reducing over a week. She has a history of recurrent pancreatitis. Lipase 335 U/L was elevated initially but started reducing within 2 days and had normalized by day 13. She was transitioned back to her pump although at higher basal rate than the previous home regimen, by 14th day. Conclusion While a constellation of factors such as stress, steroids, underlying poor glycemic control may cause hyperglycemia in COVID-19, these do not explain the high insulin demand in our patient. COVID infection with impaired insulin secretion, mild pancreatitis may have contributed to the brief remarkably high-dose insulin requirement, but it appears to be increased insulin resistance which could possibly explain the transient derangement. To our knowledge this has previously not been described in a pediatric diabetic patient. Presentation: 6/3/2024

7049 DUNNIGAN LIPODYSTROPHY AND SUCCESSFUL USE OF AID WITH U200

Abstract Disclosure: T. Kader: None. S. Seltzer: None. A. williams: None. Our patient is a 60 year old female with dunnigans partiallipodystrophy diagnosed after her niece was diagnosed and was sent to genetics; She was found to have a mutation in LMNA geneand had a heterozygous sequence variant.She was diagnosed with partial lipodystrophy and had macrovascular complications including carotid stenosis requiring surgical intervention.She was treated originally with insulin pump therapy that was sensor augmented along with glp1 agonist and sglt2 inhibitor but she developed recurrent pancreatitis and glp1 agonist was stopped. The pancreatitis was not induced by hypertriglycidemia as her levels were normal.Since then she had poorly controlled diabetes with a1c 8.7 percent and was having some hypoglycemia.;After consultation with the patient about off□ label use of AID pump technology for type 2 diabetes and off□ label use of u200 in AID pump she was willing to try and results were quite impressive with a1c falling close to 7 and time in range up to 70 percent with no lows. Her total insulin dosages were approximately 200 units q day but with u 200 she was changing every 2 days .Despite insulin resistance and dunnigan lipodystrophy this case exemplifies safety of u200 in AID pump in a patient with dunnigans lipodystrophy. It is the first of such report and more studies should be done using this technology in this rare group of patients with insulin resistance and poorly controlled diabetes. Presentation: 6/1/2024

Application of a Machine Learning Predictive Model for Recurrent Acute Pancreatitis.

Acute pancreatitis is the main cause of hospitalization for pancreatic disease. Some patients tend to have recurrent episodes after experiencing an episode of acute pancreatitis. This study aimed to construct predictive models for recurrent acute pancreatitis (RAP). A total of 531 patients who were hospitalized for the first episode of acute pancreatitis at the Affiliated Hospital of Southwest Medical University from January 2018 to December 2019 were enrolled in the study. We confirmed whether the patients had a second episode until December 31, 2021, through an electronic medical record system and telephone or WeChat follow-up. Clinical and follow-up data of patients were collected and randomly allocated to the training and test sets at a ratio of 7:3. The training set was used to select the best model, and the selected model was tested with the test set. The area under the receiver operating characteristic curves, sensitivity, specificity, positive predictive value, negative predictive value, accuracy, decision curve, and calibration plots were used to assess the efficacy of the models. Shapley additive explanation values were used to explain the model. Considering multiple indices, XGBoost was the best model. The area under the receiver operating characteristic curves, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model in the test set were 0.779, 0.763, 0.883, 0.647, 0.341, and 0.922, respectively. According to the Shapley additive explanation values, drinking, smoking, higher levels of triglyceride, and the occurrence of ANC are associated with RAP. The XGBoost model shows good performance in predicting RAP, which may help identify high-risk patients.

S2639 Smoking: An Independent Risk Factor for Acute and Recurrent Pancreatitis

S2639 Smoking: An Independent Risk Factor for Acute and Recurrent Pancreatitis

S2724 Primary Sclerosing Cholangitis in an Adolescent Presenting with Recurrent Acute Pancreatitis

S2724 Primary Sclerosing Cholangitis in an Adolescent Presenting with Recurrent Acute Pancreatitis

S2680 Acute Recurrent Pancreatitis Secondary to Superior Mesenteric Artery Syndrome

S2680 Acute Recurrent Pancreatitis Secondary to Superior Mesenteric Artery Syndrome

A Rare Etiology of Recurrent Pancreatitis: Intraductal Papillary Mucinous Neoplasm in the Santorini’s duct.

A Rare Etiology of Recurrent Pancreatitis: Intraductal Papillary Mucinous Neoplasm in the Santorini’s duct.

Optimal Timing to Perform Cholecystectomy in Patients with Acute Biliary Pancreatitis

Background: Acute biliary pancreatitis accounts for nearly 50% of acute pancreatitis cases, primarily caused by gallstones and biliary sludge. Cholecystectomy remains the definitive treatment to prevent recurrent biliary events, but the optimal timing of surgery remains debated.Objective: This study aimed to evaluate the optimal timing of cholecystectomy in patients with mild to moderate acute biliary pancreatitis, comparing early cholecystectomy during index admission to delayed cholecystectomy.Methods: A prospective cohort study was conducted over 24 months at Combined Military Hospital, Kohat, Pakistan. A total of 126 patients aged 18 years and older, diagnosed with mild to moderate acute biliary pancreatitis, were included. Patients with severe pancreatitis, ICU admissions, or requiring ERCP were excluded. Patients were divided into two groups: index admission cholecystectomy and delayed cholecystectomy. Data were analyzed using SPSS 25 with chi-square tests applied. A p-value of <0.05 was considered statistically significant.Results: Recurrent pancreatitis occurred in 0 patients in the early group versus 41 patients in the delayed group (p < 0.001). The mean hospital stay was significantly shorter in the early group (5.92 vs 12.31 days, p < 0.001).Conclusion: Early cholecystectomy significantly reduced recurrent biliary events and shortened hospital stay in patients with mild to moderate acute biliary pancreatitis without increasing complications.

Somatostatin in Treatment of Acute Recurrent Pancreatitis and Role of Endoscopic Ultrasonography in The Diagnostic Workup

The pancreas is an elongated, soft, flat, lobulated, and yellowish gland located on the posterior abdominal wall in a transverse orientation. The structure is located in the retroperitoneum and has a thin capsule. An abrupt response to pancreatic injury is known as acute pancreatitis (AP). Chronic pancreatitis can lead to enduring harm to the composition and the pancreas' endocrine and exocrine functions. The term idiopathic RAP (IRAP) is employed when the reason cannot be readily identified by the assessment of physical examination, medical history, basic laboratory tests (calcium and serum triglyceride levels, for example), and diagnostic imaging studies (e.g., CT scans and transabdominal ultrasounds). With endoscopic ultrasonography (EUS), you may see the inside of your digestive tract and any surrounding tissues in high resolution and real time. When it comes to evaluating a wide variety of benign and malignant GI illnesses, this technique is both efficient and cost-effective. Somatostatin inhibits the release and manufacture of certain enzymes, which in turn decreases the pancreas' ability to absorb amino acids. The release of somatostatin from the pancreatic islets is stimulated by high glucose concentration.

Use of a hybrid closed loop system in a child with end stage renal disease, GAD positive diabetes and recurrent pancreatitis - a game changer!

Use of a hybrid closed loop system in a child with end stage renal disease, GAD positive diabetes and recurrent pancreatitis - a game changer!

Decreased risk of recurrent acute pancreatitis with semaglutide and tirzepatide in people with type 2 diabetes or obesity with a history of acute pancreatitis: A propensity matched global federated TriNetX database-based retrospective cohort study

BackgroundAcute pancreatitis (AP) is a significant health concern with potential for recurrent episodes and serious complications. The risk of recurrence in type 2 diabetes (T2D) or obesity can be influenced by various factors and treatments, including GLP-1 receptor agonists (GLP-1RAs). This study evaluates the risk of recurrent AP among patients with a history of the condition, focusing on the effects of different GLP-1RA treatments. ObjectivesOur objective is to compare the recurrence risks of AP between patients treated with different GLP-1RAs. MethodsWe conducted a retrospective cohort study using the TriNetX platform, encompassing 258,238 individuals with T2D or obesity who have a history of AP. We assessed the recurrence of AP over a five-year period, analyzing data on treatment regimens, with a focus on the use of Semaglutide, Tirzepatide, and other GLP-1RAs. ResultsGLP-1RA users experienced significantly lower recurrence rates of AP, with those without risk factors showing GLP-1RA users had a recurrence rate of 13.8 % compared to 40.9 % for non-users. Semaglutide and Tirzepatide showed the most favorable outcomes; Semaglutide users had lower recurrence rates than Exenatide (10.1 % vs. 27 %) and slightly lower than Dulaglutide (13.6 % vs. 15.4 %), though not statistically significant with Dulaglutide. Tirzepatide users displayed the lowest recurrence risk at 6.2 %, significantly lower than those on Semaglutide (11.7 %). ConclusionsGLP-1RAs, particularly Semaglutide and Tirzepatide, are associated with a reduced risk of recurrent AP in people with T2D or obesity. The differential risk profile between these drugs highlights the need for further studies and personalized treatment plans.

Association of Serum Endocannabinoid Levels with Pancreatitis and Pancreatitis-Related Pain.

Background and Aims: This investigation examined the association of pancreatitis and pancreatitis-related pain with serum levels of two endocannabinoid molecules such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and two paracannabinoid molecules such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). Methods: A case-control study was conducted within the Prospective Evaluation of Chronic Pancreatitis for Epidemiological and Translational Studies, including participants with no pancreas disease (N = 56), chronic abdominal pain of suspected pancreatic origin or indeterminate chronic pancreatitis (CP) (N = 22), acute pancreatitis (N = 33), recurrent acute pancreatitis (N = 57), and definite CP (N = 63). Results: Circulating AEA concentrations were higher in women than in men (p = 0.0499), and PEA concentrations were higher in obese participants than those who were underweight/normal or overweight (p = 0.003). Asymptomatic controls with no pancreatic disease had significantly (p = 0.03) lower concentrations of AEA compared with all disease groups combined. The highest concentrations of AEA were observed in participants with acute pancreatitis, followed by those with recurrent acute pancreatitis, chronic abdominal pain/indeterminant CP, and definite CP. Participants with pancreatitis reporting abdominal pain in the past year had significantly (p = 0.04) higher concentrations of AEA compared with asymptomatic controls. Levels of 2-AG were significantly lower (p = 0.02) among participants reporting abdominal pain in the past week, and pain intensity was inversely associated with concentrations of 2-AG and OEA. Conclusions: Endocannabinoid levels may be associated with stage of pancreatitis, perhaps through activation of the CB1 receptor. Validation of our findings would support the investigation of novel therapeutics, including cannabinoid receptor-1 antagonists, in this patient population.

Endoscopic Retrograde Cholangio-Pancreatography and Endoscopic Ultrasound in the Management of Paediatric Acute Recurrent Pancreatitis and Chronic Pancreatitis.

Objectives: To evaluate the role of ERCP (endoscopic retrograde cholangio-pancreatography) and EUS (endoscopic ultrasound) and to describe the efficacy and safety of these procedures in a paediatric cohort with chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP). Methods: All patients (<18 years) undergoing an ERCP or EUS for ARP and CP between January 2008 and December 2022 were included. Data collection included indications for the procedure, technical success, adverse events and outcome data. Results: A total of 222 ERCPs were performed in 98 patients with CP and ARP (60% female, median age 10 years). The commonest indications were a main pancreatic duct stricture (PD) with or without a stone within the main PD. Successful cannulation was achieved in 98% of cases. Improved stricture resolution was demonstrated in 63% of patients. The overall adverse event rate for ERCP was low (n = 8/222, 3.6%). An improvement in abdominal pain was demonstrated in (75/98) 76% of patients. Their Body Mass Index also significantly improved post ERCP (15.5 ± 1.41 vs. 12.9 ± 1.16 kg/m2, p = 0.001). A total of 54 EUS procedures were undertaken in 48 individuals. Moreover, 35 individuals underwent a therapeutic EUS procedure, for which the commonest indication was the drainage of a pancreatic fluid collection. The overall complication rate was low (n = 2.4%) in all EUS cases. Conclusions: ERCP and EUS can be safely and effectively used in a paediatric population with indications analogous to an adult cohort.

Parathyroid adenoma revealed by recurrent acute pancreatitis: a case report

Parathyroid adenoma revealed by recurrent acute pancreatitis: a case report

Abstract C079: Exploring acinar to ductal metaplasia in pancreatitis and precancerous contexts using FixNCut

Abstract Acinar to ductal metaplasia (ADM) is the process by which acinar cells transition to a duct-like state acquiring ductal markers and morphology. This process can be driven by pancreas inflammation or injury, such as pancreatitis, where it is thought to be an adaptive response to help mitigate damage and facilitate repair. ADM is also observed following acinar-specific oncogenic KRAS mutations and known to precede PDAC precancerous lesions termed pancreatic intraepithelial neoplasias (PanINs). While ADM is well characterized histologically, cellular and molecular details of ADM and PanIN formation remain less well understood, in part due to high levels of digestive enzyme production in acinar cells that hamper characterization. Leveraging our recently described DSP-fixation method, FixNCut, to improve capture and transcriptome quality of acinar and ADM populations in the pancreas, we characterize ADM arising in three contexts: acute pancreatitis, recurrent acute pancreatitis, and acute pancreatitis with an oncogenic KRAS mutation known to drive the formation of PanINs. FixNCut and single-cell RNA-sequencing enabled us to elucidate the transcriptomic landscape of ADM and define changes to the microenvironment in unprecedented detail. Our findings indicate that the cellular and transcriptional landscape of recurrent acute pancreatitis closely mirrors that of acute pancreatitis for up to 6 weeks (or 6 bouts of 2-day acute pancreatitis), which was the longest timepoint tested. In contrast, acute pancreatitis in the presence of an acinar-specific oncogenic KRAS mutation results in a distinct transcriptional profile for both ADM and the surrounding microenvironment compared to pancreatitis alone. Additionally, we use FixNCut to preserve the epigenomes of acinar cells, enabling us to sort acinar cells and profile their histone modifications in various contexts of ADM. We benchmark and validate our results against existing mouse and human datasets of precancer and cancer. Through this work, we aim to enhance our understanding of ADM in various contexts, providing insights into acinar cell plasticity and early PDAC precursor formation that may inform strategies for early detection and interception. Citation Format: Katherine Aney, Woo-Jeong Jeong, Pal Koak, Isabel Kim, Sahar Nissim. Exploring acinar to ductal metaplasia in pancreatitis and precancerous contexts using FixNCut [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C079.