Browsing by Subject "pancreatitis"
Now showing 1 - 10 of 13
Results Per Page
Sort Options
Item Analysis of INSPPIRE-2 Cohort: Risk Factors and Disease Burden in Children with Acute Recurrent or Chronic Pancreatitis(Wiley, 2022-11) Uc, Aliye; Cress, Gretchen A.; Wang, Fuchenchu; Abu-El-Haija, Maisam; Ellery, Kate M.; Fishman, Douglas S.; Gariepy, Cheryl E.; Gonska, Tanja; Lin, Tom K.; Liu, Quin Y.; Mehta, Megha; Maqbool, Asim; McFerron, Brian A.; Morinville, Veronique D.; Ooi, Chee Y.; Perito, Emily R.; Schwarzenberg, Sarah Jane; Sellers, Zachary M.; Serrano, Jose; Shah, Uzma; Troendle, David M.; Wilschanski, Michael; Zheng, Yuhua; Yuan, Ying; Lowe, Mark E.; Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer; Pediatrics, School of MedicineObjectives: To investigate risk factors and disease burden in pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). Methods: Data were obtained from INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2), the largest multi-center prospective cohort study in pediatric patients with ARP or CP. Results: Of 689 children, 365 had ARP (53%), 324 CP (47%). CP was more commonly associated with female sex, younger age at first acute pancreatitis (AP) attack, Asian race, family history of CP, lower BMI%, genetic and obstructive factors, PRSS1 mutations and pancreas divisum. CFTR mutations, toxic-metabolic factors, medication use, hypertriglyceridemia, Crohn disease were more common in children with ARP. Constant or frequent abdominal pain, emergency room (ER) visits, hospitalizations, medical, endoscopic or surgical therapies were significantly more common in CP, episodic pain in ARP. 33.1% of children with CP had exocrine pancreatic insufficiency (EPI), 8.7% had diabetes mellitus. Compared to boys, girls were more likely to report pain impacting socialization and school, medical therapies, cholecystectomy, but no increased opioid use. There was no difference in race, ethnicity, age at first AP episode, age at CP diagnosis, duration of disease, risk factors, prevalence EPI or diabetes between boys and girls. Multivariate analysis revealed that family history of CP, constant pain, obstructive risk factors were predictors of CP. Conclusions: Children with family history of CP, constant pain or obstructive risk factors should raise suspicion for CP.Item Biliary Stricture after Necrotizing Pancreatitis: An Underappreciated Challenge(Wolters Kluwer, 2020-10) Maatman, Thomas K.; Ceppa, Eugene P.; Fogel, Evan L.; Easler, Jeffrey J.; Gromski, Mark A.; House, Michael G.; Nakeeb, Attila; Schmidt, C. Max; Sherman, Stuart; Zyromski, Nicholas J.; Surgery, School of MedicineObjective: Biliary stricture in necrotizing pancreatitis (NP) has not been systematically categorized; therefore, we sought to define the incidence and natural history of biliary stricture caused by NP. Summary/Background Data: Benign biliary stricture occurs secondary to bile duct injury, anastomotic narrowing, or chronic inflammation and fibrosis. The profound loco-regional inflammatory response of NP creates challenging biliary strictures. Methods: NP patients treated between 2005–2019 were reviewed. Biliary stricture was identified on cholangiography as narrowing of the extrahepatic biliary tree to < 75% of the diameter of the unaffected duct. Biliary stricture risk factors and outcomes were evaluated. Results: Among 743 NP patients, 64 died, 13 were lost to follow up; therefore, a total of 666 patients were included in the final cohort. Biliary stricture developed in 108 (16%) patients. Mean follow up was 3.5 ± 3.3 years. Median time from NP onset to biliary stricture diagnosis was 4.2 months (IQR, 1.8–10.9). Presentation was commonly clinical or biochemical jaundice, n = 30 (28%) each. Risk factors for stricture development were splanchnic vein thrombosis and pancreatic head parenchymal necrosis. Median time to stricture resolution was 6.0 months after onset (2.8–9.8). A mean of 3.3 ± 2.3 procedures were performed. Surgical intervention was required in 22 (20%) patients. Endoscopic treatment failed in 17% (17/99) of patients and was not associated with stricture length. Operative treatment of biliary stricture was more likely in patients with infected necrosis or NP disease duration ≥6 months. Conclusion: Biliary stricture occurs frequently after necrotizing pancreatitis and is associated with splanchnic vein thrombosis and pancreatic head necrosis. Surgical correction was performed in 20%.Item Can We Detect Chronic Pancreatitis With Low Serum Pancreatic Enzyme Levels?(Lippincott, Williams, and Wilkins, 2016-09) Kwon, Chang-Il; Kim, Hong Joo; Korc, Paul; Choi, Eun Kwang; McNulty, Gail M.; Easler, Jeffrey J.; El Hajj, Ihab I.; Watkins, James; Fogel, Evan L.; McHenry, Lee; Zimmerman, Michelle K.; Sherman, Stuart; Lehman, Glen A.; Department of Medicine, IU School of MedicineObjectives: The aims of this study were to evaluate whether serum pancreatic enzyme levels could be used to aid screening for chronic pancreatitis (CP). Methods: 170 healthy volunteers were screened and prospectively enrolled in the control group. 150 patients who were diagnosed with calcific CP were enrolled in the patient group by retrospective review. Serum amylase and lipase levels were compared between the 2 groups. Results: The mean values ± SD of the control group were compared with those of the patient group for serum amylase level (48.1 ± 13.2 vs 34.8 ± 17.2 U/L, P < 0.001) and serum lipase level (26.4 ± 11.3 vs 16.3 ± 11.2 U/L, P < 0.001). On the receiver operating characteristic curve analysis for amylase level, area under the curve was 0.740 (95% confidence interval), and sensitivity and specificity were 38.7% and 94.1%, respectively, with a cutoff value of 27.5 U/L. On the receiver operating characteristic curve analysis for lipase level, area under the curve was 0.748 (95% confidence interval), and sensitivity and specificity were 33.3% and 95.9%, respectively, with a cutoff value of 10.5 U/L. Conclusions: Our results suggest that low serum pancreatic enzyme levels can be used to aid in detection of CP.Item Contribution of Environment and Genetics to Pancreatic Cancer Susceptibility(Public Library of Science, 2014-03-20) Hocevar, Barbara A.; Kamendulis, Lisa M.; Pu, Xinzhu; Perkins, Susan M.; Wang, Zheng-Yu; Johnston, Erica L.; DeWitt, John M.; Li, Lang; Loehrer, Patrick J.; Klaunig, James E.; Chiorean, E. Gabriela; Medicine, School of MedicineSeveral risk factors have been identified as potential contributors to pancreatic cancer development, including environmental and lifestyle factors, such as smoking, drinking and diet, and medical conditions such as diabetes and pancreatitis, all of which generate oxidative stress and DNA damage. Oxidative stress status can be modified by environmental factors and also by an individual's unique genetic makeup. Here we examined the contribution of environment and genetics to an individual's level of oxidative stress, DNA damage and susceptibility to pancreatic cancer in a pilot study using three groups of subjects: a newly diagnosed pancreatic cancer group, a healthy genetically-unrelated control group living with the case subject, and a healthy genetically-related control group which does not reside with the subject. Oxidative stress and DNA damage was evaluated by measuring total antioxidant capacity, direct and oxidative DNA damage by Comet assay, and malondialdehyde levels. Direct DNA damage was significantly elevated in pancreatic cancer patients (age and sex adjusted mean ± standard error: 1.00±0.05) versus both healthy unrelated and related controls (0.70±0.06, p<0.001 and 0.82±0.07, p = 0.046, respectively). Analysis of 22 selected SNPs in oxidative stress and DNA damage genes revealed that CYP2A6 L160H was associated with pancreatic cancer. In addition, DNA damage was found to be associated with TNFA −308G>A and ERCC4 R415Q polymorphisms. These results suggest that measurement of DNA damage, as well as select SNPs, may provide an important screening tool to identify individuals at risk for development of pancreatic cancer.Item Development and Validation of a Machine Learning-based, Point-of-Care Risk Calculator for Post-ERCP Pancreatitis and Prophylaxis Selection(Elsevier, 2024) Brenner, Todd; Kuo, Albert; Sperna Weiland, Christina J.; Kamal, Ayesha; Elmunzer, B. Joseph; Luo, Hui; Buxbaum, James; Gardner, Timothy B.; Mok, Shaffer S.; Fogel, Evan S.; Phillip, Veit; Choi, Jun-Ho; Lua, Guan W.; Lin, Ching-Chung; Reddy, D. Nageshwar; Lakhtakia, Sundeep; Goenka, Mahesh K.; Kochhar, Rakesh; Khashab, Mouen A.; van Geenen, Erwin J. M.; Singh, Vikesh K.; Tomasetti, Cristian; Akshintala, Venkata S.; Medicine, School of MedicineBackground and Aims A robust model of post-ERCP pancreatitis (PEP) risk is not currently available. We aimed to develop a machine learning–based tool for PEP risk prediction to aid in clinical decision making related to periprocedural prophylaxis selection and postprocedural monitoring. Methods Feature selection, model training, and validation were performed using patient-level data from 12 randomized controlled trials. A gradient-boosted machine (GBM) model was trained to estimate PEP risk, and the performance of the resulting model was evaluated using the area under the receiver operating curve (AUC) with 5-fold cross-validation. A web-based clinical decision-making tool was created, and a prospective pilot study was performed using data from ERCPs performed at the Johns Hopkins Hospital over a 1-month period. Results A total of 7389 patients were included in the GBM with an 8.6% rate of PEP. The model was trained on 20 PEP risk factors and 5 prophylactic interventions (rectal nonsteroidal anti-inflammatory drugs [NSAIDs], aggressive hydration, combined rectal NSAIDs and aggressive hydration, pancreatic duct stenting, and combined rectal NSAIDs and pancreatic duct stenting). The resulting GBM model had an AUC of 0.70 (65% specificity, 65% sensitivity, 95% negative predictive value, and 15% positive predictive value). A total of 135 patients were included in the prospective pilot study, resulting in an AUC of 0.74. Conclusions This study demonstrates the feasibility and utility of a novel machine learning–based PEP risk estimation tool with high negative predictive value to aid in prophylaxis selection and identify patients at low risk who may not require extended postprocedure monitoring.Item Distinct serum immune profiles define the spectrum of acute and chronic pancreatitis from the multi-center PROCEED study(AGA, 2023-07) Lee, Bomi; Jones, Elaina K.; Manohar, Murli; Li, Liang; Yadav, Dhiraj; Conwell, Darwin L.; Hart, Phil A.; Vege, Santhi Swaroop; Fogel, Evan L.; Serrano, Jose; Anderson, Dana; Bellin, Melena D.; Topazian, Mark D.; Van Den Eeden, Stephen K.; Pandol, Stephen J.; Forsmark, Chris E.; Fisher, William E.; Park, Walter G.; Husain, Sohail Z.; Habtezion, Aida; Medicine, School of MedicineBackground & Aims Pancreatitis is a disease continuum, starting with acute pancreatitis (AP) and progressing in some cases to recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP). Currently, there are no approved therapies or early diagnostic or prognostic biomarkers for pancreatitis. The current study examined whether patient serum immune profiling could identify noninvasive biomarkers and provide mechanistic insight into the disease continuum of pancreatitis. Methods Using Olink immunoassay, we assessed the protein levels of 92 immune markers in serum samples from participants enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study of the Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) consortium. Samples (N = 231) were obtained from individuals without pancreatic disease (n = 56) and from those with chronic abdominal pain (CAP) (n = 24), AP (n = 38), RAP (n = 56), and CP (n = 57). Results A total of 33 immune markers differentiated the combined pancreatitis groups from controls. Immune markers related to interleukin (IL) 17 signaling distinguished CP from AP and RAP. Similarly, the serum level of IL17A and C-C motif chemokine ligand 20 differentiated CP from CAP, suggesting the involvement of T helper 17 cells in CP pathogenesis. The receiver operator characteristic curve with 2 immune markers (IL17A and sulfotransferase 1A1) could differentiate CP from CAP (optimistic area under the curve = 0.78). The macrophage classical activation pathway elevated along the continuum of pancreatitis, suggesting an accumulation of proinflammatory signals over disease progression. Several immune markers were associated with smoking, alcohol, and diabetes status. Conclusions Immune profiling of serum samples from a large pancreatitis cohort led to identifying distinct immune markers that could serve as potential biomarkers to differentiate the varying pancreatitis disease states. In addition, the finding of IL17 signaling in CP could provide insight into the immune mechanisms underlying disease progression.Item Evaluating Adults With Idiopathic Pancreatitis for Genetic Predisposition: Higher Prevalence of Abnormal Results With Use of Complete Gene Sequencing(Wolters Kluwer, 2015-01) Ballard, Darren D.; Flueckiger, Joyce R.; Fogel, Evan L.; McHenry, Lee; Lehman, Glen A.; Watkins, James L.; Sherman, Stuart; Coté, Gregory A.; Department of Medicine, IU School of MedicineOBJECTIVES: In adults with unexplained pancreatitis, the yield of complete gene versus select exosome sequencing on mutation detection and distinguishing clinical characteristics associated with mutations requires clarification. We sought to (1) compare frequency of mutations identified using different techniques and (2) compare clinical characteristics between adults with and without mutations. METHODS: This is a cohort study of adults with unexplained pancreatitis who underwent genetic testing between January 2008 and December 2012. We compare probabilities of having a positive mutation with complete gene sequencing versus alternatives and describe differences in characteristics among patients with and without mutations. RESULTS: Of the 370 patients, 67 (18%) had a genetic mutation; 24 (6%) were of high risk. Mutations were significantly more prevalent with use of complete sequencing (42%) versus other approaches (8%, P < 0.0001). Most (44/67, 66%) with a mutation had no family history. Those with high-risk mutations were more likely to have a family history of chronic pancreatitis (21% vs 4%, P = 0.002). Patients with pancreas divisum were more likely to have mutations (27% vs 14%, P = 0.0007). CONCLUSION: Among individuals with adult-onset pancreatic disease, the probability of finding any mutation, including high risk, is significantly higher using complete gene sequencing. The impact on patients and providers requires further investigation.Item Evolving treatment of necrotizing pancreatitis(Elsevier, 2017) Roch, Alexandra M.; Maatman, Thomas; Carr, Rose A.; Easler, Jeffrey J.; Schmidt, C. Max; House, Michael G.; Nakeeb, Attila; Ceppa, Eugene P.; Zyromski, Nicholas J.; Surgery, School of MedicineBackground Over the past decade, the treatment of necrotizing pancreatitis (NP) has incorporated greater use of minimally invasive techniques, including percutaneous drainage and endoscopic debridement. No study has yet compared outcomes of patients treated with all available techniques. We sought to evaluate the evolution of NP treatment at our high volume pancreas center. We hypothesized that minimally invasive techniques (medical only, percutaneous, and endoscopic) were used more frequently in later years. Methods Treatment strategy of NP patients at a single academic medical center between 2005 and 2014 was reviewed. Definitive management of pancreatic necrosis was categorized as: 1) medical treatment only; 2) surgical only; 3) percutaneous (interventional radiology – IR) only; 4) endoscopic only; and 5) combination (Surgery ± IR ± Endoscopy). Results 526 NP patients included biliary (45%), alcoholic (17%), and idiopathic (20%) etiology. Select patients were managed exclusively by medical, IR, or endoscopic treatment; use of these therapies remained relatively consistent over time. A combination of therapies was used in about 30% of patients. Over time, the percentage of NP patients managed without operation increased from 28% to 41%. 247 (47%) of patients had operation as the only NP treatment; an additional 143 (27%) required surgery as part of a multidisciplinary management. Conclusion Select NP patients may be managed exclusively by medical, IR, or endoscopic treatment. Combination treatment is necessary in many NP patients, and surgical treatment continues to play an important role in the definitive therapy of necrotizing pancreatitis patients.Item Rectal Indomethacin Dose Escalation (RIDE) for Prevention of Post-ERCP Pancreatitis in High-Risk Patients: a Randomized Trial(Elsevier, 2020-02) Fogel, Evan L.; Lehman, Glen A.; Tarnasky, Paul; Cote, Gregory A.; Schmidt, Suzette E.; Waljee, Akbar K.; Higgins, Peter D. R.; Watkins, James L.; Sherman, Stuart; Kwon, Richard S. Y.; Elta, Grace H.; Easler, Jeffrey J.; Pleskow, Douglas K.; Scheiman, James M.; El Hajj, Ihab I.; Guda, Nalini M.; Gromski, Mark A.; McHenry, Lee, Jr.; Arol, Seena; Korsnes, Sheryl; Suarez, Alejandro L.; Spitzer, Rebecca; Miller, Marilyn; Hofbauer, Maria; Elmunzer, Badih Joseph; Medicine, School of MedicineBackground Although rectal indometacin 100 mg is effective in reducing the frequency and severity of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients, the optimal dose is unknown, and pancreatitis incidence remains high. The aim of this study was to compare the efficacy of two dose regimens of rectal indometacin on the frequency and severity of pancreatitis after ERCP in high-risk patients. Methods In this randomised, double-blind, comparative effectiveness trial, we enrolled patients from six tertiary medical centres in the USA. Eligible patients were those at high risk for the development of pancreatitis after ERCP. We randomly assigned eligible patients (1:1) immediately after ERCP to receive either two 50 mg indometacin suppositories and a placebo suppository (standard-dose group) or three 50 mg indometacin suppositories (high-dose group). 4 h after the procedure, patients assigned to the high-dose group received an additional 50 mg indometacin suppository, whereas patients in the standard-dose group received an additional placebo suppository. The randomisation schedule, stratified according to study centre and with no other restrictions, was computer generated by an investigator who was uninvolved in the clinical care of any participants, distributed to the sites, and kept by personnel not directly involved with the study. These same personnel were responsible for packaging the drug and placebo in opaque envelopes. Patients, study personnel, and treating physicians were masked to study group assignment. The primary outcome of the study was the development of pancreatitis after ERCP. Analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01912716, and enrolment is complete. Findings Between July 9, 2013, and March 22, 2018, 1037 eligible patients were enrolled and randomly assigned to receive either standard-dose (n=515) or high-dose indometacin (n=522). Pancreatitis after ERCP occurred in 141 (14%) of 1037 patients—76 (15%) of 515 patients in the standard-dose indometacin group and 65 (12%) of 522 patients in the high-dose indometacin group (risk ratio [RR] 1·19, 95% CI 0·87–1·61; p=0·32). We observed 19 adverse events that were potentially attributable to study drug. Clinically significant bleeding occurred in 14 (1%) of 1037 patients—six (1%) of 515 patients in the standard-dose indometacin group and eight (2%) of 522 patients in the high-dose indometacin group (p=0·79). Three (1%) of 522 patients in the high-dose indometacin group developed acute kidney injury versus none in the standard-dose group (p=0·25). A non-ST elevation myocardial infarction occurred in the standard-dose indometacin group 2 days after ERCP. A transient ischaemic attack occurred in the high-dose indometacin group 5 days after ERCP. All 19 adverse events, in addition to the 141 patients who developed pancreatitis after ERCP, were considered serious as all required admission to hospital. We observed no allergic reactions or deaths at 30 day follow-up. Interpretation Dose escalation to rectal indometacin 200 mg did not confer any advantage compared with the standard 100 mg regimen, with pancreatitis incidence remaining high in high-risk patients. Current practice should continue unchanged. Further research should consider the pharmacokinetics of non-steroidal anti-inflammatory drugs to determine the optimal timing of their administration to prevent pancreatitis after ERCP.Item The Repercussions of Hereditary Pancreatitis in a 29-Year-Old Male and His Family(2020-10-01) Lugo, Adrian; Martyn, Colin; Fraser, Scott; Ahmed, KhanThe etiology of chronic pancreatitis is multifactorial, but it can frequently be attributed to an inciting factor such as alcohol use, biliary cholelithiasis, or hypertriglyceridemia. In rare cases, inherited mutations in cationic trypsinogen (PRSS1) can lead to hereditary pancreatitis (HP) and increase the risk of pancreatic cancer. In this report, we demonstrate the case of a 29-year-old male with hereditary pancreatitis who inherited a PRSS1 mutation from his mother. A 29-year-old male with a past medical history of hypertriglyceridemia, tobacco use, hypothyroidism, and hereditary pancreatitis presented with epigastric pain and nausea. Liver function tests were unremarkable. Lipase was 760 U/L (range 8-78 U/L). Triglyceride level was 163 (15-150 mg/dL). Computerized tomography imaging of the patient’s abdomen and pelvis from a year prior demonstrated parenchymal calcifications within the pancreas. The patient's symptoms abated within 4 days of aggressive IV fluid resuscitation and supportive care. Regarding his history, at the age of 8, the patient was found to possess a mutated R117H allele in the PRSS1 gene upon PCR analysis of exon 3 from chromosome 7. His mother carried this gene and underwent pancreatectomy for recurrent pancreatitis and numerous pancreatic parenchymal calcifications. In adulthood, the patient has averaged 4 to 5 episodes of pancreatitis annually and has used pancrelipase, indomethacin suppositories and injectable octreotide for symptom control. Of note, the patient’s son did not possess the PRSS1 gene mutation. Mutations in the PRSS1 gene are associated with hereditary pancreatitis due to unrestricted action of trypsin which leads to pancreatic autodigestion. Our patient inherited a mutated PRSS1 allele from his symptomatic mother, but his male offspring did not manifest such symptoms. The literature shows that penetrance of the PRSS1 gene ranges between 40-90%, which implies a high probability of passing these alleles to offspring. More importantly, patients with HP tend to also be carriers of the SPINK1 and CFTR mutations, which are linked to pancreatic cancer and cystic fibrosis, respectively. This case report highlights the importance of genetic testing as mutations can lead to both a perpetual cycle of pancreatitis and increase the risk of developing pancreatic cancer. Proper anticipation can prompt the use of pancreatic enzyme supplementation, octreotide, and indomethacin to help control symptoms and reduce chronicity.