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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 Detection of Exocrine Dysfunction by MRI in Patients with Early Chronic Pancreatitis(Springer, 2017-02) Tirkes, Temel; Fogel, Evan L.; Sherman, Stuart; Lin, Chen; Swensson, Jordan; Akisik, Fatih; Sandrasegaran, Kumaresan; Department of Radiology and Imaging Sciences, IU School of MedicinePurpose To determine if T1-weighted MR signal of the pancreas can be used to detect early CP. Methods A retrospective analysis was performed on 51 suspected CP patients, who had both secretin-enhanced magnetic resonance cholangiopancreatography (S-MRCP) and an intraductal secretin stimulation test (IDST). There were 29 patients in normal and 22 patients in the low bicarbonate group. Bicarbonate level, total pancreatic juice volume, and excretory flow rate were recorded during IDST. Signal intensity ratio of pancreas (SIR), fat signal fraction, pancreatograms findings, and grade of duodenal filling were recorded on S-MRCP by two blinded radiologists. Results There was a significant difference in the signal intensity ratio of the pancreas to spleen (SIRp/s) between the normal and low bicarbonate groups (p < 0.0001). A significant positive correlation was found between pancreatic fluid bicarbonate level and SIRp/s (p < 0.0001). SIRp/s of 1.2 yielded sensitivity of 77% and specificity of 83% for detection of pancreatic exocrine dysfunction (AUC: 0.89). Conclusion T1-weighted MR signal of the pancreas has a high sensitivity and specificity for the detection of parenchymal abnormalities related to exocrine dysfunction and can therefore be helpful in evaluation of suspected early CP.Item Different endoscopic management of 2 cases of acute buried bumper syndrome(Elsevier, 2017-11-01) Hajj, Ihab I. El; Watkins, James; Easler, Jeffrey; Fogel, Evan; Sherman, Stuart; Lehman, Glen A.; Medicine, School of MedicineItem Effectiveness and safety of serial endoscopic ultrasound–guided celiac plexus block for chronic pancreatitis(Thieme Open, 2015-02) Sey, Michael S. L.; Schmaltz, Leslie; Al-Haddad, Mohammad A.; DeWitt, John M.; Calley, Cynthia S. J.; Juan, Michelle; Lasisi, Femi; Sherman, Stuart; McHenry, Lee; Imperiale, Thomas F.; LeBlanc, Julia K.; Medicine, School of MedicineBackground and study aims: Endoscopic ultrasound – guided celiac plexus block (EUS-CPB) is an established treatment for pain in patients with chronic pancreatitis (CP), but the effectiveness and safety of repeated procedures are unknown. Our objective is to report our experience of repeated EUS-CPB procedures within a single patient. , Patients and methods: A prospectively maintained EUS database was retrospectively analyzed to identify patients who had undergone more than one EUS-CPB procedure over a 17-year period. The main outcome measures included number of EUS-CPB procedures for each patient, self-reported pain relief, duration of pain relief, and procedure-related adverse events. , Results: A total of 248 patients underwent more than one EUS-CPB procedure and were included in our study. Patients with known or suspected CP (N = 248) underwent a mean (SD) of 3.1 (1.6) EUS-CPB procedures. In 76 % of the patients with CP, the median (range) duration of the response to the first EUS-CPB procedure was 10 (1 – 54) weeks. Lack of pain relief after the initial EUS-CPB was associated with failure of the next EUS-CPB (OR 0.17, 95 %CI 0.06 – 0.54). Older age at first EUS-CPB and pain relief after the first EUS-CPB were significantly associated with pain relief after subsequent blocks (P = 0.026 and P = 0.002, respectively). Adverse events included peri-procedural hypoxia (n = 2) and hypotension (n = 1) and post-procedural orthostasis (n = 2) and diarrhea (n = 4). No major adverse events occurred., Conclusions: Repeated EUS-CPB procedures in a single patient appear to be safe. Response to the first EUS-CPB is associated with response to subsequent blocks.Item EUS pancreatic function testing and dynamic pancreatic duct evaluation for the diagnosis of exocrine pancreatic insufficiency and chronic pancreatitis(Elsevier, 2020) DeWitt, John M.; Al-Haddad, Mohammad A.; Easler, Jeffrey J.; Sherman, Stuart; Slaven, James; Gardner, Timothy B.; Medicine, School of MedicineBackground and Aims EUS and endoscopic pancreatic function tests (ePFTs) may be used to diagnose minimal- change chronic pancreatitis (MCCP). The impact of evaluation for exocrine pancreatic insufficiency (EPI) and real-time assessment of EUS changes after intravenous secretin on the clinical diagnosis of MCCP is unknown. Methods Patients with suspected MCCP underwent baseline EUS assessment of the pancreatic parenchyma and measurement of the main pancreatic duct (B-MPD) in the head, body, and tail. Human secretin 0.2 μg/kg IV was given followed 4, 8, and 12 minutes later by repeat MPD (S-MPD) measurements. Duodenal samples at 15, 30, and 45 minutes were aspirated for bicarbonate concentration. Endoscopists rated the percent clinical likelihood of CP: (1) before secretin; (2) after secretin but before aspiration; and (3) after bicarbonate results. Results 145 consecutive patients (mean age 44±13 years; 98F) were diagnosed with EPI (n=32; 22%). S-MPD/B-MPD ratios in the tail 4 and 8 minutes after secretin were higher in the group with normal exocrine function. Ratios at other times, locations and duodenal fluid volumes were similar between the 2 groups. A statistically significant change in the median percent likelihood of CP was noted after secretin in all groups. The sensitivity and specificity of EPI for the EUS diagnosis of CP (≥5 criteria) were 23.4% (95% CI, 12.3-38.0) and 78.6% (95% CI, 69.1-86.2), respectively. Conclusion Real-time EUS findings and ePFTs have a significant impact on the clinical assessment of MCCP. The diagnosis of EPI shows poor correlation with the EUS diagnosis of MCCP.Item In Brief(Elsevier, 2021-03) Maatman, Thomas K.; Zyromski, Nicholas J.; Surgery, School of MedicineItem Is Cambridge scoring in chronic pancreatitis the same using ERCP and MRCP?: A need for revision of standards(Springer, 2021-02) Swensson, Jordan; Akisik, Fatih; Collins, David; Olesen, Søren Schou; Drewes, Asbjørn Mohr; Frøkjær, Jens Brøndum; Radiology and Imaging Sciences, School of MedicinePurpose Grading of chronic pancreatitis (CP) is a clinical and radiologic challenge. Retrograde cholangiopancreatography (ERCP) and magnetic resonance cholangiopancreatography (MRCP) use a version of the Cambridge criteria for ductal evaluation and CP staging, but interchangeability between the modalities lacks validation. This work compares ERCP and MRCP Cambridge scores and evaluates diagnostic performance of MRCP in a large cohort of patients with CP. Methods A large radiology database was searched for CP patients who underwent MRCP between 2003 and 2013. Next, patients who also had an ERCP within 90 days of their MRCP were selected. These were categorized into mild, moderate, and severe CP using the standardized Cambridge classification for ERCP. Radiologists blinded to ERCP findings then rated MRCP with modified Cambridge scores. Results The cohort comprised 325 patients (mean age 51 years; 56% female). By ERCP Cambridge classification, 122 had mild CP, 109 moderate CP, and 94 severe CP. MRCP and ERCP showed total agreement of Cambridge score in only 43% of cases. With ERCP as reference, the sensitivity and specificity of MRCP in detecting Cambridge scores 4 + 5 (main-duct predominant) were 75.9% and 64.3%, and for Cambridge score 3 (side-branch predominant) it was 60.0% and 76.9%, respectively. Conclusions There is a lack of strong concordance between ERCP- and MRCP-based grading of CP using the Cambridge criteria. MRCP had moderate to good performance in diagnosing side-branch predominant versus main-duct predominant CP. This suggests an inherent challenge in comparing literature and calls for a revision of the standards.Item Pancreas transplantation following total pancreatectomy for chronic pancreatitis(Wiley, 2019-12) Cerise, Adam; Nagaraju, Santosh; Powelson, John A.; Lutz, Andrew; Fridell, Jonathan A.; Surgery, School of MedicineBackground Total pancreatectomy for chronic pancreatitis leads to brittle diabetes and challenging glycemic control with half of all patients experiencing severe hypoglycemia, many requiring medical intervention or hospitalization. Pancreas transplantation has the potential to manage both the endocrine and the exocrine insufficiency in this patient population. Methods Between June 1, 2005, and July 1, 2016, 8 patients with brittle diabetes following total pancreatectomy underwent pancreas transplantation. All grafts had systemic venous and enteric exocrine drainage. Data included demographics, graft and patient survival, pre‐ and post‐transplant supplementation with pancreatic enzymes, and narcotic usage. Results Patient survival rate at 1 and 3 years was 88%. Pancreas graft survival rate of those alive at 1 year was 100% and 86%, respectively. About 75% of these patients remained insulin‐free until their time of death, loss of follow‐up, or present day. Of the patients with maintained graft function at 3 years, none required further hospitalization for glycemic control. About 75% of these patients have also maintained exocrine function without pancreatic enzyme supplementation. Conclusions Pancreas transplant can treat both exocrine and endocrine insufficiency and give long‐term insulin‐free survival and should be considered as a viable treatment option for patients who have undergone total pancreatectomy for chronic pancreatitis.Item SpHincterotomy for Acute Recurrent Pancreatitis Randomized Trial: Rationale, Methodology, and Potential Implications(Wolters Kluwer, 2019-09-01) Coté, Gregory A.; Durkalski-Mauldin, Valerie L.; Serrano, Jose; Klintworth, Erin; Williams, April W.; Cruz-Monserrate, Zobeida; Arain, Mustafa; Buxbaum, James L.; Conwell, Darwin L.; Fogel, Evan L.; Freeman, Martin L.; Gardner, Timothy B.; van Geenen, Erwin; Groce, J. Royce; Jonnalagadda, Sreenivasa S.; Keswani, Rajesh N.; Menon, Shyam; Moffatt, Dana C.; Papachristou, Georgios I.; Ross, Andrew; Tarnasky, Paul R.; Wang, Andrew Y.; Wilcox, C. Mel; Hamilton, Frank; Yadav, Dhiraj; Consortium for the SHARP; Medicine, School of MedicineObjectives: In patients with acute recurrent pancreatitis (ARP), pancreas divisum, and no other etiologic factors, endoscopic retrograde cholangiopancreatography (ERCP) with minor papilla endoscopic sphincterotomy (miES) is often performed to enlarge the minor papillary orifice, based on limited data. The aims of this study are to describe the rationale and methodology of a sham-controlled clinical trial designed to test the hypothesis that miES reduces the risk of acute pancreatitis. Methods: The SpHincterotomy for Acute Recurrent Pancreatitis (SHARP) trial is a multicenter, international, sham-controlled, randomized trial comparing endoscopic ultrasound + ERCP with miES vs. endoscopic ultrasound + sham for the management of ARP. A total of 234 consented patients having two or more discrete episodes of acute pancreatitis, pancreas divisum confirmed by magnetic resonance cholangiopancreatography, and no other clear etiology for acute pancreatitis will be randomized. Both cohorts will be followed for a minimum of 6 months and maximum of 48 months. Results: The trial is powered to detect a 33% risk reduction of acute pancreatitis frequency. Conclusions: The SHARP trial will determine whether ERCP with miES benefits patients with idiopathic ARP and pancreas divisum. Trial planning has informed the importance of blinded outcome assessors and long-term follow-up.Item Web-based Cognitive-behavioral Intervention for Pain in Pediatric Acute Recurrent and Chronic Pancreatitis: Protocol of a Multicenter Randomized Controlled Trial from the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer (CPDPC)(Elsevier, 2020-01) Palermo, Tonya M.; Murray, Caitlin; Aalfs, Homer; Abu-El-Haija, Maisam; Barth, Bradley; Bellin, Melena D.; Ellery, Kate; Fishman, Douglas S.; Gariepy, Cheryl E.; Giefer, Matthew J.; Goday, Praveen; Gonska, Tanja; Heyman, Melvin B.; Husain, Sohail Z.; Lin, Tom K.; Liu, Quin Y.; Mascarenhas, Maria R.; Maqbool, Asim; McFerron, Brian; Morinville, Veronique D.; Nathan, Jaimie D.; Ooi, Chee Y.; Perito, Emily R.; Pohl, John F.; Schwarzenberg, Sarah Jane; Sellers, Zachary M.; Serrano, Jose; Shah, Uzma; Troendle, David; Zheng, Yuhua; Yuan, Ying; Lowe, Mark; Uc, Aliye; Pediatrics, School of MedicineIntroduction Abdominal pain is common and is associated with high disease burden and health care costs in pediatric acute recurrent and chronic pancreatitis (ARP/CP). Despite the strong central component of pain in ARP/CP and the efficacy of psychological therapies for other centralized pain syndromes, no studies have evaluated psychological pain interventions in children with ARP/CP. The current trial seeks to 1) evaluate the efficacy of a psychological pain intervention for pediatric ARP/CP, and 2) examine baseline patient-specific genetic, clinical, and psychosocial characteristics that may predict or moderate treatment response. Methods This single-blinded randomized placebo-controlled multicenter trial aims to enroll 260 youth (ages 10–18) with ARP/CP and their parents from twenty-one INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In search for a cuRE) centers. Participants will be randomly assigned to either a web-based cognitive behavioral pain management intervention (Web-based Management of Adolescent Pain Chronic Pancreatitis; WebMAP; N = 130) or to a web-based pain education program (WebED; N = 130). Assessments will be completed at baseline (T1), immediately after completion of the intervention (T2) and at 6 months post-intervention (T3). The primary study outcome is abdominal pain severity. Secondary outcomes include pain-related disability, pain interference, health-related quality of life, emotional distress, impact of pain, opioid use, and healthcare utilization. Conclusions This is the first clinical trial to evaluate the efficacy of a psychological pain intervention for children with CP for reduction of abdominal pain and improvement of health-related quality of life. Findings will inform delivery of web-based pain management and potentially identify patient-specific biological and psychosocial factors associated with favorable response to therapy.