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Item A comparative study between single-operator pancreatoscopy with intraductal lithotripsy and extracorporeal shock wave lithotripsy for the management of large main pancreatic duct stones(Springer, 2022) Bick, Benjamin L.; Patel, Feenalie; Easler, Jeffrey J.; Tong, Yan; Watkins, James L.; McHenry, Lee; Lehman, Glen; Fogel, Evan L.; Gromski, Mark A.; Sherman, Stuart; Medicine, School of MedicineBackground and aims: Endoscopic management of large main pancreatic ductal (MPD) stones often require treatment with lithotripsy. Extracorporeal shock wave lithotripsy (ESWL) has been the mainstay therapy, and single-operator pancreatoscopy with intraductal (intracorporeal) lithotripsy (SOPIL) is an emerging technique. However, no comparative studies between these techniques exist. We therefore aimed to compare ESWL to SOPIL for the treatment of large MPD stones. Methods: This is a retrospective cohort study comparing patients who were treated with ESWL or SOPIL from September 2013 to September 2019 at a single tertiary center. Logistic regression was performed to identify factors associated with technical success and efficient stone clearance (≤ 2 procedures to clear stones). Results: There were 240 patients who were treated with ESWL and 18 treated with SOPIL. The overall technical success rate of stone clearance was 224/258 (86.8%), which was similar between the ESWL and SOPIL groups (86.7% vs 88.9%, p = 1.000). A SOPIL approach required fewer total procedures (1.6 ± 0.6 vs 3.1 ± 1.5, p < 0.001) and less aggregate procedure time (101.6 ± 68.2 vs 191.8 ± 111.6 min, p = 0.001). Adverse event rates were similar between the groups (6.3% vs 5.6%, p = 1.000). The use of SOPIL was independently associated with greater efficiency compared to ESWL (OR 5.241 [1.348-20.369], p = 0.017). Stone size > 10 mm was associated with less efficient stone clearance (OR 0.484 [0.256-0.912], p = 0.025). Conclusion: Both ESWL and SOPIL are safe and effective endoscopic adjunct modalities for treating large pancreatic duct stones. SOPIL is an emerging alternative to ESWL that is potentially more efficient for lithotripsy and MPD stone clearance.Item Advanced Imaging Techniques for Chronic Pancreatitis(SpringerLink, 2020-05) Parakh, Anushri; Tirkes, Temel; Radiology and Imaging Sciences, School of MedicineMRI and MRCP play an important role in the diagnosis of chronic pancreatitis (CP) by imaging pancreatic parenchyma and ducts. MRI/MRCP is more widely used than computed tomography (CT) for mild to moderate CP due to its increased sensitivity for pancreatic ductal and gland changes; however, it does not detect the calcifications seen in advanced CP. Quantitative MR imaging offers potential advantages over conventional qualitative imaging, including simplicity of analysis, quantitative and population-based comparisons, and more direct interpretation of detected changes. These techniques may provide quantitative metrics for determining the presence and severity of acinar cell loss and aid in the diagnosis of chronic pancreatitis. Given the fact that the parenchymal changes of CP precede the ductal involvement, there would be a significant benefit from developing MRI/MRCP-based, more robust diagnostic criteria combining ductal and parenchymal findings. Among cross-sectional imaging modalities, multi-detector CT (MDCT) has been a cornerstone for evaluating chronic pancreatitis (CP) since it is ubiquitous, assesses primary disease process, identifies complications like pseudocyst or vascular thrombosis with high sensitivity and specificity, guides therapeutic management decisions, and provides images with isotropic resolution within seconds. Conventional MDCT has certain limitations and is reserved to provide predominantly morphological (e.g., calcifications, organ size) rather than functional information. The emerging applications of radiomics and artificial intelligence are poised to extend the current capabilities of MDCT. In this review article, we will review advanced imaging techniques by MRI, MRCP, CT, and ultrasound.Item Analysis of INSPPIRE-2 Cohort: Risk Factors and Disease Burden in Children with Acute Recurrent or Chronic Pancreatitis(Wiley, 2022) 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.; Pediatrics, School of MedicineObjectives: The objective of this study is 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 had 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. A total of 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 of 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 Artificial Intelligence in Endoscopic Ultrasound for Pancreatic Cancer: Where Are We Now and What Does the Future Entail?(MDPI, 2022-12-16) Dahiya, Dushyant Singh; Al-Haddad, Mohammad; Chandan, Saurabh; Gangwani, Manesh Kumar; Aziz, Muhammad; Mohan, Babu P.; Ramai, Daryl; Canakis, Andrew; Bapaye, Jay; Sharma, Neil; Medicine, School of MedicinePancreatic cancer is a highly lethal disease associated with significant morbidity and mortality. In the United States (US), the overall 5-year relative survival rate for pancreatic cancer during the 2012–2018 period was 11.5%. However, the cancer stage at diagnosis strongly influences relative survival in these patients. Per the National Cancer Institute (NCI) statistics for 2012–2018, the 5-year relative survival rate for patients with localized disease was 43.9%, while it was 3.1% for patients with distant metastasis. The poor survival rates are primarily due to the late development of clinical signs and symptoms. Hence, early diagnosis is critical in improving treatment outcomes. In recent years, artificial intelligence (AI) has gained immense popularity in gastroenterology. AI-assisted endoscopic ultrasound (EUS) models have been touted as a breakthrough in the early detection of pancreatic cancer. These models may also accurately differentiate pancreatic cancer from chronic pancreatitis and autoimmune pancreatitis, which mimics pancreatic cancer on radiological imaging. In this review, we detail the application of AI-assisted EUS models for pancreatic cancer detection. We also highlight the utility of AI-assisted EUS models in differentiating pancreatic cancer from radiological mimickers. Furthermore, we discuss the current limitations and future applications of AI technology in EUS for pancreatic cancers.Item Chronic Pancreatitis: What the Clinician Wants to Know from MR Imaging(Elsevier, 2018-08) Tirkes, Temel; Radiology and Imaging Sciences, School of MedicineDiagnosis of chronic pancreatitis requires a complete medical history and clinical investigations, including imaging technologies and function tests. MR imaging/magnetic resonance cholangiopancreatography is the preferred diagnostic tool for detection of ductal and parenchymal changes in patients with chronic pancreatitis. Ductal changes may not be present in the initial phase of chronic pancreatitis. Therefore, early diagnosis remains challenging.Item Circulating immune signatures across clinical stages of chronic pancreatitis: a pilot study(Wolters Kluwer, 2024) Hagn-Meincke, Rasmus; Hart, Phil A.; Andersen, Dana K.; Vege, Santhi S.; Fogel, Evan L.; Serrano, Jose; Bellin, Melena D.; Topazian, Mark D.; Conwell, Darwin L.; Li, Liang; Van Den Eeden, Stephen K.; Drewes, Asbjørn M.; Pandol, Stephen J.; Forsmark, Chris E.; Fisher, William E.; Yadav, Dhiraj; Olesen, Søren S.; Park, Walter G.; Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC); Medicine, School of MedicineObjective: This pilot study seeks to identify serum immune signatures across clinical stages of patients with chronic pancreatitis (CP). Methods: We performed a cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies-study. CP subjects were categorised into three clinical stages based on the presence/absence of metabolic complications: (1) CP with no diabetes and exocrine pancreatic dysfunction (EPD), (2) CP with either diabetes or EPD, and (3) CP with diabetes and EPD. Blinded samples were analysed using an 80-plex Luminex assay of cytokines/chemokines/adhesion molecules. Group and pairwise comparisons were performed to characterise immune signatures across CP subgroups. Results: A total of 135 CP subjects (evenly distributed between clinical stages) and 50 controls were studied. Interleukin-6 (IL-6), interleukin-8 (IL-8), and soluble intercellular adhesion molecule 1 (sICAM-1) were significantly elevated in CP subjects compared to controls. The levels of IL-6 and IL-8 increased with advancing disease stages, with the highest levels observed in CP with diabetes and EPD (clinical stage 3). Furthermore, hepatocyte growth factor and macrophage-derived chemokine were significantly increased in clinical stage 3 compared to controls. Conclusion: Our study reveals a progressive elevation in pro-inflammatory cytokines and chemokines with advancing clinical stages of CP. These findings indicate potential targets for the development of disease-modifying interventions.Item Clinical and Practice Variations in Pediatric Acute Recurrent or Chronic Pancreatitis: Report From the INSPPIRE Study(Wolters Kluwer, 2020-07) Dike, Chinenye R.; Zimmerman, Bridget; Zheng, Yuhua; Wilschanski, Michael; Werlin, Steven L.; Troendle, David; Shah, Uzma; Schwarzenberg, Sarah Jane; Pohl, John; Perito, Emily R.; Ooi, Chee Y.; Nathan, Jaimie D.; Morinville, Veronique D.; McFerron, Brian; Mascarenhas, Maria; Maqbool, Asim; Liu, Quin; Lin, Tom K.; Husain, Sohail Z.; Heyman, Melvin B.; Gonska, Tanja; Giefer, Matthew J.; Gariepy, Cheryl E.; Fishman, Douglas S.; Bellin, Melena; Barth, Bradley; Abu-El-Haija, Maisam; Lowe, Mark E.; Uc, Aliye; Pediatrics, School of MedicineObjective: The aim of the study was to determine whether clinical characteristics and management of pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) differ across INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In Search for a cuRE) sites. Study design: Data were collected from INSPPIRE and analyzed per US regions and "non-US" sites. Between-group differences were compared by Pearson chi-square test. Differences in disease burden were compared by Kruskal-Wallis test. Results: Out of the 479 subjects, 121 (25%) were enrolled in West, 151 (32%) Midwest, 45 Northeast (9%), 78 (16%) South, and 84 (18%) at non-US sites. Hispanic ethnicity was more common in South (P < 0.0001); white race in Northeast (P = 0.009). CP was less common and time from diagnosis of first acute pancreatitis to CP was longer in children at non-US sites (P = 0.0002 and P = 0.011, respectively). Genetic mutations were most common among all groups; PRSS1 variants predominated in Midwest (P = 0.002). Gallstones were more frequent in South (P = 0.002). Endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography (CT) imaging were more commonly utilized in United States compared with non-United States (P < 0.0001), but there were no differences in the use of MRI/MRCP. Disease burden was highest in the West and Midwest, possibly as total pancreatectomy and islet autotransplantation (TPIAT) referral sites were located in these regions. All therapies were less commonly administered in non-US sites (P < 0.0001). Conclusions: This is the first study to describe geographical variations in the INSPPIRE cohort, which possibly reflect variations in practice and referral patterns. The underlying reason behind the lower frequency of CP and fewer treatments in non-United States sites need to be further explored.Item Clinical Trials in Pancreatitis: Opportunities and Challenges in the Design and Conduct of Patient-Focused Clinical Trials in Recurrent Acute and Chronic Pancreatitis: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop(Wolters Kluwer, 2022) Hart, Phil A.; Andersen, Dana K.; Lyons, Erica; Cote, Gregory A.; Cruz-Monserrate, Zobeida; Dworkin, Robert H.; Elmunzer, B. Joseph; Fogel, Evan L.; Forsmark, Christopher E.; Gilron, Ian; Golden, Megan; Gozu, Aysegul; McNair, Lindsay; Pandol, Stephen J.; Perito, Emily R.; Evans Phillips, Anna; Rabbitts, Jennifer A.; Whitcomb, David C.; Windsor, John A.; Yadav, Dhiraj; Palermo, Tonya M.; Medicine, School of MedicineRecurrent acute pancreatitis and chronic pancreatitis represent high morbidity diseases, which are frequently associated with chronic abdominal pain, pancreatic insufficiencies, and reduced quality of life. Currently, there are no therapies to reverse or delay disease progression, and clinical trials are needed to investigate potential interventions that would address this important gap. This conference report provides details regarding information shared during a National Institute of Diabetes and Digestive and Kidney Diseases-sponsored workshop on Clinical Trials in Pancreatitis that sought to clearly delineate the current gaps and opportunities related to the design and conduct of patient-focused trials in recurrent acute pancreatitis and chronic pancreatitis. Key stakeholders including representatives from patient advocacy organizations, physician investigators (including clinical trialists), the US Food and Drug Administration, and the National Institutes of Health convened to discuss challenges and opportunities with particular emphasis on lessons learned from trials in participants with other painful conditions, as well as the value of incorporating the patient perspective throughout all stages of trials.Item Constant-Severe Pain in Chronic Pancreatitis is Associated with Genetic Loci for Major Depression in the NAPS2 Cohort(Springer, 2020) Dunbar, Ellyn; Greer, Phil J.; Melhem, Nadine; Alkaade, Samer; Amann, Stephen T.; Brand, Randall; Coté, Gregory A.; Forsmark, Christopher E.; Gardner, Timothy B.; Gelrud, Andres; Guda, Nalini M.; LaRusch, Jessica; Lewis, Michele D.; Machicado, Jorge D.; Muniraj, Thiruvengadam; Papachristou, Georgios I.; Romagnuolo, Joseph; Sandhu, Bimaljit S.; Sherman, Stuart; Wilcox, Charles M.; Singh, Vikesh K.; Yadav, Dhiraj; Whitcomb, David C.; NAPS2 study group; Medicine, School of MedicineBackground: Pain is the most debilitating symptom of recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) and often requires chronic opioids or total pancreatectomy with islet autotransplantation to manage. Pain is a complex experience that can be exacerbated by depression and vice versa. Our aim was to test the hypothesis that depression-associated genes are associated with a constant-severe pain experience in RAP/CP patients. Study: A retrospective study was done using North American Pancreatitis Study II (NAPS2) genotyped RAP and CP patients with completed case report forms (n = 1,357). Subjects were divided based on pattern of pain and pain severity as constant-severe pain (n = 787) versus not constant-severe pain (n = 570) to conduct a nested genome-wide association study. The association between reported antidepressant medication use and depression gene loci was tested. Results: Constant-severe pain was reported in 58% (n = 787) of pancreatitis patients. No differences in sex or alcohol consumption were found based on pain severity. Antidepressant use was reported in 28% (n = 223), and they had lower SF-12 mental quality of life (MCS, p < 2.2 × 10- 16). Fifteen loci associated with constant-severe pain (p < 0.00001) were found to be in or near depression-associated genes including ROBO2, CTNND2, SGCZ, CNTN5 and BAIAP2. Three of these genes respond to antidepressant use (SGCZ, ROBO2, and CTNND2). Conclusion: Depression is a major co-factor in the pain experience. This genetic predisposition to depression may have utility in counseling patients and in instituting early antidepressant therapy for pain management of pancreatitis patients. Prospective randomized trials are warranted.Item Cross-sectional imaging-based severity scoring of chronic pancreatitis: why it is necessary and how it can be done(SpringerLink, 2020-05) Dasyam, Anil K.; Shah, Zarine K.; Tirkes, Temel; Dasyam, Navya; Borhani, Amir A.; Radiology and Imaging Sciences, School of MedicineChronic pancreatitis (CP) remains a diagnostic challenge as clinical symptoms are non-specific, histopathological appearances are varied and pathogenesis remains incompletely understood. Multiple classifications and grading systems have been proposed for CP, but none leverage the full capabilities of cross-sectional imaging modalities and are not widely accepted or validated. CT and MRI/MRCP are useful in identifying a wide spectrum of histopathological changes in CP and can also assess exocrine reserve of pancreas. Advanced MRI techniques such as T1 mapping and extracellular volume fraction can potentially identify early CP. Cross-sectional imaging-based severity scoring can quantify CP disease burden and may have positive implications for clinicians and researchers. In this review, we discuss the need for cross-sectional imaging-based severity scoring for CP, role of CT, and MRI/MRCP in assessment of CP and how these modalities can be used to obtain severity scoring for CP. We summarize relevant information from recently published CT and MRI/MRCP reporting standards for CP, and from international guidelines for cross-sectional imaging and severity scoring for CP.
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