Pancreatic Enzyme Use Reduces Pancreatitis Frequency in Children With Acute Recurrent or Chronic Pancreatitis: A Report From INSPPIRE.

INTRODUCTION: Among children who suffer from acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP), acute pancreatitis (AP) episodes are painful, often require hospitalization, and contribute to disease complications and progression. Despite this recognition, there are currently no interventions to prevent AP episodes. In this retrospective cohort study, we assessed the impact of pancreatic enzyme therapy (PERT) use on clinical outcomes among children with pancreatic-sufficient ARP or CP. METHODS: Children with pancreatic-sufficient ARP or CP in the INSPPIRE-2 cohort were included. Clinical outcomes were compared for those receiving vs not receiving PERT, as well as frequency of AP before and after PERT. Logistic regression was used to study the association between development of AP episodes after starting PERT and response predictors. RESULTS: Among 356 pancreatic-sufficient participants, 270 (76%) had ARP, and 60 (17%) received PERT. Among those on PERT, 42% did not have a subsequent AP episode, during a mean 2.1 years of follow-up. Children with a SPINK1 mutation ( P = 0.005) and those with ARP (compared with CP, P = 0.008) were less likely to have an AP episode after starting PERT. After initiation of PERT, the mean AP annual incidence rate decreased from 3.14 down to 0.71 ( P < 0.001). DISCUSSION: In a retrospective analysis, use of PERT was associated with a reduction in the incidence rate of AP among children with pancreatic-sufficient ARP or CP. These results support the need for a clinical trial to evaluate the efficacy of PERT to improve clinical outcomes among children with ARP or CP.

Path Towards Biopsy-Free Diagnosis of Celiac Disease in Pediatric Patients.

BACKGROUND: Laboratory testing for celiac disease in pediatric patients integrates serology, genetic susceptibility and duodenal biopsy examination. The 2023 American College of Gastroenterology guidelines recommend a biopsy-free approach in pediatric patients utilizing tissue transglutaminase antibody titers >10 times upper limit of normal and subsequent endomysial antibody seropositivity as sufficient for diagnosis. The objective of this study is to assess the diagnostic accuracy of biopsy-free approach at our pediatric hospital. METHODS: We conducted a retrospective study involving pediatric patients who underwent biopsy for diagnostic confirmation of celiac disease between May 2019 and May 2023. For these patients, the tissue transglutaminase and endomysial antibody test results were retrieved and performance of biopsy-free approach was assessed using the duodenal histology as the gold standard for celiac disease diagnosis. RESULTS: Tissue transglutaminase antibody titers >10 times upper limit of normal alone demonstrated a positive predictive value of 99% for identifying celiac disease in children. Although endomysial antibody testing is underutilized at our center, its inclusion further improved the predictability to 100 %. CONCLUSION: Positive predictive value of tissue transglutaminase antibody titers >10 times upper limit of normal is sufficiently high for celiac disease diagnosis in children and may allow for deferral of duodenal biopsy at diagnosis.

Bone health in children with recurrent and chronic pancreatitis: A multi-center cross sectional analysis.

BACKGROUND/OBJECTIVES: Bone health of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) is not well studied. METHODS: This retrospective study was performed at three sites and included data from INSPPIRE-2. RESULTS: Of the 87 children in the study: 46 had ARP (53%), 41 had CP (47%). Mean age was 13.6 ± 3.9 years at last DXA scan. The prevalence of low height-for-age (Z-score < -2) (13%, 10/78) and low bone mineral density (BMD) adjusted for height (Z-score < -2) (6.4%, 5/78) were higher than a healthy reference sample (2.5%, p < 0.0001 and p = 0.03, respectively). CONCLUSION: Children with ARP or CP have lower height and BMD than healthy peers. Attention to deficits in growth and bone mineral accrual in children with pancreatic disease is warranted.

Pediatric Drug-Associated Pancreatitis Reveals Concomitant Risk Factors and Poor Reliability of Causality Scoring: Report From INSPPIRE.

OBJECTIVES: Drug-associated acute pancreatitis (DAP) studies typically focus on single acute pancreatitis (AP) cases. We aimed to analyze the (1) characteristics, (2) co-risk factors, and (3) reliability of the Naranjo scoring system for DAP using INSPPIRE-2 (the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2) cohort study of acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) in children. METHODS: Data were obtained from ARP group with ≥1 episode of DAP and CP group with medication exposure ± DAP. Physicians could report multiple risk factors. Pancreatitis associated with Medication (Med) (ARP+CP) was compared to Non-Medication cases, and ARP-Med vs CP-Med groups. Naranjo score was calculated for each DAP episode. RESULTS: Of 726 children, 392 had ARP and 334 had CP; 51 children (39 ARP and 12 CP) had ≥1 AP associated with a medication; 61% had ≥1 AP without concurrent medication exposure. The Med group had other risk factors present (where tested): 10 of 35 (28.6%) genetic, 1 of 48 (2.1%) autoimmune pancreatitis, 13 of 51 (25.5%) immune-mediated conditions, 11 of 50 (22.0%) obstructive/anatomic, and 28 of 51 (54.9%) systemic risk factors. In Med group, 24 of 51 (47%) had involvement of >1 medication, simultaneously or over different AP episodes. There were 20 ARP and 4 CP cases in "probable" category and 19 ARP and 7 CP in "possible" category by Naranjo scores. CONCLUSIONS: Medications were involved in 51 of 726 (7%) of ARP or CP patients in INSPPIRE-2 cohort; other pancreatitis risk factors were present in most, suggesting a potential additive role of different risks. The Naranjo scoring system failed to identify any cases as "definitive," raising questions about its reliability for DAP.

American Society for Gastrointestinal Endoscopy guideline on the role of endoscopy in the diagnosis of malignancy in biliary strictures of undetermined etiology: summary and recommendations.

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy provides an evidence-based approach for the diagnosis of malignancy in patients with biliary strictures of undetermined etiology. This document was developed using the Grading of Recommendations Assessment, Development and Evaluation framework and addresses the role of fluoroscopic-guided biopsy sampling, brush cytology, cholangioscopy, and EUS in the diagnosis of malignancy in patients with biliary strictures. In the endoscopic workup of these patients, we suggest the use of fluoroscopic-guided biopsy sampling in addition to brush cytology over brush cytology alone, especially for hilar strictures. We suggest the use of cholangioscopic and EUS-guided biopsy sampling especially for patients who undergo nondiagnostic sampling, cholangioscopic biopsy sampling for nondistal strictures and EUS-guided biopsy sampling distal strictures or those with suspected spread to surrounding lymph nodes and other structures.

American Society for Gastrointestinal Endoscopy guideline on role of endoscopy in the diagnosis of malignancy in biliary strictures of undetermined etiology: methodology and review of evidence.

Biliary strictures of undetermined etiology pose a diagnostic challenge for endoscopists. Despite advances in technology, diagnosing malignancy in biliary strictures often requires multiple procedures. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to rigorously review and synthesize the available literature on strategies used to diagnose undetermined biliary strictures. Using a systematic review and meta-analysis of each diagnostic modality, including fluoroscopic-guided biopsy sampling, brush cytology, cholangioscopy, and EUS-guided FNA or fine-needle biopsy sampling, the American Society for Gastrointestinal Endoscopy Standards of Practice Committee provides this guideline on modalities used to diagnose biliary strictures of undetermined etiology. This document summarizes the methods used in the GRADE analysis to make recommendations, whereas the accompanying article subtitled "Summary and Recommendations" contains a concise summary of our findings and final recommendations.

American Society for Gastrointestinal Endoscopy guideline on role of endoscopy in the diagnosis of malignancy in biliary strictures of undetermined etiology: methodology and review of evidence

Biliary strictures of undetermined etiology pose a diagnostic challenge for endoscopists. Despite advances in technology, diagnosing malignancy in biliary strictures often requires multiple procedures. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to rigorously review and synthesize the available literature on strategies used to diagnose undetermined biliary strictures. Using a systematic review and meta-analysis of each diagnostic modality, including fluoroscopic-guided biopsy sampling, brush cytology, cholangioscopy, and EUS-guided FNA or fine-needle biopsy sampling, the American Society for Gastrointestinal Endoscopy Standards of Practice Committee provides this guideline on modalities used to diagnose biliary strictures of undetermined etiology. This document summarizes the methods used in the GRADE analysis to make recommendations, whereas the accompanying article subtitled "Summary and Recommendations" contains a concise summary of our findings and final recommendations.

American Society for Gastrointestinal Endoscopy guideline on the role of ergonomics for prevention of endoscopy-related injury: summary and recommendations.

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy provides an evidence-based approach to strategies to prevent endoscopy-related injury (ERI) in GI endoscopists. It is accompanied by the article subtitled "Methodology and Review of Evidence," which provides a detailed account of the methodology used for the evidence review. This document was developed using the Grading of Recommendations Assessment, Development and Evaluation framework. The guideline estimates the rates, sites, and predictors of ERI. Additionally, it addresses the role of ergonomics training, microbreaks and macrobreaks, monitor and table positions, antifatigue mats, and use of ancillary devices in decreasing the risk of ERI. We recommend formal ergonomics education and neutral posture during the performance of endoscopy, achieved through adjustable monitor and optimal procedure table position, to reduce the risk of ERI. We suggest taking microbreaks and scheduled macrobreaks and using antifatigue mats during procedures to prevent ERI. We suggest the use of ancillary devices in those with risk factors predisposing them to ERI.

Upskilling Pediatric Ileocolonoscopy.

Upskilling in ileocolonoscopy is an important aspect of pediatric endoscopic practice as it enables endoscopists to learn additional skills through education and training to improve outcomes. With the advent of technologies, endoscopy is continuously evolving. Many devices can be applied to improve endoscopy quality and ergonomics. In addition, techniques such as dynamic position change can be employed to increase procedural efficiency and completeness. Key to upskilling is enhancing endoscopists' cognitive, technical and nontechnical skills and the concept of "training the trainer" to ensure trainers have the requisite skills to teach endoscopy effectively. This chapter details aspects of upskilling pediatric ileocolonoscopy.

Impact of Trainee Involvement on Pediatric ERCP Procedures: Results From the Pediatric ERCP Initiative.

This study examines the role of trainee involvement with pediatric endoscopic retrograde cholangiopancreatography (ERCP) and whether it affects the procedure's success, post-procedural adverse outcomes, and duration. A secondary analysis of the Pediatric ERCP Database Initiative, an international database, was performed. Consecutive ERCPs on children <19 years of age from 18 centers were entered prospectively into the database. In total 1124 ERCPs were entered into the database, of which 320 (28%) were performed by trainees. The results showed that the presence of trainees did not impact technical success ( P = 0.65) or adverse events rates ( P = 0.43). Rates of post-ERCP pancreatitis, pain, and bleeding were similar between groups ( P > 0.05). Fewer cases involving trainees were in the top quartile (>58 minutes) of procedural time (19% vs 26%; P = 0.02). Overall, our findings indicate trainee involvement in pediatric ERCP is safe.

Pediatric ERCP in the Setting of Acute Pancreatitis: A Secondary Analysis of an International Multicenter Cohort Study.

Previous studies have demonstrated the safety of performing endoscopic retrograde cholangiopancreatography (ERCP) in the pediatric population; however, few have addressed the outcomes of children undergoing ERCP during acute pancreatitis (AP). We hypothesize that ERCP performed in the setting of AP can be executed with similar technical success and adverse event profiles to those in pediatric patients without pancreatitis. Using the Pediatric ERCP Database Initiative, a multi-national and multi-institutional prospectively collected dataset, we analyzed 1124 ERCPs. One hundred and ninety-four (17%) of these procedures were performed in the setting of AP. There were no difference in the procedure success rate, procedure time, cannulation time, fluoroscopy time, or American Society of Anesthesiology class despite patients with AP having higher American Society of Gastrointestinal Endoscopy grading difficulty scores. This study suggests that ERCP can be safely and efficiently performed in pediatric patients with AP when appropriately indicated.

Musculoskeletal injury and ergonomics in pediatric gastrointestinal endoscopic practice.

BACKGROUND AND AIMS: Endoscopy-related musculoskeletal injuries (ERI) are increasingly prevalent in adult endoscopists; however, there are no studies that have evaluated ERI and ergonomic practices among pediatric gastroenterologists and trainees. We aimed to examine the prevalence, nature, and impact of musculoskeletal injuries in pediatric endoscopic practice and assess attitudes towards ergonomic training needs. METHODS: Pediatric gastroenterologists and trainees were surveyed to collect information on endoscopist and practice characteristics, the prevalence, nature, and impacts of ERI, ergonomics strategies employed in practice, previous ergonomics training, and perceptions of ergonomics training (elicited using a 1 (strongly disagree) to 5 (strongly agree) Likert scale). Responses were analyzed using descriptive statistics, and bivariate analyses were conducted to explore correlates of ERI. RESULTS: Among 146 survey respondents, 50 (34.2%) were trainees and 96 (65.8%) were practicing endoscopists with a mean duration of endoscopic practice of 9.7 ± 9.4 years. Overall, 55.6% (n = 80/144) reported experiencing a musculoskeletal injury, with 34.7% (n = 50/144) reporting an injury attributable to endoscopy. Among those with ERI, the most common sites were the neck/upper back (44.0%), thumb (42.0%), hand/finger (38.0%), and lower back (36.0%). Women were more likely to experience ERI compared to men (43.4% vs. 23.4%; p = 0.013). Only 20.9% of participants had formal training in ergonomics. Respondents reported being motivated to implement practice changes to prevent ERI (4.41 ± 0.95) and perceived ergonomics training as important (4.37 ± 0.96). CONCLUSIONS: Pediatric endoscopists, and particularly women, experience significant ERI; however, formal endoscopy ergonomics training is rare. Improved ergonomics training is needed for both practicing pediatric gastroenterologists and trainees.

Technical Outcomes in Pediatric Endoscopic Retrograde Cholangiopancreatography: Data from an International Collaborative.

OBJECTIVES: Endoscopic retrograde cholangiopancreatography (ERCP) in adults has been extensively studied through multicenter prospective studies. Similar pediatric studies are lacking. The Pediatric ERCP Database Initiative (PEDI) is a multicenter collaborative aiming to evaluate the indications and technical outcomes in pediatric ERCPs. METHODS: In this prospective cohort study, data were recorded for pediatric ERCPs performed across 15 centers. A pre-procedure, procedure, 2-week post-procedure follow-up, and adverse event form were completed for each ERCP performed. Univariate and stepwise linear regression was performed to identify factors associated with technically successful procedures and adverse events. RESULTS: A total of 1124 ERCPs were performed on 857 patients from May 1, 2014 to May 1, 2018. The median age was 13.5 years [interquartile range (IQR) 9.0-15.7]. Procedures were technically successful in the majority of cases (90.5%) with success more commonly encountered for procedures with biliary indications [odds ratio (OR) 4.2] and less commonly encountered for native papilla anatomy (OR 0.4) and in children <3 years (OR 0.3). Cannulation was more often successful with biliary cannulation (95.9%) compared to pancreatic cannulation via the major papilla (89.6%, P < 0.0001) or minor papilla (71.2%, P < 0.0005). The most commonly identified adverse events included post-ERCP pancreatitis (5%), pain not related to post-ERCP pancreatitis (1.8%), and bleeding (1.2%). Risk factors for the development of each were identified. CONCLUSIONS: This large prospective study demonstrates that ERCP is reliable and safe in the pediatric population. It highlights the utility of PEDI in evaluating the technical outcomes of pediatric ERCPs and demonstrates the potential of PEDI for future studies in pediatric ERCPs.

Analysis of INSPPIRE-2 Cohort: Risk Factors and Disease Burden in Children With Acute Recurrent or Chronic Pancreatitis.

OBJECTIVES: 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.

Evolution of International Pediatric Endoscopic Practice Changes During the Coronavirus Disease 2019 Pandemic.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has drastically altered endoscopic practices. We initially reported the international impact of COVID-19 on pediatric endoscopic practice. This follow-up study aimed to assess changes 7 months following the initial survey to delineate practice change patterns as the pandemic evolved. METHODS: Pediatric gastroenterologists who responded to the initial survey were re-surveyed seven months later using Research Electronic Data Capture (REDCap). The survey recorded information on changes in pediatric endoscopic practice patterns, including COVID-19 screening and testing processes and personal protective equipment (PPE) utilization. Additionally, endoscopists' risk tolerance of COVID-19 transmission was evaluated. RESULTS: Seventy-five unique institutions from 21 countries completed surveys from the 145 initial responses (51.7% response rate). Procedural volumes increased at most institutions (70.7%) and most were performing previously postponed cases (90.7%). Ninety-seven percent of institutions were performing pre-endoscopy screening with 78.7% testing all patients. Many institutions (34.7%) have performed procedures on COVID-19 positive patients. There was significantly less PPE reuse (P  < 0.05) and fewer institutions recommending full PPE for all endoscopies (43.2% vs 59.2%, P = 0.013). Overall, pediatric endoscopists' risk tolerance of COVID-19 transmission is low. CONCLUSIONS: This is the first survey to highlight the evolution of pediatric endoscopic practices related to the COVID-19 pandemic, underscoring the need for ongoing pandemic-related guidance for pediatric endoscopic practice.