Identification of Iatrogenic Perforation in Pediatric Gastrointestinal Endoscopy.

OBJECTIVES: Iatrogenic viscus perforation in pediatric gastrointestinal endoscopy (GIE) is a very rare, yet potentially life-threatening event. There are no evidence-based recommendations relating to immediate post-procedure follow-up to identify perforations and allow for timely management. This study aims to characterize the presentation of children with post-GIE perforation to better rationalize post-procedure recommendations. METHODS: Retrospective study based on unrestricted pooled data from centers throughout Europe, North America, and the Middle East affiliated with the Endoscopy Special Interest Groups of European Society for Paediatric Gastroenterology Hepatology and Nutrition and North American Society for Pediatric Gastroenterology Hepatology and Nutrition. Procedural and patient data relating to clinical presentation of the perforation were recorded on standardized REDCap case-report forms. RESULTS: Fifty-nine cases of viscus perforation were recorded [median age 6 years (interquartile range 3-13)]; 29 of 59 (49%) occurred following esophagogastroduodenoscopy, 26 of 59 (44%) following ileocolonoscopy, with 2 of 59 (3%) cases each following balloon enteroscopy and endoscopic retrograde cholangiopancreatography; 28 of 59 (48%) of perforations were identified during the procedure [26/28 (93%) endoscopically, 2/28 (7%) by fluoroscopy], and a further 5 of 59 (9%) identified within 4 hours. Overall 80% of perforations were identified within 12 hours. Among perforations identified subsequent to the procedure 19 of 31 (61%) presented with pain, 16 of 31 (52%) presented with fever, and 10 of 31 (32%) presented with abdominal rigidity or dyspnea; 30 of 59 (51%) were managed surgically, 17 of 59 (29%) managed conservatively, and 9 of 59 (15%) endoscopically; 4 of 59 (7%) patients died, all following esophageal perforation. CONCLUSIONS: Iatrogenic perforation was identified immediately in over half of cases and in 80% of cases within 12 hours. This novel data can be utilized to generate guiding principles of post-procedural follow-up and monitoring. PLAIN LANGUAGE SUMMARY: Bowel perforation following pediatric gastrointestinal endoscopy is very rare with no evidence to base post-procedure follow-up for high-risk procedures. We found that half were identified immediately with the large majority identified within 12 hours, mostly due to pain and fever.

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.

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.

Management of Magnet Ingestions at a Large Tertiary Care Children's Hospital.

OBJECTIVES: To review the clinical management and outcomes of magnet ingestions at a large tertiary children's hospital. To determine the association of frequency of high-powered magnet ingestion with the regulation of these magnets. METHODS: Children <18 years who presented to the emergency room and were admitted to the Children's Hospital of Philadelphia for ingestion of single or multiple magnets from January 2008 to December 2020 were included. Demographics, symptoms, management, and outcomes were analyzed. The frequency of magnet ingestion was compared over 3 eras: (1) pre-ban (2008-2012), (2) intra-ban (2013-2016), and (3) post-ban (2017-2020). RESULTS: There were 167 magnet ingestions, including 99 with multiple magnets. Most patients (59%) were male and median age was 6 (interquartile range, 3-9) years. Most single magnet ingestions (86%) were discharged with outpatient monitoring, and none experienced severe outcomes. Multiple magnet ingestions led to significant morbidity including hospitalizations (68%), endoscopic procedures (48%), surgical procedures (14%), and severe outcomes (12%). Most patients (75%) were asymptomatic, however, there was a higher risk of surgery and severe complications based on the presence of symptoms ( P = 0.003). The rate of surgical intervention was higher with ≥3 magnets (31.7%) compared to 2 magnets (2.4%) ( P < 0.003). Additionally, we found an 160% increase in children with magnet ingestions in the post-ban period ( P = 0.021). CONCLUSIONS: Multiple magnet ingestion is associated with high morbidity and rate of severe outcomes. There is a relationship between public policy of magnet sale and frequency of magnet ingestion.

Dynamic Contrast Magnetic Resonance Lymphangiography Localizes Lymphatic Leak to the Duodenum in Protein-Losing Enteropathy.

OBJECTIVES: Protein-losing enteropathy (PLE) is a disorder of intestinal lymphatic flow resulting in leakage of protein-rich lymph into the gut lumen. Our primary aim was to report the imaging findings of dynamic contrast magnetic resonance lymphangiography (DCMRL) in patients with PLE. Our secondary objective was to use these imaging findings to characterize lymphatic phenotypes. METHODS: Single-center retrospective cohort study of patients with PLE unrelated to single-ventricle circulation who underwent DCMRL. We report imaging findings of intranodal (IN), intrahepatic (IH), and intramesenteric (IM) access points for DCMRL. RESULTS: Nineteen patients 0.3-58 years of age (median 1.2 years) underwent 29 DCMRL studies. Primary intestinal lymphangiectasia (PIL) was the most common referring diagnosis (42%). Other etiologies included constrictive pericarditis, thoracic insufficiency syndrome, and genetic disorders. IN-DCMRL demonstrated a normal central lymphatic system in all patients with an intact thoracic duct and localized duodenal leak in one patient (1/19, 5%). IH-DCMRL detected a duodenal leak in 12 of 17 (71%), and IM-DCMRL detected duodenal leak in 5 of 6 (83%). Independent of etiology, lymphatic leak was only visualized in the duodenum. CONCLUSIONS: In patients with PLE, imaging via DCMRL reveals that leak is localized to the duodenum regardless of etiology. Comprehensive imaging evaluation with three access points can provide detailed information about the site of duodenal leak.

Overview of the Pediatric Endoscopy Quality Improvement Network Quality Standards and Indicators for Pediatric Endoscopy: A Joint NASPGHAN/ESPGHAN Guideline.

INTRODUCTION: Pediatric-specific quality standards for endoscopy are needed to define best practices, while measurement of associated indicators is critical to guide quality improvement. The international Pediatric Endoscopy Quality Improvement Network (PEnQuIN) working group was assembled to develop and define quality standards and indicators for pediatric gastrointestinal endoscopic procedures through a rigorous guideline consensus process. METHODS: The Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument guided PEnQuIN members, recruited from 31 centers of various practice types representing 11 countries, in generating and refining proposed quality standards and indicators. Consensus was sought via an iterative online Delphi process, and finalized at an in-person conference. Quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. RESULTS: Forty-nine quality standards and 47 indicators reached consensus, encompassing pediatric endoscopy facilities, procedures, endoscopists, and the patient experience. The evidence base for PEnQuIN standards and indicators was largely adult-based and observational, and downgraded for indirectness, imprecision, and study limitations to "very low" quality, resulting in "conditional" recommendations for most standards (45/49). CONCLUSIONS: The PEnQuIN guideline development process establishes international agreement on clinically meaningful metrics that can be used to promote safety and quality in endoscopic care for children. Through PEnQuIN, pediatric endoscopists and endoscopy services now have a framework for auditing, providing feedback, and ultimately, benchmarking performance. Expansion of evidence and prospective validation of PEnQuIN standards and indicators as predictors of clinically relevant outcomes and high-quality pediatric endoscopic care is now a research priority.

Pediatric Endoscopy Quality Improvement Network Quality Standards and Indicators for Pediatric Endoscopy Facilities: A Joint NASPGHAN/ESPGHAN Guideline.

INTRODUCTION: There is increasing international recognition of the impact of variability in endoscopy facilities on procedural quality and outcomes. There is also growing precedent for assessing the quality of endoscopy facilities at regional and national levels by using standardized rating scales to identify opportunities for improvement. METHODS: With support from the North American and European Societies of Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used the methodological strategy of the Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument to develop standards and indicators relevant for assessing the quality of facilities where endoscopic care is provided to children. Consensus was reached via an iterative online Delphi process and subsequent in-person meeting. The quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development and Evaluation) approach. RESULTS: The PEnQuIN working group achieved consensus on 27 standards for facilities supporting pediatric endoscopy, as well 10 indicators that can be used to identify high-quality endoscopic care in children. These standards were subcategorized into three subdomains: Quality of Clinical Operations (15 standards, 5 indicators); Patient and Caregiver Experience (9 standards, 5 indicators); and Workforce (3 standards). DISCUSSION: The rigorous PEnQuIN process successfully yielded standards and indicators that can be used to universally guide and measure high-quality facilities for procedures around the world where endoscopy is performed in children. It also underscores the current paucity of evidence for pediatric endoscopic care processes, and the need for research into this clinical area.

Pediatric Endoscopy Quality Improvement Network Quality Standards and Indicators for Pediatric Endoscopic Procedures: A Joint NASPGHAN/ESPGHAN Guideline.

INTRODUCTION: High-quality pediatric gastrointestinal procedures are performed when clinically indicated and defined by their successful performance by skilled providers in a safe, comfortable, child-oriented, and expeditious manner. The process of pediatric endoscopy begins when a plan to perform the procedure is first made and ends when all appropriate patient follow-up has occurred. Procedure-related standards and indicators developed to date for endoscopy in adults emphasize cancer screening and are thus unsuitable for pediatric medicine. METHODS: With support from the North American and European Societies of Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used the methodological strategy of the Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument to develop standards and indicators relevant for assessing the quality of endoscopic procedures. Consensus was sought via an iterative online Delphi process and finalized at an in-person conference. The quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. RESULTS: The PEnQuIN working group achieved consensus on 14 standards for pediatric endoscopic procedures, as well as 30 indicators that can be used to identify high-quality procedures. These were subcategorized into three subdomains: Preprocedural (3 standards, 7 indicators), Intraprocedural (8 standards, 18 indicators), and Postprocedural (3 standards, 5 indicators). A minimum target for the key indicator, "rate of adequate bowel preparation," was set at ≥80%. DISCUSSION: It is recommended that all facilities and individual providers performing pediatric endoscopy worldwide initiate and engage with the procedure-related standards and indicators developed by PEnQuIN to identify gaps in quality and drive improvement.

Pediatric Endoscopy Quality Improvement Network Quality Standards and Indicators for Pediatric Endoscopists and Endoscopists in Training: A Joint NASPGHAN/ESPGHAN Guideline.

INTRODUCTION: High-quality pediatric endoscopy requires reliable performance of procedures by competent individual providers who consistently uphold all standards determined to assure optimal patient outcomes. Establishing consensus expectations for ongoing monitoring and assessment of individual pediatric endoscopists is a method for confirming the highest possible quality of care for such procedures worldwide. We aim to provide guidance to define and measure quality of endoscopic care for children. METHODS: With support from the North American and European Societies of Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used the methodological strategy of the Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument to develop standards and indicators relevant for assessing the quality of endoscopists. Consensus was sought via an iterative online Delphi process and finalized at an in-person conference. The quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. RESULTS: The PEnQuIN working group achieved consensus on 6 standards that all providers who perform pediatric endoscopy should uphold and 2 standards for pediatric endoscopists in training, with 7 corresponding indicators that can be used to identify high-quality endoscopists. Additionally, these can inform continuous quality improvement at the provider level. Minimum targets for defining high-quality pediatric ileocolonoscopy were set for 2 key indicators: cecal intubation rate (≥90%) and terminal ileal intubation rate (≥85%). DISCUSSION: It is recommended that all individual providers performing or training to perform pediatric endoscopy initiate and engage with these international endoscopist-related standards and indicators developed by PEnQuIN.

Pediatric Endoscopy Quality Improvement Network Pediatric Endoscopy Reporting Elements: A Joint NASPGHAN/ESPGHAN Guideline.

INTRODUCTION: High-quality procedure reports are a cornerstone of high-quality pediatric endoscopy as they ensure the clear communication of procedural events and outcomes, guide patient care and facilitate continuous quality improvement. The aim of this document is to outline standardized reporting elements that achieved international consensus as requirements for high-quality pediatric endoscopy procedure reports. METHODS: With support from the North American and European Societies of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used Delphi methodology to identify key elements that should be found in all pediatric endoscopy reports. Item reduction was attained through iterative rounds of anonymized online voting using a 6-point scale. Responses were analyzed after each round and items were excluded from subsequent rounds if ≤50% of panelists rated them as 5 ("agree moderately") or 6 ("agree strongly"). Reporting elements that ≥70% of panelists rated as "agree moderately" or "agree strongly" were considered to have achieved consensus. RESULTS: Twenty-six PEnQuIN group members from 25 centers internationally rated 63 potential reporting elements that were generated from a systematic literature review and the Delphi panelists. The response rates were 100% for all three survey rounds. Thirty reporting elements reached consensus as essential for inclusion within a pediatric endoscopy report. DISCUSSION: It is recommended that the PEnQuIN Reporting Elements for pediatric endoscopy be universally employed across all endoscopists, procedures and facilities as a foundational means of ensuring high-quality endoscopy services, while facilitating quality improvement activities in pediatric endoscopy.

Liver lymphatic anatomy and role in systemic lymphatic disease.

OBJECTIVES: To characterize hepatic to systemic lymphatic connections in patients with systemic lymphatic disease using intra-hepatic lymphangiography and to compare outcomes after lymphatic intervention. METHODS: In this retrospective study, patients with intra-hepatic lymphangiography from May 2014 - April 2019 at our institution were included. Imaging review was performed and hepatic lymphatic connections and flow patterns were characterized. Clinical data were reviewed and comparisons between patients undergoing lymphatic intervention with or without abnormal hepatic lymphatics were performed. RESULTS: During the study period, 105 patients underwent intra-hepatic lymphangiography. Primary clinical presentation included ascites (19/105), chylothorax (27/105), plastic bronchitis (PB) (17/105), and protein losing enteropathy (PLE) (42/105). Five categories of hepatic lymphatic connections and flow patterns were identified (%): normal (25%, 26/105), hepatoperitoneal (12%, 13/105), hepatopulmonary (10.5%, 11/105), hepatomesenteric (7.5%, 8/105), and hepatoduodenal (41%, 43/105) with four patients having more than one abnormal pattern. A comparison between clinical presentation and imaging category revealed an increased likelihood of having ascites with hepatoperitoneal (p < .0001), chylothorax/PB with hepatopulmonary (p = .01), and PLE with hepatoduodenal (p < .001) connections. Seventy-six patients had a lymphatic intervention, 24% with normal, and 76% with abnormal liver lymphatics. There was no difference in length of hospital stay or mortality between the two groups, but there was a prolonged time to symptom resolution (p = .006) and persistent symptoms after 6 months (5% vs 44%, p = .002) in the group with abnormal liver lymphatics. CONCLUSION: We identified five liver lymphatic imaging categories with a substantial correlation to presenting lymphatic disease. Abnormal imaging patterns correlated with increased morbidity. Evaluation of liver lymphatics should be considered in patients with a systemic lymphatic disease if central lymphatic imaging is normal. KEY POINTS: • We identified five liver lymphatic imaging patterns: normal, hepatoperitoneal, hepatomesenteric, hepatopulmonary, and hepatoduodenal. • Imaging patterns were correlated with disease presentation (normal - chylothorax/PB, hepatoperitoneal - ascites/chylothorax, hepatopulmonary - chylothorax/PB, hepatoduodenal - PLE). • Abnormal imaging patterns correlated with increased morbidity.

Predictors of Prolonged Fluoroscopy Exposure in Pediatric Endoscopic Retrograde Cholangiopancreatography: Results From the Large Pediatric Endoscopic Retrograde Cholangiopancreatography Database Initiative Multicenter Cohort.

BACKGROUND AND AIMS: Ionizing radiation exposure during endoscopic retrograde cholangiopancreatography (ERCP) is an important quality issue especially in children. We aim to identify factors associated with extended fluoroscopy time (FT) in children undergoing ERCP. METHODS: ERCP on children <18 years from 15 centers were entered prospectively into a REDCap database from May 2014 until May 2018. Data were retrospectively evaluated for outcome and quality measures. A univariate and step-wise linear regression analysis was performed to identify factors associated with increased FT. RESULTS: 1073 ERCPs performed in 816 unique patients met inclusion criteria. Median age was 12.2 years (interquartile range [IQR] 9.3-15.8). 767 (71%) patients had native papillae. The median FT was 120 seconds (IQR 60-240). Factors associated with increased FT included procedures performed on patients with chronic pancreatitis, ERCPs with American Society of Gastrointestinal Endoscopy (ASGE) difficulty grade >3, ERCPs performed by pediatric gastroenterologist (GI) with adult GI supervision, and ERCPs performed at non-free standing children's hospitals. Hispanic ethnicity was the only factor associated with lower FT. CONCLUSION: Several factors were associated with prolonged FTs in pediatric ERCP that differed from adult studies. This underscores that adult quality indicators cannot always be translated to pediatric patients. This data can better identify children with higher risk for radiation exposure and improve quality outcomes during pediatric ERCP.

Bowel Preparation for Pediatric Colonoscopy.

Colonoscopy is an important diagnostic and therapeutic tool in evaluating and treating gastrointestinal tract pathologies. Adequate visualization of the intestinal lumen is necessary for detection of lesions, and thus bowel preparation is a key component of the process. It is estimated that over 25% percent of pediatric patients have sub-optimal bowel preparations, which can lead to longer procedure times, missed pathology, unsuccessful ileal intubation, and possibly repeat procedure/anesthesia. There is no universal protocol for bowel preparation in pediatrics and there is a wide variability of practices around the world. The purpose of this paper is to review the recent published literature regarding bowel preparations for pediatric colonoscopy with focus on published work in the last decade exploring a number of factors involved in bowel preparation including the role of patient education, types of bowel preparation, and their efficacy and safety.

Use of the functional luminal imaging probe in pediatrics: A comparison study of patients with achalasia before and after endoscopic dilation and non-achalasia controls.

BACKGROUND: Achalasia is an esophageal motility disorder characterized by esophagogastric junction (EGJ) dysfunction and impaired esophageal peristalsis with significant impact on quality of life. While the functional luminal imaging probe (FLIP) has been used to assess EGJ distensibility in achalasia, its clinical utility in pediatrics is limited due to absence of normative values and correlations with clinical outcomes in children. Thus, we sought to evaluate FLIP's use in a pediatric achalasia cohort undergoing dilations and non-achalasia controls. METHODS: We conducted a retrospective study of pediatric patients with achalasia who underwent FLIP before and immediately after balloon dilations and compared to a non-achalasia cohort. KEY RESULTS: Thirty patients with achalasia (mean age, 15.2 years; 40% female), including fourteen treatment-naïve and thirteen controls (mean age, 7.9 years; 61% female) were identified. Median EGJ distensibility index (EGJ-DI) 2.07 mm2  mmHg-1 and diameter (9.23 mm) in treatment-naïve patients were significantly lower compared to controls (EGJ-DI 6.8 mm2  mmHg-1 ; diameter 18.61 mm; (p < 0.001). Balloon dilations resulted in a significant increase in EGJ-DI immediately after the dilation, particularly in treatment-naïve patients (p < 0.001), and a significant improvement in Eckardt scores (p < 0.001). CONCLUSIONS & INFERENCES: Functional luminal imaging probe measurements of EGJ-DI in pediatric patients with achalasia are mostly consistent with adult findings. However, normal EGJ-DI is seen in symptomatic patients, including treatment-naive, highlighting the need for pediatric reference data. Balloon dilations achieve a significant increase in EGJ-DI with improvement in Eckardt scores, confirming the therapeutic value of dilations in achalasia management.

Phenotypic Differences in Juvenile Polyposis Syndrome With or Without a Disease-causing SMAD4/BMPR1A Variant.

Juvenile polyposis syndrome (JPS) is a clinically diagnosed hamartomatous polyposis syndrome that increases the risk of gastrointestinal cancer. Approximately 40%-50% of JPS is caused by a germline disease-causing variant (DCV) in the SMAD4 or BMPR1A genes. The aim of this study was to characterize the phenotype of DCV-negative JPS and compare it with DCV-positive JPS. Herein, we analyzed a cohort of 145 individuals with JPS from nine institutions, including both pediatric and adult centers. Data analyzed included age at diagnosis, family history, cancer history, need for colectomy/gastrectomy, and polyp number and location. Compared with DCV-positive JPS, DCV-negative JPS was associated with younger age at diagnosis (P < 0.001), lower likelihood of having a family history of JPS (P < 0.001), and a lower risk of colectomy (P = 0.032). None of the DCV-negative individuals had gastric or duodenal polyps, and polyp burden decreased after the first decade compared with DCV-positive JPS. Subgroup analysis between SMAD4 and BMPR1A carriers showed that SMAD4 carriers were more likely to have a family history of JPS and required gastrectomy. Taken together, these data provide the largest phenotypic characterization of individuals with DCV-negative JPS to date, showing that this group has distinct differences compared with JPS due to a SMAD4 or BMPR1A variant. Better understanding of phenotype and cancer risk associated with JPS both with and without a DCV may ultimately allow for individualized management of polyposis and cancer risk.Prevention Relevance: Juvenile Polyposis Syndrome (JPS) is a gastrointestinal cancer predisposition syndrome requiring lifelong surveillance, however there is limited data comparing individuals with and without a germline disease-causing variant in SMAD4 or BMPR1A Herein we show that individuals with JPS without an underlying disease-causing variant have distinct phenotypic differences including lack of upper gastrointestinal polyps and lower rates of a family history of JPS, suggesting that a different approach to management may be appropriate in this population.