Major Abdominal Surgery for Pediatric Crohn's Disease in the Anti-TNF Era: 10-Year Analysis of Data From the IBD Registry of Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition.

BACKGROUND: The natural history of Crohn's disease (CD) can result in complications requiring surgery. Pediatric data are scarce about major abdominal surgery. The IBD Registry from the Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition has been active since 2008 and collects data from major pediatric IBD centers in Italy. The aim of the present report was to explore the prevalence of major abdominal surgery among children affected by CD in an era when antitumor necrosis factor (anti-TNF-α) agents were already used so that we might appraise the incidence of surgical-related complications and identify the factors associated with postoperative disease recurrence. METHODS: We retrospectively analyzed data from patients enrolled in the registry from January 2009 to December 2018. Patients with monogenic IBD and patients undergoing surgery for perianal disease were excluded. RESULTS: In total, 135 of 1245 patients were identified. We report the prevalence of major abdominal surgery of 10.8%. Pediatric surgeons performed the procedure in 54.1% of cases, and a laparoscopic approach was used in 47.4% of surgical procedures. Seventeen patients (12.6%) experienced a total of 21 early postoperative complications, none of which was severe. A laparoscopic approach was the only factor negatively associated with the occurrence of postoperative complications (odds ratio, 0.22; 95% confidence interval, 0.06-0.8; P = .02). Fifty-four (40%) patients experienced postoperative endoscopic recurrence, and 33 (24.4%) of them experienced postoperative clinical recurrence. The postoperative treatment with anti-TNF-α drugs was significantly associated with a reduced risk of endoscopic recurrence (odds ratio, 0.19; 95% confidence interval, 0.05-0.79; P = .02). CONCLUSION: In our cohort, the overall prevalence of major abdominal surgery was low, as well as the rate of surgical-related complications. Postoperative anti-TNF-α therapy seems be protective against endoscopic recurrence.

Data from the IBD SIGENP registry show that the prevalence of major abdominal surgery is 10.8%, with a relatively low occurrence of short-term postoperative complications. The administration of anti-TNF-α drugs after surgery seems to effectively prevent postoperative endoscopic recurrence of disease.

Replogle Modified Endoscopic Vacuum-Assisted Closure (EVAC) Therapy: A New Strategy to Treat Anastomotic Leakage and Esophageal Perforation.

BACKGROUND: Anastomotic leakage (AL) and esophageal perforation are life-threatening complications following surgery or endoscopic dilations. "Replogle modified EVAC therapy" consists of placing a Replogle tube directly into the lumen or within an abscess cavity and remove by suction all intra-cavity fluids and secretion with a continuous low-pressure suction, promoting granulation tissue proliferation, thereby gradually decreasing the cavity size. The aim of our study was to evaluate the technical feasibility, safety, and efficacy of this technique in pediatric patients. METHODS: A retrospective review charts of consecutive pediatric patients that were treated with "Replogle modified EVAC therapy" at our pediatric referral center between 2013 and 2022 was conducted. The clinical, endoscopic, radiological, and surgical information and data of patients were collected and revised as well as their follow-up and outcomes. RESULTS: Ten patients (6/10 male; mean age: 7.8 y.o., range: 1.1-18 y.o.) were treated using the "Replogle modified EVAC therapy". Four out of ten patients developed esophageal perforations after endoscopic procedures. Six out of the ten enrolled patients had AL complications after surgical operations. All patients were successfully treated. There were no technical failures or complications with device placement. Mean treatment duration was 16 days (range 7-41 days). No additional treatment was needed for complete leak resolution. CONCLUSIONS: "Replogle modified EVAC therapy" represents a promising and mini-invasive method to treat esophageal perforations and post-surgical leak in the paediatric age group. In our experience, the use of this technique was safe, effective, and particularly well suited also in complex paediatric patients. LEVEL OF EVIDENCE: IV.

Efficacy and Tolerance of Thalidomide in Patients With Very Early Onset Inflammatory Bowel Disease.

BACKGROUND: Few drugs have been studied for patients with very early onset inflammatory bowel disease (VEOIBD). This study aimed to evaluate the efficacy and tolerance of thalidomide in children with VEOIBD compared with children with pediatric-onset IBD (pIBD). METHODS: A retrospective cohort study with a control group was conducted. Propensity score 1:1 matching was used to identify control subjects. The treatment persistence; the causes of drug withdrawal; the rate of clinical remission and mucosal healing at 1, 2, and 3 years; and adverse events (AEs) were evaluated in children with VEOIBD treated with thalidomide and compared with children with pIBD. RESULTS: Thirty-nine courses of treatment with thalidomide in VEOIBD and pIBD patients were compared. The treatment persistence at 1, 2, and 3 years was 68.2% (95% confidence interval [CI], 50.8%-80.6%), 57.0% (95% CI, 39.6%-71.1%), and 50.9% (95% CI, 33.7%-65.8%) for VEOIBD patients and 81.7% (95% CI, 65.3%-90.9%), 60.0% (95% CI, 41.7%-74.3%) and 33.0% (95% CI, 17.4%-49.5%) for pIBD patients, respectively (P = .12). A significantly higher proportion of VEOIBD patients discontinued therapy due to lack of efficacy (48.2% vs 17.2%; P = .03), while AEs were the main reason for discontinuation in pIBD patients. Clinical remission and mucosal healing rates did not significantly differ between VEOIBD and pIBD patients. A significatively lower number of VEOIBD patients experienced AEs compared with pIBD patients (14 [35.9%] vs 30 [76.9%]; P = .0005). CONCLUSIONS: Thalidomide is an effective and tolerated treatment in children with VEOIBD. Discontinuation due to lack of efficacy is more frequent, but AEs are less common than in children with pIBD.

Thalidomide is a valid therapeutic option in children with very early onset inflammatory bowel diseases unresponsive to conventional therapies. Discontinuation due to lack of efficacy is more frequent, but adverse events are less common than in children with pediatric-onset inflammatory bowel disease.

Approach to Endoscopic Balloon Dilatation in Pediatric Stricturing Crohn Disease: A Position Paper of the Endoscopy Special Interest Group of ESPGHAN.

Crohn disease (CD) is often complicated by bowel strictures that can lead to obstructive symptoms, resistant inflammation, and penetrating complications. Endoscopic balloon dilatation of CD strictures has emerged as a safe and effective technique for relieving these strictures, which may obviate the need for surgical intervention in the short and medium term. This technique appears to be underutilized in pediatric CD. This position paper of the Endoscopy Special Interest Group of European Society for Pediatric Gastroenterology, Hepatology and Nutrition describes the potential applications, appropriate evaluation, practical technique, and management of complications of this important procedure. The aim being to better integrate this therapeutic strategy in pediatric CD management.

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.

Evaluation of Safety and Immunogenicity of BNT162B2 mRNA COVID-19 Vaccine in IBD Pediatric Population with Distinct Immune Suppressive Regimens.

Patients affected by Inflammatory Bowel Disease (IBD) present higher risk for infection and suboptimal response upon vaccination. The immunogenicity of SARS-CoV2 vaccination is still largely unknown in adolescents or young adults affected by IBD (pIBD). We investigated the safety and immunogenicity of the BNT162B2 mRNA COVID-19 vaccine in 27 pIBD, as compared to 30 healthy controls (HC). Immunogenicity was measured by anti-SARS-CoV2 IgG (anti-S and anti-trim Ab) before vaccination, after 21 days (T21) and 7 days after the second dose (T28). The safety profile was investigated by close monitoring and self-reported adverse events. Vaccination was well tolerated, and short-term adverse events reported were only mild to moderate. Three out of twenty-seven patients showed IBD flare after vaccination, but no causal relationship could be established. Overall, pIBD showed a good humoral response upon vaccination compared to HC; however, pIBD on anti-TNFα treatment showed lower anti-S Ab titers compared to patients receiving other immune-suppressive regimens (p = 0.0413 at first dose and p = 0.0301 at second dose). These data show that pIBD present a good safety and immunogenicity profile following SARS-CoV-2 mRNA vaccination. Additional studies on the impact of specific immune-suppressive regimens, such as anti TNFα, on immunogenicity should be further investigated on larger cohorts.

BCL6 and the Notch pathway: a signaling axis leading to a novel druggable biotarget in triple negative breast cancer.

BACKGROUND: The transcriptional repressor B-cell lymphoma 6 (BCL6) is dysregulated in several neoplasms, but its role in triple negative breast cancer (TNBC), a highly aggressive subtype which lacks effective treatment, is unclear. The presence of intratumoral cancer stem cells (CSCs) is a main cause of tumor relapse. The Notch signaling pathway is crucial for regulating CSC self-renewal and promoting breast cancer (BC) development and resistance to anticancer therapies. Here, we investigated signaling cascades of BCL6 in the CSC compartment of TNBCs, and the mechanisms that govern its activity, mainly through Notch signaling. METHODS: Gene expression, somatic copy number alterations and clinical data from the Cancer Genome Atlas and METABRIC were accessed through the Xena and cbioportal browsers. Public transcriptome profiles from TNBC datasets were retrieved from the Gene Expression Omnibus. Mammosphere formation efficiency was calculated after BCL6 knockdown via transient siRNA transfection, stable silencing or pharmacological inhibition. The effects exhibited via BCL6 inhibition in putative TNBC stem-like cells were evaluated by immunofluorescence and qRT-PCR analyses. Chromatin immunoprecipitation experiments were performed to validate a putative BCL6 responsive element located in the first intron of the Numb gene and to define the circuit of corepressors engaged by BCL6 following its inhibition. Immunoprecipitation assays were carried out to investigate a novel interaction at the basis of BCL6 control of CSC activity in TNBC. RESULTS: In silico analyses of benchmarked public datasets revealed a significant enrichment of BCL6 in cancer stemness related pathways, particularly of Notch signaling in TNBC. In vitro stable inhibition of BCL6 significantly reduced tumor cell growth and, accordingly, we found that the mammosphere formation efficiency of BCL6 silenced cells was significantly impaired by pharmacological inhibition of Notch signaling. BCL6 was found to be expressed at significantly higher levels in TNBC mammospheres than in their adherent counterparts, and loss of BCL6 function significantly decreased mammosphere formation with preferential targeting of CD44-positive versus ALDH-positive stem-like cells. Functional interplay between BCL6 and the chromatin remodeling factor EZH2 triggered the BCL6/Notch stemness signaling axis via inhibition of Numb transcription. CONCLUSIONS: Our results may be instrumental for the prospective design of combination treatment strategies that selectively target novel TNBC-associated biomarker(s) whose activity is implicated in the regulation of cancer stemness (such as BCL6) and molecules in developmentally conserved signaling pathways (such as Notch) to achieve long-lasting tumor control and improve patient outcomes.

Systematic Review and Meta-analysis of Histological Gastric Biopsy Aspects According to the Updated Sydney System in Children.

OBJECTIVES: A descriptive and comparative study of gastric histological aspects according to the updated Sydney classification (USC), obtained from Helicobacter pylori-positive versus H pylori-negative children referred for upper gastrointestinal endoscopy. METHODS: The Prisma method was used to perform a systematic review and meta-analysis. Selection criteria were based on following key words USC, H pylori, children, endoscopy, or biopsy. Publication biases were assessed according to the Newcastle-Ottawa Scale, and a meta-regression analysis was done. The study was registered on the PROSPERO platform. RESULTS: Between 1994 and 2017, 1238 references were found; 97 studies were retained for the systematic review with a total number of 25,867 children; 75 studies were selected for the meta-analysis concerning 5990 H pylori-infected and 17,782 uninfected children.H pylori-positive versus H pylori-negative children, according to the USC, showed significantly higher relative risk for gastric antral and corpus chronic inflammation, presence of neutrophils, and of lymphoid follicles, and gastric mucosa atrophy, whereas, intestinal metaplasia showed a significantly higher RR only in antral biopsies. The meta-regression analysis showed that H pylori-positive versus H pylori-negative children had significantly higher risk only for corpus activity according to age, recurrent abdominal pain, and geographical area of low H pylori prevalence. CONCLUSIONS: H pylori infection in children was associated with higher relative risk for gastric antral and corpus chronic inflammation, presence of neutrophils, lymphoid follicles, and rare gastric mucosa atrophy, whereas, rare intestinal metaplasia was only significantly higher in the antral area.

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.

Gastric cancer, inflammatory bowel disease and polyautoimmunity in a 17-year-old boy: CTLA-4 deficiency successfully treated with Abatacept.

Gut involvement is frequent in immunologic disorders, especially with inflammatory manifestations but also with cancer. In the last years, advances in functional and genetic testing have improved the diagnostic and therapeutic approach to immune dysregulation syndromes. CTLA-4 deficiency is a rare disease with variable phenotype, ranging from absence of symptoms to severe multisystem manifestations and complications. We describe a rare case of CTLA-4 deficiency in a boy with gastric cancer, very early onset inflammatory bowel disease and polyautoimmunity, the second-ever reported in the literature with the same characteristics. A 17-year-old boy was referred to Bambino Gesù Children's Hospital of Rome, a tertiary care center, for a gastric mass and a long-term history of very early onset inflammatory bowel disease, diabetes mellitus type 1, polyarthritis and psoriasis. Histology of gastric biopsies revealed the presence of neoplastic signet ring cells. Imaging staging showed localized cancer; therefore, the patient underwent subtotal gastrectomy with termino-lateral gastro-jejunal anastomosis. Immunological work up and genetic testing by next-generation sequencing panels for primary immunodeficiencies led to the diagnosis of CTLA-4 deficiency. Good disease control was obtained with the administration of Abatacept. The patient experienced an asymptomatic SARS-CoV-2 infection without any concern. Eighteen months after treatment initiation, the patient is alive and well. Immunologic and genetic testing, such as next-generation sequencing, should always be part of the diagnostic approach to patients with complex immune dysregulation syndrome, severe clinical course, poor response to treatments or cancer. The early recognition of the monogenic disease is the key for disease management and targeted therapy.

A prospective multicenter analysis from the Pediatric ERCP Database Initiative: predictors of choledocholithiasis at ERCP in pediatric patients.

BACKGROUND AND AIMS: The management of suspected choledocholithiasis remains a challenge in pediatric endoscopy. Several recommendations are available for adult patients; however, it is unknown which pediatric patients are most likely to benefit from ERCP for evaluation of choledocholithiasis. The primary aim of this study was to evaluate adult-based criteria in the evaluation of pediatric patients with choledocholithiasis. A secondary aim was to evaluate the role of conjugated (or direct) bilirubin to improve the sensitivity of detecting choledocholithiasis. METHODS: This was a prospective multicenter study in pediatric patients as part of the Pediatric ERCP Database Initiative (PEDI) with additional post-hoc analysis of updated guidelines. Patients <19 years of age undergoing ERCP for suspected choledocholithiasis or gallstone pancreatitis were enrolled at participating sites. RESULTS: Ninety-five patients were enrolled (69 with choledocholithiasis confirmed at ERCP and 26 with no stones at ERCP). Adverse event rates were similar in both groups. Specificity ranged from 27% to 91% using adult guidelines, but a sensitivity of only 20% to 69%. The were no significant differences between the 2 groups using preprocedure transabdominal US (P = 1.0). Significant differences between groups were identified using either the total or conjugated bilirubin (P = .02). There was also a significant difference between the stone and no-stone groups when conjugated bilirubin was dichotomized to >2 mg/dL (P = .03). CONCLUSIONS: Abdominal imaging and laboratory indices may be used to predict pediatric choledocholithiasis with varying sensitivity and specificity. Pediatric-specific guidelines may allow for improved stone prediction compared with existing adult recommendations.

Evaluation of Gastroesophageal Reflux Disease 1 Year after Esophageal Atresia Repair: Paradigms Lost from a Single Snapshot?

OBJECTIVE: To analyze the findings of both multichannel intraluminal impedance with pH (MII-pH) and endoscopy/histopathology in children with esophageal atresia at age 1 year, according to current recommendations for the evaluation of gastroesophageal reflux disease (GERD) in esophageal atresia. STUDY DESIGN: We retrospectively reviewed both MII-pH and endoscopy/histopathology performed in 1-year-old children with esophageal atresia who were followed up in accordance with international recommendations. Demographic data and clinical characteristics were also reviewed to investigate factors associated with abnormal GERD investigations. RESULTS: In our study cohort of 48 children with esophageal atresia, microscopic esophagitis was found in 33 (69%) and pathological esophageal acid exposure on MII-pH was detected in 12 (25%). Among baseline variables, only the presence of long-gap esophageal atresia was associated with abnormal MII-pH. Distal baseline impedance was significantly lower in patients with microscopic esophagitis, and it showed a very good diagnostic performance in predicting histological changes. CONCLUSIONS: Histological esophagitis is highly prevalent at 1 year after esophageal atresia repair, but our results do not support a definitive causative role of acid-induced GERD. Instead, they support the hypothesis that chronic stasis in the dysmotile esophagus might lead to histological changes. MII-pH may be a helpful tool in selecting patients who need closer endoscopic surveillance and/or benefit from acid suppression.

Esophageal Retained Lithium Battery in Children Younger than 6 Years: A Prompt Structured Multidisciplinary Approach Is Essential to Reduce Long-Term Consequences.

OBJECTIVES: Disk battery esophageal retention in children younger than 6 years represents an increasing endoscopic emergency, followed by a relevant risk of life-threatening late complications. Surgical removal after a failed endoscopic approach is rarely reported in the literature. We describe our experience in this scenario. METHODS: Two female asymptomatic patients aged 26 and 29 months presented within 4 hours after a witnessed ingestion of a 2-cm, 3-V lithium battery (CR2032) retained in the cervical esophagus. Both patients underwent a prolonged unsuccessful emergent endoscopic removal with a flexible instrument performed by an adult gastroenterologist. Both batteries fused with the esophageal wall were extracted through a longitudinal left cervical esophagotomy combined with minimal resection of necrotic tissues and repaired over a 12F feeding tube. RESULTS: Patients were extubated after 12 and 72 hours, respectively. Contrast study was performed after 20 and 13 days, respectively, before resuming oral feeding. At endoscopy, the first patient developed a 3-cm-long severe esophageal stenosis (35th day), followed by an asymptomatic tracheoesophageal fistula (60th day), which was conservatively treated. After spontaneous resolution of the tracheoesophageal fistula, esophageal stenosis progressed, partially responsive to esophageal stenting. Short esophagectomy is under evaluation. The second patient developed an asymptomatic limited stenosis, not requiring dilatation. CONCLUSIONS: The emergent management of lithium battery ingestion needs a structured timely multidisciplinary approach in the emergency department, an experienced pediatric endoscopist, and a simultaneous engagement of pediatric surgical expertise, even in patients who do not show bleeding, to reduce esophageal exposure time to high-voltage current released by batteries, which represents the main factor conditioning tissue damage and prognosis.

Duodenal Duplication Cysts in Children: Clinical Features and Current Treatment Choices.

BACKGROUND: Duodenal duplication cysts are rare gastrointestinal tract malformations. Most patients experience symptom onset in the first decade of life. This review aims to examine clinical presentation, management strategies and outcomes of duodenal duplication cysts in childhood. METHODS: A Pubmed/Medline (http://www.ncbi.nlm.nih.gov/pubmed/) search in October 2019 for articles published since 1999 using the keywords "duodenal duplication cyst," "child" and "newborn" was carried out. Clinical symptoms, complications, diagnostic examinations, treatment options and outcomes were analyzed and tabulated. RESULTS: There were 41 citations in the literature providing adequate descriptions of 45 cases of duodenal duplication cysts. The age of presentation ranged from newborn to 18 years. The median interval between initial presentation and definitive diagnosis and treatment was 17 months (range: 2 months to 12 years). Overall, 67% of cases presented with abdominal pain, and 43% were complicated with pancreatitis. Different surgical and endoscopic therapeutic strategies were reported. CONCLUSIONS: Duodenal duplication cysts may be associated with life-threatening complications and/or recurrent symptoms, impairing quality of life. Early recognition of patients who demonstrate suggestive signs and symptoms is important to ensure success of treatment. This review may be useful to highlight the main diagnostic aspects and limit the risk of a delayed diagnosis.

Author Correction: The landscape of d16HER2 splice variant expression across HER2-positive cancers.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Gut Mucosal and Fecal Microbiota Profiling Combined to Intestinal Immune System in Neonates Affected by Intestinal Ischemic Injuries.

Background and Purpose: Early life microbiota plays a crucial role in human health by acting as a barrier from pathogens' invasion and maintaining the intestinal immune homoeostasis. Altered fecal microbiota (FM) ecology was reported in newborns affected by intestinal ischemia. Our purpose was to describe, in these patients, the FM, the mucosal microbiota (MM) and the mucosal immunity. Methods: Fourteen newborns underwent intestinal resection because of intestinal ischemia. FM and MM were determined through targeted-metagenomics, diversity assignment and Kruskal-Wallis analyses of Operational taxonomic units (OTUs). The mucosal immune cells were analyzed through cytofluorimetry. Results and Conclusion: Based on the severity intestinal injueris we identified two groups: extensive (EII) and focal intestinal ischemia (FII). FM and MM varied in EII and FII groups, showing in the EII group the predominance of Proteobacteria and Enterobacteriaceae and the reduction of Bacteroidetes and Verrucomicrobia for both microbiota. The MM was characterized by a statistically significant reduction of Bacteroides, Lachnospiraceae and Ruminococcaceae and by a higher diversity in the EII compared to FII group. FM showed a prevalence of Proteobacteria, while the Shannon index was lower in the EII compared to FII group. An overall increment in B- and T-lymphocytes and Natural killer (NK) T-like cells was found for EII mucosal samples associated to an increment of TNF-α and INF-γ expressing cells, compared to FII group. FM and MM carry specific signatures of intestinal ischemic lesions. Further research may be crucial to address the role of specific taxa in EII, expecially with reference to inflammation grade and ischemia extension.

Diagnostic Approach to Monogenic Inflammatory Bowel Disease in Clinical Practice: A Ten-Year Multicentric Experience.

BACKGROUND AND AIMS: Multiple monogenic disorders present as very early onset inflammatory bowel disease (VEO-IBD) or as IBD with severe and atypical features. Establishing a genetic diagnosis may change patients' management and prognosis. In this study, we describe the diagnostic approach to suspected monogenic IBD in a real clinical setting, discussing genetic and phenotypic findings and therapeutic implications of molecular diagnosis. METHODS: Information of patients with VEO-IBD and early onset IBD with severe/atypical phenotypes (EO-IBD s/a) managed between 2008-2017 who underwent a genetic workup were collected. RESULTS: Ninety-three patients were included, and 12 (13%) reached a genetic diagnosis. Candidate sequencing (CS) was performed in 47 patients (50%), and next generation sequencing (NGS) was performed in 84 patients (90%). Candidate sequencing had a good diagnostic performance only when guided by clinical features specific for known monogenic diseases, whereas NGS helped finding new causative genetic variants and would have anticipated one monogenic diagnosis (XIAP) and consequent bone marrow transplant (BMT). Patients with monogenic IBD more frequently were male (92% vs 54%; P = 0.02), had extraintestinal findings (100% vs 34%; P < 0.001), and had disease onset ≤1 month of life (25% vs 1%; P = 0.006). Genetic diagnosis impacted patient management in 11 patients (92%), 7 of whom underwent BMT. CONCLUSION: A genetic diagnosis can be established in a significant proportion of suspected monogenic IBD and has an impact on patients' management. Candidate sequencing may be deployed when clinical findings orientate toward a specific diagnosis. Next generation sequencing should be preferred in patients with nonspecific phenotypes.