Pediatric ERCP: Factors for Success and Complication-A 17-Year, Multisite Experience.

OBJECTIVES: Endoscopic retrograde cholangiopancreatography (ERCP) is an increasingly utilized procedure in pediatric populations. A lack of dedicated pediatric research has led endoscopists to extrapolate adult risk factors and preventative strategies to children. The aim of this multisite, retrospective study was to identify risks for adverse events, procedure failure, and prolonged courses in pediatric patients undergoing ERCP. METHODS: Pediatric patients who had an ERCP at one of our academic centers were identified by query of their electronic medical records. Pre-procedure and post-procedure data were collected with ERCP-related adverse events defined according to the consensus criteria developed by Cotton et al 2010. RESULTS: Between January 2004 and January 2021, 287 children had a total of 716 ERCPs. The procedure success rate was 95.5% with no mortality and an adverse event rate of 12.7%. Younger age was associated with increased case complexity, increased adverse events, and an increased rate of repeat ERCP. Case complexity score correlated with increased procedure time ( P < 0.001) and increased adverse events (tau 0.24, P < 0.01); stent removal and pancreatic stenting were more likely to precede an adverse event. Pancreatitis, pancreatic divisum, and pancreatic stricture/stenosis were associated with increased adverse events and rates of repeat ERCP. CONCLUSIONS: Pediatric ERCP adverse event rates are higher than adults. The complexity grading system proposed by the Cotton et al appears to have applicability to pediatric patients. Young age and interventions affecting the pancreatic duct are associated with adverse ERCP outcomes in pediatrics.

Management of Hepatolithiasis: Review of the Literature.

PURPOSE OF REVIEW: Hepatolithiasis is a disease characterized by intrahepatic stone formation. In this article, we review the features of this disease and explore the established and emerging treatment modalities. RECENT FINDINGS: Recent reports show an increasing prevalence of hepatolithiasis, likely owed to increased immigration and shifts in the Western diet. New pharmacotherapy options are limited and are often only supportive. Endoscopic intervention still cruxes on removal of impacted stones, though new techniques such as bile duct exploratory lithotomy and lithotripsy continue to advance management. Although hepatectomy of the effected portion of the liver offers definitive therapy, alternative less invasive modalities such as combined endoscopic/interventional radiology modalities have been utilized in select patients. Additionally, liver transplant serves as an option for otherwise incurable hepatolithiasis with coexisting liver dysfunction. Multiple emerging pharmacologic and procedural interventions may provide novel treatment for hepatolithiasis. While definitive therapy remains resection of affected liver segments, these modalities offer hope for less invasive approaches in the future.

ISG15 deregulates autophagy in genotoxin-treated ataxia telangiectasia cells.

Ataxia-telangiectasia (A-T) is a cerebellar neurodegenerative disorder; however, the basis for the neurodegeneration in A-T is not well established. Lesions in the ubiquitin and autophagy pathways are speculated to contribute to the neurodegeneration in other neurological diseases and may have a role in A-T neurodegeneration. Our recent studies revealed that the constitutively elevated ISG15 pathway impairs targeted proteasome-mediated protein degradation in A-T cells. Here, we demonstrate that the basal autophagy pathway is activated in the ubiquitin pathway-compromised A-T cells. We also show that genotoxic stress triggers aberrant degradation of the proteasome and autophagy substrates (autophagic flux) in A-T cells. Inhibition of autophagy at an early stage using 3-methyladenine blocked UV-induced autophagic flux in A-T cells. On the other hand, bafilomycin A1, which inhibits autophagy at a late stage, failed to block UV-induced autophagic flux, suggesting that overinduction of autophagy may underlie aberrant autophagic flux in A-T cells. The ISG15-specific shRNA that restored proteasome function restores autophagic function in A-T cells. These findings suggest that autophagy compensates for the ISG15-dependent ablation of proteasome-mediated protein degradation in A-T cells. Genotoxic stress overactivates this compensatory mechanism, triggering aberrant autophagic flux in A-T cells. Supporting the model, we show that autophagy is activated in the brain tissues of human A-T patients. This highlights a plausible causal contribution of a novel "ISG15 proteinopathy" in A-T neuronal cell death.

Expanding the Use of Endoscopic Retrograde Cholangiopancreatography in Pediatrics: A National Database Analysis of Demographics and Complication Rates.

Background: This study aimed to aid in risk assessment of pediatric endoscopic retrograde cholangiopancreatography (ERCP) candidates by utilizing a national pediatric database with a large sample to assess how patient characteristics may affect ERCP complication rates. Methods: The Kids' Inpatient Database (KID) is a sample of pediatric discharges in states participating in the Healthcare Cost and Utilization Project (HCUP). This database provides demographic information, hospitalization duration, and outcome information for hospitalizations during which an ERCP occurred. International Classification of Diseases (ICD) codes were used to determine the hospitalization indication. ERCP complication rate was ascertained via ICD codes. All statistical analyses were performed using SAS 9.4. Results: Complications were seen in 5.4% of hospitalizations with mortality observed in less than 0.2%. This analysis captured a large Hispanic population, specifically in the South and West regions. Gallbladder calculus and cholecystitis were more likely to occur in females. A higher percentage of patients in the age 10 - 17 group were female (72.2% vs. 52.7%, P < 0.01) and Hispanic (33.4% vs. 22.7%, P < 0.01) compared to the age 0 - 9 group. Age 0 - 5 and male gender were associated with lower routine home discharge rates and longer lengths of stay. Complications occurred at a higher rate in ages 0 - 5, though the difference was not statistically significant. Conclusions: ERCP is a safe procedure for pediatric patients with low complication rates and rare mortality. We found statistically significant differences in the procedure indications between pediatric age groups, races, and genders. Age ≤ 5 years and male gender were associated with more complicated healthcare courses.

Appendectomy Hospital Stay: No Difference in Obese Adult or Pediatric Patient Length of Stay Compared to Nonobese Patients.

Background: Studies of adult and pediatric patients undergoing appendectomy have reported variable outcomes and operative metrics related to the effect of obesity. The purpose of this study was to investigate the effect of obesity in adult and pediatric patients undergoing appendectomy at our institution. Methods: This single-center retrospective study evaluated the relationship between length of hospital stay for appendectomy and body mass index (BMI). Data obtained from the electronic medical record included age, sex, weight, height, BMI, the number of hours the patient experienced symptoms prior to presentation to the emergency room, the number of hours the patient was admitted prior to surgery, the number of hours of hospital admission after surgery, perforated appendix, preoperative comorbidities, and evidence of preoperative sepsis. Results: During the 3-year study period, 118 adults and 38 children who underwent appendectomy composed the study groups. Patients were stratified by obese and nonobese, with obesity defined as BMI ≥30.0 kg/m2. In adults, we found no significant difference between length of stay in obese (n=45) and nonobese (n=73) patients (79.6 ± 65.5 hours vs 101.6 ± 123.0 hours; P=0.21). In children, we found no significant difference between length of stay in obese (n=9) and nonobese (n=29) patients (92.9 ± 64.6 hours vs 109.0 ± 93.5 hours; P=0.54). Conclusion: Obesity did not affect length of stay in adults and children who underwent appendectomy in the present series.

Cholestasis in Benign Recurrent Intrahepatic Cholestasis 2.

Benign recurrent intrahepatic cholestasis represents a rare class of autosomal recessive chronic cholestasis disorders, usually presenting with recurrent episodes of intense pruritus and jaundice. We report a 27-year-old woman presenting with benign recurrent intrahepatic cholestasis type 2 due to heterozygosity in ABCB11. Interestingly, she was also found to be heterozygous in cystic fibrosis transmembrane conductance regulator, NPHP4, and A1ATD (SERPINA1), which may explain the severe nature of her disease expression because heterozygosity in each of these genes has been associated with cholestasis. Finally, she exhibited a response to steroids that may have implications for future treatment of bile salt export pump-related diseases.