Efficacy and safety of endoscopic retrograde cholangiopancreatography in recurrent pancreatitis of pediatric asparaginase-associated pancreatitis.

BACKGROUND: Asparaginase (ASP) is an important drug in combined chemotherapy regimens for pediatric acute lymphoblastic leukemia (ALL); ASP-associated pancreatitis (AAP) is the main adverse reaction of ASP. Recurrent pancreatitis is a complication of AAP, for which medication is ineffective. AIM: To evaluate the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) in treating recurrent pancreatitis due to AAP. METHODS: From May 2018 to August 2021, ten children (five males and five females; age range: 4-13 years) with AAP were treated using ERCP due to recurrent pancreatitis. Clinical data of the ten children were collected, including their sex, age, weight, ALL risk grading, clinical symptoms at the onset of pancreatitis, time from the first pancreatitis onset to ERCP, ERCP operation status, and postoperative complications. The symptomatic relief, weight change, and number of pancreatitis onsets before and after ERCP were compared. RESULTS: The preoperative symptoms were abdominal pain, vomiting, inability to eat, weight loss of 2-7 kg, and 2-9 pancreatitis onsets. After the operation, nine of ten patients did not develop pancreatitis, had no abdominal pain, could eat normally; the remaining patient developed three pancreatitis onsets due to the continuous administration of ASP, but eating was not affected. The postoperative weight gain was 1.5-8 kg. There was one case of post ERCP pancreatitis and two cases of postoperative infections; all recovered after medication. CONCLUSION: ERCP improved clinical symptoms and reduced the incidence of pancreatitis, and was shown to be a safe and effective method for improving the management of recurrent pancreatitis due to AAP.

External use of mirabilite to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis in children: A multicenter randomized controlled trial.

BACKGROUND: Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Currently, there is no suitable treatment for post-ERCP pancreatitis (PEP) prophylaxis. Few studies have prospectively evaluated interventions to prevent PEP in children. AIM: To assess the efficacy and safety of the external use of mirabilite to prevent PEP in children. METHODS: This multicenter, randomized controlled clinical trial enrolled patients with chronic pancreatitis scheduled for ERCP according to eligibility criteria. Patients were randomly divided into the external use of mirabilite group (external use of mirabilite in a bag on the projected abdominal area within 30 min before ERCP) and blank group. The primary outcome was the incidence of PEP. The secondary outcomes included the severity of PEP, abdominal pain scores, levels of serum inflammatory markers [tumor necrosis factor-alpha (TNF-α) and serum interleukin-10 (IL-10)], and intestinal barrier function markers [diamine oxidase (DAO), D-lactic acid, and endotoxin]. Additionally, the side effects of topical mirabilite were investigated. RESULTS: A total of 234 patients were enrolled, including 117 in the external use of mirabilite group and the other 117 in the blank group. The pre-procedure and procedure-related factors were not significantly different between the two groups. The incidence of PEP in the external use of mirabilite group was significantly lower than that in the blank group (7.7% vs 26.5%, P < 0.001). The severity of PEP decreased in the mirabilite group (P = 0.023). At 24 h after the procedure, the visual analog scale score in the external use of mirabilite group was lower than that in the blank group (P = 0.001). Compared with those in the blank group, the TNF-α expressions were significantly lower and the IL-10 expressions were significantly higher at 24 h after the procedure in the external use of mirabilite group (P = 0.032 and P = 0.011, respectively). There were no significant differences in serum DAO, D-lactic acid, and endotoxin levels before and after ERCP between the two groups. No adverse effects of mirabilite were observed. CONCLUSION: External use of mirabilite reduced the PEP occurrence. It significantly alleviated post-procedural pain and reduced inflammatory response. Our results favor the external use of mirabilite to prevent PEP in children.

Risk factors for the progression from acute recurrent to chronic pancreatitis among children in China.

Background: Risk factors for progression from acute recurrent pancreatitis (ARP) to chronic pancreatitis (CP) in children are poorly understood. Aim: To summarize the clinical characteristics of children with ARP and CP, identify the risk factors of CP, and investigate the factors associated with rapid progression from initial onset of ARP to CP. Methods: The following variables were included in the risk factor analysis: sex, age at onset, family history, pancreas or biliary tract structural abnormalities, and genetic variations. Univariate and multivariate logistic regression analyses were used to assess the risk factors of CP. The Kaplan-Meier curves of the ARP progression to CP for various risk factor groupings were constructed and compared using the log-rank test. The Cox proportional hazard regression model was fitted to estimate the hazard ratio (HR) of progression to CP for each risk variable. Results: In total, 276 children were studied, of whom 136 progressed to CP. Among them, 41 had pancreatic duct obstructive disease; 105 underwent genetic testing, of whom 68 were found to have genetic variations. Among the remaining 140 patients who did not progress to CP, 61 had biliary obstructions. Forty-three of these children underwent genetic testing, and 15 were found to have genetic variations. Risk factor analysis showed that children with gene mutations were at a higher risk of progressing to CP [odds ratio (OR) = 3.482; 95% confidence interval (CI): 1.444-8.398; P = 0.005]; children with pancreas divisum (PD) had a higher risk of CP than those without (OR = 8.665; 95% CI: 1.884, 9.851; P = 0.006). Further, children whose first ARP occurred at an older age might develop CP faster (HR = 1.070; 95% CI: 1.003, 1.141; P = 0.039). Children with gene mutations had a faster rate of progression to CP after onset than children without gene mutations (HR = 1.607; 95% CI: 1.024, 2.522; P = 0.039), PRSS1 gene mutations were more associated (P = 0.025). There was no difference in the rate of progression from ARP to CP in children with PD (P = 0.887); however, endoscopic retrograde cholangiopancreatography (ERCP) intervention delayed the progression to CP in ARP patients with PD (P = 0.033). Conclusion: PRSS1 gene mutations and PD are key risk factors for ARP progression to CP in children. PD itself does not affect the disease progression rate, but therapeutic ERCP can be beneficial to patients with ARP with symptomatic PD and delay the progression to CP.

Prevalence and Factors Associated with Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis in Children.

BACKGROUND: Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). AIM: To assess the prevalence and factors associated with post-ERCP pancreatitis (PEP) in a Chinese pediatric population. METHODS: Sixty-six children who underwent ERCP between March 2018 and March 2019 at Shanghai Children's Medical Center were retrospectively recruited for the study. Clinical data, including demographics, indications, comorbidities, and procedural data, were reviewed to identify the prevalence and factors associated with PEP. RESULTS: Ninety-two ERCPs were performed on 66 pediatric patients aged from 8 months to 14 years. The indications for ERCP were chronic pancreatitis (49, 53.2%), pancreaticobiliary maljunction (19, 20.7%), pancreas divisum (19, 20.7%), and pancreatic pseudocyst (5, 5.4%). All ERCPs were performed for therapeutic purposes. PEP was identified in 19 (20.7%) patients; there were ten mild cases, eight moderate cases, and one severe case. The univariate analysis revealed that a history of chronic pancreatitis was negatively associated with PEP (P = 0.033), and sphincterotomy was positively associated with PEP (P = 0.01). The multivariate analysis showed that sphincterotomy was a risk factor for PEP (P = 0.017, OR 4.17; 95% CI, 1.29, 13.54). CONCLUSIONS: Our data revealed a high prevalence of PEP in a Chinese pediatric population. Chronic pancreatitis was a protective factor, and sphincterotomy was a risk factor for PEP development.

Endoscopic retrograde cholangiopancreatography in children with symptomatic pancreaticobiliary maljunction: A retrospective multicenter study.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) has been widely used in pediatric patients with cholangiopancreatic diseases. AIM: To evaluate the efficacy, safety, and long-term follow-up results of ERCP in symptomatic pancreaticobiliary maljunction (PBM). METHODS: A multicenter, retrospective study was conducted on 75 pediatric patients who were diagnosed with PBM and underwent therapeutic ERCP at three endoscopy centers between January 2008 and March 2019. They were divided into four PBM groups based on the fluoroscopy in ERCP. Their clinical characteristics, specific ERCP procedures, adverse events, and long-term follow-up results were retrospectively reviewed. RESULTS: Totally, 112 ERCPs were performed on the 75 children with symptomatic PBM. Clinical manifestations included abdominal pain (62/75, 82.7%), vomiting (35/75, 46.7%), acholic stool (4/75, 5.3%), fever (3/75, 4.0%), acute pancreatitis (47/75, 62.7%), hyperbilirubinemia (13/75, 17.3%), and elevated liver enzymes (22/75, 29.3%). ERCP interventions included endoscopic sphincterotomy, endoscopic retrograde biliary or pancreatic drainage, stone extraction, etc. Procedure-related complications were observed in 12 patients and included post-ERCP pancreatitis (9/75, 12.0%), gastrointestinal bleeding (1/75, 1.3%), and infection (2/75, 2.7%). During a mean follow-up period of 46 mo (range: 2 to 134 mo), ERCP therapy alleviated the biliary obstruction and reduced the incidence of pancreatitis. The overall effective rate of ERCP therapy was 82.4%; seven patients (9.3%) were lost to follow-up, eight (11.8%) re-experienced pancreatitis, and eleven (16.2%) underwent radical surgery, known as prophylactic excision of the extrahepatic bile duct and hepaticojejunostomy. CONCLUSION: ERCP is a safe and effective treatment option to relieve biliary or pancreatic obstruction in symptomatic PBM, with the characteristics of minor trauma, fewer complications, and repeatability.

Fecal microbiota transplantation for refractory diarrhea in immunocompromised diseases: a pediatric case report.

BACKGROUND: Immunocompromised (IC) patients have an increased risk of refractory diarrhea. Fecal microbiota transplantation (FMT) is a safe and effective therapy for infection-related diarrhea which are mainly mediated by the loss of the microbial colonization, although there is concern that IC patients may be at higher risk of infectious complications related to FMT. And reports of FMT in IC children are limited. CASE PRESENTATION: We describe two cases of FMT in IC children with refractory diarrhea. One IC child had polyendocrinopathy, enteropathy, X-linked syndrome and the other child had graft-versus-host disease. Both of the children had a long course of diarrhea and no response to traditional treatment. FMT was performed on both patients via nasojejunal tubes under guidance of gastroduodenoscopy. After FMT, the patients achieved remission of symptoms and neither of them had related infectious complications. Microbiota analysis showed that FMT resulted in reconstruction of a diverse microbiota. CONCLUSIONS: Use of FMT is safe and effective in treatment of refractory diarrhea in IC children with a damaged microbiota.

Enterocyte dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin expression in inflammatory bowel disease.

AIM: To investigate dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) expression in intestinal epithelial cells (IECs) in inflammatory bowel disease (IBD). METHODS: The expression of DC-SIGN in IECs was examined by immunohistochemistry of intestinal mucosal biopsies from 32 patients with IBD and 10 controls. Disease activity indices and histopathology scores were used to assess the tissue lesions and pathologic damage. Animal studies utilized BALB/c mice with dextran sodium sulfate (DSS)-induced colitis treated with anti-P-selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb). Controls, untreated and treated mice were sacrificed after 7 d, followed by isolation of colon tissue and IECs. Colonic expression of DC-SIGN, CD80, CD86 and MHC II was examined by immunohistochemistry or flow cytometry. The capacity of mouse enterocytes or dendritic cells to activate T cells was determined by co-culture with naïve CD4(+) T cells. Culture supernatant and intracellular levels of interleukin (IL)-4 and interferon (IFN)-γ were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively. The ability of IECs to promote T cell proliferation was detected by flow cytometry staining with carboxyfluorescein diacetate succinimidyl ester. RESULTS: Compared with controls, DC-SIGN expression was significantly increased in IECs from patients with Crohn's disease (P < 0.01) or ulcerative colitis (P < 0.05). DC-SIGN expression was strongly correlated with disease severity in IBD (r = 0.48; P < 0.05). Similarly, in the DSS-induced colitis mouse model, IECs showed upregulated expression of DC-SIGN, CD80, CD86 and MHC, and DC-SIGN expression was positively correlated with disease activity (r = 0.62: P < 0.01). IECs from mouse colitis stimulated naïve T cells to generate IL-4 (P < 0.05). Otherwise, dendritic cells promoted a T-helper-1-skewing phenotype by stimulating IFN-γ secretion. However, DC-SIGN expression and T cell differentiation were suppressed following treatment of mice with DSS-induced colitis with PsL-EGFmAb. The proliferation cycles of CD4(+) T cells from mice with DSS-induced colitis appeared as five cycles, which was more than in the control and treated groups. These results suggest that IECs can promote T cell proliferation. CONCLUSION: IECs regulate tissue-associated immune compartments under the control of DC-SIGN in IBD.

Role of DC-SIGN in Helicobacter pylori infection of gastrointestinal cells.

H. pylori causes gastritis and increases the risk of gastric ulcer and gastric cancer. However, it was recently shown that H. pylori provides protection against inflammatory bowel diseases. To assess the molecular mechanism of such functions, we studied the role of DC-SIGN in H. pylori-infected gastrointestinal epithelial cells. DC-SIGN was found to be over-expressed in the gastric epithelial cells infected with H. pylori and mediated Th1 differentiation, which may be involved in H. pylori-induced gastric mucosal injury. In addition, DC-SIGN was also up-regulated in the intestinal epithelial cells derived from colitis mouse model, but the expression levels were blocked upon H. pylori infection, indicating that H. pylori infection may reduce both local and systemic inflammatory responses. In conclusion, we propose that gastrointestinal epithelial cells infected with H. pylori may lead to acquiring of immune properties via a trans-differentiation process, and regulate tissue-associated immune compartments under the control of DC-SIGN.

[The research on two different algorithms used in generating MLC fields of IMRT plan].

PURPOSE: To validate that DMPO model for "one step" algorithm can reduce the total MLC segments number, we compare the dosage distribution of "one-step" algorithm with "two-step" algorithm for generating IMRT MLC segments. METHODS: On the platform of "Pinnacle 8.0h" version radiation treatment planning system developed by Philips, we respectively select one head and neck tumor case, one thorax tumor case and one abdomen tumor case, by means of designing seven fields IMRT planning, then utilized "one-step" algorithm and "two-step" algorithm to optimize and generate IMRT MLC segments, and then calculated dosage distribution, evaluated dosage distribution lines and DVH diagram, in order to compare the two MLC segment groups generated by the two different algorithm. RESULT: For the three IMRT plans selected by us, the number of MLC segments generated by "two-step" algorithm appear to be larger than "one-step" algorithm but dosage distribution seems to be worse than the latter. DISCUSSION: For utilizing the "Pinnacle" plan system to design IMRT plan, "one-step" algorithm with "DMPO" definitely can effectively reduce the number of MLC segments, what's more, the result of dosage distribution seems to be better.