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Background/purpose: Limited studies have addressed the exacerbation of symptoms and long COVID in inflammatory bowel disease (IBD) patients following non-severe COVID-19 infection, particularly with post-COVID-19 vaccination. We aim to investigate factors associated with exacerbated gastrointestinal symptoms (EGS) and long COVID in IBD patients with non-severe COVID-19, which is most common situation in daily practice. Methods: This is an observational study by multiple centers in Taiwan from May 2020 to March 2023. We collected clinical manifestation, data, and medication information from IBD patients with non-severe COVID-19. EGS was defined as increased frequency of diarrhea, bloody stool, and abdomen pain within 14 days after SARS-COV-2 infection. Long COVID was defined following the guidelines of the World Health Organization. Results: Out of 90 patients, most of them (88.9%) received at least standard two doses of COVID-19 vaccination and the majority (87.8%) were mild diseases of COVID-19.30% of patients experienced EGS during COVID-19 with higher ESR levels serving as a predictive factor (Odds ratio: 3.6, 95% confidence interval: 1.2–10.5, P = 0.02). 38.1% of those patients developed long COVID. The patients who experienced EGS during COVID-19 and with a history of longer IBD duration showed a significant association with long COVID (p = 0.03 and p = 0.02). Conclusion: Our study revealed that EGS and long COVID occurred in one third of IBD patients with non-severe COVID-19, even though most of them had received the standard plus booster vaccination. We identified associated factors for EGS and long COVID, emphasizing the importance of post-COVID-19 follow-up in IBD patients.

Background/Purpose: We investigated the diagnostic performance of the anal sphincter relaxation integral (ASRI) for infants with Hirschsprung's disease (HD). Methods: We performed water-perfused high-resolution anorectal manometry (HRAM) in 18 infants (9 with HD), and solid-state HRAM in another 18 infants (4 with HD). We calculated the ASRI during the rectoanal inhibitory reflex (RAIR) maneuver at pressure cutoffs of

Background/Purpose: Peroral endoscopic myotomy (POEM), a novel minimally invasive treatment for esophageal achalasia, has been shown to be effective and safe for both adult and pediatric patients. However, studies on its application in children in Taiwan and its impact on growth and esophageal motility are lacking. Methods: We conducted a retrospective study on consecutive pediatric patients who were diagnosed with esophageal achalasia at National Taiwan University Hospital and underwent POEM during 2015–2022. Disease characteristics and treatment outcomes were analyzed. Results: Ten patients (age 16.9 ± 3.1 years), nine newly diagnosed and one previously treated with pneumatic dilatation, underwent POEM for achalasia (type I/II/III: 3/7/0). Average symptom duration before diagnosis was 19.4 ± 19.9 months, mean POEM procedure time was 83.6 ± 30.7 min, and clinical success (Eckardt score ≤3) was achieved in all patients. Eight patients experienced mild adverse events during POEM, but none required further endoscopic or surgical intervention. Over a mean follow-up period of 3.7 ± 1.6 years, mean Eckardt score decreased significantly from 5.7 ± 2.4 to 1.1 ± 0.7 (p = 0.0001). The BMI z-score also increased significantly after POEM (p = 0.023). Five patients received follow-up high-resolution impedance manometry (HRIM), and all had improved lower esophageal sphincter resting pressures (p = 0.011), body contractility, and bolus transit (p = 0.019). Conclusion: POEM is an effective and safe treatment for pediatric achalasia in Taiwan. Early diagnosis and treatment with POEM may help to restore esophageal function and nutrition status in children.

Background/purpose: This study aimed to explore the anatomical and physiological characteristics of patients with laryngopharyngeal reflux (LPR) symptoms, such as hoarseness, throat clearing, throat pain, globus, and chronic cough, with the novel high-resolution impedance manometry (HRIM). Methods: Consecutive patients exhibited at least one LPR symptom for ≥4 weeks after 2-month proton-pump inhibitor treatment were enrolled during November 2014 and March 2018 from single tertiary medical center. All patients completed validated symptom questionnaires, esophagogastroduodenoscopy, and HRIM. Healthy volunteers were also recruited for comparison of esophageal parameters on HRIM. Results: Eighty-nine LPR patients and 63 healthy volunteers were analyzed. Compared with healthy volunteers, LPR patients had significantly shorter upper and lower esophageal sphincters (UES and LES), a shorter intraabdominal esophagus (all P

Background/Objective: Peroral endoscopic myotomy (POEM), a novel minimally invasive treatment for esophageal achalasia, is becoming more popular globally because of its efficacy and safety. We aimed to clarify the technical concerns, efficacy, and safety of POEM for treating esophageal achalasia in Taiwan. Methods: We conducted a retrospective study on consecutive patients with achalasia who underwent POEM between October 2016 and May 2021 at three medical centers in Taiwan. All patients underwent a comprehensive work-up before POEM, including symptom questionnaires, esophagogastroduodenoscopy, timed barium esophagogram (TBE), and high-resolution impedance manometry (HRIM), and were re-evaluated three months after POEM. We compared procedure variables, adverse events, and clinical responses, including Eckardt score ≤3 and TBE and HRIM findings. Results: We analyzed 92 patients in total (54 men; mean age 49.5 years [range: 20–87]; type I/II/III/unclassified: 24/51/1/16). The mean POEM procedure duration was 89.5 ± 38.2 min, though it was significantly longer in patients with prior treatment or sigmoid-type achalasia. In total, 91 patients (98.9%) showed immediate technical success, and the overall clinical success rate at three months after POEM was 95.7%. Nearly 60% of patients experienced adverse events during POEM, but most of these were mild and none required further endoscopic or surgical intervention. During a follow-up period of up to five years (median 25 months), only four patients (4.3%) showed symptomatic recurrence, but none required further treatment. Conclusion: POEM is a very effective and safe treatment for Taiwanese patients with achalasia, irrespective of their achalasia subtype or prior treatment failure.

Background/purpose: Helicobacter pylori infection is one of the most common causes of peptic ulcer disease among children. This study is aimed to investigate the eradication rate of 14-day sequential therapy and the antibiotic resistance of H. pylori in children. Methods: Eighty-seven treatment-naïve children (55 males; median age, 13.5 years) with H. pylori infection from January 2009 to August 2019 were recruited in this study. The status of H. pylori infection was confirmed by culture or histology with the aid of urea rapid test or C-13 urea breathe test. Patients treated with either triple therapy for 7 days or 14 days, or sequential therapy for 14 days was analyzed retrospectively. Results: Thirty-eight (43.7%) patients received 14-day sequential therapy, 24 (27.6%) patients received 14-day triple therapy and the remaining 25 (28.7%) patients received 7-day triple therapy. The eradication rate of 14-day sequential therapy was significantly superior to 7-day triple therapy (97.4% vs. 80%, p = 0.032), and tended to be better than 14-day triple therapy (83%, p = 0.07). Of the 54 patients with available antibiotic resistance data, the resistant rate of clarithromycin, metronidazole, levofloxacin, and amoxicillin were 22.2%, 16.7%, 9.1% and 2.2%, respectively. Clarithromycin resistance demonstrated an inverse association with eradication success (Odds ratio = 0.017, p

Background/purpose: Anastomotic stricture (AS) is a major morbidity of patients with esophageal atresia (EA) after surgical reconstruction. Our study determined the risk factors of AS after EA reconstruction. The therapeutic efficacy and complications of esophageal dilatation for children with AS were also evaluated. Methods: Forty children treated for EA between January 2008 and December 2018 were included in this retrospective analysis. Esophageal dilatation was performed when AS was diagnosed. The therapeutic effect of esophageal dilatation was determined based on nutritional status, as assessed by the weight-for-age z-score. Results: Sixteen EA patients developed AS. A gap >1.5 cm between the esophageal pouches (P = 0.02) in patients with EA and type A EA was a risk factor for developing AS. A mean of 7.7 sessions of esophageal dilatation were performed per patient, and no complications occurred. The nutritional status of EA children with AS after dilatation was not inferior to that of the children without AS at the 6-month follow-up. Conclusion: A gap >1.5 cm between the esophageal pouches and type A EA are risk factors for AS after esophageal reconstruction. Esophageal dilatation is both safe and effective for managing strictures and improves nutritional status in EA children with AS.

Background/purpose: To investigate the role of microRNA (miRNA) dysregulation in liver cancer by assessing the miRNA profiles of human hepatic stem cells (HpSCs), marker-carrying human hepatoblastoma (HB) cells, and hepatocellular carcinoma (HCC) cells vs. those of fetal hepatocytes. Methods: We subjected human HCC and HB tumor specimens to immunohistochemical (IHC) staining for markers of HpSCs. We analyzed the miRNA patterns of HpSCs, HCC cells, HB cells, and fetal hepatocytes using microarray analysis, with confirmation via quantitative real-time polymerase chain reaction. The roles of the miRNAs in liver cancer stem cells (CSCs) were also elucidated. Results: The epithelial cell adhesion molecule (EpCAM) was the most prevalent HpSCs marker in human HB and HCC tumor cells and hepatoma cells. EpCAM-positive HB and HCC cells exhibited greater self-renewal and tumorigenicity than their EpCAM-negative counterparts or EpCAM-positive fetal hepatocytes. In EpCAM-positive fetal hepatocytes, miR-126 expression level increased with gestational age. The EpCAM-positive HB cells exhibited downregulation of miR-126 in comparison to EpCAM-positive fetal hepatocytes. An miR-126 mimic reduced sphere and colony formation in, and induced apoptosis of, HB cells. In comparison to EpCAM-positive fetal hepatocytes, EpCAM-positive HCC cells exhibited downregulation of miR-126, miR-144, and miR-451. Transfection of miR-126, miR-144, and miR-451 induced apoptosis of, and reduced sphere and colony formation in, HCC cells. Conclusion: Dysregulation of liver developmental miRNAs, which exert a tumor suppressant effect, in EpCAM-positive HpSCs may contribute to liver carcinogenesis by promoting the transformation of HpSCs to CSCs of HB and HCC.

Background/purpose: One-man method had shown several advantages over two-man method in adult colonoscopy insertion. However, whether this advantage can be extended to children is largely unknown. The aim of this study is to test the hypothesis that one-man method is the preferred method to two-man method in pediatric colonoscopy. Methods: In this retrospective study, from July 2010 to June 2014, colonoscopy examinations in children were recruited. These colonoscopy examinations were performed by second-year pediatric GI fellows under the supervision of an experienced attending physician. Colonoscopy indicators such as cecal intubation rate (CIR), cecal intubation time (CIT), and terminal ileum (TI) intubation rate between one-man and two-man method group were recorded. The primary outcome is CIR. Results: Total 72 colonoscopy examinations by one-man method and 162 examinations by two-man method were studied. Univariate logistic regression showed two patient factors: poor preparation and underweight were associated with lower CIR. (Odds ratio, OR: 0.46 and 0.40, P = 0.046 and 0.01, respectively) The CIR was higher in one-man than in two-man method group (81.9% vs 69.1%, OR = 2.03, P = 0.04). One-man method had a higher TI intubation rate than that of two-man method. (66.7% vs 44.4%, OR = 2.51, P = 0.002) The mean CIT was 27.1 ± 11.7 min in one-man method and 26.9 ± 13.3 min in two-man method. (P = 0.93) No significant difference in complications was noted. Conclusion: One-man method colonoscopy is safe and has higher CIR and TI intubation rate than two-man method colonoscopy in children, even performed by second-year GI fellows. Keywords: Colonoscopy, One-man method, Pediatrics

Background/Purpose: The study aim to investigate the correlation between diffusion-weighted magnetic resonance imaging (DW-MRI) and transient elastography (TE) liver fibrosis findings in children with cholestatic liver diseases, and the utility of TE findings to predict cholestatic complications in children. Methods: This cross-sectional study enrolled 36 cholestatic children (21 boys and 15 girls). All study subjects underwent TE and DW-MRI studies to assess liver stiffness. All study subjects were followed prospectively, and their cholestatic complications were analyzed. The optimum cut-off TE value for the prediction of cholestatic complications was determined by receiver operating characteristic (ROC) analysis. Results: A significant negative correlation between liver stiffness measurements (LSMs) and right-liver-to-psoas apparent diffusion coefficient ratios (LTPARs) was found in the study cohort (correlation coefficient = −0.52, p = 0.001). An LSM cut-off > 8.6 kPa was optimal for predicting complications of cholestasis in 6 months of this cohort (p 8.6 kPa was significantly predictive of cholestatic complications in 6 months (hazard ratio = 4.89; 95% CI = 1.41–16.97; p = 0.01). Conclusion: TE and DW-MRI findings showed a similar ability to predict liver fibrosis in cholestatic children. The LSMs measured by TE are predictive of the occurrence of cholestatic complications in 6 months in children with cholestatic liver diseases. Keywords: Liver fibrosis, Diffusion-weighted magnetic resonance imaging, Transient elastography, Liver stiffness measurement

Background: Post-transplantation lymphoproliferative disorder (PTLD) is a heterogeneous, potentially life-threatening complication after liver transplantation in children. In this study, the disease characteristics, outcomes, and prognostic factors of PTLD were investigated. Methods: A retrospective, observational study was conducted on 16 pediatric liver transplant (LT) recipients who developed PTLD between February 2001 and December 2013 at a tertiary referral center in Taiwan. The disease characteristics and treatment outcomes of the patients were analyzed. Results: The median time from liver transplantation to the development of PTLD was 8 months. Early onset (

Background: Esophageal motility disorders are the major cause of non-obstructive dysphagia (NOD), but may be underdiagnosed. In this high-resolution impedance manometry (HRIM)-based study, we aimed to clarify the etiologies and clinical characteristics of patients presenting with NOD in a Taiwanese population. Methods: From October 2014 to July 2017, consecutive patients with the chief complaint of dysphagia were prospectively enrolled in the study at a tertiary medical center. All subjects underwent a comprehensive diagnostic work-up, which included validated symptom questionnaires, esophagogastroduodenoscopy, timed barium esophagogram, and HRIM. Those with obstructive esophageal lesions were excluded. Esophageal motility disorders were diagnosed using the updated Chicago Classification v3.0. We categorized all patients based on the HRIM results, and compared the clinical characteristics and parameters between groups. Results: A total of 120 patients (55 men; mean age [range], 52 [13–87] years) were analyzed. Achalasia was the most common diagnosis by HRIM (n = 66, 55%), followed by ineffective esophageal motility (n = 15, 12.5%), and absent contractility (n = 6, 5%). Patients with achalasia experienced increased vomiting (62.1% vs. 31.5%, p = 0.001), significant weight loss (22.7% vs. 7.4%, p = 0.025), delayed esophageal emptying (90.9% vs. 12.9%, p

Background/Purpose: This study is aimed to investigate the risk factors and clinical characteristics of posttransplant lymphoproliferative disorder (PTLD) after conducting Epstein–Barr virus (EBV) viral load monitoring in pediatric liver transplant (LT) patients in Taiwan, where EBV infection is endemic. Methods: From 2007 to 2013, pediatric LT recipients who underwent EBV viral load monitoring within 3 months after LT were recruited in this study. The impact of clinical parameters—including age at LT, sex, peak EBV viral load and immunosuppressant levels after LT—on the risk of PTLD were assessed. Results: A total 39 patients underwent LT at a median age of 1.3 years (range: 0.6–14.0 years), and 5 patients developed PTLD during follow-up. Cox's proportional-hazards model identified two predictors of PTLD: peak EBV viral load within 3 months of LT >4100 copies/μg peripheral blood mononuclear cells (PBMC) DNA and peak tacrolimus level within 3 months of LT >14.8 ng/mL (Hazard ratio = 17.14 and 11.54, P = 0.02 and 0.03, respectively). Kaplan–Meier survival analysis revealed significant higher cumulative incidence rates of PTLD (27.3% and 41.8% at 0.3 and 1.2 years after LT) in subjects with peak EBV viral load >4100 copies/μg PBMC DNA within 3 months after LT. (P = 0.001, log-rank test). Conclusion: Close monitoring of EBV viral load within 3 months after LT is helpful to predict a high risk of PTLD. Tapering of immunosuppressants is suggested if the EBV viral load is >4100 copies/μg PBMC DNA in LT children. Keywords: Epstein–Barr virus infections, Liver transplantation, Lymphoproliferative disorders, Pediatrics, Viral load

Background/Purpose: Biliary complications remain a major morbidity after liver transplantation in children. Inadequate arterial supply to the bile duct after transplantation plays an important role in developing anastomotic biliary complications. We aimed to elucidate the relationship between the resistance index (RI) of hepatic artery and the anastomotic biliary complications after liver transplantation in children. Methods: This is a retrospective, case–control design study. We enrolled 11 pediatric patients under 18 years of age with anastomotic biliary complication after liver transplantation and another 26 matched pediatric transplanted patients without biliary complication as the control group. All patients received liver Doppler ultrasonography within 15 months after liver transplantation. We focused on the ultrasound parameters including waveforms, RI and acceleration time (AT) of hepatic artery. Results: We used the receiver operating characteristic curve to analyze the RI in these 37 patients and yielded a cutoff of RI ≦ 0.57 (63.6% sensitivity and 92.3% specificity) for the best prediction of anastomotic biliary complications. Patients with RI ≦ 0.57 have a higher chance of having biliary complications, with an Odds ratio of 21 (95% CI = 3.16–139.66). The Cox's proportional hazard analysis also confirmed the significance of RI ≦ 0.57 in predicting biliary complications (Hazard ratio = 8.11, 95% CI = 2.35–28.01, P = 0.001) after liver transplantation in children. Three (27.3%) patients with biliary complications received hepatojejunostomy reconstruction, and another 8 patients (72.7%) were successfully managed by percutaneous biliary intervention alone. Conclusion: The RI of hepatic artery ≦0.57 may serve as an important non-invasive predictor for anastomotic biliary complications after liver transplantation in children. Keywords: Biliary complication, Children, Doppler ultrasonography, Resistance index

Background/Purpose: This study aimed to investigate the epidemiology, the preference of medication, and the potential outcome of Wilson disease in Taiwan. We aimed to provide better therapeutic options for patients with Wilson disease based on the data generated from this study. Methods: We utilized the National Health Insurance Research Database (NHIRD), which stores clinical records of nearly 99% of Taiwan's residents. The database used is a random sample of two-million out of 23-million beneficiaries in Taiwan's NHIRD in 2005. The integrated medical records of these two-million cases were collected from 2000 to 2011. Subjects of Wilson disease were identified as those with International Classification of Diseases, Ninth Revision (ICD-9) code 275.1 and the specific prescription drugs (including d-penicillamine, zinc, and trientine) in either outpatient clinic or inpatient records. Results: During the study period, 66 cases of Wilson disease were identified. The male to female ratio was 1.75. The average prevalence rate was 1.81 per 100,000 and the average annual diagnosis rate was 0.22 per 100,000. The diagnosis was mostly established at 20–24 and 10–14 years of age, followed by 25–29 years. Fifty four of all subjects (81.8%) started the treatment with d-penicillamine, compared with zinc (12.1%) and trientine (6.1%). Among these 66 cases, 27 (40.9%) had liver cirrhosis and three (4.5%) underwent liver transplantation due to liver failure. Conclusion: d-penicillamine is still the most popular prescription of Wilson disease, followed by zinc monotherapy. Although chronic liver injury cannot be avoided, a favorable potential outcome is well demonstrated in this population-based study. Keywords: Outcome, Taiwan, Therapy, Wilson disease

Primary intestinal lymphangiectasia is a rare disease of children, which is characterized by chronic diarrhea and complicated with malnutrition, including fat-soluble vitamin deficiency. We report a girl aged 4 years and 8 months who was diagnosed with the disease by endoscopic duodenal biopsy at 8 months of age. She presented initially with chronic diarrhea at 4 months of age. Generalized edema with hypoalbuminemia frequently occurred despite regular albumin supplements. Multiple vitamins initially were not supplied regularly. Episodes of tetany caused by hypocalcemia developed 4 years after the diagnosis of intestinal lymphangiectasia. Imaging study (long-bone X-ray and dual-energy X-ray absorptiometry) revealed low bone density. Complicated vitamin D deficiency [low serum 25-hydroxy vitamin D concentration (< 12.48 mmol/L, the detection limit)] and secondary hyperparathyroidism were confirmed via blood testing. Vitamin D supplementation for 3 months improved her bone density, secondary hyperparathyroidism and frequent tetany. Vitamin D status should be monitored in patients with intestinal lymphangiectasia.

Background/purpose: This study aimed to investigate the epidemiology, the preference of medication, and the potential outcome of Wilson disease in Taiwan. We aimed to provide better therapeutic options for patients with Wilson disease based on the data generated from this study.Methods: We utilized the National Health Insurance Research Database (NHIRD), which stores clinical records of nearly 99% of Taiwan's residents. The database used is a random sample of two-million out of 23-million beneficiaries in Taiwan's NHIRD in 2005. The integrated medical records of these two-million cases were collected from 2000 to 2011. Subjects of Wilson disease were identified as those with International Classification of Diseases, Ninth Revision (ICD-9) code 275.1 and the specific prescription drugs (including d-penicillamine, zinc, and trientine) in either outpatient clinic or inpatient records.Results: During the study period, 66 cases of Wilson disease were identified. The male to female ratio was 1.75. The average prevalence rate was 1.81 per 100,000 and the average annual diagnosis rate was 0.22 per 100,000. The diagnosis was mostly established at 20-24 and 10-14 years of age, followed by 25-29 years. Fifty four of all subjects (81.8%) started the treatment with d-penicillamine, compared with zinc (12.1%) and trientine (6.1%). Among these 66 cases, 27 (40.9%) had liver cirrhosis and three (4.5%) underwent liver transplantation due to liver failure.Conclusion: d-penicillamine is still the most popular prescription of Wilson disease, followed by zinc monotherapy. Although chronic liver injury cannot be avoided, a favorable potential outcome is well demonstrated in this population-based study. [ABSTRACT FROM AUTHOR]