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Diseases of bile duct in children

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World Journal of Gastroenterology 2024年第9期30卷 1043-1072页

作者： Sutha Eiamkulbutr Chomchanat Tubjareon Anapat Sanpavat Teerasak Phewplung Nimmita Srisan Palittiya Sintusek Department of Pediatrics King Chulalongkorn Memorial HospitalBangkok 10330Thailand Department of Pediatrics Faculty of MedicineChulalongkorn University and King Chulalongkorn Memorial HospitalBangkok 10330Thailand Department of Pathology Chulalongkorn UniversityBangkok 10330Thailand Department of Radiology Chulalongkorn UniversityBangkok 10330Thailand Department of Surgery Faculty of MedicineChulalongkorn University and King Chulalongkorn Memorial HospitalBangkok 10330Thailand Center of Excellence in Thai Pediatric Gastroenterology Hepatology and ImmunologyDivision of GastroenterologyDepartment of PediatricsKing Chulalongkorn Memorial HospitalChulalongkorn UniversityBangkok 10330Thailand

Several diseases originate from bile duct pathology.Despite studies on these diseases,certain etiologies of some of them still cannot be concluded.The most common disease of the bile duct in newborns is biliary atresia,whose prognosis varies according to the age of surgical correction.Other diseases such as Alagille syndrome,inspissated bile duct syndrome,and choledochal cysts are also time-sensitive because they can cause severe liver damage due to obstruction.The majority of these diseases present with cholestatic jaundice in the newborn or infant period,which is quite difficult to differentiate regarding clinical acumen and initial investigations.Intraoperative cholangiography is potentially necessary to make an accurate diagnosis,and further treatment will be performed synchronously or planned as findings suggest.This article provides a concise review of bile duct diseases,with interesting cases.

关键词： Bile duct Cholestasis Biliary atresia Biliary hypoplasia Biliary imaging Inspissated bile syndrome Choledochal cyst

Prevalence of gastroesophageal reflux disease in children with extraesophageal manifestations using combined-video,multichannel intraluminal impedance-pH study

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World Journal of Clinical Pediatrics 2023年第3期12卷 151-161页

作者： Sutha Eiamkulbutr Termpong Dumrisilp Anapat Sanpavat Palittiya Sintusek Department of Pediatrics King Chulalongkorn Memorial HospitalBangkok 10330Thailand Department of Pediatrics Bhumibol Adulyadej HospitalBangkok 10220Thailand Department of Pathology Chulalongkorn UniversityBangkok 10330Thailand Thai Pediatric Gastroenterology Hepatology and Immunology Research UnitKing Chulalongkorn Memorial HospitalFaculty of MedicineChulalongkorn UniversityBangkok 10330Thailand

BACKGROUND Gastroesophageal reflux disease(GERD)might be either a cause or comorbidity in children with extraesophageal problems especially as refractory respiratory symptoms,without any best methods or criterion for diagnosing it in children.AIM To evaluate the prevalence of extraesophageal GERD using conventional and combined-video,multichannel intraluminal impedance-pH(MII-pH),and to propose novel diagnostic parameters.METHODS The study was conducted among children suspected of extraesophageal GERD at King Chulalongkorn Memorial Hospital between 2019 and 2022.The children underwent conventional and/or combined-video MII-pH.The potential parameters were assessed and receiver operating characteristic was used for the significant parameters.RESULTS Of 51 patients(52.9%males),aged 2.24 years were recruited.The common problems were cough,recurrent pneumonia,and hypersecretion.Using MII-pH,35.3%of the children were diagnosed with GERD by reflux index(31.4%),total reflux events(3.9%),and symptom indices(9.8%)with higher symptom recorded in the GERD group(94 vs 171,P=0.033).In the video monitoring group(n=17),there were more symptoms recorded(120 vs 220,P=0.062)and more GERD(11.8%vs 29.4%,P=0.398)by symptom indices.Longest reflux time and mean nocturnal baseline impedance were significant parameters for diagnosis with receiver operating characteristic areas of 0.907(P=0.001)and 0.726(P=0.014).CONCLUSION The prevalence of extraesophageal GERD in children was not high as expected.The diagnostic yield of symptom indices increased using video monitoring.Long reflux time and mean nocturnal baseline impedance are novel parameters that should be integrated into the GERD diagnostic criteria in children.

关键词： Extraesophageal reflux pH-impedance Children Gastroesophageal reflux Mean nocturnal baseline impedance

Liver tumors in children with chronic liver diseases

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World Journal of Gastrointestinal Oncology 2021年第11期13卷 1680-1695页

作者： Palittiya Sintusek Teerasak Phewplung Anapat Sanpavat Yong Poovorawan Thai Pediatric Gastroenterology Hepatology and Immunology Research UnitDepartment of PediatricsDivision of GastroenterologyFaculty of MedicineKing Chulalongkorn Memorial HospitalChulalongkorn UniversityBangkok 10330Thailand Department of Radiology Faculty of MedicineChulalongkorn UniversityKing Chulalongkorn Memorial HospitalBangkok 10330Thailand Department of Pathology Faculty of MedicineChulalongkorn UniversityBangkok 10330Thailand Center of Excellence in Clinical Virology Chulalongkorn UniversityBangkok 10330Thailand

Liver tumors are rare in children,but the incidence may increase in some circumstances and particularly in chronic liver diseases.Most liver tumors consequent to chronic liver diseases are malignant hepatocellular carcinoma.Other liver tumors include hepatoblastoma,focal nodular hyperplasia,adenoma,pseudotumor,and nodular regenerative hyperplasia.Screening of suspected cases is beneficial.Imaging and surrogate markers of alpha-fetoprotein are used initially as noninvasive tools for surveillance.However,liver biopsy for histopathology evaluation might be necessary for patients with inconclusive findings.Once the malignant liver tumor is detected in children with cirrhosis,liver transplantation is currently considered the preferred option and achieves favorable outcomes.Based on the current evidence,this review focuses on liver tumors with underlying chronic liver disease,their epidemiology,pathogenesis,early recognition,and effective management.

关键词： Liver tumor Chronic liver disease Children Hepatocellular carcinoma Liver cancer Liver neoplasm

Unremitting diarrhoea in a girl diagnosed anti-N-methyl-D-aspartatereceptor encephalitis:A case report

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World Journal of Clinical Cases 2020年第20期8卷 4866-4875页

作者： Norrapat Onpoaree Montida Veeravigrom Anapat Sanpavat Narissara Suratannon Palittiya Sintusek Faculty of Medicine Chulalongkorn UniversityBangkok 10330Thailand Division of Neurology Department of PediatricsFaculty of MedicineChulalongkorn UniversityBangkok 10330Thailand Division of Pathology Faculty of MedicineChulalongkorn UniversityBangkok 10330Thailand Division of Allergy Department of PediatricsFaculty of MedicineChulalongkorn UniversityBangkok 10330Thailand Division of Gastroenterology and Pediatric Gastroenterology and Hepatology Research Unit Department of PediatricsFaculty of MedicineChulalongkorn UniversityBangkok 10330Thailand

BACKGROUND Asymptomatic cytomegalovirus(CMV)infection is common in children;in contrast,in children with a weakened immune system,invasive CMV can occur.This is the first case report of a severe manifestation of CMV esophagoenterocolitis in a girl diagnosed with anti-N-methyl-D-aspartate-receptor(antiNMDAR)encephalitis who received only a moderate dose of corticosteroid therapy.CASE SUMMARY A 12-year-old-Thai girl presented with acute behavioural change and headache for 6 d.Electroencephalogram and positivity for NMDAR autoantibodies were compatible with anti-NMDAR encephalitis.Hence,she received pulse methylprednisolone 10 mg/kg per day for 4 d and continued with prednisolone 1.2 mg/kg per day.On day 42 of corticosteroid therapy,she developed unremitting vomiting and diarrhoea.Endoscopy showed multiple ulcers and erythaematous mucosa along the gastrointestinal tract.Tissue CMV viral load and viral-infected cells confirmed CMV esophago-enterocolitis.Therefore,the patient received ganciclovir 5 mg/kg per dose every 12 h for 3 wk and then 5 mg/kg per dose once daily for 3 wk.Unremitting diarrhoea slowly improved from stool output 1-4 L per day to 1-2 L per day after 3 wk of treatment.Pulse methylprednisolone 20 mg/kg for 5 d was initiated and continued with prednisolone 1 mg/kg per day.After this repeated pulse methylprednisolone treatment,surprisingly,diarrhoea subsided.Immunologic work-up was performed to rule out underlying immune deficiency with unremarkable results.CONCLUSION Unremitting diarrhoea from CMV esophago-enterocolitis subsided with antiviral and methylprednisolone therapy,implying the immune and NMDAR dysregulation in anti-NMDAR encephalitis.

关键词： Diarrhoea Vomiting Autoimmune encephalitis Children Cytomegalovirus Gastrointestinal Case report

Delta-like ligand 4 in hepatocellular carcinoma intrinsically promotes tumour growth and suppresses hepatitis B virus replication

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World Journal of Gastroenterology 2018年第34期24卷 3861-3870页

作者： Areerat Kunanopparat Jiraphorn Issara-Amphorn Asada Leelahavanichkul Anapat Sanpavat Suthiluk Patumraj Pisit Tangkijvanich Tanapat Palaga Nattiya Hirankarn Center of Excellence in Immunology and Immune Mediated Diseases Department of Microbiology Faculty of Medicine Chulalongkorn University Department of Pathology Faculty of Medicine Chulalongkorn University Center of Excellence for Microcirculation Department of Physiology Faculty of Medicine Chulalongkorn University Research Unit of Hepatitis and Liver Cancer Department of Biochemistry Faculty of Medicine Chulalongkorn University Department of Microbiology Faculty of Science Chulalongkorn University

AIM To investigate the role of Delta-like ligand 4(DLL4) on tumour growth in hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC) in vivo.METHODS We suppressed DLL4 expression in an HBV expressing HCC cell line, HepG2.2.15 and analysed the growth ability of cells as subcutaneous tumours in nude mice. The expression of tumour angiogenesis regulators, VEGF-A and VEGF-R2 in tumour xenografts were examined by western blotting. The tumour proliferation and neovasculature were examined by immunohistochemistry. The viral replication and viral protein expression were measured by quantitative PCR and western blotting, respectively.RESULTS Eighteen days after implantation, tumour volume in mice implanted with sh DLL4 HepG2.2.15 was significantly smaller than in mice implanted with control HepG2.2.15(P < 0.0001). The levels of angiogenesis regulators, VEGF-A and VEGF-R2 were significantly decreased in implanted tumours with suppressed DLL4 compared with the control group(P < 0.001 and P < 0.05, respectively). Furthermore, the suppression of DLL4 expression in tumour cells reduced cell proliferation and the formation of new blood vessels in tumours. Unexpectedly, increased viral replication was observed after suppression of DLL4 in the tumours.CONCLUSION This study demonstrates that DLL4 is important in regulating the tumour growth of HBV-associated HCC as well as the neovascularization and suppression of HBV replication.

关键词： hepatocellular carcinoma Notch signalling Delta-like ligand 4 HepG2.2.15

Pediatric liver transplantation outcomes from a single center in Thailand

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World Journal of Hepatology 2022年第3期14卷 583-591页

作者： Sittichoke Prachuapthunyachart Palittiya Sintusek Chomchanat Tubjareon Nataruks Chaijitraruch Anapat Sanpavat Teerasak Phewplung Piyaporn Wanawongsawad Ai-lada Intrarakamhang Voranush Chongsrisawat Department of Pediatrics Faculty of MedicineChulalongkorn University and King Chulalongkorn Memorial HospitalBangkok 10330Thailand Thai Pediatric Gastroenterology Hepatology and Immunology Research UnitDepartment of PediatricsFaculty of MedicineKing Chulalongkorn Memorial HospitalThai Red CrossChulalongkorn UniversityBangkok 10330Thailand Excellence Center of Organ Transplantation King Chulalongkorn Memorial HospitalBangkok 10330Thailand Department of Pathology Faculty of MedicineChulalongkorn University and King Chulalongkorn Memorial HospitalBangkok 10330Thailand Department of Radiology Faculty of MedicineChulalongkorn University and King Chulalongkorn Memorial HospitalBangkok 10330Thailand

BACKGROUND Liver transplantation(LT)has become an acceptable curative method for children with several liver diseases,especially irreversible acute liver failure and chronic liver diseases.King Chulalongkorn Memorial Hospital is one of Thailand’s largest liver transplant centers and is responsible for many pediatric cases.AIM To report the experience with pediatric LT and evaluate outcomes of livingrelated vs deceased-donor grafts.METHODS This evaluation included children who underwent LT between August 2004 and November 2019.Data were retrospectively reviewed,including demographics,diagnoses,laboratory values of donors and recipients,the pediatric end-stage liver disease(PELD)or model for end-stage liver disease(MELD)score,graft source,wait time,perioperative course,postoperative complications,and survival rates.Continuous data were reported using the median and interquartile range.The Mann–Whitney U-test was used to compare the wait time between the living-related and deceased-donor groups.The chi-square or Fisher's exact test were used to compare the frequencies of between-group complications.Survival rates were calculated using the Kaplan–Meier method.RESULTS Ninety-four operated pediatric liver transplant patients were identified(54%were females).The median age at transplantation was 1.2(0.8-3.8)years.The median PELD and MELD scores were 20(13-26.8)and 19.5(15.8-26.3),respectively.Most grafts(81.9%)were obtained from living-related donors.The median wait time for the living donors was significantly shorter compared with the deceased donors at 1.6(0.3-3.1)mo vs 11.2(2.1-33.3)mo(P=0.01).Most patients were diagnosed with biliary atresia(74.5%),and infection was the most common complication within 30 d posttransplantation(14.9%).Without a desensitization protocol,9%of transplants were ABOincompatible.Eight hepatitis B core antibodies(anti-HBc)-negative recipients received positive anti-HBc grafts without different observed complications.The overall survival rate was 93.6%and 90.3%at 1 and 5 years,respectively.No

关键词： Pediatric Liver transplantation Living-donor Hepatitis B ABO-incompatible Survival

Detection of reflux-symptom association in children with esophageal atresia by video-pH-impedance study

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World Journal of Gastroenterology 2020年第28期26卷 4159-4169页

作者： Settachote Maholarnkij Anapat Sanpavat Katawaetee Decharun Termpong Dumrisilp Chomchanat Tubjareon Benjawan Kanghom Tanisa Patcharatrakul Nataruks Chaijitraruch Voranush Chongsrisawat Palittiya Sintusek Department of Pediatrics King Chulalongkorn Memorial Hospital and Faculty of MedicineChulalongkorn UniversityBangkok 10330Thailand Division of Pathology King Chulalongkorn Memorial HospitalFaculty of MedicineChulalongkorn UniversityBangkok 10330Thailand Division of Pediatric Surgery King Chulalongkorn Memorial HospitalFaculty of MedicineChulalongkorn UniversityBangkok 10330Thailand Division of Gastroenterology and Pediatric Gastroenterology and Hepatology STAR(Special Task Force for Activating Research)Department of PediatricsKing Chulalongkorn Memorial Hospital and Faculty of MedicineChulalongkorn UniversityBangkok 10330Thailand Division of Gastroenterology Department of PediatricsKing Chulalongkorn Memorial HospitalFaculty of MedicineChulalongkorn UniversityBangkok 10330Thailand Center of Excellence in Neurogastroenterology and Motility Department of GastroenterologyFaculty of MedicineChulalongkorn UniversityBangkok 10330Thailand Division of Gastroenterology Department of MedicineFaculty of MedicineKing Chulalongkorn Memorial HospitalBangkok 10330Thailand

BACKGROUND Children with esophageal atresia(EA)have risk of gastroesophageal reflux disease(GERD),suggesting reflux monitoring for prompt management.AIM To evaluate GERD in children with EA and specific symptom association from combined Video with Multichannel Intraluminal Impedance and pH(MII-pH)study.METHODS Children diagnosed with EA with suspected GERD and followed up at King Chulalongkorn Memorial Hospital between January 2000 and December 2018 were prospectively studied.All underwent esophagogastroduodenoscopy with esophageal biopsy and Video MII-pH study on the same day.Symptoms of GERD which included both esophageal and extra-esophageal symptom were recorded from video monitoring and abnormal reflux from MII-pH study based on the statement from the European Paediatric Impedance Group.Prevalence of GERD was also reported by using histopathology as a gold standard.Endoscopic appearance was recorded using Los Angeles Classification and esophagitis severity was graded using Esohisto criteria.RESULTS Fifteen children were recruited with age of 3.1(2.2,9.8)years(40%,male)and the common type was C(93.3%).The symptoms recorded were cough(75.2%),vomiting(15.2%),irritability or unexplained crying(7.6%)and dysphagia(1.9%)with the symptom-reflux association of 45.7%,89%,71%and 0%,respectively.There were abnormal endoscopic appearance in 52.9%,esophagitis in 64.7%and high reflux score in 47.1%.Video MII-pH study has high diagnostic value with the sensitivity,specificity and accuracy of 72.7%,100%and 82.4%,respectively.CONCLUSION Prevalence of GERD in children with EA was high.Video MII-pH study to detect GERD in children with EA had high diagnostic value with the trend of specific symptom association.

关键词： Gastroesophageal reflux disease Esophageal atresia Children Impedance pH study Video Symptom association