Prevalence, Clinical Characteristics, and Management of Functional Constipation at Pediatric Gastroenterology Clinics

The purpose of this study was to investigate the prevalence, clinical characteristics, and management of functional constipation at pediatric gastroenterology clinics. A prospective survey using the Rome III criteria was distributed to a group of parents of children with a constipation history and its control group in May 2008. The mean prevalence of constipation was 6.4%, which was similar to those in other countries. Statistically significant variables for children without constipation were that more children had a body mass index of below the 10th percentile even though they received more mother's care and ate balanced meals compared to the constipation group. Meanwhile, the constipation group frequently showed a history of constipation in infancy, picky-eating, lack of exercise, and retentive posturing. When analyzed with the Rome III criteria, the children showed greater than 60% rate of hard stools, painful stools, a history of large fecal mass in rectum, and its disappearance of constipation symptoms after passing a large stool. Our study found different approaches amongst pediatric gastroenterologists like rectal examinations, disimpaction, or drug treatment. Several factors addressed in our study can provide better guidelines for clinicians treating constipation and its future research.

Gastro-Esophageal Reflux Disease in Healthy Older Children and Adolescents / 대한소아소화기영양학회지

Gastro-esophageal reflux disease (GERD) in otherwise healthy older children and adolescents is commonly encountered in pediatric clinics and poses a complex treatment problem involving changes of diets and lifestyle. After an initial history taking and a physical examination, typical symptoms of GERD in older children and adolescenct are initially treated with the trials of acid suppressants. With an increase of severe cases, more and more GERD children have been evaluated with endoscopy, which helps to delineate an erosive esophagitis from a non-erosive reflux disease as they are presumed to have different pathogenesis. For the pediatric patients without a significant underlying disease, a reflux esophagitis can be treated adequately with acid suppressants. Recently, the rapid increase of children who are taking anti-reflux medication has brought up a serious alarm among pediatricians. Some at risk pediatric patients with recurrent and/or chronic GERD have been linked to adulthood GERD. In this paper, pediatric GERD with and without erosive esophagitis was reviewed along with treatment options and issues specifically for the otherwise healthy older children and adolescents in the primary clinics or the secondary hospitals.

Organic Upper Digestive Diseases in Children with Chronic Abdominal Pain / 대한소아소화기영양학회지

Organic diseases are prevalent in about 5 to 10% of children with chronic abdominal pain. The most common diseases of the upper digestive tract include gastroesophageal reflux disease (GERD), chronic gastritis with or without Helicobacter pylori (H. pylori), and peptic ulcer. The H. pylori infections acquired during childhood persist lifelong without eradication. Although the majority of H. pylori infected children remain asymptomatic, H. pylori infection may cause various digestive and extra-digestive diseases. There are still debates about a causal relationship between H. pylori-gastritis and abdominal symptoms in the absence of peptic ulcer disease. The number of Korean children infected with antibiotic resistant H. pylori is increasing even though the prevalence decreases after eradication. The choices of rescue therapy are limited in children after eradication failure. Antioxidant supplements with regimens against H. pylori have been tried with limited effects. Here I wanted to review the findings of recent reports on common upper digestive diseases such as GERD, peptic ulcer, and H. pylori infection in children with chronic abdominal pain.

Development of a Nutrition Questionnaire and Guidelines for the Korea National Health Screening Program for Infants and Children / 대한소아소화기영양학회지

PURPOSE: A new health policy, referred to as the National Health Screening Program for Infants and Children, was launched in November 2007 by the Ministry of Health and Welfare and National Health Insurance Corporation in Korea. We have developed a nutrition-counseling program that was incorporated into this project. METHODS: We reviewed the nutritional guidelines published by The Korean Pediatric Society and internationally well-known screening programs such as Bright Future in the United States. We also reviewed the recent Korean national surveys on nutritional issues, including the Korea National Health and Nutrition Examination Survey (KNHANES) and the 2005 National Survey of Physical Body and Blood Pressure in Children and Adolescents. The development of questions, pamphlets, computer programs, and manuals for doctors was carried out after several meetings of researchers and governmental officers. RESULTS: We summarized the key nutritional issues according to age, including breastfeeding in infants, healthier complementary feeding, and prevention of iron deficiency anemia, establishment of healthier diets, as well as dietary prevention of overweight children with an emphasis on physical exercise. We have constructed a new Korean nutrition questionnaire and an anticipatory guidance program based on the primary care schedule of visits at 4, 9, 18, 30, and 60 months of age. Five to eight questions were asked at each visit and age-matched pamphlets for parents and guidelines for doctors were provided. CONCLUSION: We developed a nutrition-counseling program based on recent scientific evidence for Korean infants and children. Further research on this national program for screening the nutritional problems in detail and setting the therapeutic approaches may help identify areas of success as well as those that need further attention.

A Case of Herpes simplex Esophagitis in an Immunocompetent Boy / 대한소아소화기영양학회지

Herpes simplex virus has rarely been identified as a cause of esophagitis in immunocompetent children. This virus affects predominantly males presenting with symptoms of fever, odynophagia, dysphagia, and retrosternal pain of acute onset. Esophagoscopy typically reveals exudative well-circumscribed ulcerations of the distal and/or mid-esophagus. Further investigations using biopsy, viral culture, polymerase chain reaction (PCR), and seroconversion of antibodies to Herpes simplex are recommended to assist with a definitive diagnosis. This esophagitis is often a self-limited infection in immunocompetent children. Nevertheless, antiviral treatment may expedite symptom relief with Herpes simplex virus infection. It is imperative to document herpes esophagitis in cases with subsequent severe odynophagia in immunocompetent children. Here we present the case of a 12-year-old immunocompetent boy with herpes esophagitis.

Assessment of the Effectiveness of Biofeedback Therapyin Children with Pelvic Floor Dyssynergia / 대한소아소화기영양학회지

PURPOSE: Recently well-developed anorectal function tests have revealed that there is an obvious pelvic floor dyssynergia (PFD) pattern in pediatric patients with constipation, as well as in adult's. The use of biofeedback therapy (BT) has been widely implemented in adult PFD patients; however, this approach has only rarely been considered for pediatric PFD patients. Therefore, we assessed the effectiveness of BT in children with PFD. METHODS: We studied 70 children with PFD, who were referred to the department of pediatrics at the Asan Medical Center for the management of soiling or chronic constipation from September 2002 to February 2005. Diagnosis of PFD and assessment of the efficacy of BT for PFD treatment were carried out along with several ano-rectal function tests (cine-defecography, ano-rectal manometry, balloon expulsion test and intra-anal EMG); in addition, a questionnaire was administered. The BT based intra-anal EMG was performed. A follow-up telephone interview was performed more than 6 months later. RESULTS: Most of the symptoms and results of the ano-rectal function tests were statistically improved after BT. In comparisons between the BT and control groups (BT refusal group due to poor compliance), the symptoms were statistically improved at follow-up. Therefore, for the short- term improvement of symptoms, BT was better than conservative therapy alone. The negative feelings associated with ano-rectal function testing and BT were directly associated with failure or success of therapy. CONCLUSION: Pediatric patients with constipation or soiling that presented with an obvious PFD pattern showed that BT was a useful therapeutic tool for rapid improvement of symptoms.

Copper Deficient Anemia in Severe Protein-EnergyMalnutrition due to Child Abuse / 대한소아소화기영양학회지

An unconscious 5-year-old girl was admitted to the Intensive Care Unit. She was neglected by her parents; she suffered from inadequate nutritional, medical and emotional care. The girl appeared to be emotionally detached, dehydrated and malnourished; she had edematous extremities, moderately bruised skin and brittle coarse hair. Laboratory testing showed electrolyte imbalance, anemia, pneumonia, copper deficiency, and liver dysfunction in addition to severe protein-energy malnutrition (PEM). Medical intervention was followed by improvement of most of the symptoms. During the rehabilitation phase, the patient showed a voracious appetite and gained weight too fast. The liver became enlarged and the patient developed a mild fever due to excessive nutrition. The microcytic anemia with severe PEM did not responded to iron supplementation possibly due to the copper deficiency. Addition of copper without zinc and iron helped to improve the anemia. The patient was discharged to a childcare center where she received cognitive and psychosocial therapy.

UDP-glucuronosyltransferase 1A1 Gene Polymorphism in Severe Neonatal Hyperbilirubinemia

PURPOSE: TATA box mutation/polymorphism in the promoter region of the bilirubin uridinediphosphoglucuronate glucuronosyltransferase 1A1 (UGT-1A1) gene is known to be an etiology of hyperbilirubinemia. This study examined if a TATA box mutation/polymorphism in UGT-1A1 gene promoter could be associated with the development of severe early neonatal jaundice in Korean infants. METHODS: Thirty-nine neonatal jaundice patients and 40 controlled infants were analyzed for UGT-1A1 promoter genotypes by using DNA sequencing. RESULTS: The homozygote for (TA)7TAA mutation was not found in this study. Comparison of the prevalence of UGT-1A1 promoter (TA)7TAA heterozygotes revealed no difference between the group with jaundice and the controlled group (15.4% vs. 10%). The peak bilirubin level was higher and the onset of jaundice was earlier in the jaundice group with (TA)7TAA heterozygote compared to the jaundice group without (TA)7TAA heterozygote (23.2+/-1.0 mg/dL vs. 19.7+/-2.4 mg/dL, P=0.004, 5.0+/-1.5 days vs. 8.3+/-4.1 days, P= 0.057). CONCLUSION: The results of this study showed that TATA box polymorphism in UGT-1A1 gene promoter did not increase the prevalence of severe early neonatal jaundice in Korean infants.

Efficacy of Nutritional Therapy in Children with Crohn Disease / 대한소아소화기영양학회지

PURPOSE: Crohn disease (CD) in children is frequently complicated by malnutrition and growth retardation. Conventional treatment with corticosteroid may also affect the growth of children, which may be alleviated by nutritional therapy. Therefore, we performed this study to evaluate the role of nutritional therapy in the treatment of CD in children. METHODS: The study cohort consisted of thirty children under the age of 17 years, admitted to the Asan Medical Center from 2001 to 2005. While 11 children received nutritional therapy (NT) with an elemental diet, 19 received conventional corticosteroid therapy (ST). Comparative analysis was performed for the rate of the induction of remission, recurrence, disease activity index of pre and post-treatment, and changes of the growth using mean standard deviation score for weight (zW) and height (zH). RESULTS: Ten of 11 children with NT and 18 of 19 children with ST completed the therapy. Two of them were lost to follow-up during the treatment. All 10 children with NT and 15 of 18 children with ST achieved remission. While there was no recurrence in children with NT, 7 with ST showed recurrence within 1 year. Pre- and post treatment Pediatric Crohn disease Activity Index (PCDAI) did not show a difference between the two groups. There were no differences in zW and zH between the two groups after 1 year of follow-up. CONCLUSION: This study showed that nutritional therapy could be considered instead of steroid therapy for treatment of children with CD. However, a long-term study will be needed to determine the long-term efficacy.

Hemophagocytic Syndrome Presenting as Severe Acute Hepatitis / 대한소아소화기영양학회지

PURPOSE: Hemophagocytic syndrome (HPS) is characterized by persistent high fever, hepatosplenomegaly, cytopenias, hypertriglyceridemia, and/or hypofibrinogenemia. Hepatic manifestations including overt hepatic failure and fulminant hepatitis are common in HPS. Liver transplantation (LT) should be considered in a case of fulminant hepatitis by other than HPS, but LT is contraindicated and complete cure is possible by chemotherapy in HPS. Therefore, we conducted this study to define the characteristics of HPS presenting as severe acute hepatitis. METHODS: Among the total of 23 patients diagnosed as HPS by bone marrow examination between 1994 and 2005 in Asan Medical Center, 11 cases presented as severe acute hepatitis were enrolled in this study. We analyzed the clinical features, laboratory findings and outcome retrospectively. RESULTS: Seven (64%) of the 11 children with HPS and hepatitis were referred to pediatric gastroenterologist at first. The mean age of onset was 50 months. There was no case with family history of primary HPS. Epstein-Barr virus was positive in 4, and herpes Simplex virus was positive simultaneously in 1 case. As the presenting symptoms and signs, fever was present in 10, hepatosplenomagaly was noted in all and jaundice in 10. Anemia was observed in 10, thrombocytopenia in 10, leukopenia in 8, hypertriglyceridemia in 9, hypofibrinogenemia in 8 and hyperferritinemia in 7 cases, respectively. Nine children received chemotherapy including etopside. The overall mortality rate was 72% (8/11). CONCLUSION: HPS, which needs chemotherapy, should be considered as a cause of severe acute hepatitis especially when accompanied with prolonged high fever and cytopenias.

A Case of Gastric Outlet Obstruction Complicated by Peptic Ulcer Secondary to Non-Steroidal Anti-Inflammatory Drug (NSAID) / 대한소아소화기영양학회지

Peptic ulcer disease complicated with gastric outlet obstruction is rare in children. Even though NSAIDs have been reported to cause various adverse events, they are still regarded as safe and, therefore, widely utilized in children. In the past, pediatric patients who were at risk of seizure due to high fever, were treated with dipyrone (Metamizole sodium) injection which inhibits cyclooxygenase-1 and inhibit prostaglandin, to weaken the gastro-duodenal defensive mechanism. A case of an infant with multiple esophagogatroduodenal ulcers and bleeding caused by NSAID complicated with gastric outlet obstruction is reported in this paper.

Long-term Growth of Pediatric Patients Following Living-Donor Liver Transplantation

In order to determine the influence of living donor liver transplantation (LDLT) on long-term growth, we studied the progress of 36 children who had survived more than 5 yr after LDLT from 1994 to 1999. The median age at the transplantation was 1.5 yr (range: 6 months-15 yr) and the median follow-up period was 6.5 yr (range: 5-9 yr). A height standard deviation score (zH) was analyzed for each patient according to medical records. Significant catch-up growth occurred within 2 yr after LDLT with a mean zH changing from -1.2 to 0.0 and was maintained for up to 7 yr post-transplantation (zH-0.1). Younger children (<2 yr) were more growth-retarded at the time of LDLT, but showed higher catch-up growth rates and their final zH was greater than that of older children. Children with liver cirrhosis were more growth-retarded at the time of LDLT, but showed significant catch-up growth and their final height was similar to children with fulminant hepatitis. Growth in children who experienced significant hepatic dysfunction after LDLT was not significantly different from those without graft dysfunction. There was no difference between the types of immunosuppressants used. Our finding suggests that LDLT can result in adequate catchup linear growth, and this effect can persist even after 7 yr post-transplantation.

Allograft Rejection after Liver Transplantation in Children / 대한이식학회지

PURPOSE: We performed this study to assess the clinical course of acute rejection and chronic rejection after liver transplantation in children. METHODS: Seventy-six liver transplantations were performed in 75 children between December 1994 and March 2002. Twenty-five boys and 50 girls were included in this study, and the mean age was 20 months old. We analyzed the incidence, clinical course and outcome of acute and chronic rejection after liver transplantation retrospectively. RESULTS: Forty out of 75 children (53%) experienced 45 episodes of acute rejection, and 32 episodes (71%) of them occurred within 1 month after transplantation. The degree of acute rejection was mild in 16 (36%), moderate in 14 (31%) and severe in 2 (4%) cases. Younger (<2 years old) recipient experienced higher incidence of acute rejection. But there was no association with recipient's sex, ABO matching, type of donor, and the kind of immunosuppressant. All 40 children with acute rejection improved with conventional treatment. There was no significant statistical relation between acute rejection and recipient's survival. Chronic rejection occurred in 7 (9%) children, and 3 of them died of chronic rejection itself but another 3 children improved during the follow-up periods. CONCLUSION: Acute rejection occurred in more than half of the pediatric liver transplantation recipients. Most rejection episodes were mild and occurred within 1 month after transplantation. Acute rejection did not affect the recipient's survival and graft function.

Mucopolysaccharidosis and mucolipidosis / 한양의대학술지

Mucopolysaccharidosis (MPS) and mucolipidosis(ML) belong to a group of rare genetic disorders of lysosomal enzymes and share some clinical manifestations. MPS is characterized by the accumulation of glycosaminoglycans (GAG) and results from the impaired function of one of 11 enzymes required for normal GAG degradation. ML, which is clinically similar to several forms of MPS, is caused by deficiency of Nacetylglucosamine-1-phosphotransferase activity. Therapeutic strategies for MPS, including enzyme replacement therapy and bone marrow transplantation, have been developed with some success. In this review, we discuss clinical feature, diagnostic methods, management and the present status of research on MPS and ML.

Complications of Percutaneous Endoscopic Gastrostomy (PEG) in Children / 대한소아소화기영양학회지

PURPOSE: This study was conducted to identify potential dangers involved in procedure and evaluate complications of percutaneous endoscopic gastrostomy (PEG) comparing to surgical gastrostomy (SG). METHODS: A retrospective study of 66 children with feeding gastrostomy between 1994 and 2002 was done. RESULTS: Of 66 children, 23 (mean age 29 months) had PEG and 43 (mean age 49 months) had SG. 31 cases of SG group had fundoplication for gastroesophageal reflux disease. PEG groups were followed up with an average 13 months and SG groups with 21 months. Major complications occurred in 33% of PEG group (8/23) and 55% of SG group (24/43). Major complications were significantly lower in PEG group than SG group and minor complications, too (p<0.05). Of major complications, aspiration pneumonia was the most common but paralytic ileus was significantly higher in SG group than PEG group. 8 patients died of underlying disease but not related to gastrostomy. Removals of stomata were done in 5 of PEG group and 3 of SG group. GER recurred in 25% of SG group with fundoplication and newly developed in 17% of SG group. GER persisted in 17% and newly developed in 5% of PEG group. CONCLUSION: The gastrostomy was a significant procedure with the potential to produce complications. PEG is recommended as an initial procedure in children requiring a feeding gastrostomy but should be considered a major undertaking.

Living-Related Liver Transplantation with Heterozygote Carrier Graft in Children with Wilson Disease / 대한소아소화기영양학회지

PURPOSE: The purpose of this study was to evaluate the efficiency of treatment of living-related liver transplantation (LRLT) with the parental heterozygote carrier graft in children with Wilson disease. METHODS: We retrospectively evaluated 7 children with Wilson disease who had received liver transplantation from 1994 to 2002 at Asan Medical Center. All the donors were parental. Liver functions, Kayser-Fleischer ring, and other factors regarding to copper metabolism were analyzed. RESULTS: Of the 7 children, 5 had fulminant hepatitis and 2 had decompensated liver cirrhosis irresponsive to medical therapy. All donors being parental, all grafts came to be heterozygote carrier grafts. Survival rate was 100% in those 7 children, 87% in all children with liver transplantation in the same period, and 84% in children with non-metabolic liver disease. After liver transplantation, all 7 children could stop low copper diet and penicillamine therapy and their AST, total bilirubin and prothrombin time were recovered to normal. After liver transplantation, ceruloplasmin and serum copper levels were also recovered to normal. A marked reduction in 24 hr-urinary copper excretion was observed in all recipients after transplantation. During follow-up, Kayser-Fleischer rings resolved completely after LRLT in 5 children and partially in 1 child. CONCLUSION: We concluded that living-related liver tranplantation in children with Wilson disease with parental heterozygote carrier graft is an effective treatment modality.

Venous Complications after Pediatric Liver Transplantation / 대한이식학회지

PURPOSE: We performed this study to assess the incidence of venous complications, including portal vein and hepatic vein stenosis, in both split cadaveric and living donor liver transplants and to assess the diagnostic and therapeutic modalities of these lesions. METHODS: Seventy-six liver transplantations were performed in 75 children with split (5) or living donor (71) graft between December 1994 and March 2002. Patients' data were analyzed retrospectively with special emphasis on venous complications. RESULTS: Venous complications occurred in 14 patients (18.6%) including hepatic vein stenosis in 8, portal vein stenosis in 4, portal vein thrombosis in 1, and combined portal vein thrombosis and hepatic artery stenosis in 1 patient. Venous complications were accompanied by abnormality of liver fuction, ascites, progressed splenomegaly, and gastrointestinal bleeding. To diagnose the venous complications, Doppler ultrasonography was performd at first, and those were confirmed by angiography or CT. Hepatic vein stenosis was managed by percutaneous transhepatic angioplasty (6), angioplasty followed by reposition of graft (1), and supportive care only 1 patient. Portal vein complications were managed by angioplasty (4), angioplasty followed by mesocaval shunt (1), and combined revascularization and angioplasty (1). The overall survival rate was 86% (12 of 14 patients). CONCLUSION: Close surveillance of the complication of vascular anastomoses and multidisciplinary approach to treat of venous complication after pediatric liver transplantation have made it possible to reduce the graft loss and mortality. Aggressive and successful radiologic intervention should be considered to eliminate the need for surgical revision, portacaval shunting or retransplantation.

Diagnostic Efficacy of Anorectal Manometry for the Diagnosis of Hirschsprung's Disease / 대한소아소화기영양학회지

PURPOSE: As diagnostic tools for Hirschsprung's disease (HD), barium enema and rectal biopsy have radiation exposure and invasiveness respectively; however anorectal manometry does not have these disadvantages. We therefore performed this study to evaluate the diagnostic efficacy of anorectal manometry. METHODS: We reviewed medical records of infants with one or two symptoms of vomiting, abdominal distension, chronic diarrhea or constipation who had a anorectal manometry followed by barium enema and/or biopsy from July 1995 to May 2002. We evaluated the sensitivity, specificity and predictive value of anorectal manometry and barium enema for diagnosis of HD. We also measured sphincter length, median value of balloon volume at which rectoanal inhibitory reflex (RAIR) occurred. RESULTS: All 61 patients received anorectal manometry, 33 of 61 received barium enema. 18 of 61 were diagnosed as HD according to histology and 43 of 61 were evaluated as a control. The sensitivity, specificity, positive predictive value, negative predictive value of anorectal manometry and barium enema for diagnosis of HD were 1.00, 0.91, 0.82, 1.00 and 0.93, 0.67, 0.70, 0.92 respectively. The mean value of sphincter length in control was 1.68+/-0.67 cm and correlated with age, weight and significantly longitudinal length. The median value of balloon volume at which RAIR occurred was 10 mL and did not correlated with age, weight and longitudinal length. CONCLUSION: This study suggests that anorectal manometry is an excellent initial screening test for Hirschsprung's disease because of its safety and accuracy.

Survival, Differentiation and ATM Phenotype of PC-12 Cells by Down - regulation of AT Gene / 대한암학회지

PURPOSE: Ataxia Telangiectasia (AT) is a hereditary multi-systemic disease resulting from mutations of AT gene and is characterized by progressive neurodegeneration, cancer, immune system defects, and hypersensitivity to ionizing radiation. AT gene has a homologue sequence of PI3-kinase. The activity and cellular function of PI3-kinase in AT gene remains unclear. This study was undertaken to evaluate the function of AT gene through the effect on cell survival and differentiation by the inhibition of AT gene expression. MATERIALS AND METHODS: NH2-terminal portion of AT gene was isolated from MCF-7 cells by RT-PCR. The isolated DNA fragment was ligated in reverse orientation in pcDNA3. This antisense ATM expression vector was transfected to PC-12 cells by calcium phosphate method, and the transformed cells were selected using G418 and immunohisto- chemistry. To analyze the cell survival and differentiation, cells were cultured in serum free medium supplemented with/without NGF. We performed the immunoprecipitation for the p53 induction of cells after ionizing radiation, and the FACS for the apoptosis of cells after the exposure of wortmanin. RESULTS: PC-12 cells which down-regulated AT gene (like ATM, AT mutated) showed decreased survival and ceased differentiation with NGF. Also, PC-12 (ATM) cells showed increased apoptosis with wortmanin and reduced or delayed p53 induction after ionizingradiation. CONCLUSION: Results obtained from these studies suggest that AT gene regulates survival and differentiation of PC-12 cells through PI3-kinase activity. It seems that apoptosis is induced by the inhibition of AT gene expression.

Clinical Observation of Congenital Urinary Tract Anomalies

We present the cytologic features of a case of solid and papillary neoplasm of the pancreas. Cytologically, the tumor was composed of a monotonous population of polygonal cells containing eccentrically located round nuclei with one or two distinct small nucleoli and a finely stippled chromatin pattern. The tumor cells were similar to those of the islet cell tumor and showed isolated loosely aggregated and solid sheets or large cell clumps. The large cell clumps revealed a branching papillary structure containing fibrovascular central core, which is characteristic histologic feature of solid and papillary neoplasm of the pancreas. This case was confirmed by tissue examination including histochemical, immunohistochemical and electron microscopical studies. Ultrastructurally, the tumor cells contained a few membrane-bound electron dense granules.