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Cytomegalovirus (CMV) infection is a common complication of liver trans-plantation in children. The CMV serostatus of recipients and donors is the primary risk factor, and prophylaxis or pre-emptive strategies are recommended for high-risk patients. Graft rejection, coinfection and Epstein-Bar virus reactivation, which can lead to post-transplant lymphoproliferative disease, are indirect effects of CMV infection. Assessment of CMV infection viral load should be routinely performed upon clinical suspicion. However, tissue-invasive CMV disease is not associated with CMV viraemia and requires confirmation by tissue pathology. Oral valganciclovir and intravenous ganciclovir are equivalent treatments, and the duration of treatment depends on factors including CMV viral load, tissue pathology, and clinical response. Risk stratification by donor and recipient status prior to transplantation and post-transplantation antiviral prophylaxis or pre-emptive therapy are recommended. Adult guidelines have been established but additional study of the effectiveness of the preventive guidelines in children is needed. This review summarizes the burden, risk factors, clinical manifestations, laboratory evaluation, treatment, and prevention of CMV infection in children after liver transplantation.

Viral hepatitis infections are a great burden in children who have received liver transplant. Hepatotropic viruses can cause liver inflammation that can develop into liver graft fibrosis and cirrhosis over the long term. Immunological reactions due to viral hepatitis infections are associated with or can mimic graft rejection, rendering the condition difficult to manage. Prevention strategies using vaccinations are agreeable to patients, safe, cost-effective and practical. Hence, strategies to eliminate viral hepatitis A and B focus mainly on immunization programmes for children who have received a liver transplant. Although a vaccine has been developed to prevent hepatitis C and E viruses, its use is not licensed worldwide. Consequently, eliminating hepatitis C and E viruses mainly involves early detection in children with suspected cases and effective treatment with antiviral therapy. Good hygiene and sanitation are also important to prevent hepatitis A and E infections. Donor blood products and liver grafts should be screened for hepatitis B, C and E in children who are undergoing liver transplantation. Future research on early detection of viral hepatitis infections should include molecular techniques for detecting hepatitis B and E. Moreover, novel antiviral drugs for eradicating viral hepatitis that are highly effective and safe are needed for children who have undergone liver transplantation.

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 esophago-enterocolitis in a girl diagnosed with anti-N-methyl-D-aspartate-receptor (anti-NMDAR) 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.

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.

BACKGROUND Spinal muscular atrophy (SMA) is caused by genetic defects in the survival motor neuron 1 (SMN1) gene that lead to SMN deficiency. Different SMN‐restoring therapies substantially prolong survival and function in transgenic mice of SMA. However, these therapies do not entirely prevent muscle atrophy and restore function completely. To further improve the outcome, we explored the potential of a combinatorial therapy by modulating SMN production and muscle‐enhancing approach as a novel therapeutic strategy for SMA. METHODS The experiments were performed in a mouse model of severe SMA. A previously reported 25‐mer morpholino antisense oligomer PMO25 was used to restore SMN expression. The adeno‐associated virus‐mediated expression of myostatin propeptide was used to block the myostatin pathway. Newborn SMA mice were treated with a single subcutaneous injection of 40 μg/g (therapeutic dose) or 10 μg/g (low‐dose) PMO25 on its own or together with systemic delivery of a single dose of adeno‐associated virus‐mediated expression of myostatin propeptide. The multiple effects of myostatin inhibition on survival, skeletal muscle phenotype, motor function, neuromuscular junction maturation, and proprioceptive afferences were evaluated. RESULTS We show that myostatin inhibition acts synergistically with SMN‐restoring antisense therapy in SMA mice treated with the higher therapeutic dose PMO25 (40 μg/g), by increasing not only body weight (21% increase in male mice at Day 40), muscle mass (38% increase), and fibre size (35% increase in tibialis anterior muscle in 3 month female SMA mice), but also motor function and physical performance as measured in hanging wire test (two‐fold increase in time score) and treadmill exercise test (two‐fold increase in running distance). In SMA mice treated with low‐dose PMO25 (10 μg/g), the early application of myostatin inhibition prolongs survival (40% increase), improves neuromuscular junction maturation (50% increase) and innervation (30% increase), and increases both the size of sensory neurons in dorsal root ganglia (60% increase) and the preservation of proprioceptive synapses in the spinal cord (30% increase). CONCLUSIONS These data suggest that myostatin inhibition, in addition to the well‐known effect on muscle mass, can also positively influence the sensory neural circuits that may enhance motor neurons function. While the availability of the antisense drug Spinraza for SMA and other SMN‐enhancing therapies has provided unprecedented improvement in SMA patients, there are still unmet needs in these patients. Our study provides further rationale for considering myostatin inhibitors as a therapeutic intervention in SMA patients, in combination with SMN‐restoring drugs.

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.To report the experience with pediatric LT and evaluate outcomes of living-relatedThis 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-WhitneyNinety-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) moA significant number of pediatric LT cases were reported in Thailand. Based on relatively comparable outcomes, ABO-incompatible and HBc antibody-positive grafts may be considered in an organ shortage situation.

The aim of the study was to determine the accuracy of noninvasive parameters, such as liver (LS) and spleen stiffness (SS) to detect esophageal varices (EV) in children with biliary atresia (BA).Children with BA between 2000 and 2015 were recruited. All underwent esophagogastroduodenoscopy and transient elastography. Demographic data, laboratory investigations, alanine transferase-to-platelet ratio index (APRI), and Varices Prediction Rule (VPR) score were collected.A total of 51 children (mean age 10.63 years, standard deviation (SD) = 6.08 years; 53% boys) were enrolled. There were differences in onset and outcome of portoenterostomy, spleen palpablility, platelet count, albumin, LS, SS, and VPR between the varice and varice-free groups (P 0.05). In the varice group, the median LS was 18.12 (interquartile ratio, IQR 13.15-19.12) and the median SS was 46.85 (IQR 25.95-54.55) kPa. In the varice-free group, the median LS was 7.85 (IQR 5.88-16.75) and the median SS was 16.54 (IQR 11.75-21.75) kPa. Both LS and SS were higher in the varice than the varice-free group (P 0001). The area under the receiver operating characteristic curve of LS, SS, spleen palpability, platelet count, APRI, and VPR were 0.734, 0.870, 0.817, 0.810, 0.751, and 0.794, respectively. Using a cut-off value of 12.5 kPa for LS, the sensitivity and specificity were 80 and 70%, respectively. Using a cut-off value of 28.9 kPa for SS, the sensitivity and specificity were 75 and 87%, respectively. Combination of LS and SS to diagnose varices increased the specificity to 93%.SS as a single marker had the best diagnostic value to predict esophageal varices in children with BA. The combination of SS and LS furthermore, increased the diagnostic yield.

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.

Prior results investigating a correlation between obesity and hepatitis A virus (HAV) vaccine response have been inconclusive, with limited data involving live attenuated HAV vaccines. The aim of this study is to evaluate the effect of overweight and obesity on the response to live attenuated HAV vaccine in children and young adults. This prospective cohort study was conducted in Thailand with subjects ranging in age from seven to twenty-five years. The subjects were administered 0.5 mL of MEVAC™-A and tested for anti-HAV antibodies before and at 8–9 weeks after vaccination. Baseline seronegative subjects (anti-HAV antibodies &lt, 20 mIU/mL) were divided into non-obese (underweight/normal weight) and obese (overweight/obesity/severe obesity) groups. A total of 212 (117 non-obese and 95 obese) subjects completed the study (mean age (SD) = 13.95 (3.90) years). The seroprotection rates were 100%. Postvaccination geometric mean titers (95% CI) were 429.51 (401.97, 458.94) and 467.45 (424.47, 514.79) mIU/mL in the non-obese and obese groups, respectively. Females (p = 0.013) and subjects with truncal obesity (p = 0.002) had significantly higher titers than other participants. Live attenuated HAV vaccine is safe and has comparably high immunogenicity in both underweight/normal weight and overweight/obese persons.

Chulalongkorn Medical Journal, 65, 4, 481-487

BACKGROUND Infections and associated morbidity and mortality may be more frequent in children who have undergone liver transplant than in healthy children. Immunization strategies to prevent vaccine-preventable infections (VPIs) can effectively minimize this infection burden. However, data on age-appropriate immunization and VPIs in children after liver transplant in Asia are limited. AIM To evaluate the immunization status, VPIs and non-VPIs requiring hospitalization in children who have undergone a liver transplant. METHODS The medical records of children who had a liver transplant between 2004 and 2018 at King Chulalongkorn Memorial Hospital (Bangkok, Thailand) were retrospectively reviewed. Immunization status was evaluated via their vaccination books. Hospitalization for infections that occurred up to 5 years after liver transplantation were evaluated, and divided into VPIs and non-VPIs. Hospitalizations for cytomegalovirus and Epstein-Barr virus were excluded. Severity of infection, length of hospital stay, ventilator support, intensive care unit requirement, and mortality were assessed. RESULTS Seventy-seven children with a mean age of 3.29 ± 4.17 years were included in the study, of whom 41 (53.2%) were female. The mean follow-up duration was 3.68 ± 1.45 years. Fortyeight children (62.3%) had vaccination records. There was a significant difference in the proportion of children with incomplete vaccination according to Thailand's Expanded Program on Immunization (52.0%) and accelerated vaccine from Infectious Diseases Society of America (89.5%) (P < 0.001). Post-liver transplant, 47.9% of the children did not catch up with age-appropriate immunizations. There were 237 infections requiring hospitalization during the 5 years of follow-up. There were no significant differences in hospitalization for VPIs or non-VPIs in children with complete and incomplete immunizations. The risk of serious infection was high in the first year after receiving a liver transplant, and two children died. Respiratory and gastrointestinal systems were common sites of infection. The most common pathogens that caused VPIs were rotavirus, influenza virus, and varicella-zoster virus. CONCLUSION Incomplete immunization was common pre- and post-transplant, and nearly all children required hospitalization for non-VPIs or VPIs within 5 years post-transplant. Infection severity was high in the first year post-transplant.

AIM To assess the seroprevalence of hepatitis B virus (HBV) immunity among previously vaccinated pediatric liver transplant recipients and present a case report of de novo hepatitis B infection after liver transplantation. METHODS This study focused on children with chronic liver diseases who received primary hepatitis B immunization and had a complete dataset of anti-HBs before and after liver transplantation between May 2001 and June 2017. Medical records were retrospectively reviewed for potential factors relating to HBV immunity loss. RESULTS In total, 50 children were recruited. The mean time from liver transplantation to anti-HBs testing was 2.53 ± 2.11 years. The mean anti-HBs levels before and after liver transplantation were 584.41 ± 415.45 and 58.56 ± 6.40 IU/L, respectively. The rate of non-immunity (anti-HBs < 10 IU/L) in the participants was 46% (n = 26) at one year, 57% (n = 7) at two years and 82% (n = 17) at > three years following liver transplantation. The potential factors relating to HBV immunity loss after liver transplantation were identified as anti-HBs (P = 0.002), serum albumin (P = 0.04), total bilirubin (P = 0.001) and direct bilirubin (P = 0.003) before liver transplantation. A five-year-old boy with biliary cirrhosis received 4 doses of HBV vaccine with an anti-HBs titer of > 1000 IU/L and underwent liver transplantation; his anti-HBc-negative father was the donor. After liver transplantation, the boy had stenosis of the hepatic artery up to the inferior vena cava anastomosis and underwent venoplasty three times. He also received subcutaneous injections of enoxaparin for 5 mo and 20 transfusions of blood components. Three years and ten months after the liver transplantation, transaminitis was detected with positive tests for HBsAg, HBeAg, and anti-HBc (2169.61, 1706 and 8.45, respectively; cutoff value: < 1.00) and an HBV viral load of 33212320 IU/mL. CONCLUSION The present study showed that loss of hepatitis B immunity after liver transplantation is unexpectedly common. In our case report, despite high levels of anti-HBs prior to transplantation, infection occurred at a time when, unfortunately, the child had lost immunity to hepatitis B after liver transplantation.

Chulalongkorn Medical Journal, 63, 4, 253-260

Hepatitis A virus (HAV) infection is one of the most common causes of acute viral hepatitis worldwide. HAV is transmitted mainly by person-to-person and spread by the fecal-oral route. Public health measures, including improved sanitation and hygiene, are the main factors leading to the reduction in the incidence of HAV infection in developing countries. The symptoms of HAV infection in children are varied, from asymptomatic to nonspecific (fever, lethargy) and to acute hepatitis and fulminant hepatitis. HAV infection is more severe in persons with underlying chronic liver disease. Because infection is usually spread silently by asymptomatic and very young children, outbreaks of infection commonly occur in diapered infants in childcare centers. When HAV infection occurs, public health organizations should be involved. Serological testing for IgM anti-HAV antibodies combined with molecular techniques for detecting HAV RNA are valuable techniques for the diagnosis of early-stage infection, leading to timely management of disease outbreaks. Advanced molecular techniques, including reverse transcription-polymerase chain reaction (RT-PCR), or real-time RT-PCR are very sensitive for the detection of HAV RNA and viral genotype by sequencing, either in suspected cases or in the environment as sources of infection. Treatment of acute hepatitis A is symptomatic. An HAV vaccine was licensed in 1995, which, in many countries, led to the recommendation for universal vaccination of young children, following which, the incidence of HAV infection has greatly reduced. Apart from rapid HAV detection and immunization programs, other strategies to prevent childhood outbreaks of HAV infection include health education, prevention of contact with the infection, improved sanitation campaigns, and post-exposure prophylaxis. Ideally, to eradicate HAV infection, universal immunization would be the goal.

Wilson disease (WD) is a rare autosomal recessive disorder of copper metabolism with a variety of clinical and biochemical manifestations. WD should be considered in patients with unexplained liver impairment or neuropsychiatric abnormalities. Currently, there are several diagnostic parameters postulated for WD, but no single test has been specific enough. Therefore, several diagnostic algorithms that include copper parameters and other surrogate markers like alkaline phosphatase have been evaluated. Worldwide since 2001, a diagnostic scoring system has been used, and since 2012, the WD scoring system has been adopted into the diagnostic algorithm included in the European Association for the Study of the Liver (EASL) guidelines. The availability of liver transplantation is a lifesaving treatment option for patients with WD presenting with encephalopathy and liver failure, but it has a potential of misuse in severe decompensated liver disease where chelation therapy could improve the liver disease avoiding the need for liver transplantation. In this chapter, a critical appraisal will be conducted of each parameter for the diagnosis of WD, together with other proposed diagnostic parameters.

Viral hepatitis is a global problem with mortality comparable to HIV, tuberculosis and malaria. The WHO aims to eliminate hepatitis B (HBV) and hepatitis C (HCV) by 2030. Improved socioeconomic status of developing countries such as Thailand has reduced the incidence and morbidity associated with hepatitis A. Since the beginning of hepatitis B vaccination in all Thai newborns in 1992, at least 95% of one-year-olds are currently receiving 3–4 hepatitis B doses. The second vaccination of newborns of carrier mothers at 1 month of age has contributed to an effective reduction in mother-to-child transmission. Universal vaccination, blood donation screening, and decreasing needle sharing have reduced hepatitis B infection. Under the test and treat model, cost-effective screening at the point-of-care (health center or village hospital) is recommended for adults >30 years-old. Following referral to a tertiary healthcare center for a treatment plan in developing disease management plan, its implementation by trained healthcare professionals is preferably administered at the point-of-care. Hepatitis C prevalence is also decreasing as a result of blood-borne pathogen awareness. Current hepatitis C infection is highest for adults >35 years who were born prior to 1983, with screening is recommend once in their lifetime. Treatment strategy recommendation follows that of hepatitis B. The availability of direct antiviral agents with high cure rates is expected to contribute to the reduction in hepatitis C transmission and mortality as set forth by the WHO policy. Thus, ensuring the successful planning of hepatitis elimination in Thailand requires pilot regional assessment prior to national implementation.

Objective This study aimed to determine the seroprevalence of anti-HAV IgG in Thai medical students in 2016 compared with the previous data and to demonstrate the cross-effective strategy to screen HAV seropositivity. Results Sera from 176 first-year medical students (age 19.07 ± 0.59 years; 50% female) at a university hospital in Thailand were tested for anti-HAV IgG. Data from HAV vaccination records and questionnaires were also collected. HAV seropositivity was unexpectedly high (62.5%, n = 110). 37.5% (n = 66) had an HAV vaccination record. Of these, 60.6% received the full HAV vaccination series, 4.5% received one HAV vaccination, 34.8% did not receive HAV vaccination, and 3.0% had natural HAV immunity. The long-term efficacy of HAV vaccination was at least 97.5% over a mean of 15.55 ± 2.44 years. There was a significant difference in immunity between students with (66.7%) and without (50.9%) vaccination records (P = 0.028). Most of the student’s parents had a bachelor’s degree or higher (87.9%; n = 272) and above average income (mean 17,000.76 ± 194.22 USD/person/year). Parental education and socioeconomic status influenced vaccination accessibility in these medical students. Screening of vaccination records instead of routine anti-HAV IgG testing is a cost-effective and reliable strategy to determine HAV immunity in medical students in Thailand.

OBJECTIVES Wilson disease (WD) is a rare inborn error of copper metabolism with diverse manifestations. There has been no study of zinc (Zn), the copper's antagonist, in WD diagnosis and severity so far. Our aims were to evaluate serum Zn in WD and its correlation with the disease severity score (revised WD index). Although the ATP7B mutation analysis is highly accurate for WD diagnosis, it may not be readily available in a resource-limiting setting. We proposed a disease diagnostic score (Proposed WD diagnostic score) which incorporates serum Zn. METHODS Medical records of WD and non-WD children seen at King's College Hospital from 2005 to 2015 were reviewed for the selected parameters using the Proposed WD diagnostic score. Available serum Zn data in WD children before disease diagnosis and the calculated severity score were statistically analyzed. Diagnostic values of the Proposed WD diagnostic score were evaluated. RESULTS Serum Zn level was significantly lower in 8 WD-acute liver failure (ALF) (5.8 [4.1-8.3] μmol/L) compared to 18 WD-non-ALF (13.5 [6.1-22.2] μmol/L) and 9 ALF from indeterminate cause (9.8 [7.0-12.1] μmol/L) (P

Multichannel intraluminal impedance combined with pH (MII-pH) is the gold standard test for diagnosing gastro-esophageal reflux disease (GERD). It provides an opportunity to study acid and non-acid GOR and temporal association between symptoms and reflux. Accurate catheter placement is essential to prevent erroneous recording of reflux events. The aims of our study were to assess the accuracy of our devised method in predicting the catheter length for MII-pH in children (Great Ormond Street Hospital (GOSH) Table) and to compare the results with Strobel and Monreau methods.Retrospective review of all records of infants and children who underwent MII-pH studies between January to October 2014. Desired catheter position was calculated using Strobel, Monreau and GOSH formulas and compared to X ray position.One hundred and forty-four children were included; mean age was 5.1 (±4.5) years, 73 males and 71 females. In the whole group, the correlation between desired catheter position and GOSH Table was 0.95, for Strobel was 0.84, and Monreau was 0.85. In the first group (age3 years), the correlation was: GOSH Table 0.91, Strobel 0.56, and Monreau 0.6; in the second group (3-10 years): GOSH Table 0.78, Strobel 0.82, and Monreau 0.82; the third group (10 years): GOSH 0.81, Strobel 0.43, and Monreau 0.43.GOSH Table is an accurate method to estimate the insertion length of MII-pH catheters from nares to a point of approximately two vertebral bodies above the diaphragm in children. Although radiography is required to confirm final catheter position, using GOSH Table will reduce the need for repeated catheter manipulation after initial insertion and will reduce the use of a mathematically complicated formulae.

Background The colo-anal reflex is a distinct reflex whereby the internal anal sphincter (IAS) relaxes in association with colonic high amplitude propagating contractions (HAPCs) in contrast to the recto-anal inhibitory reflex (RAIR), which is characterized by IAS relaxation upon rectal distension. The RAIR is mediated by the myenteric plexus and therefore absent in Hirschsprung disease. We retrospectively assessed the presence and the characteristics of the colo-anal reflex in children in whom large bowel continuity had been surgically disrupted to assess the role of the extrinsic nervous system in the reflex. Methods High-resolution (HR) colonic manometry and HR-anorectal manometry were used to evaluate both colonic and anal motor activity in ten children with treatment-unresponsive slow transit constipation (STC), who had previously undergone left-sided colostomy formation with consequent disruption of the bowel continuity, and in two children with Hirschsprung's disease (HSCR), who had previously undergone distal colon resection followed by Duhamel pull-through. Eight children with STC, normal colonic motor activity, and preserved large bowel continuity served as a control group. The presence and characteristics of colo-anal reflex were analyzed. Key results In the study group, all patients showed the presence of both normal HAPCs and the presence of the colo-anal reflex. In two cases of HSCR, RAIR was absent; however, both patients demonstrated a colo-anal reflex. Conclusions In children with disrupted continuity of the colon and/or abnormal anal reflex, the colo-anal reflex is still preserved suggesting that it is mediated by a different pathway from the RAIR, possibly an extrinsic neural pathway.

Wilson's disease (WD) is a rare autosomal recessive disorder characterized by copper accumulation. Clinical presentations are extraordinarily diverse, and currently no single diagnostic test can confirm WD with high accuracy. A complete understanding of the presentations and improved diagnostic methods are important for disease management. The authors' aimed to examine disease characteristics, management, and treatment outcome of WD in children, especially when genetic analysis and liver copper measurements were limited.Data was collected from 21 WD children who were treated at King Chulalongkorn Memorial Hospital between 2000 and 2012. Inclusion criteria followed the WD scoring system, where other liver diseases are ruled out systematically.The mean age at diagnosis was 13.5 ± 3.36 years, with 19 symptomatic patients, and two asymptomatic individuals who were diagnosed through family screening. Presentations varied, jaundice (52%), ascites (52%), edema (52%), Coombs-negative hemolytic anemia (14%), neurological abnormalities (33%), renal involvement (19%), and fulminant hepatic failure (5%). Based on the key parameters in WD scoring system, 14 patients (66%) had Kayser-Fleischer (KF) rings. Seventeen (89%) had low serum ceruloplasmin, and 20 (95%) had increased urinary copper excretion. These positive findings made WD scoring system accurately diagnose 66% of patients. Chelation therapy was the first line of therapy for all patients except one, who underwent liver transplantation. After therapy, liver function test returned to normal in all patients. However, neurological symptoms did not improve with combined drug therapy using chelating and neuropsychiatric agents.WD in children mostly affected the liver WD was suspected in seven patients (34%), thus needed further investigation. Therefore, long-term follow-up in those with suspected WD is the appropriate method for diagnosis and management in limited diagnostic tests. We suggest further treatment, and use of clinical response to treatment, as a criterion for confirming the WD diagnosis.

Chronic watery diarrhoea can be a presentation of gastrointestinal disease itself or a less-evident systemic disease. A 17-month-old boy presented with intractable diarrhoea, failure to gain weight, refractory tachycardia and severe hypertension. The ability to recognise and make a quick diagnosis of secretory type of diarrhoea dictated the outcome of patients with this ailment. Catecholamine hypersecretion was considered with the additional clues of refractory tachycardia and hypertension, a well-recognised phenomenon of neuroblastic tumours. A neuroblastic tumour can lead to vasoactive intestinal peptide (VIP) overexpression, which may result in secretory diarrhoea. In this situation, measurements of plasma VIP enabled crucial diagnosis. Imaging studies were used to identify and localise a neuroblastic tumour. Subsequent removal of the tumour was curative and led to the resolution of the symptoms.

BACKGROUND: Chronic constipation is one of the most common chronic disease in children. Most of cases are functional, however some has problem of organic myopathic or neuropathic colon. Colonic transit study with oro-anal transit markers is the basic diagnostic tool for colonic dysmotility in clinical practice, colonic manometry is the recommended investigation in the next step. Nevertheless, the colonic manometry is considered more invasive, expensive and also unavailable in many countries. The aim of this study is to assess the diagnostic value of conventional method as colonic transit study compared with the novel high-resolution colonic manometry in diagnose colonic abnormalities. METHODS: Fifty constipated children in Great Ormond Street hospital were retrospectively reviewed in demographic data and investigation result. The diagnosis of constipation was based on history and physical examination which followed Rome III criteria. All of enrolled patients received colonic manometry investigation before colonic transit study in order to reduce the bias. For colonic transit protocol, patients had to ingest a 10-markers capsule on 3 consecutive days and an abdominal x-ray was obtained on day 4. The cut-off values for abnormal segmental and total colonic transit time(CTT) were based on Arhan et al publication. RESULTS: Fifty constipated children with the mean age of 9.77 years (1.15-17.32) were included. Of all, 39(78%) patients had colonic abnormality detected by colonic manometry while 38(76%) patients had abnormal CTT.The sensitivity, specificity, and positive predictive value(PPV) of colonic transit study for abnormal total CTT were 46.2%, 72.7% and 85.7%, respectively. In aspect of abnormal segmental CTT, the sensitivity, specificity and PPV of right colon are 66.7%, 63.6% and 20%; left colon are 16.7%, 72.7% and 7.69%; and rectosigmoid colon are 29.4%, 68.8% and 66.7%, respectively. CONCLUSIONS: Colonic transit study seemed to have satisfied posttest probability to diagnose total colonic abnormality. However, for segmental CTT, this test might be invalid and the consideration to use as predictor of segmental abnormality was not recommended.