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Perivascular epithelioid cell tumour (PEComa) is an extremely rare neoplasm with distinctive morphology and specific expression of immunohistochemical markers. The lesion is typically diagnosed in middle-aged women, with few reports of paediatric cases, and there is no standardized treatment for the tumour type. Here, the case of a 17-year-old female, who presented with painless haematochezia for 2 days and was diagnosed with gastrointestinal PEComa of the sigmoid colon with regional lymph node metastasis after serial examination, is presented. She was treated by surgical resection of the tumour and cytotoxic chemotherapy comprising 900 mg/m2 gemcitabine and 100 mg/m2 docetaxel every 3 weeks for six cycles. Haematochezia did not recur, and complete response was achieved, with progression-free survival at the 24-month follow-up examination. Surgical resection with adjuvant conventional cytotoxic chemotherapy may be considered as an option for treating gastrointestinal PEComa.

Background Primary lymphomas of the gastrointestinal tract are rare, accounting for only 1 to 4% of malignancies arising in the stomach, small intestine, or colon. The stomach is the most common extranodal site of lymphoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma accounts for 40% of primary gastric lymphoma. Gastric MALT lymphoma reaches its peak incidence between 50 to 60 years of age, therefore, it is rarely encountered in pediatric population. The presenting symptoms of gastric MALT lymphoma are usually nonspecific and primary perforation of gastric MALT lymphoma is uncommon. Case presentation A 12 year-old female presented with iron deficient anemia developed gastric perforation. Emergency laparoscopic repair of the perforation was performed and tissue pathology showed gastric MALT lymphoma infiltration. Helicobacter pylori eradication and radiotherapy were sequentially performed. Complete remission was achieved at two months after radiotherapy. To our best knowledge, she is the youngest patient with gastric MALT lymphoma reported in the literature. Conclusion Iron deficient anemia is a common presenting manifestation of malignancies in adulthood. In pediatric population, iron deficient anemia is usually caused by nutritional deficient or blood loss. In this case report, we present a teenaged female without previous gastric ulcer history who presented with a rare gastric tumor and an uncommon primary perforation. Even if there is an uncertainty about the exact diagnosis prior to the surgery, the strategy of stomach-preserving therapy by laparoscopy for primary perforation was successful and provided a good quality of life. Electronic supplementary material The online version of this article (10.1186/s12887-019-1431-9) contains supplementary material, which is available to authorized users.

Background/Purpose: Viral infections and innate immunity signaling, especially Toll-like receptor 7 (TLR7) have been implicated in the pathogenesis of biliary atresia (BA). Administration of rhesus rotavirus-type A to newborn Balb/c mice produces inflammatory obstruction of bile ducts, which resembles human BA. However, whether activation of TLR7 signaling plays a role in neonatal hepatobiliary injury remains to be investigated. Methods: TLR7 agonist, imiquimod (R837), was intraperitoneally administered to Balb/c mice within 24 hours of birth and then every other day. Morphological and histological injuries of liver and gallbladder were examined at 2 weeks. Hepatic messenger RNA expression of TLR7 signaling was studied. Terminal deoxynucleotidyl transferase 2′-deoxyuridine 5′-triphosphate nick end labeling staining was used to delineate hepatobiliary apoptosis upon TLR7 stimulation. Results: TLR7 agonist, imiquimod, induced hypoplasia of the biliary system of neonatal Balb/c mice both in atrophic gallbladder and in paucity of intrahepatic bile ducts. There was significantly higher hepatic expression of TLR7 and downstream innate immunity-mediated interferon regulatory factor 7, interferon-α, and tumor necrosis factor-α. In addition, terminal deoxynucleotidyl transferase 2′-deoxyuridine 5′-triphosphate nick end labeling-positive cells in the liver were increased after injections of TLR7 agonist. Conclusion: The results demonstrate that TLR7 activation may trigger innate immunity pathways and induce apoptosis and hypoplasia of neonatal biliary trees in Balb/c mice. The novel findings give an implication of pathogenesis of infantile cholestasis, such as BA. Keywords: animal model, Balb/c mice, biliary atresia, infantile cholestasis, innate immunity, toll-like receptor 7

OBJECTIVES: The pathogenesis of biliary atresia (BA) is unclear, but epidemiological studies may help to elucidate possible causes. The goals of this study were to identify BA incidence changes in Taiwan in 2004–2009 and to survey the factors that might influence incidence changes to elucidate the possible causes of BA. METHODS: A Taiwan national registry system for BA has been established since 2004. By using data from the national registry system for BA, we identified BA incidence changes in 2004–2009. We also evaluated the correlations between BA incidences and estimated rotavirus vaccine coverage rates and between BA incidences and the gross domestic product. RESULTS: A total of 185 patients with BA were identified in 2004–2009 in Taiwan, whereas the number of live births was 1 221 189. Compared with the incidence of BA in 2004–2006 (1.79 cases per 10 000 live births), the incidence of BA in 2007–2009 (1.23 cases per 10 000 live births) was decreased significantly (P = .01). BA incidences were negatively correlated with the gross domestic product (P = .02) and marginally negatively correlated with rotavirus vaccine coverage rates (P = .07). CONCLUSIONS: A significant decrease in BA incidence in Taiwan since 2007 has been noted and may be related to improvements in the general socioeconomic status and the popularity of rotavirus vaccination. Although more evidence is needed to establish a direct correlation, this phenomenon may shed light on possible causes of and preventive interventions for BA.

To study the influence of clinical audit on diagnosis, complications, and factors contributing to hospitalization of patients with infantile hypertrophic pyloric stenosis. Study Design: Retrospective cohort study. Method: There were 214 patients from 1991 to 2004 from three medical centers in Kaohsiung. Data were analyzed with respect to diagnostic methods, complications, and factors requiring patient hospitalization. Results: The ratio of male to female was 4.8:1 (177 males and 37 females). The diagnoses before admission were as follows: 22% had milk intolerance and 14.5% had esophageal reflux. There was a significant increase in the use of sonogram diagnostic test (p=0.005) and a decrease in the incidence of diagnosis by olive mass palpation but not by barium meal test. Surgery time of 48 hours after admission was significant with barium meal examination and related to longer hospital stay (p

Background: Most infantile hypertrophic pyloric stenosis (IHPS) cases are diagnosed between 3 and 12 weeks after birth. Few data exist regarding Asian infants with IHPS who are younger than 3 weeks or are preterm. The goal of this study is to identify unusual clinical manifestations, clinical course, duration of hospital stay, and complications of Asian infants with IHPS who are preterm or younger than 3 weeks of age. Methbods: From 1991 to 2004, all IHPS patients admitted to three tertiary centers in southern Taiwan were enrolled. The clinical manifestations, duration of hospital stay and complications were further compared between the IHPS patients diagnosed before and after 3 weeks; preterm and term infants. Results: A total of 214 patients were enrolled into the study; the mean age of diagnosis was 40 days of age; the average duration of hospital stay was 6.27 days. Eighteen (8.41%) patients were diagnosed before 3 weeks of age. A significantly shorter timeframe of diagnosis, a higher rate of jaundice, a lower daily body weight gain and longer duration of hospital stay were noted in the IHPS group prior to 3 weeks compared with those in IHPS group after 3 weeks. Eighteen were preterm infants. A significantly older age of symptom onset, a lower body weight at admission, more cases diagnosed by barium meal study and higher postoperative complication rates were noted in the preterm group versus full-term infants with IHPS. Conclusions: The IHPS cases diagnosed before 3 weeks of age had longer duration of hospital stay. Preterm infants with IHPS had more postoperative complications.

Aberrant congenital bands are a rare cause of acute intestinal obstruction and usually present a diagnostic challenge. In 2008, the authors encountered 2 children with acute terminal ileal herniation. In the first case, it was caused by a mesodiverticular band, and numerous freely hanging filmy membranes attached to the antimesenteric side of the small intestine were found concurrently; whereas, an anomalous band from the distal ileum to the cecum was the leading cause in the second case. The vascularity of both herniated intestines was not compromised, and laparoscopy was successfully carried out 84 and 93 hours after the onset of the symptoms, respectively. Instead of cohesive adhesions, both of the causes related to a single vascular band, and laparoscopy was an effective and safe tool in diagnosis and subsequent treatment. The case with a mesodiverticular band and filmy membranes is the first case report with incomplete regression of both the vitelline circulation and the ventral mesentery.

Recurrent cholangitis may aggravate cholestatic liver cirrhosis in biliary atresia (BA) after the Kasai operation. This pilot study aimed to investigate whether Lactobacillus casei rhamnosus has the prophylactic efficacy for recurrent cholangitis in comparison with the conventional neomycin prophylaxis.Twenty jaundice-free patients with BA ages 0 to 3 years who underwent a Kasai operation were enrolled and randomized into 2 groups with 10 patients each: neomycin (25 mg · kg · day for 4 days/wk) and L casei rhamnosus (8 × 10 colony-forming unit per day) groups. The treatment duration was 6 months. Bacterial stool cultures were performed before treatment and 1, 3, and 6 months after starting treatment. In addition, 10 patients with BA with similar status but without prophylaxis served as the historical control group.In the Lactobacillus group, 2 patients (20%, mean 0.03 ± 0.07 episodes per month) developed cholangitis during the study period, with the same frequency as in the neomycin group and significantly lower than that in the control group (80%, P = 0.005, mean 0.22 ± 0.16 episodes per month). The mean change in body weight z score during the 6 months in the Lactobacillus group was 0.97 ± 0.59, which was significantly better than that in the control group (-0.01 ± 0.79, P = 0.006). In bacterial stool cultures, the Lactobacillus and Escherichia coli populations significantly increased and decreased, respectively, in the Lactobacillus group.The use of L casei rhamnosus was as effective as neomycin in preventing cholangitis in patients with BA who underwent Kasai operation, and therefore could be considered as a potential alternative prophylactic regimen.

Objective.To investigate whether single-nucleotide polymorphisms in the promoter regions of endotoxin-responsive genes CD14 and tumor necrosis factor-α (TNF-α) are associated with biliary atresia (BA) and idiopathic neonatal cholestasis (INC).Methods.We obtained genomic DNA from 90 patients with established diagnosis of BA and 28 patients with INC. Forty-two adult patients with hepatitis B–related cirrhosis and 143 healthy children served as control populations. The genotypes of CD14/C(−159)T and TNF-α/G(−308)A (G allele, TNF*1; A allele, TNF*2) were determined by using a restriction enzyme–based assay. Plasma soluble CD14 levels were determined in different disease stages and genotypes of BA.Results.The frequencies of T allele and T/T homozygosity of the CD14/−159 promoter polymorphism were significantly higher in patients with BA (T allele: 61.7%; T/T genotype: 42.2%) and in patients with INC (T allele: 67.9%; T/T genotype: 53.6%) but not in control populations. Decrease of plasma soluble CD14 from the early stage of BA when the patients received a Kasai operation to the late stage of liver cirrhosis was observed in carriers of the T/T and T/C genotypes but not in carriers of the C/C genotype. The TNF-α/−308 promoter polymorphisms (TNF*1 and TNF*2) were not associated with BA.Conclusion.These findings show that the single-nucleotide polymorphism at CD14/−159 is associated with the development of BA and INC. Endotoxin susceptibility may play a role in the pathogenesis of infantile cholestasis.

The pathogenesis of necrotizing enterocolitis (NEC) is unknown. Ischemia and reperfusion (I/R) injury has been considered to be a major contributing factor. More recent reports have noted that apoptosis is a significant and perhaps the principal contributor to cell death after I/R. Some reports revealed that infants with NEC and perforated bowel can completely recover with drainage alone. This study aims to assess the ability of newborn rat intestine to resist apoptosis after I/R injury compared with adult rat intestine. Intestines from 10 groups of rats (n = 6 for each study group) were studied: (1) normal control group; (2) ischemia group, receiving vascular occlusion for 60 min; (3) I/R groups receiving vascular occlusion for 60 min and reperfusion for 15, 30, and 60 min, respectively. Apoptosis was quantified by TUNEL methods. Statistical analysis was performed using ANOVA with Dunn’s test. TUNEL-positive cells per 10 crypts were significantly increased in the ischemia and I/R groups compared to the control group. The peak number of positive cells by TUNEL was recognized 30 min after reperfusion in adult and newborn rats and then reduced gradually. The newborn rats had significantly less TUNEL-positive cells per 10 crypts than adult rats subjected to I/R injury (p < 0.05). We demonstrated that the activation of apoptosis occurred after intestinal I/R injury, especially during the reperfusion phase. The newborn intestine was more resistant to I/R injury and thus may have significant clinical application.

Many patients with sepsis have bacteremia for which no septic focus is identified either clinically or by autopsy. This study was designed to determine the relationship between the ischemia-reperfusion injury (IRI) and bacterial translocation that might be involved in the pathogenesis of necrotizing enterocolitis. In the first experiment, a total of 32 Sprague-Dawley rats weighing 150–200 g were divided into four groups. The mesentery to isolated loop was occluded for 30, 60, and 90 min following 30-min reperfusion in the three groups of experimental animals with a micro-bulldog clamp. A control group involved the same technique and exposure, without occlusion of the mesentery. Two sets of blood culture were taken through a catheter in the portal vein immediately and 15 min after the reperfusion, respectively. In another experiment, bacteria isolated were fed in different doses to control rats and those after 30- or 60-min ischemia and 30-min reperfusion. Two sets of blood culture were taken following the procedure. Invasion and transcytosis of the bacteria through epithelial cells were studied in vitro using a Madin-Derby canine kidney (MDCK) cell monolayer model. PCR for delta toxin gene was performed on all bacteria isolated, using Staphylococcus epidermidis as the control. Coagulase-negative staphylococci (CoNS) were invariably isolated from mice with prolonged ischemia (90 min) and reperfusion. When bacteria were fed into mice with only 30-min ischemia, an inoculum as low as 5 × 105 CFU/ml could induce bacteremia. No bacterial translocation was found in control mice even fed with a higher dose of bacteria (5 × 108 CFU/ml). In vitro experiments showed that CoNS failed to transcytose MDCK monolayer. These isolates were not cytotoxic to MDCK cells and contained no delta toxin gene. Bacterial translocation of CoNS occurred following severe bowel ischemia and reperfusion injury. Intact mucosa integrity readily prevented bacterial translocation; however, bacterial translocation could occur in rats following mild IRI in the presence of a higher number of CoNS in the gut.

The efficacy of hepatitis B immunoglobulin (HBIG) in infants of hepatitis B e antigen (HBeAg)-negative hepatitis B surface antigen (HBsAg) carrier mothers in Taiwan is not clear.To describe the responses of infants born to HBeAg-negative carrier mothers receiving HBIG combined with hepatitis B vaccine.Term babies born to HBeAg-negative carrier mothers were assigned based on chart number to 1 of the 2 treatment groups. Group A infants (n = 94) received 0.5 ml (145 IU) of HBIG within 24 h of birth and 3 subsequent doses of recombinant hepatitis B virus (HBV) vaccine at 3 to 5 days, 1 month and 6 months of age. Group B infants (n = 122) received 3 doses of vaccines only. Infants (n = 19) born to HBeAg-positive carrier mothers were treated like those in Group A and are referred to as Group C. Sera obtained from infants at 2 and 7 months of age were tested for hepatitis B virus (HBV) markers.There were 2 (1%; one in Group A and one in Group B) subclinical breakthrough hepatitis B infections among studied infants. One (5%) child of Group C had asymptomatic HBV infection at the age of 7 months and became a chronic carrier. The rate of protective anti-hepatitis B surface antibody (anti-HBs) titers achieved (10 mIU/ml) by 2 months of age was significantly higher in Group A than that in Group B (98% vs. 57%, P0.001). However, it was not different by 7 months of age. Infants (Group A) immunized with HBIG and vaccine had a significantly higher geometric mean titer (GMT, milli-International Units/ml) of anti-HBs than those (Group B) with vaccines only at 2 months of age (P0.001). Conversely at 7 months of age, the GMT of anti-HBs was significantly higher in infants who received vaccine only (P = 0.001).A protective level of antibodies was achieved earlier in those infants receiving both passive and active immunizations. However, infants receiving active immunizations alone achieved a higher GMT at 7 months of age. There was no clear benefit of passive-active vs.active immunization alone for chronic HBV infection in infants of HBsAg-positive, HBeAg-negative mothers.

Figure 1 Kayser-Fleischer ring, copper deposition in Descemet’s membrane, was revealed as a crescent at the top of the cornea (arrow) by ocular slit-lamp examination. A previously healthy 11-year-old boy had puzzling pitting edema of his lower legs for 5 weeks prior to presentation, as well as progressive weight gain (46e52 kg), puffy eyelids, and scrotal edema. Laboratory tests showed severe hypoalbuminemia (1.67 g/dL), absence of urinary protein, and hypertransaminasemia (AST 311 IU/L, ALT 72 IU/L, bilirubin 0.97/0.26 mg/dL). Ocular slit-lamp examination revealed yellowish cloudy crescent Kayser-Fleischer rings at the upper cornea (Figure 1). An axial computed tomography scan of the abdomen demonstrated cirrhotic liver with encapsulated and intraperitoneal ascites (Figure 2). Wilson’s disease with Child’s class C cirrhosis was confirmed by low serum ceruloplasmin (8.65 mg/dL; normal range, 20e35 mg/dL) and high urinary copper excretion (353.8 mg in 24 hours; normal

Contrary to the classical form, infantile facioscapulohumeral muscular dystrophy (FSHD) usually denotes a severe phenotype and is frequently associated with extramuscular involvements. To elucidate the genotype-phenotype correlation in this severe subgroup, we identified a cohort of nine patients with infantile FSHD who also carried a very short (10-13kb) EcoRI fragment. Their current age ranged from 8 to 33 years and age of onset ranged from 0.4 to 5 years. One patient even manifested his first FSHD-related symptoms at as early as 5 months of age, including inability to smile, poor response to call, and infantile spasms. To date, four patients were wheelchair-bound and six patients had asymmetric weakness. Sensorineural hearing loss and abnormal fundoscopic findings were observed in eight and all of patients respectively. Three with the smallest EcoRI fragments (10-11kb, with normal length being 50-300kb) had mental retardation. Two of these had epilepsy. Cardiac arrhythmias were found in five patients. Restrictive ventilatory defects were observed in seven patients, with one progressing to chronic respiratory failure. Two had swallowing difficulties; one of these required gastrostomy. We identified several rarely reported phenotypes in infantile FSHD, including cardiac arrhythmia, respiratory insufficiency, and swallowing difficulties. There seems to be a correlation between the severity of phenotype and the very short EcoRI fragment in the chromosome 4q35 region. We conclude that the high frequency of multi-organ involvements in this severe FSHD variant suggests the need for an early and multidisciplinary intervention.

The pancreatic functions of children with cholestatic liver diseases were unclear. Due to anatomic vicinity and common ontogenic origin, hepatobiliary disorders of infancy may also affect pancreatic function. The aim of the study was to evaluate the exocrine pancreatic function and common pancreatic function tests in children with cholestatic disorders.In 40 children with cholestasis, fecal elastase 1 (FE1) concentrations were measured. Serum amylase and lipase values were tested. The diagnoses included 32 patients with extrahepatic cholestasis (biliary atresia (BA) and choledochal cyst), and 8 patients with intrahepatic cholestasis (progressive familial intrahepatic cholestasis and Alagille syndrome). None had renal insufficiency or clinical symptoms/signs of acute pancreatitis.All the patients had normal FE1 (200 microg/g). Nineteen percent (7/37) had elevated serum amylase levels (100 U/l). Thirty-two percent (12/37) had elevated serum lipase levels above the normal (120 U/l). Seventy-three percent (8/11) of BA patients with bilirubin2 mg/dl had elevated serum lipase levels compared to 18% (3/17) with bilirubinor = 2 mg/dl (p = 0.0036). None had detectable pancreatic abnormality on ultrasonography and magnetic resonance images.None of the cholestatic children in this study had exocrine pancreatic insufficiency as detected by FE1. Hyperamylasemia and/or hyperlipasemia were frequently found. In children with BA, those with impaired biliary excretion tended to have elevated serum pancreatic enzymes as compared with those who had no jaundice. A decreased hepatic metabolism may be the cause.

Objective To identify the prevalence and risk factors of feeding and swallowing problems in patients with type II and type III spinal muscular atrophy (SMA). Study design Cross-sectional data from 108 genetically confirmed patients with SMA (age range, 3-45 years; 60 with type II and 48 with type III) were analyzed. The questionnaire survey included demographic data, current motor function and respiratory status, feeding and swallowing difficulties, and consequences. The risk factors were analyzed via logistic regression. Results The 3 most common feeding and swallowing difficulties in patients with type II and III SMA were choking (30.6%), difficulty conveying food to the mouth (20.4%), and difficulty chewing (20.4%). Current motor function status was an independent risk factor for feeding and swallowing difficulties (sitters vs walkers: OR, 7.59; 95% CI, 1.22-47.46). All 4 nonsitters (ie, patients with type II SMA who had lost their sitting ability) had feeding and swallowing difficulties. Patients with feeding and swallowing difficulties had significantly higher rates of underweight and aspiration pneumonia than those without these problems. Conclusion Patients with type II and III SMA have a high prevalence of risk factors for feeding and swallowing difficulties, suggesting that an individualized treatment plan should depend on current motor function status.

Background Transport protein particle (TRAPP) is a multiprotein complex involved in endoplasmic reticulum-to-Golgi trafficking. Zebrafish with a mutation in the TRAPPC11 orthologue showed hepatomegaly with steatosis and defects in visual system development. In humans, TRAPPC11 mutations have been reported in only three families showing limb-girdle muscular dystrophy (LGMD) or myopathy with movement disorders and intellectual disability. Methods We screened muscular dystrophy genes using next-generation sequencing and performed associated molecular and biochemical analyses in a patient with fatty liver and cataract in addition to infantile-onset muscle weakness. Results We identified the first Asian patient with TRAPPC11 mutations. Muscle pathology demonstrated typical dystrophic changes and liver biopsy revealed steatosis. The patient carried compound heterozygous mutations of a previously reported missense and a novel splice-site mutation. The splice-site change produced two aberrantly-spliced transcripts that were both predicted to result in translational frameshift and truncated proteins. Full-length TRAPPC11 protein was undetectable on immunoblotting. Conclusion This report widens the phenotype of TRAPPC11-opathy as the patient showed the following: (1) congenital muscular dystrophy phenotype rather than LGMD; (2) steatosis and infantile-onset cataract, both not observed in previously reported patients; but (3) no ataxia or abnormal movement, clearly indicating that TRAPPC11 plays a physiological role in multiple tissues in human.