Diagnostic Significance of Absence of Post-Feeding Contraction of the Gallbladder in Biliary Atresia: Two Case Reports.

Ultrasonography is an essential part of the diagnostic process of biliary atresia (BA). The characteristic findings of BA include a hilar hyperechoic zone, the triangular cord sign (TCS), an absence of gallbladder contraction after feeding, and gallbladder atrophy. However, approximately 10% of patients with BA have a normal gallbladder. We herein present two cases of BA with normal morphology of the gallbladder as shown by ultrasonography. In the first case, the patient was positive for the TCS, negative for gallbladder atrophy, and positive for contraction of the gallbladder after feeding; the final diagnosis was hilar obstructive BA complicated by pancreaticobiliary maljunction. In the second case, the patient was positive for the TCS, negative for gallbladder atrophy, and negative for contraction of the gallbladder after feeding; the patient also had common bile duct obstruction and stenosis of the hepatic duct in the hilar region. Based on these two cases, we conclude that gallbladder findings are not diagnostic for BA because in some types, the gallbladder may be normal in morphology and even have the capacity for contraction after feeding.

Combined Single Nucleotide Variants of ORAI1 and BLK in a Child with Refractory Kawasaki Disease.

Kawasaki disease (KD) is a systemic vasculitis with an unknown etiology affecting young children. Although intravenous immunoglobulin (IVIG) plus acetylsalicylic acid is effective in most cases, approximately 10-20% of patients do not respond to this therapy. An 8-month-old boy was admitted to a local hospital with the presumptive diagnosis of KD. He received IVIG twice and four series of methylprednisolone pulse therapy from the third to the tenth day of illness. Despite these treatments, his fever persisted with the development of moderate dilatations of the coronary arteries. A diagnosis of refractory KD was made, and infliximab with oral prednisolone was administered without success. Defervescence was finally achieved by cyclosporine A, an inhibitor of the signaling pathway of the calcineurin/nuclear factor of activated T cells (NFAT). Whole-genome sequencing of his deoxyribonucleic acid samples disclosed two single nucleotide variants (SNVs) in disease-susceptibility genes in Japanese KD patients, ORAI1 (rs3741596) and BLK (rs2254546). In summary, the refractory nature of the present case could be explained by the presence of combined SNVs in susceptibility genes associated with upregulation of the calcineurin/NFAT signaling pathway. It may provide insights for stratifying KD patients based on the SNVs in their susceptibility genes.

Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease, 2017.

BACKGROUND: Despite the presence of ganglion cells in the rectum, some patients have symptoms similar to those of Hirschsprung's disease. A consensus has yet to be established regarding the terminology for these diseases. We defined this group of diseases as "allied disorders of Hirschsprung's disease" and compiled these guidelines to facilitate accurate clinician diagnosis and provide appropriate treatment strategies for each disease. METHODS: These guidelines were developed using the methodologies in the Medical Information Network Distribution System (MINDS). Of seven allied disorders, isolated hypoganglionosis; megacystis-microcolon-intestinal hypoperistalsis syndrome; and chronic idiopathic intestinal pseudo-obstruction were selected as targets of clinical questions (CQ). In a comprehensive search of the Japanese- and English-language articles in PubMed and Ichu-Shi Web, 836 pieces of evidence related to the CQ were extracted from 288 articles; these pieces of evidence were summarized in an evidence table. RESULTS: We herein outline the newly established Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease. Given that the target diseases are rare and intractable, most evidence was drawn from case reports and case series. In the CQ, the diagnosis, medication, nutritional support, surgical therapy, and prognosis for each disease are given. We emphasize the importance of full-thickness intestinal biopsy specimens for the histopathological evaluation of enteric ganglia. Considering the practicality of the guidelines, the recommendations for each CQ were created with protracted discussions among specialists. CONCLUSIONS: Clinical practice recommendations for allied disorders of Hirschprung's disease are given for each CQ, along with an assessment of the current evidence. We hope that the information will be helpful in daily practice and future studies.

Shwachman-Diamond syndrome: Nationwide survey and systematic review in Japan.

BACKGROUND: Shwachman-Diamond syndrome (SDS) is a rare multisystem disorder associated with exocrine pancreatic insufficiency. The present study reports the results of a nationwide survey and a systematic review on SDS to develop consensus guidelines for intractable diarrhea including SDS. METHODS: Questionnaires were sent to 616 departments of pediatrics or of pediatric surgery in Japan in a nationwide survey. A second questionnaire was sent to doctors who had treated SDS patients and included questions on clinical information. Additionally, a systematic review was performed using digital literature databases to assess the influence of medical (i.e. non-surgical) treatment on SDS prognosis. RESULTS: Answers were received from 529 institutions (85.9%), which included information on 24 patients with SDS (median age, 10.4 years; male, n = 15) treated from January 2005 to December 2014. Although 75% of patients received pancreatic enzyme replacement therapy, there was no significant association between treatment and prognosis. Systematic review identified one clinical practice guideline, two case series, eight case reports and 26 reviews. Patient information from those studies was insufficient for meta-analysis. CONCLUSIONS: The rarity of SDS makes it difficult to establish evidence-based treatment for SDS. According to the limited information from patients and published reports, medical treatment for malabsorption due to SDS should be performed to improve fat absorption and stool condition, but it is not clear whether this treatment improves the prognosis of malabsorption.

The Diagnostic Significance of Comorbidities of Congenital Heart Diseases, Low-Set Ears, and Intrauterine Growth Restriction in Neonates With Trisomies 13 and 18.

BACKGROUND: Trisomies 13 and 18 (T13/18) are autosomal trisomy syndromes with dismal prognoses. Deciding whether to perform a chromosomal analysis for the definitive diagnosis is often difficult (even for experienced pediatricians) because representative clinical signs may not be found in all T13/18 neonates. OBJECTIVES: This study aimed to investigate any clinical signs that could be useful for screening for T13/18 in participants without the representative clinical signs traditionally found in odd-looking neonates with malformation syndromes. PATIENTS AND METHODS: We retrospectively analyzed 15 T13/18 patients, 33 trisomy 21 patients, and 48 controls with other malformation syndromes, for apparent clinical signs during the neonatal period. All participants had been admitted to the neonatal intensive care unit of Kansai Medical University over a nine-year period. RESULTS: The three leading clinical signs in patients with T13/18 were congenital heart diseases (CHD; 100%), low-set ears (LSE; 80%), and intrauterine growth restriction (IUGR; 73.3%). A comorbidity of these two leading non-specific clinical signs was CHD with LSE, which showed the highest diagnostic accuracy between T13/18 and controls with a sensitivity of 80.0% and a negative predictive value of 92.5%. The chi-square test among these three groups (P < 0.01) and multiple comparison tests of proportional differences showed that the comorbidity of CHD with LSE was specific for autosomal trisomy syndromes. A comorbidity of CHD with IUGR also revealed a similar diagnostic accuracy with a sensitivity of 73.3% and a negative predictive value of 90.9% as well as a specificity for T13/18. CONCLUSIONS: The comorbidities of either CHD with LSE or CHD with IUGR should be suspected in neonates with autosomal trisomy syndromes, particularly T13/18 without the expected representative clinical signs.

Significance of twinkling artifact on ultrasound in the diagnosis of cystine urolithiasis.

Twinkling artifact (TA) refers to the finding characterized by both a high-echoic mass upon B-mode ultrasound (US) and turbulence-like signals over the entire mass without significant blood flow on color Doppler US. TA is a characteristic sign of urolithiasis, and there has been no previous report on this finding in the digestive tract. The authors recently encountered a 2-year 9-month-old boy with cystinuria presenting with an opacified abdominal mass. Although he was originally diagnosed as having calcified stool mass, the finding of TA upon US led to the correct diagnosis of huge urolith (4.2 cm in diameter) in the urinary bladder. Laparotomic stone removal was successfully conducted and the calculus was confirmed to be composed of cystine. The finding of TA upon US facilitates identification of the structure and location of the intra-abdominal mass.

Novel mutation (L157X) in the succinate dehydrogenase B gene (SDHB) in a Japanese family with abdominal paraganglioma following lung metastasis.

Recently, nuclear genes encoding two mitochondrial complex II subunit proteins, SDHD and SDHB, have been found to be associated with the development of familial pheochromocytomas and paragangliomas (hereditary pheochromocytoma/paraganglioma syndrome: HPPS). Growing evidence suggests that the mutation of SDHB is highly associated with abdominal paraganglioma and the following distant metastasis (malignant paraganglioma). In the present study, we report the case of a novel SDHB mutation (L157X) in a Japanese patient with abdominal paraganglioma following malignant lung metastasis. In addition, we identified an asymptomatic carrier of the SDHB mutation in this family.

Cecal volvulus in children with mental disability.

Two cases of cecal volvulus in children with mental disability are described. Case 1: a 3-year-old girl with trisomy 18 was admitted with abdominal pain and vomiting. She had received left lateral segmentectomy 6 months earlier because of hepatoblastoma. Release of the cecal volvulus followed by the fixation of the cecum and ascending colon to the right retroperitonium was performed. Case 2: a 15-month-old boy with Cornelia de Lange syndrome who had undergone a standard Nissen's fundoplication. On the sixth postoperative day, progressive abdominal distention developed. Abdominal color Doppler ultrasonography from the right rear side revealed a clockwise-twisted ileocecal artery and vein and a dilated colon with tapering configuration. On the ninth postoperative day, emergent release of the cecal volvulus followed by ascending colostomy through a perforation site was performed. Approximately 40 children with cecal volvulus have so far been reported, of whom 13 are mentally disabled. We speculated that in the cases reported here, distention of the intestine accompanying the mental disability and the previous surgery contributed to the development of cecal volvulus in addition to the prerequisite of abnormal mobility of the cecum. Pediatric surgeons should consider the cecal volvulus as a cause of intestinal obstruction in mentally disabled children.

Usefulness of magnetic resonance cholangiopancreatography in biliary structures in infants: a four-case report.

In this paper, we report the usefulness of magnetic resonance cholangiopancreatography (MRCP) in excluding biliary atresia (BA) as the cause of neonatal cholestasis. MRCP with a 1.5-T magnetic resonance (MR) imaging unit was performed on four jaundiced neonates and infants aged from 38 days to 106 days. The diagnosis of BA (n=2) was confirmed with surgery, liver biopsy and surgical cholangiography. Diagnosis of neonatal hepatitis (NH, n=2) was confirmed with clinical follow-up until jaundice resolved, while one of them was diagnosed with surgical cholangiography. In all discoloured acholic stools, increased direct bilirubin (4.4-11.3 mg/dl) with positive lipoprotein X prompted technetium 99mTc disofenin scanning, which showed no excretion. Computed tomography (CT) showed a gallbladder in one with hepatitis but no intrahepatic bile duct in two with BA. The Kasai operation was performed in two patients with BA. In two patients with BA, neither the common bile duct nor the common hepatic ducts were visible at MRCP. In two patients with NH, MRCP clearly depicted both the common hepatic and the common bile ducts. MRCP was accurate in excluding BA as the cause of neonatal cholestasis, while 99mTc disofenin cholescintigraphic findings were false-positive in two patients with non-obstructive cholestasis. We conclude that MRCP can be used to depict the major biliary structures of neonates and small infants and to exclude BA as the cause of neonatal cholestasis by allowing visualisation of the biliary tract.

The role of a mutation of the CXCR4 gene in WHIM syndrome.

We investigated the role of a mutation of the CXCR4 gene in 11-year-old twin sisters with WHIM syndrome. The mutated gene may result in production of the mutant CXCR4 protein causing abnormal apoptosis and migratory function, which are thought to be related to the cause of chronic neutropenia in WHIM syndrome.