Prostaglandin E-major urinary metabolite as a noninvasive surrogate marker for infantile necrotizing enterocolitis.

BACKGROUND: Early definitive diagnosis of necrotizing enterocolitis (NEC) based on Bell's staging criteria is difficult because there are few observable changes on abdominal imaging and blood chemistry tests at the onset of the disease. PURPOSE: To investigate whether prostaglandin E-2 major urinary metabolite (PGE-MUM) can be a useful surrogate marker reflecting the disease state and severity of NEC in infants. METHODS: Infants were enrolled in this study between January 2014 and December 2016. NEC diagnosis was based on Bell's staging criteria > Stage II or necrotic bowel observed at surgery. After diagnosis, PGE-MUM level was measured and compared with that of the other disease and healthy infant groups. RESULTS: Median PGE-MUM value was highest in the NEC group (576 [65-3672] µg/g•Cre/BSA × 1000), followed by the other disease group (94 [57-296] µg/g•Cre/BSA × 1000) and the healthy infant group (19 [10-44] µg/g•Cre/BSA × 1000) (sensitivity: 92.3%, specificity: 81.5%, accuracy: 85.0%; p < 0.01). PGE-MUM level correlated with improved status of NEC, length of necrotic intestine, and Bell's staging criteria. CONCLUSIONS: PGE-MUM level may be a useful surrogate biomarker reflecting the disease state of NEC. The method of urine sample collection is also advantageous, being noninvasive for infants. This is the first study reporting PGE-MUM level in NEC. TYPE OF STUDY: Study of diagnostic test. LEVEL OF EVIDENCE: LEVEL II.

Identification and metastatic potential of tumor-initiating cells in malignant rhabdoid tumor of the kidney.

PURPOSE: Malignant rhabdoid tumor of the kidney (MRTK) is a rare and highly aggressive malignancy of infanthood. In an effort to delineate MRTK progression, we investigated the metastatic fate of some MRTK cells using xenotransplantation animal models and the tumor-initiating potential of CD133(+) MRTK cells. EXPERIMENTAL DESIGN: We established two MRTK cell lines (JMU-RTK-1 and JMU-RTK-2) from patients with MRTK. We generated five luciferase-expressing MRTK cells for in vivo luminescent imaging and evaluated the metastatic fate in an orthotopic xenotransplantation model. Capacities of MRTK-initiating cells were examined in nonobese diabetic/severe combined immunodeficient mice after antibody-mediated magnetic bead sorting. Use of chemokine receptor CXCR4 expression as a metastatic marker was evaluated by flow cytometry and Western blotting. RESULTS: MRTK cell lines showed distant organ metastasis. JMU-RTK-1, JMU-RTK-2, and G401 cells showed considerable aggressiveness compared with SWT-1 and SWT-2 cells (P < 0.05). Moreover, as few as 1,000 CD133(+) MRTK cells initiated tumor development in nonobese diabetic/severe combined immunodeficient mice by 21 days (60-100%) in all examined cell lines, although the same number of CD133(-) MRTK cells could not form tumors (0%). Interestingly, the metastatic potential of the CD133(+) population remained unaffected compared with a nonenriched population. The potential metastatic marker CXCR4 was expressed in CD133(+) and CD133(-) MRTK cells, and CD133(-) cells seemed to play a cooperative role in terms of tumorigenicity and metastasis. CONCLUSIONS: These results suggest that CD133(+) cells may determine the metastatic fate of MRTK cells and that CD133(-) cells may play an auxiliary role in tumor progression and metastasis.

Cholelithiasis and choledocholithiasis associated with anomalous junction of the cystic duct in a child.

We report an extremely rare case of cholelithiasis, presumably owing to cholestasis resulting from an anomalous course of the cystic duct. A 10-year-old girl visited our hospital because of right epigastric pain and fever. Cholelithiasis and choledocholithiasis were diagnosed by ultrasound examination. Magnetic resonance cholangiopancreatography showed no pancreaticobiliary maljunction but confirmed a dilated, tortuous cystic duct anomalously draining into the right hepatic duct. Because cholangitis and obstructive jaundice progressed after admission, emergent endoscopic retrograde cholangiopancreatography was performed, and a common bile duct stone was removed endoscopically. It was a bilirubin stone. At a later date, laparoscopic cholecystectomy was performed for cholelithiasis. Preoperative 3-dimensional computed tomography and intraoperative cholangiography enabled us to treat the cystic duct safely.

Duplication of the paternal IGF2 allele in trisomy 11 and elevated expression levels of IGF2 mRNA in congenital mesoblastic nephroma of the cellular or mixed type.

In a metaphase comparative genomic hybridization and fluorescence in situ hybridization study of 13 congenital mesoblastic nephroma (CMN) tumors, trisomy 11 was found in seven cellular or mixed type tumors, disomy 11 with other chromosome changes in two cellular type tumors, and no chromosome changes in four classical type tumors. Reverse-transcription (RT)-PCR analysis detected the ETV6-NTRK3 fusion transcript in all eight cellular or mixed type tumors examined, but not in four classical type tumors. All seven tumors with trisomy 11 showed duplication of the paternal IGF2 allele, and six cellular or classical type tumors with disomy 11 showed one paternal and one maternal allele of IGF2, analyzing the methylation status of the sixth CTCF site of the H19-differentially methylated region. Allelic expression study using the ApaI/AvaII polymorphism site at exon 9 of IGF2 showed retention of imprinting in all seven tumors examined. Quantitative real-time RT-PCR analysis showed higher expression levels of IGF2 mRNA in three of three cellular type tumors with trisomy 11, in one cellular type tumor with disomy 11, and in three of four classical tumors than in fetal kidneys or normal kidney tissues. Thus, duplicated paternal IGF2 resulted in elevated IGF2 mRNA levels, and may provide CMN or its precursor cells with a proliferative advantage. The mechanism explaining that some cellular or classical type tumors with disomy 11 also showed elevated IGF2 mRNA levels remains unresolved. IGF2 clearly plays an important role in the tumorigenic process of CMN, although it is difficult to assess its exact role.

Pyloromyotomy through a sliding umbilical window.

PURPOSE: The semi-circumumbilical incision for treatment of infantile hypertrophic pyloric stenosis, described by Tan and Bianchi (Tan KC, Bianchi A. Circumumbilical incision for pyloromyotomy. Br J Surg 1986;73:399), does not allow a comfortable access to the pylorus in up to 30% of cases, resulting, not infrequently, in unexpected seromuscular lacerations. To get easier access to the pylorus we have performed the Ramstedt pyloromyotomy through a sliding umbilical window after full-circumumbilical incision in 13 initial consecutive cases. PATIENTS AND METHODS: Skin was incised along the entire circumference of the umbilicus, and then was undermined, creating a circular subcutaneous space, 8 cm in diameter. The umbilical window, about 1.5 cm in diameter, was slid diagonally toward the right upper quadrant, by shifting a pair of muscle retractors, 3 to 4 cm from the umbilicus, with the umbilicus left in its original position under the slid skin. Through the sliding window at the right upper quadrant, the abdomen was entered, and the hypertrophied pylorus was identified within the center of the window. Then the pyloromyotomy was performed intracorporeally with ease. RESULTS: In all 13 infants, an adequate pyloromyotomy was safely performed. The wound healed primarily in all cases, without leaving conspicuous scar, subcutaneous abscess formation, or incisional hernia. The postoperative course was quite uneventful in each. CONCLUSION: This new approach allows far easier access to and exposure of the pylorus, and facilitates a safe intracorporeal pyloromyotomy, and achieves an excellent cosmetic outcome.

Successful second autologous peripheral blood stem cell transplantation conditioned with total body irradiation for progressive neuroblastoma after recurrence.

A girl with recurrent neuroblastoma was successfully treated with second autologous stem cell transplantation (SCT) conditioned with total body irradiation (TBI). This patient was diagnosed as stage IV neuroblastoma at the age of 18 months. Pathological finding was stroma-poor unfavorable histology and amplification of MYCN gene was extremely high (153 copies). In spite of autologous SCT with non-TBI regimen in the status of disease-free, neuroblastoma relapsed at the primary site 6 months later. Second autologous SCT conditioned with TBI and melphalan was performed although the tumor was progressive. Over 3 years after second SCT, she has been well with no evidence of further recurrence of neuroblastoma, but she was complicated with permanent atrophy of left kidney. TBI might be effective for relapsed neuroblastoma who previously received SCT with non-TBI regimen.

Ganglion of the groin in a child: an unusual cause of soft-tissue swelling of the groin.

A case of groin ganglion with asymptomatic compression of the femoral vein is described. A 2-year-old girl was referred because of a symptomless groin mass. A mass was palpable in the right femoral triangle. Computed tomography and ultrasonography revealed a cystic lesion compressing the femoral vein ventrally. Prompt surgical removal of the cystic lesion was done without complications. Histopathological examination showed a benign structure similar to that of a ganglion.

Aberrations of the hSNF5/INI1 gene are restricted to malignant rhabdoid tumors or atypical teratoid/rhabdoid tumors in pediatric solid tumors.

The hSNF5/INI1 gene, which encodes a subunit of the SWI/SNF family of chromatin-remodeling complexes and is located at 22q11.2, has been reported as a tumor suppressor gene inactivated in malignant rhabdoid tumors (MRTs). We analyzed this gene in varieties of pediatric solid tumors including MRTs, using the reverse transcription-polymerase chain reaction (PCR) and PCR-single strand conformation polymorphism method. We found 5 homozygous deletions, 2 truncated mutations, one missense mutation, and one silent mutation of the hSNF5/INI1 gene in 7 MRT cell lines, and one homozygous deletion, one microdeletion, one splicing acceptor site mutation, and one absence of expression in 7 fresh tumor tissues of MRT and atypical teratoid (AT)/rhabdoid tumors (RTs). Homozygous deletions were also found in one (KYM-1) of 8 rhabdomyosarcoma (RMS) cell lines. To investigate characteristics of the KYM-1 cell line, we have established KYM-1 tumors in nude mice into which KYM-1 cells were transplanted. Notably, we found that MyoD1, known as a marker for RMS, was not expressed in the KYM-1 cell line as well as MRT cell lines and fresh tumors. Histopathologic, cytogenetic, and molecular studies of the KYM-1 cell line and KYM-1 tumors in nude mice have revealed that this RMS cell line should be MRT rather than RMS. RMS-carrying aberrations of the hSNF5/INI1 gene should be reevaluated. No aberrations of this gene were found in the other 34 cell lines or 80 fresh tumor specimens except the single nucleotide polymorphisms in the 3' noncoding region. These results suggest that alterations of the hSNF5/INI1 gene were restricted to MRTs or AT/RTs in pediatric solid tumors.