Kensuke Ohashi

Long-term follow-up of nutritional status, pancreatic function, and morphological changes of the pancreatic remnant after pancreatic tumor resection in children.

Objectives The objectives of the present study were to determine nutritional status, pancreatic function, and morphological changes of the pancreatic remnant after pancreatic tumor resection in children. Methods The nutritional status was evaluated by the patterns of growth. Pancreatic function was evaluated by using a questionnaire, the Bristol stool form chart, the serum levels of fasting blood glucose, and hemoglobin A1c (HbA1c). Morphological changes of the pancreatic remnant were evaluated by computed tomography, magnetic resonance image, or magnetic resonance cholangiopancreatography. Results The present study consisted of 6 patients with pancreatic tumor (5 solid pseudopapillary tumors of the pancreas and 1 pancreatoblastoma) who underwent the following operations: tumor enucleation (3), distal pancreatectomy with splenectomy (1), and pylorus-preserving pancreatoduodenectomy (PPPD [2]). The serum levels of HbA1c have been gradually elevated in 2 patients with PPPD. A significant decrease in pancreatic parenchymal thickness and dilatation of the main pancreatic duct were observed in 2 patients with PPPD. Conclusion Endocrine pancreatic insufficiency after PPPD may be explainable by obstructive pancreatitis after operation. Taking together the results of pancreatic endocrine function and morphological changes of pancreatic remnant after PPPD, tumor enucleation should be considered as surgical approach in children with pancreas head tumor whenever possible.

The clinical course in pediatric solid tumor patients with focal nodular hyperplasia of the liver

BackgroundFocal nodular hyperplasia (FNH) of the liver is a rare benign lesion that may be related to the vascular and hepatic damage induced by completion of tumor therapy and a reaction to localized vascular abnormality. The aim of this study was to analyze the clinical course in pediatric solid tumor patients with FNH.MethodsWe analyzed thirty-two patients with pediatric solid tumors who received multiagent chemotherapy (15 advanced neuroblastomas, 7 hepatoblastomas, 5 rhabdomyosarcomas, 2 nephroblastomas, 1 rhabdoid tumor of the kidney, 1 clear cell sarcoma of the kidney and 1 pancreatoblastoma). All of them had been previously treated at our hospital, and have been alive for over 3 years without recurrence.ResultsFNH lesions were discovered in three (9.4%) of 32 patients, and were neuroblastoma (NB) stage 4. All 3 patients received induction chemotherapy and high-dose alkylating agents, and developed grade 3 (National Cancer Institute Common Toxicity Criteria; NCI-CTC) liver dysfunction during completion of tumor therapy without veno-occlusive disease. Two of the 3 patients received the same induction chemotherapy and high doses of alkylating agents with total body irradiation for cytoreductive agents prior to peripheral blood cell transplantation. FNH lesions in both female patients who received estrogen replacement therapy after completion of tumor therapy have expanded and are increasing.ConclusionFNH appears to be a late complication of iatrogenic disease in NB stage 4 patients. The therapeutic agents for NB stage 4 and estrogen replacement therapy should be considered as risk factors for the development of FNH.

Successful treatment for hepatoblastoma in a 1‐year‐old boy with trisomy 18

type GCT, relapses may occur even decades after diagnosis, although the survival rate is 95% if diagnosed in the early stages. The presented case indicates the need to emphasize the possibility of occurrence of endocrinological disorders as a symptom of hormone-secreting tumors in children. GnRh-independent precocious puberty may be the first symptom of hormone-secreting ovarian tumors in children, even if tumors are not detectable in preliminary radiologic examinations. In such cases, profound diagnostics with systematic ultrasound examination are essential.

Therapeutic strategies of meconium obstruction of the small bowel in very‐low‐birthweight neonates

Background:  Meconium obstruction without cystic fibrosis in low‐birthweight neonates is a distinct clinical entity. We aimed to determine what therapeutic strategies work best in very‐low‐birthweight neonates with meconium obstruction of the small bowel under varied clinical conditions caused by the associated diseases of prematurity.

Risk factors for surgical intestinal disorders in VLBW infants: Case-control study

Very low‐birthweight (VLBW) infants (VLBWI) are at increased risk for surgical intestinal disorders including necrotizing enterocolitis (NEC), focal intestinal perforation (FIP) and meconium‐related ileus (MRI). The aim of this study was to identify disease‐specific risk factors for surgical intestinal disorders in VLBWI.

Non-promoter DNA hypermethylation of Zygote Arrest 1 (ZAR1) in neuroblastomas

BACKGROUND The comprehensive methylation analysis of tumor-specific differently methylated regions in malignant melanomas and brain tumors has led to the identification of non-promoter hypermethylation of zygote arrest 1 (ZAR1). To search the non-promoter ZAR1 hypermethylation in neuroblastomas, we analyzed the levels of the methylation and transcript expression of ZAR1. METHODS The MassARRAY® EpiTYPER (Sequenom Inc., San Diego, CA, USA) system was optimized to determine the quantitative methylation levels of ZAR1 for 12 neuroblastoma cell lines, 23 neuroblastoma samples and four adrenal samples. ZAR1 expression levels were evaluated through a quantitative, real-time reverse transcription-polymerase chain reaction. The quantitative methylation levels of ZAR1 were subjected to correlation studies with the established markers of progressive disease and outcome. RESULTS Strikingly, the hypermethylation of ZAR1 regions and ZAR1 expression levels was observed in the neuroblastoma cell lines and neuroblastoma samples, compared to the adrenal samples. Somatic changes in ZAR1 methylation and ZAR1 expression were found in all three neuroblastoma patients. In the ZAR1 regions, poor-outcome tumors that were MYCN-amplified and/or Stage 3 or 4 and/or the age at diagnosis was≥18months, and/or showed an unfavorable histology were frequently hypermethylated. CONCLUSION Our results indicate that the hypermethylation of ZAR1 regions is extremely frequent in neuroblastomas and correlates with established markers of progressive disease and outcome.

Outcome in VLBW infants with surgical intestinal disorder at 18 months of corrected age

Surgical intestinal disorders, such as necrotizing enterocolitis (NEC), focal intestinal perforation (FIP), and meconium‐related ileus (MRI), are serious morbidities in very low‐birthweight infants (VLBWI). The aim of this study was to compare the composite outcomes of death or neurodevelopmental impairment (NDI) in VLBWI with surgical intestinal disorders and assess independent risk factors for death and NDI at 18 months of corrected age.

Identification of aberrant methylation regions in neuroblastoma by screening of tissue-specific differentially methylated regions†‡§

The identification of tissue‐specific differentially methylated regions (tDMRs) is key to our understanding of mammalian development. Research has indicated that tDMRs are aberrantly methylated in cancer and may affect the oncogenic process.

Usefulness of power Doppler ultrasonography and superparamagnetic iron oxide enhanced magnetic resonance imaging for diagnosis of focal nodular hyperplasia of the liver after treatment of neuroblastoma.

Focal nodular hyperplasia (FNH) of the liver is rare in children, and it is usually diagnosed through a biopsy of the liver or hepatectomy. The authors report a case of a 10-year-old girl with multiple focal nodular hyperplasia lesions of the liver after the completion of tumor therapy for advanced neuroblastoma, and review the usefulness of the combination of power Doppler ultrasonography (US) and superparamagnetic iron oxide (SPIO) enhanced magnetic resonance imaging (MRI) for the diagnosis of FNH without a biopsy of the liver or hepatectomy.

Depletion of TFAP2E attenuates adriamycin-mediated apoptosis in human neuroblastoma cells

Neuroblastoma is a childhood malignancy originating from the sympathetic nervous system and accounts for approximately 15% of all pediatric cancer-related deaths. To newly identify gene(s) implicated in the progression of neuroblastoma, we investigated aberrantly methylated genomic regions in mouse skin tumors. Previously, we reported that TFAP2E, a member of activator protein-2 transcription factor family, is highly methylated within its intron and its expression is strongly suppressed in mouse skin tumors compared with the normal skin. In the present study, we analyzed public data of neuroblastoma patients and found that lower expression levels of TFAP2E are significantly associated with a shorter survival. The data indicate that TFAP2E acts as a tumor suppressor of neuroblastoma. Consistent with this notion, TFAP2E-depleted neuroblastoma NB1 and NB9 cells displayed a substantial resistance to DNA damage arising from adriamycin (ADR), cisplatin (CDDP) and ionizing radiation (IR). Silencing of TFAP2E caused a reduced ADR-induced proteolytic cleavage of caspase-3 and PARP. Of note, compared with the untransfected control cells, ADR-mediated stimulation of CDK inhibitor p21WAF1 was markedly upregulated in TFAP2E‑knocked down cells. Therefore, our present findings strongly suggest that TFAP2E has a pivotal role in the regulation of DNA damage response in NB cells through the induction of p21WAF1.