Atsuko Nakazawa

Improved treatment results of children with B‐cell non‐Hodgkin lymphoma: A report from the Japanese Pediatric Leukemia/Lymphoma Study Group B‐NHL03 study

Previous Japanese studies of childhood B‐cell non‐Hodgkin lymphoma (B‐NHL) have shown a favorable outcome, though the study size was too small to effectively assess the efficacy and safety of treatment for childhood B‐NHL.

The classification based on intrahepatic portal system for congenital portosystemic shunts

BACKGROUND/PURPOSE Liver transplantation was previously indicated as a curative operation for congenital absence of portal vein. Recent advances in radiological interventional techniques can precisely visualize the architecture of the intrahepatic portal system (IHPS). Therefore, the therapeutic approach for congenital portosystemic shunt (CPS) needs to be reevaluated from a viewpoint of radiological appearances. The aim of this study was to propose the IHPS classification which could explain the pathophysiological characteristics and play a complementary role of a therapeutic approach and management for CPS. METHODS Nineteen patients with CPS were retrospectively reviewed. The median age at diagnosis was 6.8 years old. Eighteen of these patients underwent angiography with a shunt occlusion test and were classified based of the severity of the hypoplasia of IHPS. RESULTS The eighteen cases who could undergo the shunt occlusion test were classified into mild (n=7), moderate (n=6) and severe types (n=5) according to the IHPS classification. The IHPS classification correlated with the portal venous pressure under shunt occlusion, the histopathological findings, postoperative portal venous flow and liver regeneration. Shunt closure resulted in dramatic improvement in the laboratory data and subclinical encephalopathy. Two patients with the severe type suffered from sepsis associated with portal hypertension after treatment, and from the portal flow steal phenomenon because of the development of unexpected collateral vessels. The patients with the severe type had a high risk of postoperative complications after shunt closure in one step, even if the PVP was relatively low during the shunt occlusion test. CONCLUSION The IHPS could be visualized by the shunt occlusion test. The IHPS classification reflected the clinicopathological features of CPS, and was useful to determine the therapeutic approach and management for CPS.

Bmi1 regulates cell fate via tumor suppressor WWOX repression in small‐cell lung cancer cells

Mortality from lung cancer is important worldwide. Recently, epigenetic aberration of lung cancer, not only genomic DNA methylation but also chromatin modification, has become an important target for lung cancer research, although previous research has demonstrated that lung cancer develops as a result of both environmental and genetic factors. Here, we demonstrated that an epigenetic regulator/polycomb group protein Bmi1 is more highly expressed in small‐cell lung cancer (SCLC) than in non‐small‐cell lung cancer by immunohistochemical analysis. In vitro experiments indicated that Bmi1 reduction by lentivirus‐derived shRNA significantly suppressed proliferation, colony formation and in vivo tumor formation. Importantly, apoptosis was induced by Bmi1 depletion in small‐cell lung cancer cells. Furthermore, a tumor suppressor WWOX was identified as a Bmi1 target in the cells by a chromatin immunoprecipitation assay and a quantitative real‐time PCR assay; WWOX had a role as a tumor suppressor in SCLC cells; therefore, the Bmi1/WWOX pathway could be a new candidate for a new therapeutic approach for SCLC. (Cancer Sci 2011; 102: 983–990)

Living‐donor liver transplantation for propionic acidemia

Kasahara M, Sakamoto S, Kanazawa H, Karaki C, Kakiuchi T, Shigeta T, Fukuda A, Kosaki R, Nakazawa A, Ishige M, Nagao M, Shigematsu Y, Yorifuji T, Naiki Y, Horikawa R. Living‐donor liver transplantation for propionic acidemia.

Successful treatment of kaposiform hemangioendothelioma with everolimus

There is currently no consensus on the second‐line management of Kaposiform hemangioendothelioma (KHE) that was resistant to prednisolone and vincristine. We described an eight‐year‐old male with KHE in the right femur that was resistant to prednisolone, vincristine and propranolol. Everolimus, an inhibitor of mammalian target of rapamycin (mTOR) at the dosage of 0.1 mg/kg/day, successfully decreased the tumor size and controlled the symptoms. Everolimus should be further studied as an alternative agent to sirolimus in the management of KHE. Pediatr Blood Cancer 2015;62:536–538.

Critical infantile hepatic hemangioma: results of a nationwide survey by the Japanese Infantile Hepatic Hemangioma Study Group

BACKGROUND The current survey aimed to describe the clinical features of critical infantile hepatic hemangioma (IHH) and the implications of recent treatments. MATERIALS AND METHODS A nationwide survey of critical IHH patients treated between 2005 and 2010 was performed in all 117 registered pediatric surgical hospitals in Japan. As a result, 19 patients were identified and reviewed using a statistical analysis. RESULTS Abdominal distention (47.4%), high-output cardiac failure (47.4%), coagulopathy (42.1%), and respiratory distress (31.6%) were the major symptoms. Three patients died (1 of coagulopathy, 1 of cardiac failure, and 1 of both). An accompanying portovenous shunt was also highlighted. Infantile hepatic hemangioma was totally insensitive to steroid treatment in 3 (23.1%) of the 13 patients, and 9 (47.4%) of the 19 patients required other treatments. Surgical resection and β-blocker improved the hematologic data, whereas hepatic arterial ligation and embolization seemed to produce a limited effect. Among the dead patients, several hematologic parameters were significantly worse: the thrombocyte count (pretherapeutic: 73,000 vs 300,000/mm(3), dead vs survivor, respectively [P < .03]; posttherapeutic: 66,000 vs 388,700/mm(3) [P < .003]) and the prothrombin time (posttherapeutic, 35.0 vs 12.1 seconds [P < .0001], dead vs survivor, respectively). CONCLUSION For critical IHH cases with steroid-insensitive hematologic disorders, alternative treatments including β-blocker therapy, surgery, and liver transplantation should be considered.

Gorham–Stout syndrome affecting the temporal bone with cerebrospinal fluid leakage

Gorham-Stout syndrome is a rare disorder characterized by progressive osteolysis that leads to the disappearance of bone. Lymphvascular proliferation causes the local destruction of bony tissue. Owing to the low incidence of this syndrome, little is known about its etiology or treatment. We present an 11-year-old girl with Gorham-Stout syndrome that involved right petrous apex in temporal bone and upper clivus, which cause intracranial pressure increase and cerebrospinal fluid (CSF) leakage. The patient required surgical repair of CSF leakage by extradural middle fossa approach with temporal fascia flap. Combined treatment with interferon and propranolol prevented the progression of osteolysis.

Portal vein reconstruction in pediatric living donor liver transplantation for patients younger than 1 year with biliary atresia.

BACKGROUND/PURPOSE Infants with biliary atresia undergoing living donor liver transplantation (LDLT) are at increased risk of portal vein (PV) complications because of their smaller vascular caliber and sclerosis because of previous Kasai portoenterostomy and recurrent cholangitis. METHOD Of 154 children who underwent transplantation between November 2005 and January 2011, 34 with biliary atresia received a transplant while younger than 1 year. Six patients underwent PV reconstruction with an interposition vein graft, and the others underwent the branch patch technique. The clinical characteristics of those who underwent the interposition reconstruction or the branch patch technique were compared, and the PV complications were assessed. RESULTS Portal vein complications occurred in 5 patients (14.7%) in the branch patch group. There were 4 patient deaths, and all of them had received branch patch reconstruction. The branch patch reconstruction cases with a sclerotic small caliber (<4 mm) determined by using preoperative ultrasonography showed a significantly high mortality rate (44.4%). All patients with interposition vein graft reconstruction are still alive with excellent graft function without anticoagulation therapy. CONCLUSION The interposition vein graft appears to be a feasible option with better graft survival and less PV complications when performing LDLT for biliary atresia in infants younger than 1.

Expression of NLRR3 Orphan Receptor Gene Is Negatively Regulated by MYCN and Miz-1, and Its Downregulation Is Associated with Unfavorable Outcome in Neuroblastoma

Purpose: Our previous study showed that expression of NLRR3 is significantly high in favorable neuroblastomas (NBL), whereas that of NLRR1 is significantly high in unfavorable NBLs. However, the molecular mechanism of transcriptional regulation of NLRR3 remains elusive. This study was undertaken to clarify the transcriptional regulation of NLRR3 and its association with the prognosis of NBL. Experimental Design:NLRR3 and MYCN expressions in NBL cell lines were analyzed after induction of cell differentiation, MYCN knockdown, and overexpression. The transcriptional regulation of NLRR3 was analyzed by luciferase reporter and chromatin immunoprecipitation assays. Quantitative PCR was used for examining the expression of NLRR3, Miz-1, or MYCN in 87 primary NBLs. Results: The expression of NLRR3 mRNA was upregulated during differentiation of NBL cells induced by retinoic acid, accompanied with reduced expression of MYCN, suggesting that NLRR3 expression was inversely correlated with MYCN in differentiation. Indeed, knockdown of MYCN induced NLRR3 expression, whereas exogenously expressed MYCN reduced cellular NLRR3 expression. We found that Miz-1 was highly expressed in favorable NBLs and NLRR3 was induced by Miz-1 expression in NBL cells. MYCN and Miz-1 complexes bound to NLRR3 promoter and showed a negative regulation of NLRR3 expression. In addition, a combination of low expression of NLRR3 and high expression of MYCN was highly associated with poor prognosis. Conclusions:NLRR3 is a direct target of MYCN, which associates with Miz-1 and negatively regulates NLRR3 expression. NLRR3 may play a role in NBL differentiation and the survival of NBL patients by inversely correlating with MYCN amplification. Clin Cancer Res; 17(21); 6681–92. ©2011 AACR.

Living-donor liver transplantation for carbamoyl phosphate synthetase 1 deficiency.

Kasahara M, Sakamoto S, Shigeta T, Fukuda A, Kosaki R, Nakazawa A, Uemoto S, Noda M, Naiki Y, Horikawa R. Living‐donor liver transplantation for carbamoyl phosphate synthetase 1 deficiency.
Pediatr Transplantation 2010: 14:1036–1040.