After my daughter was diagnosed with acute myelomonocytic leukemia at the age of 7 years and was successfully treated, I began to support childhood cancer survivors and their families through various activities. In 2005, we established the Heart-link Mutual Aid program to resolve the difficulties faced by children with cancer in availing life insurance. Furthermore, in 2011, we established the nonprofit organization, Heart-link Working Project, to support childhood cancer survivors who have difficulty finding employment due to the late effects and in 2013 we opened the employment facility, Heart-link Cafe. Its aim is to provide support to childhood cancer survivors who live independently. Through our association, we provide instructions tailored to each individual and emphasize vocational social training. In particular, we focus on financial management education and encourage individuals to save from their salaries; moreover, childhood cancer survivors learn how to use honorifics and polite language to improve their communication skills. Through self-evaluation, they confirmed their growth and preparation for employment at general companies. However, through our employment support activities, we recognize that even with high abilities and knowledge, it is difficult for people to get hired by companies and that individualized education is necessary. Furthermore, we emphasize the importance of becoming independent from parents. Other activities include the Childhood Cancer Follow-up Research Grant Project, charity concerts, and support for children in hospitals through live broadcasts and remote education. Finally, we call for medical professionals to support those who have difficulty finding employment.

In April 2008, liver transplantation (LT) for hepatoblastoma became covered under the Japanese medical insurance. Unresectable hepatoblastoma is considered an indication for LT; however, identifying “unresectable” hepatoblastoma is often difficult. Generally, unresectable tumors are those in cases categorized into post-treatment extent of disease grouping system POST-TEXT IV or III P+, V+. However, there are cases in which it is difficult to determine the resectability by preoperative imaging; although the tumor is considered resectable, a final surgical decision should be made at a facility capable of LT. Previously, it was safe to prioritize LT in cases of doubtful resectability owing to reports of extremely poor post-transplantation outcomes in salvage LT for reasons, such as recurrence after hepatectomy. Recently, there have been reports, including those from Japan, that the outcomes of salvage LT are good, and if the risk of long-term complications after LT is considered, challenging liver resection is reevaluated in this LT era. This article outlines the potential of atypical extreme hepatectomy using techniques used in transplant surgery, such as vascular reconstruction and organ preservation, and the surgical approach in cases with insufficient residual liver volume.

More than 400 causative genes cause inborn errors of immunity. Severe forms of the disease require hematopoietic cell transplantation. The incidence of inborn errors of immunity is low and each disease is rare with different pathogeneses. The strategy for hematopoietic cell transplantation needs to be considered for each patient. In particular, hematopoietic cell transplantation is often performed in infants, and improvements in the choice of conditioning regimens and management of complications are necessary. A total of 54 hematopoietic cell transplantation procedures were performed in 47 patients (40 boys and 7 girls) in Hokkaido between April 1993 and March 2023. The diseases included 12 cases of immunodeficiencies affecting cellular and humoral immunity, 9 combined immunodeficiencies with associated or syndromic features, 2 predominantly antibody deficiencies, 6 immune dysregulations, 16 congenital defects of phagocyte number or function, one defect in intrinsic and innate immunity, and one autoinflammatory disorder. Considering the regional characteristics of Hokkaido, it is possible to include a long-term follow-up. Through a survey of hematopoietic cell transplantation for inborn errors of immunity in Hokkaido over the past 30 years, we describe these challenges.

All pediatric brain tumors are orphan diseases. As each clinician has limited experience, treatment disparities can exist for pediatric brain tumors, thus emphasizing the importance for clinicians to share information and experience in these cases.

In our institution, we have weekly meetings of the Cancer Board for Pediatric Brain Tumors to enable seamless treatment cooperation among neurosurgeons, pediatric oncologists, radiation oncologists, and other related doctors and healthcare staff. We present conditions of the patients receiving treatment, discuss treatment strategies, and adjust treatment schedules. Treatment efficacy and adverse events are objectively evaluated, leading to the provision of appropriate and expeditious treatment.

Since 2013, 161 patients aged <20 years with brain tumors have been treated; 150 cases were treated at disease onset: 28 low-grade gliomas, 22 high-grade gliomas, nine ependymomas, 27 germ cell tumors, and 21 embryonal tumors such as medulloblastomas. Overall, 128 patients underwent surgery and 70 underwent radiotherapy, mainly proton beam therapy, as primary treatment. In addition to cases of diffuse intrinsic pontine gliomas, nine (six germ cell tumors and three low-grade gliomas) were diagnosed during this meeting and received adjuvant therapy without histological confirmation by agreement. Since some patients required salvage resection for residual lesions after adjuvant therapy, the indications and timing of surgery were determined during this meeting. We usually discuss individualized treatment approaches for each patient according to age or presumed sequelae. Regular weekly cancer board meetings play a key role in treating pediatric brain tumors through multidisciplinary collaborations.

Atypical teratoid/rhabdoid tumors (AT/RTs) are aggressive pediatric tumors that frequently emerge during early childhood. The pathogenesis of AT/RTs results from the inactivation of the SMARCB1 and SMARCA4 genes and is partially linked to rhabdoid predisposition syndrome. Currently, treatment typically involves high-dose chemotherapy with peripheral blood stem cell rescue and local irradiation, with the aim of improving prognosis. Ependymomas are classified into two subgroups based on their molecular features and tumor location. Supratentorial ependymomas are classified as either ZFTA-fusion or YAP1-fusion, depending on fusion gene mutations, whereas infratentorial ependymomas are categorized as PFA or PFB based on DNA methylation status. The prognosis for ZFTA fusion and PFA is poor compared with that of their counterparts. Surgical resection is crucial for all types of ependymomas, while radiotherapy and/or chemotherapy are administered based on the extent of resection and molecular subgroup. Intracranial germ cell tumors (IGCTs) mainly occur in the neurohypophysis, pineal, and basal ganglia. These tumors are more prevalent in East Asia and pineal IGCTs primarily affect males, suggesting the involvement of genetic factors in disease pathogenesis. IGCTs are classified as germinomas or non-germinomatous germ cell tumors (NGGCTs). NGGCTSs are further divided into an intermediate-prognosis group, including immature teratomas, and a poor-prognosis group. The treatment strategy for IGCT varies according to the tumor group. Germinoma is highly curable with radio-chemotherapy but often leads to irreversible neurological deficits due to tumor invasion, making early diagnosis and effective treatment crucial. Although a standard treatment strategy for NGGCTs has not yet been established, the outcomes of ongoing clinical trials are eagerly awaited.

Preclinical discovery and testing of therapies for pediatric relapsed and refractory acute lymphoblastic leukemia (ALL), which has poor outcomes, is limited, in Japan, due to a lack of practical resources. We have established 57 patient-derived xenografts (PDXs) in NOD.Cg-Prkdcscidll2rgtm1Sug/ShiJic (NOG) mice and created a biobank by preserving the PDX cells, including three extramedullary relapsed ALL PDXs. We demonstrated that our PDX mice and PDX cells mimicked the biological features of relapsed ALL and that the PDX models reproduced treatment-mediated clonal selection. Our PDX biobank is a useful resource for capturing features of drug sensitivity in pediatric patients with ALL, providing an essential tool for the development of targeted therapies.

Background: The current situation regarding the prevention and treatment of oral mucosal disorders in pediatric patients with cancer is unknown in Japan. Therefore, we investigated institutions participating in the Japanese Children’s Cancer Group (JCCG). Methods: Between April and July 2017, the JCCG Supportive Care Committee conducted a web questionnaire survey of 153 institutions partici­pating in the JCCG for the prevention and treatment of oral mucosal disorders. Results: Responses were received from 110 departments in 108 institutions (71%). Approximately 72% of the departments provided oral care instructions to patients. In addition, 65% of the departments provided oral care with mouthwashes and brushing. Cryotherapy was performed in 64% of the departments, of which 84% used cryotherapy for melphalan administration. When oral mucosal damage occurred, acetaminophen, nonsteroidal anti-inflammatory drugs, and opioids were used to alleviate pain. Discussion: Oral care for children with cancer has not yet been standardized in Japan. Further research is needed to improve the oral care of pediatric patients with cancer.

Background: We report our experience with anti-GD2 immunotherapy using dinutuximab (DIN) with granulocyte colony-stimulating factor (G-CSF) and interleukin-2 (IL-2) in patients with high-risk neuroblastoma (HRNB).

Procedure: We retrospectively examined anti-GD2 immunotherapy adverse events and their management in children with HRNB at our hospital between September 2021 and March 2023.

Results: Eight patients (four males and four females) were included in this study. The median age of patients at the start of immuno­therapy was 4.9 years. Seven patients had complete remission at the start of immunotherapy. We administered 43 cycles (22 cycles of the CSF regimen and 21 cycles of the IL-2 regimen) to eight patients. Seven patients completed all six cycles, and one patient discontinued treatment after the first cycle due to progressive disease. The common terminology criteria for adverse events grade 3 or more hematological adverse events (neutropenia, thrombocytopenia, and anemia) were observed in 7, 5, and 4 cycles, respectively. Additionally, grade 3–4 infusion reactions, capillary leak syndrome, and elevated liver enzymes were observed after 4, 5, and 13 cycles, respectively. Although DIN had to be temporarily discontinued for five cycles, all adverse events were feasible, and immunotherapy was completed in seven patients. During the observation period, five of the eight patients survived without relapse, two patients relapsed at the end of anti-GD2 antibody therapy, and one patient died of the primary disease progression shortly after.

Conclusion: Anti-GD2 immunotherapy is feasible for patients with HRNB.

Complete tumor resection is a critical prognostic factor in pediatric hepatic malignancies. In this study, we administered indocyanine green (ICG) preoperatively in two cases of pediatric hepatic malignant tumors to facilitate intraoperative navigation surgery. We observed the fluorescence histological images using a confocal microscope. Case 1, a seven-year-old girl diagnosed with undifferentiated embryonal sarcoma of the liver (UESL), underwent an extended right lobectomy. ICG did not accumulate in the tumor; however, it showed significant accumulation in the adjacent normal liver tissue. Case 2, a two-year-old girl diagnosed with hepatoblastoma (HB), underwent a right hepatic lobectomy. The patient exhibited strong accumulation of ICG in the tumor tissue, while no ICG accumulation was observed in the surrounding normal liver tissue. Confocal microscopy further elucidated distinct patterns of ICG accumulation between UESL and HB. Despite the variability in ICG accumulation patterns observed in each tumor type, ICG navigation surgery for these tumors was extremely effective in achieving complete tumor resection.

A 2-year-old boy with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) developed herpes zoster from the right shoulder to the forearm during induction therapy. He had no history of varicella (chickenpox) and had received a single dose of live attenuated varicella vaccine at the age of 1year-1 month. He was diagnosed with herpes zoster caused by the varicella vaccine strain, as revealed from genetic analysis of the blister fluid in his right arm. He responded well to acyclovir therapy. The vaccine strain was more attenuated than the wild-type strain, and the amount of latent virus in the ganglia was low and decreased over time. However, children with compromised cell-mediated immunity due to chemotherapy or immunosuppressants may develop herpes zoster caused by the vaccine strain even relatively longer after varicella vaccination. Early treatment is important when herpes zoster is suspected to be caused by a varicella vaccine strain.