Retinoids are vitamin A derivatives and include trans-retinoic acid, isotretinoin, tamibarotene, and bexarotene, all of which are currently available for clinical use. The clinical development of retinoid therapy for neuroblastoma has a history spanning more than four decades. The most promising agent is isotretinoin, which can contribute to improving event-free survival in patients with high-risk neuroblastoma by approximately 10% when administered over six months as maintenance therapy. Although isotretinoin is regarded as an essential component in the standard clinical management of high-risk neuroblastoma, its use for this purpose in the US and EU is off-label. To promote isotretinoin use in Japan as a treatment for neuroblastoma, our clinical research team is planning to launch an investigator-initiated, registration-directed clinical trial. The present review article discusses the basic science behind retinoid therapy, pre-clinical/clinical evidence on neuroblastoma, the concept of the proposed clinical trial, and prospects for this therapy.

Neuroblastomas (NBs) exhibit broad and divergent clinical behaviors and tumor risk classification at diagnosis is crucial for the selection of an appropriate therapeutic strategy for each patient. The present study aimed to validate the clinical relevance of International Neuroblastoma Risk Group (INRG) prognostic and genomic markers in a Japanese NB cohort using a retrospective analysis. Follow-up data based on 30 common INRG queries in 605 NB cases diagnosed in Japan between 1990 and 2014 were collected and the genome signature of each tumor sample was integrated. As previously indicated, age, tumor stage, MYCN, DNA ploidy, the adrenals as the primary tumor site, serum ferritin and lactate dehydrogenase (LDH) levels, segmental chromosome aberrations, and the number of chromosome breakpoints (BP) correlated with lower survival rates, while the thorax as the primary tumor site and numerical chromosome aberrations correlated with a favorable prognosis. In the patient group with stage 4, MYCN non-amplified tumors (n = 225), one of the challenging subsets for risk stratification, age ≥ 18 months, LDH ≥ 1400 U/L, and BP ≥ 7 correlated with lower overall and event-free survival rates (p < 0.05). The genome subgroup GG-P2s (partial chromosome gain/loss type with 1p/11q losses and 17q gain, n = 30) was strongly associated with a lower overall survival rate (5-year survival rate: 34%, p < 0.05). Therefore, the combination of the tumor genomic pattern (GG-P2s and BP ≥ 7) with age at diagnosis and LDH will be a promising predictor for MYCN-non-amplified high-risk NBs in patient subsets, in accordance with previous findings from the INRG project.

Severe obesity in young children prompts for a differential diagnosis that includes syndromic conditions. Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) syndrome is a potentially fatal disorder characterized by rapid-onset obesity associated with hypoventilation, neural crest tumors, and endocrine and behavioral abnormalities. The etiology of ROHHAD syndrome remains to be established, but recent research has been focusing on autoimmunity. We report on a 2-year-old girl with rapid-onset obesity during the first year of life who progressed to hypoventilation and encephalitis in less than four months since the start of accelerated weight gain. The patient had a high titer of anti-ZSCAN1 antibodies (348; reference range < 40), and the increased values did not decline after acute phase treatment. Other encephalitis-related antibodies, such as the anti-NDMA antibody, were not detected. The rapid progression from obesity onset to central hypoventilation with encephalitis warns about the severe consequences of early-onset ROHHAD syndrome. These data indicate that serial measurements of anti-ZSCAN1 antibodies might be useful for the diagnosis and estimation of disease severity. Further research is needed to determine whether it can predict the clinical course of ROHHAD syndrome and whether there is any difference in antibody production between patients with and without tumors.

Laparoscopic surgery (LS) for choledochal cyst (CC) is now performed at many institutions. This study aimed to compare LS and open surgery (OS) for CC in children based on multicenter study at all institutions in Kyushu, Japan. A regional multicenter study was conducted among institutions affiliated with Kyushu Pediatric Surgery Study Group. Kyushu is located in the southern region of Japan, where approximately 10 % of the population live. Patients with CC who underwent definitive surgery between 2014 and 2023 were enrolled in this study. Patients' backgrounds, operative results, and postoperative complications were investigated. All 28 affiliated institutions joined the study. There were 231 cases, including 75 (32.5 %) cases treated with LS and 154 (67.5 %) treated with OS. In comparison to with OS, LS was associated with a significantly higher rate of preoperative cholangitis (LS: 61.3 % vs. OS: 40.4 %, p < 0.01) and lower rate of preoperative bile duct perforation (LS: 0.0 % vs. OS: 6.4 %, p = 0.025). LS had a significantly longer operative time (LS: 511.0 min vs. OS: 376.8 min, p < 0.01) and lower blood loss than OS. Hepaticojejunostomy was performed in all patients with LS and 98.7 % of patients with OS. There were no significant differences in postoperative complications during hospitalization between the 2 groups. Regarding late postoperative complications, anastomotic stenosis tended to be more common in the LS group, but the difference was not statistically significant (LS: 6.7 % vs. OS: 2.0 %, p = 0.065). The clinical outcomes of LS for CC were comparable to those of OS.