Background The present study aimed to identify the predictive factors of acute respiratory events (ARE), including severe hypoxia, during initial induction chemotherapy in patients with newly diagnosed advanced neuroblastoma. Method The medical records of 75 consecutive patients in whom stage III or IV neuroblastoma was newly diagnosed between January 2003 and December 2018 at two medical institutions were retrospectively reviewed. The outcome was ARE concomitant with severe hypoxia between the first and 14th days of initial induction chemotherapy. Severe hypoxia was defined as grade 3 or higher according to the Common Terminology Criteria for Adverse Events version 4 (CTCAE v4.0) or decreased oxygen saturation at rest (e.g., pulse oximeter < 88% or PaO2 ≤ 55 mmHg). Possible predictive factors on admission were first screened for using univariate analyses with a P value of 0.05, then models of the predictive power of the outcome were evaluated by generating receiver operating characteristic (ROC) curves. Results Eleven patients (14.7%) had the outcome, including three (4.0%) who required respiratory support in the intensive care unit. The area under the curve of the ROC for the predictive factors screened by univariate analyses were 0.84 (95% confidence interval (CI): 0.73-0.95) for lactate dehydrogenase (LDH) and 0.90 (95% CI: 0.82-0.98) for the disseminated intravascular coagulation (DIC) score. Conclusion The LDH value and DIC score on admission may be clinically useful predictors of ARE during initial induction chemotherapy in patients with advanced neuroblastoma.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is caused by heterozygous germline mutations in the fumarate hydratase (FH) gene and is associated with increased susceptibility to cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma (RCC). This report describes a seven-year-old male who developed a large right kidney tumor with multiple cystic lesions that contained enhanced solid components. Whole-exome sequencing identified his germline mutation in the FH gene and its loss of heterozygosity in the tumor. This was the youngest-onset case of HLRCC-associated RCC to date. This report may affect the starting age for future RCC-surveillance programs for patients with HLRCC.

Background: Patients with relapsed or refractory neuroblastoma have a poor prognosis; there are limited effective and safe rescue chemotherapies for these patients. Development of new chemotherapy regimens for these patients is a key imperative. Procedure: We retrospectively analyzed patients with refractory or relapsed neuroblastoma who received irinotecan, etoposide, and carboplatin (IREC) as a second-line treatment for neuroblastoma. We evaluated the therapeutic response, toxicity, and survival outcomes. We also assessed the impact of UGT1A1 gene polymorphisms, which are involved in irinotecan metabolism, on the outcomes and toxicity. Results: A total of 131 cycles of IREC were administered to 43 patients with a median of two cycles per patient (range, 1–10). All patients were classified as high-risk (International Neuroblastoma Risk Group). Seven patients had relapsed before IREC. One patient (2%) showed partial response and 37 patients (86%) developed stable disease (disease control rate: 88%). Grade IV neutropenia was observed in 127 cycles (97%), while ≥ grade III gastrointestinal toxicity was observed in 3 cycles (2%). There was no IREC-related mortality. The one-year overall survival and progression-free survival rates were 65% and 52%, respectively. Patients with UGT1A1 polymorphisms showed a higher frequency of grade IV neutropenia; however, there was no increase in treatment-related mortality or nonhematological toxicity in these patients. Patients with UGT1A1 gene polymorphisms showed better one-year survival rate than the wild type (80% vs. 44%, p = 0.012). Conclusions: This study suggests that IREC is well-tolerated by patients with UGT1A1 polymorphisms and is a promising second-line chemotherapy for refractory/relapsed neuroblastoma.

Background: Central venous catheters (CVCs) have been essential devices for the treatment of children with hematological and oncological disorders. Only few studies investigated the complications and selections of different types of CVCs in these pediatric patients. This study aimed to compare risk factors for unplanned removal of two commonly used CVCs, i.e., peripherally inserted central catheters (PICCs) and tunneled CVCs, and propose better device selection for the patient. Procedure: This retrospective, single center cohort analysis was conducted on pediatric patients with hematological and oncological disorders inserted with either a PICC or a tunneled CVC. Results: Between January 1, 2013, and December 31, 2015, 89 patients inserted with tunneled CVCs (total 21,395 catheter-days) and 84 with PICCs (total 9,177 catheter-days) were followed up until the catheter removal. The median duration of catheterization was 88 days in PICCs and 186 days in tunneled CVCs (p = 1.24×10-9). PICCs at the 3-month cumulative incidence of catheter occlusion (5.2% vs. 0%, p = 4.08×10-3) and total unplanned removal (29.0% vs 7.0%, p = 0.0316) were significantly higher, whereas no significant difference was observed in the cumulative incidence of central line-associated bloodstream infection (11.8% vs. 2.3%, p = 0.664). Multivariable analysis identified younger age (<2 years) (subdistribution hazard ratio [SHR], 2.29; 95% confidence interval [CI], 1.27–4.14) and PICCs (SHR, 2.73; 95% CI, 1.48–5.02) were independent risk factors for unplanned removal. Conclusion: Our results suggest that tunnel CVCs would be a preferred device for children with hematological and oncological disorders requiring long-term, intensive treatment.

Microsatellites are a set of repeating base sequences of one to several bases in a chromosome. In general, mismatch repair (MMR) proteins correct the base mismatches that occur during DNA replication. However, tumor cells with deficient MMR function accumulate genetic mutations and cause changes in the repeat counts in microsatellite sites, and such a status is referred to as microsatellite instability (MSI)-high status. According to recent research, MSI-high status is associated with responsiveness to therapies with immune checkpoint inhibitors [1].MSI status has been well described in various adult solid tumors; for instance, one of the largest studies has demonstrated that 1188 (9.9%) of 12,019 patients exhibited an MSI-high signature in various types of tumors [2]. However, there are no sufficient investigations on the MSI status in pediatric solid tumors, except those on limited tumor subtypes, including glioblastoma and medulloblastoma [3, 4]. Herein, we investigated the MSI status in pediatric patients with various solid tumors who died due to the tumor and also evaluated the potential of immune checkpoint inhibitors in refractory pediatric solid tumors.From April 2000 to May 2019, a total of 334 pediatric patients with solid tumors were admitted to the Nagoya University Hospital (Table 1 ). Although the majority of patients survived, 74 (22%) died, including 68 due to relapse or refractory tumor, 4 due to pulmonary complications after stem cell transplantations, and 2 due to infection after chemotherapies. We retrospectively analyzed the formalin-fixed paraffin-embedded tumor tissues of 40 (54%) of the 74 patients who died to assess the MSI status (Supplemental Table 1 , Supplemental Figure 1 ) using five multiplexed markers for determining the MSI-high phenotype (BAT-25, BAT-26, MONO-27, NR-21, and NR-24) (Supplemental methods ). Results demonstrated that 36 cases were microsatellite-stable and none of the patients had an MSI-high status; however, this observation could not be confirmed for the remaining four patients because of poor sample quality.These results indicate that MSI-high status is rare in pediatric patients with solid tumors who die of the disease. Therefore, surveillance of MSI status in children with refractory/relapsed solid tumors might have a limited role in predicting the responsiveness to immune checkpoint inhibitors.