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In radiotherapy for pediatric abdominal tumors, determining the effect of concurrent chemotherapy on polyglycolic acid (PGA) spacers is crucial; yet this effect has not been validated. Therefore, we aimed to evaluate the impact of cyclophosphamide (CPA) chemotherapy on the PGA spacer using a rat model. Twenty-four rats were implanted with the spacer, and morphological changes in the spacer were assessed on CT for both the CPA-dosed group (40 mg/kg) and the control group. The size and volume of the spacer were quantified using CT, while the degree of adhesion and microscopic examination of the tissue were determined using pathology specimens. Morphologically, the size of the spacer decreased over time in both the CPA-dosed and control groups, with no significant differences observed between groups. No significant differences in adhesion were observed between the two groups. Macrophages were observed around the PGA fibers, suggesting their involvement in the degradation of the PGA spacer. These results suggest that CPA does not cause significant clinically problematic degradation or adverse tissue reactions to the PGA spacer. This study reinforced the benefits of PGA spacers; however, future research focusing on in vivo longitudinal monitoring of individual rats, as well as on humans, is required.

The clinical utility of a recently developed bioabsorbable polyglycolic acid (PGA) spacer has not yet been established in pediatric patients; therefore, we aimed to investigate its utility during chemo-proton therapy for pediatric cancer. Proton depth–dose curves were obtained in a water phantom with or without the spacer. Computed tomography (CT) scans were performed for the PGA spacer immersed in saline for 2 weeks to measure CT numbers and estimate the relative stopping power (RSP) for the proton beams. The spacer was placed in a patient with sacral Ewing sarcoma receiving 55.8 Gy [relative biological effectiveness (RBE)] in 31 fractions and was evaluated using CT scans performed every other week. In addition, the images were used to quantitatively evaluate changes in volume and RSP of the spacer and dose distributions in normal tissues. The spacer immersed in saline had a CT number of 91 ± 7 (mean ± standard deviation) Hounsfield units, and the corresponding RSP was predicted to be 1.07 ± 0.01. The measured RSP agreed with the predicted one. The volumes of the large bowel and rectum receiving ≥45 Gy(RBE) (V45Gy) were significantly reduced by placing the spacer; V45Gy without and with the spacer were 48.5 and 0.01%, respectively, for the rectum and 7.2 and 0%, respectively, for the large bowel. The volume of the spacer and RSP decreased at rates of 4.6 and 0.44% per week, respectively, whereas the target dose coverage was maintained until the end of treatment. The PGA spacer was considered effective for pediatric cancer patients undergoing chemo-proton therapy.

Background Limited evidence is available regarding the dissemination of tumor tissues due to compression during massage therapy, a routine procedure in patients with various symptoms in Asian countries. Case presentation A 12-year-old male presented at a massage clinic with pain and swelling of his left knee, which worsened the same night. Consistent with conventional osteosarcoma, radiography revealed cortical bone destruction, osteoblastic changes, and periosteal reactions. Magnetic resonance imaging revealed a tumor in the distal femur, an extraskeletal mass, and an infiltrative lesion in the intramuscular and neurovascular areas surrounding the distal femur; this was considered as hemorrhage and dissemination of the tumor tissue. 18 Fluorine-labelled fluorodeoxyglucose-positron emission tomography and computed tomography revealed multiple metastases in the spine, liver, and lung. Consistent with osteosarcoma, histopathological examination revealed tumor cell proliferation with extensive pleomorphism and mitoses. Despite undergoing chemotherapy, radiation therapy, and hip disarticulation, the patient died due to multiple metastases 13 months after the initial diagnosis. Conclusions The present case suggests association of massage therapy with the local dissemination of tumor tissues, although influence of massage therapy on metastatic lesions remains unclear. Massage therapists should be aware of the possibility for dissemination of hidden malignancies due to the procedure.

Central venous catheters (CVCs) are essential devices in the treatment of pediatric patients with hematological and oncological disorders; however, the most suitable type of CVC for these patients remains unclear. We retrospectively compared risk factors for unplanned removal of two commonly used CVCs, peripherally inserted central catheters (PICCs) and tunneled CVCs, to propose which is the better device. We followed 89 patients fitted with a tunneled CVC (total 21,395 catheter-days) and 84 fitted with a PICC (total 9177 catheter-days) between January 1, 2013 and December 31, 2015, until catheter removal. Patients with a PICC had a significantly higher 3-month cumulative incidence of catheter occlusion (5.2% vs. 0%, p = 4.08 × 10−3) and total unplanned removals (29.0% vs. 6.9%, p = 0.0316) than those with tunneled CVCs. However, the cumulative incidence of central line-associated bloodstream infection did not differ significantly by CVC type. Multivariable analysis identified younger age (< 2 years) [sub-distribution hazard ratio (SHR) 2.29; 95% confidence interval (CI) 1.27–4.14] and PICC (SHR 2.73; 95% CI 1.48–5.02) as independent risk factors for unplanned removal. Thus, our results suggest that tunneled CVCs are preferable in pediatric patients with hematological and oncological disorders requiring long-term, intensive treatment.

IntroductionChildren and adolescents with mature B cell non-Hodgkin lymphoma (B-NHL) are treated with short-intensive chemotherapy. The burden of short-term and long-term toxicity is highly relative to its high cure rate in good-risk patients. Although the addition of rituximab to standard lymphome Malin B (LMB) chemotherapy markedly prolongs event-free survival and overall survival in high-risk patients, the benefit of rituximab in good-risk patients remains to be elucidated. This clinical trial will examine whether the addition of rituximab eliminates anthracyclines in good-risk patients without compromising treatment outcomes.Methods and analysisWe will perform a single-arm, open-label, multicentre phase II study. Low-risk (stage I – completely resected, stage II abdominal) and intermediate-risk (stages I and II – incompletely resected; stage II – resected, other than abdominal; stage III with LDH <2× upper limit of normal) patients with newly diagnosed B-NHL are eligible. Low-risk patients receive two courses of R-COM1P (rituximab, cyclophosphamide, vincristine, methotrexate, prednisolone and intrathecal methotrexate with hydrocortisone), and intermediate-risk patients receive COP (cyclophosphamide, vincristine, prednisolone and intrathecal methotrexate with hydrocortisone) followed by two courses each of R-COM3P and R-CYM (rituximab, cytarabine, methotrexate and intrathecal methotrexate with hydrocortisone). The primary endpoint is a 3-year event-free survival rate in paediatric patients (<18 years) with intermediate-risk disease. 100 patients (10 low-risk and 90 intermediate-risk) will enrol within a 4-year enrolment period and the follow-up period will be 3 years. 108 institutions are participating as of 1 January 2024 (64 university hospitals, 29 general hospitals, 12 children’s hospitals and three cancer centres).Ethics and disseminationThis research was approved by the Certified Review Board at NHO Nagoya Medical Center (Nagoya, Japan) on 21 September 2021. Written informed consent is obtained from all patients and/or their guardians. The results of this study will be disseminated through peer-reviewed publications and conference presentations.Study registrationJapan Registry of Clinical Trials, jRCTs041210104.

Hereditary stomatocytosis (HSt) is a type of congenital hemolytic anemia caused by abnormally increased cation permeability of erythrocyte membranes. Dehydrated HSt (DHSt) is the most common subtype of HSt and is diagnosed based on clinical and laboratory findings related to erythrocytes. PIEZO1 and KCNN4 have been recognized as causative genes, and many related variants have been reported. We analyzed the genomic background of 23 patients from 20 Japanese families suspected of having DHSt using a target capture sequence and identified pathogenic/likely pathogenic variants of PIEZO1 or KCNN4 in 12 families.Hemolytic anemia: new variants in hereditary subtypesGenetic variants identified in 12 Japanese families are likely to be responsible for a rare hereditary condition causing red blood cells (RBCs) to rupture. Keiko Shimojima Yamamoto of Tokyo Women’s Medical University, Japan, and colleagues conducted genetic analyses on blood samples from 23 people in 20 Japanese families with suspected dehydrated hereditary spherocytosis (DHSt), caused by RBC ion imbalances leading to dehydration and rupture. In 12 families, the analyses revealed probable disease-causing variants in two genes, PIEZO1 and KCNN4, some of which were identified for the first time. Both genes are related to RBC ion channels and the mutations lead to two slightly different forms of DHSt. Further understanding could improve treatment strategies. Comprehensive genomic analysis is a powerful tool for understanding the genetic cause of congenital hemolytic anemia.

For the treatment of osteosarcoma, cisplatin (CDDP) can be substituted by carboplatin (CBDCA) to reduce toxicity. We report a single institution experience of CBDCA-based regimen. Two to three cycles of CBDCA + ifosfamide (IFO) therapy (window therapy) were administered as neoadjuvant therapy for osteosarcoma. Depending on the response of window therapy, the subsequent protocols were determined; for good responders, surgery is performed, and postoperative therapies with CBDCA + IFO, adriamycin (ADM) and high-dose methotrexate (MTX) were administered; for stable disease, the postoperative regimens were advanced before surgery, and the remaining amount of postoperative chemotherapy is deduced; for progressive disease, CBDCA-based regimen is changed to CDDP-based regimen. From 2009 to 2019, seven patients were treated with this protocol. During the window therapy, two patients (28.6%) were assessed as good responders and completed the regimen as planned. Four patients (57.1%) had stable disease, and the chemotherapy schedules were modified. One patient (14.2%) with progressive disease was shifted to the CDDP-based regimen. At final follow-up, four patients showed no evidence of disease and three patients died of the disease. Since the efficacy during window therapy was limited, a CBDCA-based regimen in the neoadjuvant setting was considered insufficient for performing adequate surgery.

Follicular lymphoma (FL) is quite rare in children. There have been only two major reports on pediatric FL. The present retrospective study on pediatric FL in Japan, including FL with diffuse large B cell lymphoma (DLBCL), analyzed data from 1991 to 2014. Twenty-two patients with pediatric FL were analyzed. Sixteen patients were boys and six were girls. Median age of onset was 9 years (range 4–17 years). In 11 patients, DLBCL co-existed with FL. The initial lesions involved cervical lesions in 16 patients, and the abdomen in six. With regard to stage of disease at diagnosis, 17 patients were at stage I or II, four were at stage III, and one was at stage IV. Chemotherapy was administered in 18 patients, and only resection was performed in four patients. Mature B lymphoma regimens were selected for 17 patients who received chemotherapy. Although two patients relapsed, all patients are currently alive and disease free. The median follow-up period was 54.5 months (range 6–126 months). Patients having FL with DLBCL were younger compared with those having FL, and this disease was more frequently observed in female patients. Our data revealed that FL in Japanese children is a tumor with good prognosis, as in reports from the United States and Europe.

The efficient isolation and ex vivo expansion of antigen-specific T cells are crucial for successful adoptive immunotherapy against uncontrollable infections and cancers. Several methods have been reported for this purpose, for example, employing MHC-multimeric complexes, interferon-gamma secretion, and antibodies specific for molecules expressed on T-cell surfaces, including CD25, CD69, CD107a, CD137, and CD154. Of the latter, CD137 has been shown to be one of the most promising targets since it is only expressed on CD8 + T cells early after encountering antigen, while being almost undetectable on resting cells. However, detailed comparisons between CD137-based and other methods have not yet been conducted. In this study, we therefore compared three approaches (with CD137, CD107a, and tetramers) using HLA-A24-restricted CMV pp65 and EBV BRLF1 epitopes as model antigens. We found that the CD137-based isolation of antigen-stimulated CD8 + T cells was comparable to tetramer-based sorting in terms of purity and superior to the other two methods in terms of subsequent cell expansion. The method was less applicable to CD4 + T cells since their CD137 upregulation is not sufficiently high. Collectively, this approach is most likely to be optimal among the methods tested for the isolation and expansion of antigen-specific CD8 + cells.

The aim of this study was to assess whether oxidative and inflammatory mediators in the cord blood of newborns with funisitis and chorioamnionitis can serve as indicators of their inflammatory status, and whether there is a positive association between higher mediator levels and an increased risk of admission to the neonatal intensive care unit (NICU). This study was conducted prospectively in a neonatology department of a university hospital. In total, 52 full-term newborns were evaluated, including 17 funisitis cases, 13 chorioamnionitis cases, and 22 control newborns without funisitis or chorioamnionitis. Cord blood samples were measured for oxidative stress and inflammatory status markers. The oxidative stress markers included the total nitric oxide (NO), total hydroperoxide (TH), biological antioxidant potential (BAP), and TH/BAP ratio, comprising the oxidative stress index (OSI). Inflammatory markers included interleukin (IL)-1b, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNFα), interferon γ (IFNγ), and complement component C5a. TH, OSI, IL-1b, IL-6, and IL-8 concentrations were higher in the funisitis group than in the chorioamnionitis and control groups. C5a was higher in the funisitis and chorioamnionitis groups than in the control group. Among all enrolled newborns, 14 were admitted to the NICU. Multiple logistic regression analysis showed that elevated umbilical cord blood levels of OSI and TH were associated with a higher risk of admission to the NICU (OSI: R = 2.3, 95% CI 1.26–4.29, p = 0.007 and TH: R = 1.02, 95%CI = 1.004–1.040, p = 0.015). In conclusion, OSI and TH in cord blood from full-term newborns can provide an index of inflammatory status, and higher levels are associated with the risk of admission to the NICU and, therefore, could serve as an early indicator of inflammatory conditions in newborns.