Characteristics and clinical course of thyroid abnormalities arisen in long term survivors of childhood cancer.

BACKGROUND: Thyroid abnormality is a common late effect seen in childhood cancer survivors (CCSs). We analyzed the prevalence and risk factors of thyroid abnormalities based on diagnoses and treatment modalities in CCSs. METHODS: The medical records of 257 CCSs who were diagnosed with cancer less than 20 year of age were retrospectively reviewed. The median age was 11.8 years (0.1-19.8). The median follow-up period after completion of therapy was 9.6 years (5.0-19.5). RESULTS: Of 257 subjects, thyroid abnormalities were identified in 107 (41.6%). Sixty-five out of 257 (25.3%) had subclinical hypothyroidism, and 16 (6.2%) developed central hypothyroidism. Five CCSs (1.9%) had primary overt hypothyroidism. Five (1.9%) and 6 (2.3%) CCSs were diagnosed with autoimmune thyroiditis and thyroid cancer, respectively. Among the different diagnostic groups, thyroid abnormalities were frequent in the brain tumor or Hodgkin disease or nasopharyngeal cancer groups. CCSs who received irradiation directly or near hypothalamus-pituitary-thyroid (HPT) axis had more thyroid abnormalities compared to the rest CCSs (P < 0.0001). CCSs who were treated with SCT had an increased prevalence of thyroid abnormalities (60.5%) compared to the other CCSs (37.9%) (P = 0.0069). Forty-five (42%) of 107 subjects with thyroid abnormalities had normalized thyroid hormone levels at the last follow-up. Irradiation directly or near HPT axis were thought to be a predicting factor of persistent subclinical hypothyroidism. CONCLUSIONS: Subclinical hypothyroidism was common in CCSs. CCSs with irradiation directly or near HPT axis were at risk for persistent thyroid dysfunction.

Growth, puberty, and bone health in children and adolescents with inflammatory bowel disease.

BACKGROUND: Endocrine complications such as impaired growth, delayed puberty, and low bone mineral density (BMD) can be associated with inflammatory bowel disease (IBD) in children and adolescents. This study was performed to investigate the frequency, characteristics, and outcomes of endocrine complications of IBD in children and adolescents. METHODS: This study included 127 patients with IBD diagnosed before 18 years of age [117 with Crohn disease (CD) and 10 with ulcerative colitis (UC)]. Growth profiles, pubertal status, 25-hydroxyvitamin D3 [25(OH)D3] levels, and BMD were reviewed retrospectively. RESULTS: Short stature was observed in 14 of 127 (11.0 %) with a mean height-SDS of -2.31 ± 0.72. During a 2-year follow-up period, height-SDS did not significantly improve, while weight-SDS significantly improved. Among 109 patients who were older than 13 (girls) or 14 (boys) years of age during the study period, 11 patients (10.1 %) showed delayed puberty, which was associated with low weight-SDS. Vitamin D deficiency was documented in 81.7 % (94/115) with the average 25(OH)D3 level of 14.5 ± 7.0 ng/mL. Lumbar BMD Z-score was below - 2 SDS in 25 of 119 patients (21.0 %). Height-SDS, weight-SDS, and body mass index (BMI)-SDS were lower in patients with osteoporosis than those without osteoporosis. When pediatric CD activity index scores were high (≥ 30), weight-SDS, BMI-SDS, insulin-like growth factor 1 (IGF-1)-SDS, and testosterone levels were significantly decreased. CONCLUSIONS: Vitamin D deficiency and osteoporosis are common in pediatric IBD patients. As disease severity deteriorates, weight-SDS, IGF-1-SDS, and testosterone levels were decreased. Optimal pubertal development is necessary for bone health.

Diagnostic Odyssey and Application of Targeted Exome Sequencing in the Investigation of Recurrent Infant Deaths in a Syrian Consanguineous Family: a Case of Spinal Muscular Atrophy with Respiratory Distress Type 1.

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a rare autosomal recessive disorder caused by a defect in the immunoglobulin mu binding protein 2 (IGHMBP2) gene, leading to motor neuron degeneration. We identified an infant with SMARD1 by targeted exome sequencing from a consanguineous Syrian family having a history of recurrent infant deaths. The patient initially presented intrauterine growth retardation, poor sucking, failure to thrive, and respiratory failure at the age of two months, and an inborn error of metabolism was suspected at first. Over a period of one month, the infant showed rapid progression of distal muscular weakness with hand and foot contractures, which were suggestive of neuromuscular disease. Using targeted exome sequencing, the mutation in IGHMBP2 was confirmed, although the first report was normal. Targeted exome sequencing enabled identification of the genetic cause of recurrent mysterious deaths in the consanguineous family. Additionally, it is suggested that a detailed phenotypic description and communication between bioinformaticians and clinicians is important to reduce false negative results in exome sequencing.

Prevalence of subclinical hypothyroidism in obese children or adolescents and association between thyroid hormone and the components of metabolic syndrome.

AIM: Subclinical hypothyroidism is defined as elevated thyroid-stimulating hormone (TSH) levels with the normal concentrations of thyroxine (T4) or free thyroxine (fT4), and its clinical significance is unclear. The purpose of this study is to investigate the prevalence of subclinical hypothyroidism in children and adolescents and determine the relationship between lipid profiles, insulin resistance and thyroid hormones. METHODS: A retrospective, cross-sectional study was performed using data from a subset of the KNHANES VI. The subjects whose ages were in the range of 10-19 years were enrolled when their thyroid function tests were available (n = 1104), and their laboratory and anthropometric data were analysed. RESULTS: Subclinical hypothyroidism was more commonly identified in the obese group (27 of 111) compared to the other groups (127 of 993) (24.3 vs. 12.8%, P = 0.002). Total cholesterol and triglyceride levels were higher in a group with subclinical hypothyroidism. Body mass index (BMI) was positively correlated with serum concentrations of the TSH and negatively correlated with serum concentrations of fT4 after adjusting for age. The concentrations of total cholesterol and triglyceride were positively correlated with the TSH concentrations following adjustment for age and BMI standard deviation scores. The fT4 concentrations were negatively linked with total cholesterol after adjusting for age and BMI standard deviation scores. No significant correlation was found between insulin resistance index and TSH and fT4. CONCLUSIONS: Subclinical hypothyroidism was common in the obese group, and the concentrations of TSH were linked with the lipid profile. Subclinical hypothyroidism in obese children or adolescents should be closely monitored while also evaluating metabolic risk factors.

Triglyceride Glucose Index is Associated with Ultrasonographic Fatty Liver Indicator in Children and Adolescents with Non-alcoholic Fatty Liver Disease.

Objective: Non-alcoholic fatty liver disease (NAFLD) is defined as chronic hepatic steatosis and is becoming prevalent along with the increasing trend of obesity in children and adolescents. A non-invasive and reliable tool is needed to differentiate non-alcoholic steatohepatitis (NASH) from simple steatosis. This study evaluates the association between the triglyceride glucose (TyG) index and the ultrasonographic fatty liver indicator (US-FLI), and the possibility of using the TyG index for prediction of severity of pediatric NAFLD. Methods: One hundred twenty one patients who were diagnosed with NAFLD by ultrasonography were included. They were categorized into 3 groups according to body mass index (BMI). Ninety two were obese, and 19 and 10 were overweight and normal weight, respectively. Results: The homeostatic model assessment for insulin resistance (HOMA-IR) was highest in the group with obesity (P=0.044). The TyG index and US-FLI did not differ significantly among the 3 BMI groups (P=0.186). Fourteen (11.6 %) of the 121 patients had US-FLI  6, in whom the BMI-SDS and TyG index were higher (P=0.017, P=0.004), whereas HOMA-IR did not differ significantly from the group with US-FLI < 6 (P=0.366). US-FLI was associated with BMI-SDS and the TyG index. TyG index was significantly associated with US-FLI after adjustment for BMI-SDS. The cut-off value for the TyG index for predicting US-FLI  6 was 8.91, with an area under the curve of 0.785. Conclusion: TyG index was associated with the degree of hepatic steatosis, suggesting that it might be a useful tool for predicting the severity of pediatric NAFLD.

Comparative proteomic analysis in children with idiopathic short stature (ISS) before and after short-term recombinant human growth hormone (rhGH) therapy.

This study was undertaken to identify growth hormone (GH) responsive proteins and protein expression patterns by short-term recombinant human growth hormone (rhGH) therapy in patients with idiopathic short stature (ISS) using proteomic analysis. Seventeen children (14 males and three females) with ISS were included. They were treated with rhGH at a dose of 0.31 ± 0.078 mg/kg/week for 3 months. Immunodepletion of six highly-abundant serum proteins followed by 2D DIGE analysis, and subsequent MALDI TOF MS, were employed to generate a panel of proteins differentially expressed after short-term rhGH therapy and verify the differences in serum levels of specific proteins by rhGH therapy. Fourteen spots were differentially expressed after rhGH treatment. Among them, apo E and apo L-1 expression were consistently enhanced, whereas serum amyloid A was reduced after rhGH therapy. The differential expressions of these proteins were subsequently verified by Western blot analysis using sera of the before and after rhGH treatment. This study suggests that rhGH therapy influences lipoprotein metabolism and enhances apo L-1 protein expression in ISS patients.

Prevalence and Risk Factors of Metabolic Syndrome Components in Childhood Cancer Survivors.

Purpose: It is crucial for childhood cancer survivors (CCSs) to manage metabolic syndrome. The prevalence and predictive factors of metabolic syndrome components in CCSs were investigated. Methods: This study included CCSs who were diagnosed with cancer under the age of 20 and completed therapy more than 1 year ago. The anthropometric and laboratory data were obtained from the medical records retrospectively. The reference group was extracted from the Korea National Health and Nutrition Examination Survey (2016-2019). Results: Of the participants, 29.1% (75 of 258) of the CCSs and 26.4% (1339 of 5081) of the reference group were obese. Blood pressure and triglyceride levels were significantly different in the two groups. Metabolic syndrome was identified in 35 of 258 (13.6%) patients. The reference group showed a 9.4% of prevalence (480 of 5086) (p = 0.028). A total of 127 of 230 (59.6%) met at least one of the dyslipidemia criteria. In multivariate analysis, current age and growth hormone deficiency (GHD) (OR = 5.905) were significant prognostic factors for dyslipidemia, and GHD was a significant prognostic factor for hypertriglyceridemia (OR = 2.864, p = 0.0316) and hypercholesterolemia (OR = 3.053, p = 0.0467). Cranial radiotherapy (RT) was a prognostic variable for hyper low-density lipoprotein cholesterolemia (OR = 2.866, p = 0.0032). Conclusions: The frequency of metabolic syndrome was higher in CCSs compared with the reference group. Dyslipidemia was common in CCSs with clinical parameters such as GHD and cranial RT. Risk-based long-term follow-up is needed, and early intervention is required for CCSs.

Gonadal Function in Female Adolescent and Young Adult Survivors of Childhood Cancer.

PURPOSE: Childhood cancer survivors (CCSs) are at risk for premature ovarian insufficiency (POI). The aim of this study is to evaluate ovarian function and associated health outcomes in female adolescent and young adult survivors of childhood cancer. Materials and Methods: Sixty-nine female CCSs were enrolled. Medical records of CCSs were retrospectively reviewed. The subjects were categorized into three groups according to follicular stimulating hormone (FSH) levels (cutoff, 12, 40 IU/L). Anti-müllerian hormone (AMH) level less than 1 ng/mL was considered low AMH level. RESULTS: Of 69 subjects, 14 (20.3%) had POI and 14 (20.3%) had FSH levels between 12 and 40 IU/L. Forty-one of 69 (59.4%) had normal FSH levels. Pelvic irradiation and stem cell transplantation (SCT) were more frequently performed in subjects with POI (p=0.001 and p < 0.001). AMH levels were remarkably low when FSH levels were over 12 IU/L (p < 0.001). In multivariate analysis, cyclophosphamide equivalent dose and SCT were significant treatment factors for developing low AMH levels (p=0.005 and p=0.002, respectively). Total, low-density lipoprotein cholesterol and triglyceride were significantly different in three groups according to FSH levels (p=0.047, p=0.030, and p=0.045). Z-score of femur neck bone mineral density was significantly reduced when FSH levels were increased (p=0.011). CONCLUSION: Gonadal dysfunction is common in CCSs. Gonadal function was associated with a few treatment factors known to increase the risk of POI. Regular monitoring of gonadal function is needed for better health outcomes.

The mechanisms of nature-based therapy on depression, anxiety, stress, and life satisfaction: examining mindfulness in a two-wave mediation model.

Background: Nature-based therapy (NBT), which centers around engaging in activities within natural surroundings, has consistently demonstrated therapeutic benefits for mental health. While NBT highlights the potential of nature as a therapeutic resource for promoting mental health, there is limited knowledge regarding its underlying mechanisms. Methods: Two hundred seventy-six Korean participants (204 women, mean age = 54.99 ± 23.25 years) participated in a 30-session gardening program held twice weekly for 15 weeks. Structural equation modeling with a two-wave autoregressive cross-lagged model was used to investigate the mediating effects of mindfulness. Results: NBT significantly improved the mean scores of all psychological variables. The mediation model was partially confirmed, with mindfulness at post-intervention (T2) mediating the relationship between baseline (T1) depression and anxiety and post-intervention (T2) life satisfaction. However, no significant indirect effect was observed between the path from stress (T1) to life satisfaction (T2). Conclusion: Mindfulness is a crucial component for improving mental health outcomes. This study underscores the need to prioritize and emphasize mindfulness practices in NBT.

Clinical characteristics and long-term outcomes of rhabdomyosarcoma in Korean children, adolescents and young adults: a single-center experience.

PURPOSE: This study aimed to analyze characteristics, treatment, long-term outcomes, and prognostic factors for children, adolescents and young adults with rhabdomysosarcoma (RMS). METHODS: This retrospective historical study included 75 patients with RMS treated between 2002 and 2019. Clinical data and follow-up results were collected including all diagnosis, treatment and prognosis information. RESULTS: Patients median-age-at-diagnosis was 6 years. Embryonal and alveolar histology occurred in 51 (68.0%) and 21 (28.0%) patients, respectively. The tumors most frequently originated from parameningeal site (28.0%). Of 74 evaluable patients for treatment outcome, 60 (81.1%) achieved complete response for first-line treatment, of whom, 34 (56.6%) maintained complete response, 26 (43.3%; 23/26, local relapse) showed relapse. Of 40 patients with treatment failure, 16 and 6 occurred in parameningeal area and retroperitoneum/perineum, respectively. The 5-year progression-free survival (PFS) and overall survival (OS) were 45.0% and 64.5%, respectively. In multivariate analyses, parameningeal site (p = 0.027), no gross total resection (p = 0.047), and no radiation therapy (RT) (p < 0.001) for PFS; and parameningeal site (p < 0.001) and no RT (p = 0.010) for worse OS, were significant. The median PFS and OS from treatment failure date in 40 patients with primary treatment failure were 1.3 and 4.1 years, respectively. Of 26 patients with relapse, interval to relapse < 7 months, retroperitoneum/perineum site, TNM stages III/IIV, and no salvage RT were independently associated with OS. CONCLUSION: The importance of adequate local therapy was highlighted in RMS treatment. Treatment failure was largely a local failure. Whether as a component of initial or salvage treatment, RT could improve patients' survival.

The effectiveness of nature-based therapy for community psychological distress and well-being during COVID-19: a multi-site trial.

During the COVID-19 pandemic, the world population faced various mental health challenges, highlighting a need for new community-based psychosocial interventions. This study aimed to investigate the effectiveness and feasibility of Nature-Based Therapy (NBT) for the community experiencing psychological distress during the pandemic. A multi-site trial comparing NBT and control groups was conducted in Korea with 291 participants exhibiting mild to severe depression or anxiety. A total of 192 participated in 30 sessions of therapeutic gardening, while 99 remained in the control group. Psychological distress and well-being were assessed using seven measures of depression, anxiety, daily activity, life satisfaction, mindfulness, stress, and loneliness. The effect sizes (Cohen's d) of NBT compared to the control group were medium to large: depression (0.583), anxiety (0.728), daily activity (1.002), life satisfaction (0.786), mindfulness (0.645), stress (0.903), and loneliness (0.695). Multilevel analysis revealed significant Time × Group interaction effects for all measures. Pearson correlation (r = - 0.28 to 0.71) showed that changes in all variables correlated significantly with each other, with small to large effect sizes. Therapeutic alliance at post-test positively moderated the intervention effects on the outcomes. We concluded that NBT is a promising psychosocial intervention for treating psychological distress for community dwellers.

Incidence Patterns and Outcomes of Ewing Sarcoma in South Korea (1999-2017): A Retrospective Analysis Using Korea Central Cancer Registry Data.

PURPOSE: Due to low incidence, epidemiologic data of Ewing sarcoma in the Asian population are scarce. We aimed to examine the incidence pattern and outcome of patients with Ewing sarcoma in the Republic of Korea. MATERIALS AND METHODS: Data of patients with Ewing sarcoma diagnosed between 1999 and 2017 were obtained from the Korea Central Cancer Registry (KCCR). Incidence, clinical characteristics, and survival rates were analyzed and compared between different age groups. RESULTS: There were 788 cases (459 males, 329 females), with a median age at diagnosis of 20 years. The age-standardized rate of Ewing sarcoma was 1.01. The number of cases and incidence rates in each age group were as follows: children, 1.6; adolescents and young adults (AYA), 0.93; adults, 0.44; and elderly, 0.53. There were more male cases in children and the AYA group (p < 0.001). Extraskeletal tumors (p < 0.001), primary sites other than extremity (p=0.007), and presence of metastasis at diagnosis (p=0.031) were more frequent in the adults and elderly group. With a median survival time of 78 months, the 5-year overall survival (OS) rate of the entire cohort was 52%. Children fared best (5-year OS, 75%), and the 5-year OS of AYA patients (51%) approximated the OS of the entire cohort. A two-fold difference of 5-year OS was observed between adults and elderly patients (42% vs. 19%). On univariate and multivariate analyses, age ≥ 15 years and presence of metastasis were adverse prognostic factors. CONCLUSION: This was the first epidemiologic study of Ewing sarcoma using the KCCR data. With a similar incidence to other Asian countries, the survival rate was slightly lower than that of Euro-American cases. Collaborative clinical studies are necessary to improve the outcome of Ewing sarcoma in low-incidence populations.

The Multi-Sites Trial on the Effects of Therapeutic Gardening on Mental Health and Well-Being.

Although many people affected by COVID-19 suffer from some form of psychological distress, access to proper treatment or psychosocial interventions has been limited. This study aimed to examine the feasibility and preliminary effects of a therapeutic gardening program conducted during the COVID-19 pandemic. The program consisted of 30 sessions and was conducted at 10 nationwide sites in Korea from June to November 2021. Mental health and well-being were assessed using the Mental Health Screening Tool for Depressive Disorders, Mental Health Screening Tool for Anxiety Disorders, Engagement in Daily Activity Scale, brief version of World Health Organization Quality of Life, and Mindful Attention Awareness Scale. Cohen's d value was calculated for the effect size, and a multilevel analysis was used to determine the longitudinal effects of therapeutic gardening. The effect sizes for depression, anxiety, daily activities, quality of life, and mindfulness were 0.84, 0.72, 0.61, 0.64, and 0.40, respectively. Multilevel analyses showed that all five mental health variables improved significantly over time as the therapeutic gardening program progressed. Therapeutic gardening is promising and applicable as a nature-based intervention to improve the mental health of individuals experiencing psychological distress especially in the COVID-19 pandemic.

Spectrum of mutations in Noonan syndrome and their correlation with phenotypes.

OBJECTIVES: To investigate mutation spectrums and their correlations to phenotypes in Noonan syndrome (NS) and NS-related disorders that share functional alterations of the Ras-mitogen-activated protein kinase pathway. STUDY DESIGN: Clinical characteristics and genotypes of 10 previously known and 2 candidate genes, SPRY1-4 and SPRED1, were investigated in 59 patients with NS, 17 with cardiofaciocutaneous syndrome, 5 with Costello syndrome, and 2 with LEOPARD syndrome. RESULTS: PTPN11 (39.0%), SOS1 (20.3%), RAF1 (6.8%), KRAS (5.1%), and BRAF (1.7%) mutations were identified in NS; BRAF (41.2%), SHOC2 (23.5%), and MEK1 (5.9%) mutations in cardiofaciocutaneous syndrome; and HRAS and PTPN11 mutations in Costello syndrome and LEOPARD syndrome, respectively. No additional mutations were identified in 28.9% of NS and 35.3% of cardiofaciocutaneous syndrome. Functional characterizations of 2 RAF1 novel variants, p.P261T and p.S259T, and one SOS1 variant, p.K170E, showed enhanced activity of Ras-mitogen-activated protein kinase pathway. Normal stature was frequent in SOS1 mutations, hypertrophic cardiomyopathy in RAF1, and developmental delay in RAF1, BRAF, or SHOC2 mutations. CONCLUSIONS: By identifying genotype-phenotype correlations, our study highlights the role of molecular genetic testing in the process of differential diagnosis of NS and NS-related disorders. Pathophysiologies that underlie these correlations are needed to be investigated in terms of their effects on Ras-mitogen-activated protein kinase pathway.

Clinical characterization and identification of two novel mutations of the GNAS gene in patients with pseudohypoparathyroidism and pseudopseudohypoparathyroidism.

OBJECTIVE: Pseudohypoparathyroidism (PHP) and pseudopseudohypoparathyroidism (PPHP) are rare disorders resulting from genetic and epigenetic aberrations in the GNAS locus. DESIGN: Investigation of clinical characteristics and molecular analysis in PHP and PPHP. PATIENTS: Fourteen subjects from 13 unrelated families including subjects with PPHP (n = 1), PHP-Ia (n = 6) and PHP-Ib (n = 7) were enrolled. MEASUREMENTS: Clinical data, including age at presentation, presenting symptom, auxological findings, family history, presence of Albright hereditary osteodystrophy (AHO) features and hormonal and biochemical findings, were analysed. The GNAS locus was subjected to direct sequencing and methylation analysis using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). RESULTS: Of the 13 PHP subjects, 10 (three PHP-Ia and seven PHP-Ib) presented with hypocalcemic tetany at ages ranging from 7 to 14·8 years. Subcutaneous calcification was observed as an early manifestation of AHO in one PHP-Ia patient (age, 2·9 years) and one PPHP patient (age, 7 months). Six PHP-Ia and one PPHP harboured four different heterozygous mutations within the coding region of GNAS, p.Asp189_Tyr190delinsMetfxX14, p.Val117fsX23, p.Tyr190CysfsX19, and a splicing mutation (c.659 + 1G>A), of which the latter two were novel. Five subjects with PHP-Ib exhibited complete loss of the maternal-specific methylation pattern. The remaining two PHP-Ib showed a loss of methylation of exon 1A on the maternal allele as a consequence of heterozygous 3-kb microdeletions within the STX16 gene. CONCLUSIONS: GNAS mutation analyses and MS-MLPA assays are useful molecular tools for understanding the molecular bases and confirming the diagnosis of PHP and PPHP.

Ovarian cyst torsion in a patient with congenital lipoid adrenal hyperplasia.

Congenital lipoid adrenal hyperplasia (CLAH) is the most severe form of congenital adrenal hyperplasia, characterized by lack of synthesis of all gonadal and adrenal steroid hormones. Ovarian cysts can develop as complications of CLAH. However, the precise mechanism of development and natural history of such cysts in patients with CLAH have not yet been determined. We recently treated a 14-year-old female patient with CLAH and ovarian cyst torsion. As a neonate, she presented with vomiting, skin pigmentation, and electrolyte imbalance. At that time, her serum adrenocorticotropic hormone concentration was elevated, while 17-hydroxypregnenolone level was normal, as were her normal female external genitalia. Mutation analysis showed that she was homozygous for p.Q258X in the StAR gene. She underwent spontaneous puberty and menstruation. At 14 years of age, she received salpingo-oophorectomy because of ovarian cyst torsion presenting as acute pelvic pain. Ovarian cysts are important clinical manifestations in 46,XX patients with CLAH, although onset time and severity can vary depending on individuals. Thus, patients with CLAH should be carefully monitored for ovarian complications to preserve as much ovarian function as possible.

Osteosarcoma in Adolescents and Young Adults.

The epidemiology of osteosarcoma in adolescents and young adults (AYA) remains unclear. We aimed to assess and compare the clinical features of osteosarcoma between AYA and other age groups. We retrieved osteosarcoma cases diagnosed between 1999 and 2017 from the Korea Central Cancer Registry. We compared survival trends and clinical characteristics between AYA and other age groups. AYA comprised 43.3% (1309/3022) of the osteosarcoma cases. Compared to other age groups, the male-to-female ratio was highest in AYA (1.61:1). The proportion of tumors located in an extremity was 80.3% in AYA, which was lower than in young children (92.5%) or pubertal children (93.8%) but higher than in adults (55.7%) or the elderly (47.5%). As for treatments, 71.2% of AYA received local treatment and systemic chemotherapy, and 28.8% received only local treatment (surgery: 261, radiotherapy: 9, surgery and radiotherapy: 5). The 5-year overall survival (OS) was lower in AYA (68%) than in young children (78%) or pubertal children (73%) but higher than in adults (47%) or the elderly (25%). When AYA were divided into five subgroups by age, patients aged 15-19 years constituted the largest proportion (45.4%, n = 594). Additionally, the proportion of patients with a non-extremity tumor increased in an age-dependent manner, from 10.3% in AYA aged 15-19 years to 35.3% in AYA aged 35-39 years. OS did not significantly differ among the different age subgroups of AYA. The clinical characteristics and OS of the AYA were more similar to those of children than to those of adults. There is a need for cooperation between pediatric and adult oncologists for effective osteosarcoma treatment in AYA.

Hyperammonemic Encephalopathy Mimicking Ornithine Transcarbamylase Deficiency in Fibrolamellar Hepatocellular Carcinoma: Successful Treatment with Continuous Venovenous Hemofiltration and Ammonia Scavengers.

Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare liver cancer affecting adolescents and young adults without any pre existing liver disease. Hyperammonemic encephalopathy (HAE) is a serious paraneoplastic syndrome, and several cases of HAE have been reported in patients with FLHCC. This condition is rare; hence, there are currently no management guidelines for cancer-related HAE. Herein, we report a case of an 18-year-old man with advanced FLHCC who developed HAE during the first course of chemotherapy consisting of cisplatin, doxorubicin, 5-fluorouracil, and interferon-α. He was successfully treated with continuous venovenous hemofiltration, sodium benzoate, sodium phenylbutyrate, and amino acid supplementation for HAE. After the second course of chemotherapy, he underwent surgery, and thereafter, his ammonia levels were normal without any ammonia scavenger therapy. Treatments for HAE described here will be helpful for this rare, but serious metabolic complication of FLHCC and could partially applied to HAE related to any malignancies.

Low bone mineral density in children and adolescents with cancer.

Maximizing accumulation of bone mass during childhood and adolescence is essential to attaining optimal peak bone mass. Childhood cancer survivors (CCS) have lower bone mineral density (BMD) than the general population. Chemotherapeutic agents including steroids and radiotherapy can affect BMD. Cancer itself, hormonal insufficiency, a poor nutritional state, and a deficit of physical activities during or after treatment also influence BMD in CCS, resulting in failure to achieve appropriate peak bone mass. Low BMD in childhood and adolescence can lead to osteoporosis in adult life and complications such as bone pain, bone deformity, and fractures. Thus, BMD in CCS should be monitored with appropriate intervention. Adequate intake of calcium and vitamin D and an increase in physical activity are recommended. Timely supplements of hormones are needed in some cases. Some publications have reported that bisphosphonate therapies using pamidronate or alendronate were well tolerated in CCS and helped increase BMD.