An infant with concurrent serotype 6C invasive pneumococcal disease and infectious mononucleosis.

Streptococcus pneumoniae is a main causative agent of serious invasive bacterial infections. However, concurrent infection with invasive pneumococcal disease (IPD) and viral infectious mononucleosis (IM) is rare. We report an infant with serotype 6C infection causing IPD occurring simultaneously with IM. A previously healthy 11-month-old girl referred to our hospital because of fever, leukopenia, and elevated C-reactive protein presented to us with disturbance of consciousness, tachycardia, tachypnea and agranulocytosis. Other findings included tonsillitis with purulent exudates and white spots, bilateral cervical adenopathy, and hepatosplenomegaly. We diagnosed her illness as sepsis and administered a broad-spectrum antibiotic, an antiviral agent, and granulocyte transfusions. After treatment was initiated, fever gradually decreased and general condition improved. IPD was diagnosed based upon isolation of S. pneumoniae of serotype 6C from blood cultures obtained on admission. Concurrently the girl had IM, based upon quantitation of Epstein-Barr viral DNA copies in blood and fluctuating serum antibody titers. Although simultaneous IPD and IM is a rare occurrence, this possibility is important to keep in mind.

Predictors of Posttraumatic Stress Symptoms Among Adolescent and Young Adult Survivors of Childhood Cancer: Importance of Monitoring Survivors' Experiences of Family Functioning.

The purpose of this study was to identify factors associated with posttraumatic stress symptoms (PTSS) among Japanese long-term childhood cancer survivors (CCSs). Subjects comprised 185 adolescent and young adult (AYA) CCSs who completed anonymous self-report questionnaires. Attending physicians also completed an anonymous disease/treatment data sheet. Mean age of survivors was approximately 8 years at diagnosis and 23 years at participation. Multiple regression analysis showed that family functioning, satisfaction with social support, being female, and interactions between family functioning and gender and age at the time of diagnosis were associated with PTSS among survivors. This study revealed family functioning as the most predictive factor of PTSS among AYA CCSs in Japan. Even when the survivor may have unchangeable risk factors, family functioning can potentially moderate the effects on PTSS. Thus, it is crucial for health professionals to carefully monitor and attend to survivors' experiences of family functioning to mitigate PTSS.

General health status and late effects among adolescent and young adult survivors of childhood cancer in Japan.

OBJECTIVE: We sought to investigate general health status and late effects among adolescent and young adult survivors of childhood cancer. METHODS: We conducted a cross-sectional survey, using self-rated questionnaires on current and past health problems. Questionnaires were provided to childhood cancer survivors, a comparison group of siblings and a general population control group that was recruited online. χ(2) tests were used to compare responses to the 72 survey items. RESULTS: The final sample included 185 childhood cancer survivors (72% response rate), 72 siblings and 1000 general population controls. In the childhood cancer survivors group, the median age of diagnosis was 8 years and the median age at survey was 23 years. According to the physicians' reports, 56% of the childhood cancer survivors experienced at least one late effect. In descending order of prevalence, the current symptoms in the childhood cancer survivors group were (i) impaired visual acuity (45%), (ii) dizziness (36%) and (iii) any allergy (34%). The three most common symptoms had similar prevalence rates in each of the groups. As compared with the control group, the following physical symptoms were significantly more common in the childhood cancer survivors group: mental retardation (odds ratio: 48.6, P < 0.01); cataract (odds ratio: 29.7); suspected infertility (odds ratio: 25.1); delayed puberty (odds ratio 24.9); growth hormone deficiency (odds ratio: 23.0); and other audiovisual, urinary, endocrine, infertility, cardiovascular, respiratory, gastrointestinal, spinal, extremity and neuromuscular problems. CONCLUSIONS: Many adolescent/young adult childhood cancer survivors could be suffering from ongoing late effects that stem from cancer and its treatment. Overall health monitoring for childhood cancer survivors can provide indispensable benefits.

Assessment of corticosteroid-induced osteonecrosis in children undergoing chemotherapy for acute lymphoblastic leukemia: a report from the Japanese Childhood Cancer and Leukemia Study Group.

Steroid-induced osteonecrosis (ON) is a challenging complication encountered during modern chemotherapy for childhood acute lymphoblastic leukemia (ALL). We retrospectively assessed the incidence of ON and its risk factors in a total of 1095 patients enrolled in 3 consecutive Japanese Children's Cancer and Leukemia Study Group ALL studies (ALL941 [1994 to 2000], n=464; ALL2000 [2000 to 2004], n=305; and ALL2004 [2004 to 2010], n=326). ON was diagnosed in 16 patients, of whom 15 were symptomatic. The cumulative incidence of ON was 0.76% in ALL941, 0.35% in ALL2000, and 3.6% in ALL2004. The incidence of ON in ALL941/2000, in which only prednisolone was administered as a steroid, was significantly lower than that in ALL2004, in which dexamethasone was used as a partial substitute for prednisolone (P<0.01). In ALL2004, sex and age were significantly correlated with the incidence of ON (1.3% in boys vs. 6.7% in girls, P=0.0132; 0.42% for age <10 y vs. 15.6% for age ≥10 y, P<0.0001), suggesting that girls aged 10 years and above are at a greater risk of ON onset. These results indicate that the risk of ON should be considered when administering dexamethasone as part of ALL protocol treatment in girls aged 10 years and above.

Pediatric subcutaneous panniculitis-like T-cell lymphoma with favorable result by immunosuppressive therapy: a report of two cases.

Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is a rare type of skin lymphoma. Histopathology mimicking a lobular panniculitis makes it difficult to distinguish SPTL from benign autoimmune disease. We present cases of a 10-year-old female and an 11-year-old male with SPTL showing recurrent panniculitis and systemic manifestations. Initially, antibiotics and steroids were administered to treat infectious disease and benign panniculitis. However, they experienced recurrent fever and erythema nodosum. Additional immunohistochemistry and T-cell receptor (TCR) gene rearrangement analyses were performed, enabling the establishment of an SPTL diagnosis. The affected patients were given immunosuppressive therapy with favorable results.

Validation of the Japanese version of the Pediatric Quality of Life Inventory (PedsQL) Cancer Module.

BACKGROUND: The PedsQL 3.0 Cancer Module is a widely used instrument to measure pediatric cancer specific health-related quality of life (HRQOL) for children aged 2 to 18 years. We developed the Japanese version of the PedsQL Cancer Module and investigated its reliability and validity among Japanese children and their parents. METHODS: Participants were 212 children with cancer and 253 of their parents. Reliability was determined by internal consistency using Cronbach's coefficient alpha and test-retest reliability using intra-class correlation coefficient (ICC). Validity was assessed through factor validity, convergent and discriminant validity, concurrent validity, and clinical validity. Factor validity was examined by exploratory factor analysis. Convergent and discriminant validity were examined by multitrait scaling analysis. Concurrent validity was assessed using Spearman's correlation coefficients between the Cancer Module and Generic Core Scales, and the comparison of the scores of child self-reports with those of other self-rating depression scales for children. Clinical validity was assessed by comparing the on- and off- treatment scores using Kruskal-Wallis and Mann-Whitney U tests. RESULTS: Cronbach's coefficient alpha was over 0.70 for the total scale and over 0.60 for each subscale by age except for the 'pain and hurt' subscale for children aged 5 to 7 years. For test-retest reliability, the ICC exceeded 0.70 for the total scale for each age. Exploratory factor analysis demonstrated sufficient factorial validity. Multitrait scaling analysis showed high success rates. Strong correlations were found between the reports by children and their parents, and the scores of the Cancer Module and the Generic Core Scales except for 'treatment anxiety' subscales for child reports. The Depression Self-Rating Scale for Children (DSRS-C) scores were significantly correlated with emotional domains and the total score of the cancer module. Children who had been off treatment over 12 months demonstrated significantly higher scores than those on treatment. CONCLUSIONS: The results demonstrate the reliability and validity of the Japanese version of the PedsQL Cancer Module among Japanese children.

Medical visits of childhood cancer survivors in Japan: a cross-sectional survey.

BACKGROUND: Although more children with cancer continue to be cured, these survivors experience various late effects. Details of the medical visit behaviors of childhood cancer survivors (CCS) in adulthood remain to be elucidated. METHODS: In order to examine medical visits in the past and future of CCS, we performed a cross-sectional survey with self-rating questionnaires on medical visits of CCS compared with control groups (their siblings and the general population). RESULTS: Questionnaires were completed by 185 CCS, 72 of their siblings and 1000 subjects from the general population and the results were analyzed. Mean ages at this survey and the duration after therapy completions of CCS were 23 and 12 years, respectively. We found that the previous treatment hospitals (where CCS were treated for their cancer) were the most commonly visited medical facilities for the CCS group (74% for female patients and 64% for male patients) and more than half of the CCS preferred to continue visiting the previous treatment hospital with enough satisfaction in Japan. The multivariate analysis showed that female sex and relapse were significantly associated with the past visits to the previous treatment hospital and that the CCS with brain tumors or bone/soft tissue sarcomas and CCS with any late effects tended to continue the relationships with the hospital. In addition female sex was also significantly associated with desired future visits to the previous treatment hospital. On the other hand, the married CCS tended to be disinclined to visit the hospital it in the future. CONCLUSIONS: In order to optimize risk-based care and promote health for CCS after adulthood, we should discuss the medical transition with CCS and their parents.

Methyl-CpG binding protein 2 gene (MECP2) variations in Japanese patients with Rett syndrome: pathological mutations and polymorphisms.

A total of 45 different mutations of methyl-CpG-binding protein 2 gene (MECP2) were identified in 145 of 219 Japanese patients with typical or atypical Rett syndrome (RTT) (66.2%). A missense mutation, T158M was the most common mutation of MECP2, identified in 22 (19.1%) patients, followed by four nonsense mutations, R168X (14.8%), R270X (13.0%), R255X (9.6%), and R294X (6.1%) in 115 patients with classical RTT. Two missense mutations, R133C (33.3%) and R306C (23.3%), and a nonsense mutation, R294X (13.3%), were common in 30 patients with atypical RTT, including the preserved speech variant (PSV). Frameshift mutations due to nucleotide deletion or insertion were identified in 22 patients with MECP2 mutations, and one of them had a 3.6 kb deletion encompassing exons 3 and 4. Three patients with classical RTT had a splicing anomaly. The wide spectrum of phenotypic variability in patients with RTT has been considered to be correlated with the mutation type and location in MECP2, and X-inactivation. However, most patients showed a random X-inactivation pattern evaluated by an androgen receptor gene polymorphism in this study, suggesting that a skewed X-inactivation might not be a main modification factor on clinical phenotypes of RTT. In addition, three new missense mutations, P176R, A378V and T479M, were identified in patients with RTT, but also in healthy Japanese, indicating that these mutations are non-pathogenic in Japanese. Information about rare polymorphic variations is very important for the molecular diagnosis of RTT, although rare polymorphic variants might differ among ethnic groups.

Mutations in CDCA7 and HELLS cause immunodeficiency-centromeric instability-facial anomalies syndrome.

The life-threatening Immunodeficiency, Centromeric Instability and Facial Anomalies (ICF) syndrome is a genetically heterogeneous autosomal recessive disorder. Twenty percent of patients cannot be explained by mutations in the known ICF genes DNA methyltransferase 3B or zinc-finger and BTB domain containing 24. Here we report mutations in the cell division cycle associated 7 and the helicase, lymphoid-specific genes in 10 unexplained ICF cases. Our data highlight the genetic heterogeneity of ICF syndrome; however, they provide evidence that all genes act in common or converging pathways leading to the ICF phenotype.

Social outcomes and quality of life of childhood cancer survivors in Japan: a cross-sectional study on marriage, education, employment and health-related QOL (SF-36).

Social outcomes and quality of life (QOL) of childhood cancer survivors (CCSs) remain unknown in Japan. We investigated these outcomes in young adult CCSs compared to those of their siblings in Japan, and analyzed the association between social outcome and SF-36 health survey subscale scores. Between 2007 and 2009, we performed a cross-sectional survey using self-rating questionnaires. We estimated social outcomes and health-related QOL by performing the SF-36 in each group: CCSs with or without stem cell transplantation (SCT)/radiotherapy (RT) and their siblings. Adjusted odds ratios for outcomes of interest were estimated using logistic regression analysis. Questionnaires from 185 CCSs and 72 CCS's siblings were analyzed. There were no differences in educational attainment or annual income. The SF-36 subscale scores of CCSs with SCT and RT were significantly lower than those of siblings in physical functioning (PF) (p < 0.001 and 0.003, respectively) and general health (GH) (both p = 0.001). Lower PF scores correlated with recurrence (p = 0.041) and late effects (p = 0.010), and poor GH scores with late effects (p = 0.006). The CCSs had made efforts to attain educational/vocational goals; however, a significant proportion of CCSs who had experienced late effects remain at increased risk of experiencing diminished QOL.

Mental health among young adult survivors of childhood cancer and their siblings including posttraumatic growth.

BACKGROUND: Few studies have addressed the mental health status of young adult childhood cancer survivors (CCSs) and their siblings (SIBs). This paper focuses on depression, anxiety, posttraumatic stress symptoms (PTSS), and posttraumatic growth (PTG) among Japanese CCSs and their SIBs. METHODS: Adolescent and young adult CCSs (n=185), in remission for more than 1 year, their SIBs (n=72), and general controls (CONTs) (n=1,000) completed anonymous self-report questionnaires for depression, anxiety, PTSS, and PTG. The physicians in charge also completed an anonymous disease/treatment data sheet. RESULTS: CCSs were approximately 8 years old at diagnosis and approximately 23 years old at the time of the survey. Their diagnoses included leukemia (57%), lymphoma (12%), and solid tumors (30%). Thirty-eight percent underwent surgery and 25% received stem cell transplantation. No significant differences were found between CCSs and CONTs in terms of depression and anxiety. CCSs had significantly more PTSS and had remarkably greater PTG compared to CONTs. Although no significant differences were found between SIBs and CONTs regarding depression, anxiety, or PTSS, female SIBs exhibited greater PTG compared to female CONTs. CONCLUSION: To empower CCSs, they should be evaluated periodically regarding PTSS and PTG and should be provided appropriate care and feedback. The fact that the mental health status of young adult SIBs was similar to CONTs at 15 years after their siblings' diagnoses may help reassure parents who worry about mental health among the siblings of an affected child during and after his/her treatment.

Late effects and quality of life of childhood cancer survivors: part 1. Impact of stem cell transplantation.

To examine the late effects and health-related quality of life among childhood cancer survivors (CCS) after stem cell transplantation (SCT), we performed a cross-sectional survey using self-rating questionnaires. The subjects were divided into 3 groups: SCT-treated CCS, CCS treated without SCT, and the general population who matched for age, gender, residential area, and work status with the CCS. We analyzed the questionnaires of 185 CCS and 1,000 control participants. The median ages of CCS at diagnosis and survey were 8 and 22 years, respectively. The mean final heights of male and female participants were significantly lower for SCT-treated CCS than for CCS treated without SCT and the controls. Among the SCT-treated CCS, >40% were underweight (BMI < 18.5). Late effects were observed in 78% of SCT-treated CCS versus 45% of CCS treated without SCT. Multivariate analysis revealed that >15 years' duration after therapy completion (OR 2.95; p = 0.014), solid tumors (4.31; p = 0.040), radiotherapy (2.82; p = 0.009), recurrence (4.22; p = 0.017), and SCT (3.39; p = 0.014) were significant risk factors for late effects. Subjective symptoms were significantly frequent in SCT-treated CCS. Physical dysfunction, psychological stress, and social adaptation problems were observed in >70% of SCT-treated CCS.

Late effects and quality of life of childhood cancer survivors: Part 2. Impact of radiotherapy.

To examine the late effects and health-related quality of life of childhood cancer survivors (CCS) after radiotherapy (RT), we performed a cross-sectional survey using self-rating questionnaires. The subjects were divided into 3 groups: CCS treated with or without RT, and a general population matched for age, gender, residential area, and work status. The numbers in each group were 113, 72, and 1,000, respectively. The median ages of CCS at diagnosis and the time of the survey were 8 and 22 years, respectively. The mean final heights of males and females were significantly lower in CCS with RT than in the other 2 groups. Risk factors for a short stature were total body irradiation (TBI) [odds ratio (OR) 17.8, p < 0.001], spinal irradiation (OR 8.31, p = 0.033), and an age younger than 10 years at diagnosis. Late effects were observed in 68% of CCS with RT compared with 36% of CCS without RT. Multivariate analysis revealed that TBI was significantly associated with endocrine dysfunction (OR 12.3), skull and spinal irradiation with cognitive dysfunction (OR 16.1 and 11.5, respectively), and spinal irradiation with a short stature (OR 14.1), respectively. Physical dysfunction, psychological stress, and problems of social adaptation were observed in >50% of CCS with RT.