Genetic Profile and Microsatellite Instability in a Case of Secondary Esophageal Squamous Cell Carcinoma 12 Years After Allogeneic Hematopoietic Stem Cell Transplantation for Aplastic Anemia.

We report on a 16-year-old Japanese boy in whom an esophageal squamous cell carcinoma (ESCC) developed 12 years after allogeneic hematopoietic stem cell transplantation was performed for aplastic anemia. A high frequency of microsatellite instability was detected in samples of ESCC. Moreover, the detection of pathogenic variants, including single nucleotide substitution of TP53 (c.346C>T) and BRCA2 (c.6952C>T) and splicing of KDM6A (c.1194+2T>G), suggest that the development of ESCC in the patient was triggered by impairment of checkpoint and repair for DNA damage and epigenetic modification through accumulation of gene mutations induced by chronic graft-versus-host disease and prolonged administration of tacrolimus.

Factors associated with posttraumatic growth among parents of children with cancer.

BACKGROUND: Parents of children with cancer are susceptible to psychological distress; however, many parents also report posttraumatic growth (PTG). The objective of this study was to explore the variables associated with PTG in parents of children with cancer who were either on treatment or off treatment. METHODS: One hundred and nineteen parents (71 mothers and 48 fathers) of children with cancer completed self-report questionnaires, including the PTG Inventory, Center for Epidemiologic Studies Depression Scale, State-Trait Anxiety Inventory, and Impact of Event Scale-Revised. Demographic data and children's medical information were also collected. Multivariate linear regression analyses were conducted to investigate the variables associated with PTG. RESULTS: The mean age of participants was 41.4 years (SD = 6). Higher PTG Inventory scores were associated with parents' lower trait anxiety (P = .028), parents' sex (female; P = .004), treatment status (within 12 months from treatment end compared with on-treatment; P = .048), surgery (P = .007), and late effects (P = .01). CONCLUSIONS: Parents' PTG was associated with children's clinical characteristics, parents' sex, and parents' anxiety levels. When dealing with PTG, the parents' psychological characteristics and children's clinical characteristics should be considered. Particularly for parents with high trait anxiety, it is important to reduce anxiety first before addressing PTG.

[Maternal Crohn's disease-related vitamin B12 deficient megaloblastic anemia in an infant].

We report an 11-month-old breast-fed boy with feeding difficulties, lethargy, and developmental delay. Blood examination showed pancytopenia and decreased serum levels of vitamin B12. Anisocytosis and poikilocytes were detected in his peripheral blood, and increased megaloblastosis without leukemic cells was detected in his bone marrow. After the diagnosis of megaloblastic anemia due to vitamin B12 deficiency, symptoms were improved by vitamin B12 administration. Further investigation of the mother identified Crohn's disease and suggested that the supply of vitamin B12 from the mother to the infant, via the placenta during pregnancy and via breast milk after birth, was decreased due to impaired absorption of vitamin B12 in the mother's small intestine. Magnetic resonance imaging of the boy's brain on admission showed cerebral cortex atrophy which had improved by the age of 1 year and 10 months after vitamin B12 treatment, though developmental delay was still evident at the age of 3 years. Infantile vitamin B12 deficiency often presents with nonspecific manifestations, such as developmental delay and failure to thrive, in addition to anemia and is thus not easily diagnosed. To prevent severe neurological sequelae, this condition must be rapidly diagnosed, because a prolonged duration increases the risk of permanent disabilities.

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.

Aggressive B-Cell Lymphoma Involving the Appendix and Bilateral Ovaries in an 11-Year-Old Girl.

BACKGROUND: The appendix and ovaries are rarely involved simultaneously in malignancies. The decision to perform an ovarian biopsy or a surgical resection in young patients can be challenging without sufficient clinical information. CASE: We describe an 11-year-old girl with bilateral ovarian masses, an enlarged appendix, associated pleural effusion, and ascites. Appendectomy and biopsy of the bilateral ovarian masses led to a diagnosis of aggressive B-cell non-Hodgkin lymphoma. The patient was treated with chemotherapy, which achieved complete remission and bilateral ovarian preservation. SUMMARY AND CONCLUSION: If ovarian involvement in malignant lymphoma is suspected, diagnostic methods should spare the ovary and prevent a loss of fertility. To evaluate for possible chemotherapy-induced ovarian damage, including infertility and premature menopause, an interdisciplinary approach is needed for the long-term follow-up of adolescent girls.

Scribbles for Metric Learning in Histological Image Segmentation.

Segmentation is a fundamental process in biomedical image analysis that enables various types of analysis. Segmenting organs in histological microscopy images is problematic because the boundaries between regions are ambiguous, the images have various appearances, and the amount of training data is limited. To address these difficulties, supervised learning methods (e.g., convolutional neural networking (CNN)) are insufficient to predict regions accurately because they usually require a large amount of training data to learn the various appearances. In this paper, we propose a semi-automatic segmentation method that effectively uses scribble annotations for metric learning. Deep discriminative metric learning re-trains the representation of the feature space so that the distances between the samples with the same class labels are reduced, while those between ones with different class labels are enlarged. It makes pixel classification easy. Evaluation of the proposed method in a heart region segmentation task demonstrated that it performed better than three other methods.

Somatic mosaic mutations of IDH1 and NPM1 associated with cup-like acute myeloid leukemia in a patient with Maffucci syndrome.

Maffucci syndrome is a nonhereditary congenital disorder characterized by multiple enchondromas and with soft-tissue hemangiomas. Somatic mutations of the isocitrate dehydrogenase (IDH) gene have been detected in enchondroma and hemangioma tissue from patients with Maffucci syndrome. The rate of malignant transformation in Maffucci syndrome is high, with enchondromas transforming into chondrosarcomas and the development of secondary neoplasms, including pancreatic and hepatic adenocarcinoma, mesenchymal ovarian tumors, and brain tumors such as glioma. However, hematopoietic malignancies arising in Maffucci syndrome are rare. We report a 7-year-old girl with Maffucci syndrome in whom acute myeloid leukemia (AML) with cup-like nuclear invagination developed. Both leukemic cells and hemangioma had the same gene mutations: an insertion frameshift c.863_864insTCTG (p.W288 fs) in the nucleophosmin (NPM1) gene and a missense mutation c.392_395GTCG > CTCT (p.G131_R132 > AL) in the IDH1 gene. However, buccal mucosa cells and peripheral blood mononuclear cells harvested after two cycles of chemotherapy showed wild-type genotypes. These results suggest that the multiple somatic mutations of the IDH1 and NPM1 genes in hemangioblasts are related to the development of cup-like AML associated with Maffucci syndrome. However, further studies are needed to identify additional molecular events in AML but not in hemangioma.