Central nervous system involvement of systemic ALK-positive histiocytosis with KIF5B-ALK fusion.

ALK-positive histiocytosis is an emerging histiocytic entity that can involve a single organ or multiple organs. This disease frequently involves the central nervous system, and the importance of immunohistochemical and genetic analyses is emphasized for the accurate diagnosis of this rare entity. However, radiological findings of this disease have not been sufficiently described. Here, we report a case of a 3-year-old boy with ALK-positive histiocytosis with systemic masses that was identified to harbor KIF5B-ALK gene fusion.

Oncologic outcomes in elderly patients who underwent hysterectomy for endometrial cancer: a multi-institutional survey in Kinki District, Japan.

BACKGROUND: The goal of this study is to assess the oncologic outcomes of elderly patients who underwent hysterectomy for endometrial cancer across three variables: hysterectomy approach, lymph node resection, and adjuvant therapy. METHODS: Hospital records of patients aged ≥ 70 years who underwent hysterectomy for endometrial cancer were obtained from 19 institutions. Patients were categorized into three risk groups: low, intermediate, and high. In each group, disease-free survival and overall survival were compared according to hysterectomy approach, lymph node resection, and adjuvant therapy using Kaplan-Meier method. Cox regression analysis with a 95% confidence interval was performed to estimate relative risk (RR) of death. RESULTS: A total of 1246 patients were included. In the low-risk group, the adjusted RR for death for minimally invasive surgery (MIS) versus laparotomy and lymph node resection versus no lymph node resection were 0.64 (0.24-1.72) and 0.52 (0.24-1.12), respectively. In the intermediate-risk group, the adjusted RR for death for MIS versus laparotomy, lymph node resection versus no lymph node resection, and adjuvant therapy versus no adjuvant therapy were 0.80 (0.36-1.77), 0.60 (0.37-0.98), and 0.89 (0.55-1.46), respectively. In the high-risk group, the adjusted RRs for death for lymph node resection versus no lymph node resection and adjuvant therapy versus no adjuvant therapy were 0.56 (0.37-0.86) and 0.60 (0.38-0.96), respectively. CONCLUSIONS: MIS is not inferior to laparotomy in uterine-confined diseases. Lymph node resection improved the outcome for all disease stages and histological types. In contrast, adjuvant therapy improved the outcomes only in high-risk patients.

Squamous cell carcinoma antigens are sensitive biomarkers for atopic dermatitis in children and adolescents: a cross-sectional study.

BACKGROUND: We recently reported that squamous cell carcinoma antigen 2 (SCCA2) is a reliable biomarker for atopic dermatitis (AD). OBJECTIVE: To further clarify its utility, we investigated for effects of comorbid allergies and AD treatment on serum SCCA levels. METHODS: Volunteers <18 years old were recruited through our website. Their allergic status was elucidated using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. We also recruited pediatric patients who were hospitalized because of severe AD. The serum levels of SCCA1 and SCCA2 were measured by enzyme-linked immunosorbent assays. In the severe AD patients, the levels of thymus and activation-regulated chemokine (TARC), SCCA1, and SCCA2 were measured before and after hospitalization. The severity of AD was assessed using the severity scoring of atopic dermatitis (SCORAD). RESULTS: A total of 576 participants (547 volunteers and 29 patients) were enrolled in the study. The levels of SCCA1 and SCCA2 were significantly higher in volunteers with mild AD and patients with severe AD than in healthy volunteers without allergic diseases. The levels were not elevated in those who had mild bronchial asthma or allergic rhinitis without AD. TARC, SCCA1, and SCCA2 were decreased during the treatment in severe AD patients, reflecting clinical improvement in response to treatment. Linear regression analysis for predicting a decrease in the SCORAD index showed R2 values of 0.16, 0.38, and 0.48 for TARC, SCCA1, and SCCA2, respectively. CONCLUSION: SCCAs, especially SCCA2, are sensitive biomarkers for detecting AD in children and adolescents and for assessing the severity and response to treatment of severe AD.

Novel TNFAIP3 microdeletion in a girl with infantile-onset inflammatory bowel disease complicated by a severe perianal lesion.

A20 haploinsufficiency (HA20), a disease caused by loss-of-function TNFAIP3 mutations, manifests various autoinflammatory and/or autoimmune symptoms. Some cases of HA20 were initially diagnosed as very early onset inflammatory bowel disease (VEO-IBD). We performed whole-exome sequencing (WES) for a Japanese girl with infantile-onset IBD and a severe perianal lesion and detected a novel de novo 119 kb microdeletion containing only TNFAIP3 (arr[GRCh37] 6q23.3(138125829_138244816) × 1).

Clinical outcome of patients with recurrent or refractory localized Ewing's sarcoma family of tumors: A retrospective report from the Japan Ewing Sarcoma Study Group.

BACKGROUND: Patients with Ewing's sarcoma family of tumors (ESFT) who experience relapse or progression have a poor prognosis. AIM: This study aimed to identify the prognostic and therapeutic factors affecting overall survival (OS) of patients with recurrent or refractory localized ESFT. METHODS AND RESULTS: Thirty-eight patients with localized ESFT who experienced first relapse or progression between 2000 and 2018 were retrospectively reviewed. The 5-year OS rate of the entire cohort was 48.3% (95% confidence interval, 29.9%-64.5%). Multivariate analysis of OS identified time to relapse or progression, but not stem cell transplantation (SCT), as the sole independent risk factor (hazard ratio, 35.8; P = .002). Among 31 patients who received salvage chemotherapy before local treatment, 21 received chemotherapy regimens that are not conventionally used for newly diagnosed ESFT. The objective response rate to first-line salvage chemotherapy was 55.2% in the 29 evaluable patients. Time to relapse or progression was significantly associated with response to first-line salvage chemotherapy (P = .006). CONCLUSIONS: The present study fails to demonstrate significant clinical benefit of SCT for recurrent or refractory localized ESFT. Recently established chemotherapy regimens may increase the survival rate of patients with recurrent or refractory localized ESFT while attenuating the beneficial effect of SCT.

OHVIRA syndrome pre-operatively diagnosed using vaginoscopy and hysteroscopy: A case report.

Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome is a rare Mullerian duct anomaly. Cases with pelvic inflammatory disease or endometriosis have been reported, which may influence fertility or the quality of life of patients; therefore, an accurate and early diagnosis is essential. The present study reports the case of patient (25-year-old female, gravida 0 para 0) with OHVIRA syndrome. Magnetic resonance imaging and a computed tomography scan revealed uterus didelphys and right renal agenesis. An opening was found on the vaginal septum during the menstrual period. Upon diagnostic vaginoscopy and hysteroscopy through the opening, the right vaginal cavity was enclosed, and the right uterine cervix and cavity were normal. The patient was diagnosed with OHVIRA syndrome. Her vaginal septum was surgically removed under direct visualization and the pathological findings of the resected septum revealed a benign squamous epithelium. The post-operative course was uneventful and restenosis of the vagina was not observed. On the whole, the present study demonstrates that the technique, diagnostic vaginoscopy and hysteroscopy, is minimally invasive and is sufficient for the diagnosis of incomplete vaginal obstruction-type OHVIRA syndrome.

Report of 2 Pediatric Cases With Li-Fraumeni Syndrome Related Malignancy in a Family.

Li-Fraumeni syndrome (LFS) is a rare inherited disease characterized by a high and early-onset cancer risk. A cancer surveillance program is important to reduce cancer-related morbidity and mortality in individuals with LFS. We report 2 pediatric cases with LFS-related malignancy in a family. Eight-year-old elder brother was diagnosed with adrenocortical carcinoma and was found to have a heterozygous missense germline mutation c.736A>G: p.Met246Val in the TP53 gene. Cancer screening led to the diagnosis of rhabdomyosarcoma at a curable stage in his 2-year-old younger brother. Comprehensive surveillance resulted in early tumor detection and improved survival.

Nile blue can photosensitize DNA damage through electron transfer.

The mechanism of DNA damage photosensitized by Nile blue (NB) was studied using (32)P-5'-end-labeled DNA fragments. NB bound to the DNA strand was possibly intercalated through an electrostatic interaction. Photoirradiated NB caused DNA cleavage at guanine residues when the DNA fragments were treated with piperidine. Consecutive guanines, the underlined G in 5'-GG and 5'-GGG, were selectively damaged through photoinduced electron transfer. The fluorescence lifetime of NB was decreased by guanine-containing DNA sequence, supporting this mechanism. Single guanines were also slightly damaged by photoexcited NB, and DNA photodamage by NB was slightly enhanced in D2O. These results suggest that the singlet oxygen mechanism also partly contributes to DNA photodamage by NB. DNA damage photosensitized by NB via electron transfer may be an important mechanism in medicinal applications of photosensitizers, such as photodynamic therapy in low oxygen.

DNA damage and apoptosis induced by photosensitization of 5,10,15,20-tetrakis (N-methyl-4-pyridyl)-21H,23H-porphyrin via singlet oxygen generation.

Cancer photodynamic therapy (PDT) requires photosensitizers that efficiently and selectively destroy tumor cells. We investigated 5,10,15,20-tetrakis (N-methyl-4-pyridyl)-21H,23H-porphyrin (TMPyP) as a potential cancer treatment. Confocal fluorescence microscopy showed that TMPyP was localized in the nuclei, whereas 5-aminolevulinic acid (ALA)-derived protoporphyrin IX (PPIX) was localized diffusely in the cytoplasm of human leukemia (HL-60) cells. In HL-60 cells under UVA irradiation, TMPyP effectively induced apoptosis. Moreover, 8-oxo-7,8-dihydro-2'-deoxyguanosine, an oxidative product of 2'-deoxyguanosine, was accumulated in the DNA of cells treated with photoirradiated TMPyP, whereas only small amounts were observed in ALA-treated cells in the presence of UVA light. TMPyP and UVA caused extensive damage at every guanine residue in DNA fragments obtained from the human p53 tumor suppressor gene and the c-Ha-ras-1 proto-oncogene, whereas PPIX induced little DNA damage under these conditions. Electron spin resonance spectroscopy using a singlet oxygen (1O2) probe and D2O showed that photoexcited TMPyP generated 1O2. These results suggest that photoexcited TMPyP reacts with oxygen to generate 1O2, which in turn, oxidizes guanine residues. Taken together, the results demonstrated that TMPyP was localized in the nucleus where it was photosensitized to induce DNA damage, suggesting that TMPyP may have clinical utility as a nucleus-targeted PDT.