Shuichi Ashizuka

Periostin as a biomarker for the diagnosis of pediatric asthma

There are some biomarkers for asthma diagnosis but they are often difficult in clinical use, particularly in pediatric cases. Periostin is an extracellular matrix protein, upregulated in response to IL‐4 or IL‐13. Serum periostin is expected to be used as a non‐invasive biomarker for asthma diagnosis and management.

Repair of Bochdalek hernia in an adult complicated by abdominal compartment syndrome, gastropleural fistula and pleural empyema: Report of a case

INTRODUCTION Bochdaleks diaphragmatic hernia (BDH) rarely developed symptomatic in adulthood but mostly required an operation. In adult BDH cases, long-term residing of the massive intraabdominal organs in the thoracic cavity passively causes loss of domain for abdominal organs (LOD). PRESENTATION OF CASE A 63-year-old man presented at our institution complaining of sudden left upper quadrant abdominal pain. Chest radiography showed a hyperdense lesion containing bowel gas in the left pleural space. Computed tomography revealed a dilated bowel above the diaphragm and intestinal obstruction suggestive of gangrenous changes. These findings were consistent with the diagnosis of incarcerated BDH and an emergency laparotomy was performed. Operative findings revealed the hypoplastic lung, lack of hernia sac, and location of the diaphragmatic defect, which indicated that his hernia was true congenital. Organs were reduced into the abdominal cavity, and large defect of the diaphragm was repaired with combination of direct vascular closure and intraperitoneal onlay mesh reinforcement using with expanded polytetrafluoroethylene (ePTFE) mesh. On the postoperative day 1, the patient fell into the shock and was diagnosed to have abdominal compartment syndrome (ACS). Conservative therapies were administered, but resulted in gastropleural fistula and pleural empyema, which required an emergency surgery. Mesh extraction and fistulectomy were performed. DISCUSSION A PubMed search for the case of ACS after repair of the adult BDH revealed only three cases, making this very rare condition. CONCLUSION In dealing with adult BDH, possible post-repair ACS should be considered.

Paraneoplastic Syndrome of Angiomatoid Fibrous Histiocytoma May Be Caused by EWSR1-CREB1 Fusion-induced Excessive Interleukin-6 Production.

We describe a 7-year-old girl with angiomatoid fibrous histiocytoma (AFH) presenting severe inflammatory symptoms. The cytokine/chemokine profile of serum samples before and after surgery demonstrated that interleukin (IL)-6 had decreased by the greatest percentage. The AFH cells were immunopathologically positive for IL-6 and Tyr705-phosphorylation of signal transducer and activator of transcription 3. The EWSR1-CREB1 fusion gene detected in the tumor leads to continuous activation of CREB1 and IL-6 production, because the promoter region of IL-6 has a CREB binding site. Thus, IL-6 plays pivotal roles in both paraneoplastic syndrome and the oncogenesis of AFH.

Thalidomide potentiates etoposide-induced apoptosis in murine neuroblastoma through suppression of NF-κB activation

PurposeTreatment for high-risk neuroblastoma is still challenging. The purpose of the present study was to determine whether thalidomide suppresses etoposide-induced NF-κB activation and thus potentiates apoptosis in murine neuroblastoma.MethodsA murine neuroblastoma cell line, C1300, and A/J mice were used in this study. We evaluated NF-κB activation after using etoposide with or without thalidomide by quantitative analysis of NF-κB by ELISA and by Western blot analysis of IκB phosphorylation in vitro and in vivo. Induction of apoptosis was evaluated by Western blot analysis of the apoptotic signals caspase-3, 8, and 9 in vitro and by TUNEL assays in vivo. We also evaluated the efficacy of the combination of etoposide and thalidomide by assessing tumor growth and mouse survival in vivo.ResultsEtoposide activated NF-κB in C1300 cells. This activation was suppressed by thalidomide and IκB was re-upregulated. The apoptotic signals were enhanced by the combination of thalidomide and etoposide compared with etoposide alone in vitro, which was consistent with TUNEL assays. The combination of etoposide and thalidomide also slowed tumor growth and mouse survival.ConclusionThalidomide potentiates etoposide-induced apoptosis in murine neuroblastoma by suppressing NF-κB.

Solid pseudopapillary neoplasm expresses inhibin‐α and Tcf‐3

To the Editor: Solid pseudopapillary neoplasm (SPN) of the pancreas is an uncommon tumor of low malignant potential. SPN is classified as an epithelial tumor and shows the characteristic cytomorphological features of loosely cohesive cells lining several layers and monotonous round nucleoli. Kosmahl et al. and Geers et al. hypothesized that SPN might immigrate from gonadal embryonic tissues to developing fetal pancreatic tissues on the basis of the following: first, the strikingly high preponderance of SPN in female; second, the close proximity of the genital ridges to the pancreatic angle during embryogenesis; third, the progesterone receptor being consistently present in SPN, in conjunction with the recent report of the expression of the luteinizing hormone receptor in SPN. However, SPNs arising in the ovary are quite rare compared with those in the pancreas and Yan et al. reported the case of SPN colliding with a welldifferentiated pancreatic endocrine neoplasm and suggested that SPN may originate from a multipotential primordial cell. In this study, we performed immunohistochemical examinations of inhibin-a to investigate the hypothesis, furthermore, we performed immunohistochemical examination of Tcf-3 (T cell factor 3) to investigate the tumor genesis in seven cases of SPNs resected at Toho University Ohashi Hospital and Jikei University Hospital. This study was approved by the Toho University Ohashi Hospital Ethical Committee (No.15–51) and Jikei University Hospital Ethical Committee (No.27–169). Formalin-fixed, paraffin-embedded 4mm thick tumor specimens were used for immunohistochemical analysis. The antibodies used in this study were anti-inhibin-a antibody (anti-human inhibin-a polyclonal antibody, clone R1, Neomarkers for Lab Vision Corporation, United States) and anti-Tcf-3 antibody (anti-mouse tcf-3 monoclonal antibody, clone sc8635 Santa Cruz Biochemistry, Shanghai, China, kindly gifted by Professor Shinsuke Ohba, Division of Clinical Biotechnology Center for Disease Biology and Integrative Medicine The University of Tokyo Graduate School of Medicine). The immunoreactive scores (IRS) for inhibin-a were calculated multiplying intensity score (0, negative; 1, weak; 2, moderate; and 3, strong) by percentage of positively-stained cells (0, no staining; 1, 10% staining; 2, 11–50%; 3, 51%–80%; and 4, 81% staining). Positive inhibin-a expression was defined as 1 or more IRS. As for Tcf-3, the immunohistochemical assay was scored as histological score (H-score) multiplying intensity of staining (0, no staining; 1, weak; 2, moderate; or 3, strong) by the distribution of specific staining (0.0–1.0). Positive Tcf3 expression was defined as 0.1 or more H-score. Among seven cases of SPNs, six cases (85.7%) were female, and the mean age at surgery was 27.9 (10–49) years. One of the seven cases showed invasion of atypical cells into vessel, but the other cases did not. None of the seven patients had recurrence after surgical resection. All of the seven patients had typical histopathological features compatible with SPN showing loosely cohesive cells lining several layers and the nucleoli are uniformly round (Fig. 1a). The results of immunohistochemical analysis using anti-b-catenin antibody for all seven cases definitely confirmed the diagnosis of SPNs showing positivity of b-catenin in the nucleoli (Fig. 1b). The specimens of SPN were positively stained by inhibina focally in all of seven cases (Fig. 1c). 10%–90% of cells showed positivity in the cytosol from weak to strong and IRS were calculated as 2–12 (8.43 2.82). As for Tcf-3, the nucleoli were focally positive in tumor cells of five cases (Fig. 1d). Around 10%–20% of tumor cells showed positivity from weak to moderate and H-score were calculated as 0.1–0.4 (0.14 0.05). Inhibin-a is a member of the transforming growth factor-b (TGF-b) family and a regulatory factor in the ovary and testis, with a wide range of functions. Although inhibin-a did not express in the normal tissue of the pancreas, the expression level of the inhibin-a subunit in both ovary and testis; follicle granulosa cells, Sertoli cells, and Leydig cells in late-gestation human fetuses significantly increases during gestational age. Some pancreatic neuroendocrine tumors (pNETs) are positive for inhibin-a, but histopathological features of the SPN are different from pNETs. Tcf-3 is an important transcriptional factor counters pluripotency and is stimulated by b-catenin signaling pathways in embryonic stem cells. In this study, Tcf-3 was weakly positive in the nucleoli of five SPN cases. The pathophysiological mechanisms underlying the development of SPN has not been fully clarified, the ectopic expression of b-catenin in the nucleus is consistently associated with SPN. This aberrant nuclear localization of b-catenin is the result of mutations in exon 3 of the b-catenin gene which would cause b-catenin to bind to Tcf3 and form complex localizing in the nuclei. b-catenin signaling stimulates Tcf-3 associated with differentiation programs, neutralize the destabilizing activity of Tcf-3 in the pluripotency network, and subsequently activate