Masato Moriyama

Late Onset Post-Transfusion Hepatitis E Developing during Chemotherapy for Acute Promyelocytic Leukemia

We herein report the case of a leukemia patient who developed hepatitis E seven months after undergoing a transfusion with contaminated blood products. The latency period in this case was significantly longer than that of typical hepatitis E. Recently, chronic infection with hepatitis E virus (HEV) genotype 3 has been reported in immunocompromised patients. There is a possibility that our patient was unable to eliminate the virus due to immunosuppression following chemotherapy and the administration of steroids. The prevalence of HEV in healthy Japanese individuals is relatively high and constitutes a critical source of infection via transfusion. Hepatitis E is an important post-transfusion infection, and immunocompromised patients may exhibit a long latency period before developing the disease.

Differentiation of Mouse Induced Pluripotent Stem Cells Into Alveolar Epithelial Cells In Vitro for Use In Vivo

Alveolar epithelial cells (AECs) differentiated from induced pluripotent stem cells (iPSCs) represent new opportunities in lung tissue engineering and cell therapy. In this study, we modified a two‐step protocol for embryonic stem cells that resulted in a yield of ∼9% surfactant protein C (SPC)+ alveolar epithelial type II (AEC II) cells from mouse iPSCs in a 12‐day period. The differentiated iPSCs showed morphological characteristics similar to those of AEC II cells. When differentiated iPSCs were seeded and cultured in a decellularized mouse lung scaffold, the cells reformed an alveolar structure and expressed SPC or T1α protein (markers of AEC II or AEC I cells, respectively). Finally, the differentiated iPSCs were instilled intratracheally into a bleomycin‐induced mouse acute lung injury model. The transplanted cells integrated into the lung alveolar structure and expressed SPC and T1α. Significantly reduced lung inflammation and decreased collagen deposition were observed following differentiated iPSC transplantation. In conclusion, we report a simple and rapid protocol for in vitro differentiation of mouse iPSCs into AECs. Differentiated iPSCs show potential for regenerating three‐dimensional alveolar lung structure and can be used to abrogate lung injury.

Relationship between HMGB1 and PAI-1 after allogeneic hematopoietic stem cell transplantation

Background Conditioning regimens including total body irradiation (TBI) or cyclophosphamide can mobilize high-mobility group box 1 (HMGB1) to peripheral blood. Additionally, increased plasminogen activator inhibitor (PAI)-1 levels are associated with post-allogeneic hematopoietic stem cell transplantation (aHSCT). However, changes to circulating levels of HMGB1 after aHSCT are poorly understood. Materials and methods The study cohort included 289 patients who underwent aHSCT at one of 25 institutions in Japan. We have investigated the relationship between HMGB1 and PAI-1 following aHSCT. A significant increase in HMGB1 levels occurred after conditioning treatment. Additionally, levels of HMGB1 at day 0 were significantly increased in TBI+ patients and cyclophosphamide/TBI patients. Conclusion Our data revealed that an increased level of HMGB1 at day 0 following aHSCT correlates with increased PAI-1 after aHSCT, which is consistent with previous reports. Increased HMGB1 at day 0 after a conditioning regimen may play a role in transplantation-associated coagulopathy following aHSCT, because PAI-1 can accelerate procoagulant activity.

A case of severe thrombocytopaenia associated with acute HIV-1 infection

A 23-year-old man was admitted to our hospital with severe thrombocytopaenia. He had unprotected sexual contact 6 weeks earlier. He was diagnosed with acute HIV infection by means of HIV RNA viral load testing and HIV-associated thrombocytopaenia. Although his thrombocytopaenia improved immediately with short-term dexamethasone therapy, this effect was not sustained after cessation of therapy. Antiretroviral therapy including raltegravir was initiated, and the patient recovered from severe thrombocytopaenia within several days. The findings from this case suggest that acute HIV infection should be suspected with unexplained thrombocytopaenia, and that antiretroviral therapy is the treatment of choice for severe HIV-associated thrombocytopaenia, even when in the early period following acquisition of the virus.

The Prognostic Nutrition Index Predicts the Development of Hematological Toxicities in and the Prognosis of Esophageal Cancer Patients Treated with Cisplatin Plus 5-Fluorouracil Chemotherapy

ABSTRACT The prognostic nutrition index (PNI), calculated based on serum albumin and lymphocyte counts, predicts the prognosis of several cancers, including operated esophageal cancers. In this study, we determined whether PNI could predict the occurrence of severe adverse events by chemotherapy and chemoradiotherapy, and overall survival in esophageal cancer. We collected data from 191 patients with esophageal cancer treated with at least one course of cisplatin and 5-fluorouracil from 2005 to 2016. We compared the incidences of severe adverse events and overall survival between a high- and a low-PNI group. The optimal cut-off value of the Onodera PNI was 43.2. Patients with low PNIs suffered more frequent severe adverse events than did those with high PNIs, and the latter patients survived longer. The PNI was independently prognostic of overall survival and stage. The PNI predicted the development of severe adverse events caused by chemotherapy or chemoradiotherapy, and overall survival, in esophageal cancer patients.

A novel synthetic derivative of human erythropoietin designed to bind to glycosaminoglycans

To synthesize long-acting and antiangiogenic erythropoietin to be clinically applied for treatment of patients with solid tumors, we synthesized a hybrid molecule of human erythropoietin added onto the C-terminus with a heparin-binding motif of human PLGF-2 to develop a novel derivative of long-acting and antiangiogenic erythropoietin: heparin-binding erythropoietin (HEPO), and studied the characteristics of this novel erythropoietin derivative. HEPO cDNA was synthesized, expressed in insect cells, and the protein was purified using a heparin-sepharose affinity column. The erythropoietic and angiogenic effects of the partially purified protein were analyzed in vitro and in vivo. The erythropoietic activity of the protein was equivalent to natural EPO in vitro. In vivo administration of the protein to mice revealed its long-acting erythropoietic activity as expected. Administration of the protein inhibited angiogenesis in a mouse limb ischemia model. In conclusion, the heparin-binding motif of PLGF-2 may act as, so to speak, a superendostatin. This novel long-acting erythropoietin derivative may have an advantage to inhibit tumor growth while preserving hematopoietic and tissue-protective effects.

Cancers among adolescents and young adults at one institution in Japan

Adolescents and young adults (AYAs) with cancer often live long lives following treatment and face many life events. No detailed studies of cancers in AYAs have described the epidemiology, treatment outcome, and social status in Japan. The present study defined AYAs as those aged 15–29 years old based on the US National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program. Data was collected from the hospital-based cancer registry and electronic medical charts at Niigata University Medical and Dental Hospital from 2007 to 2015. The present study analyzed the types of cancer, treatment methods and outcomes, fertility preservation, marital status, raising children, school admission, and employment status. A total of 362 (1.9%) cancer cases in AYAs (males 119, females 243) were identified. Carcinoma was the most common type of cancer in both sexes. Females had a high incidence of carcinoma of the genitourinary tract (28.0%). Fertility-sparing surgery (16.0%) was the most common method of fertility preservation. The 5-year survival was better in females (88.4%) than in males (79.9%). The percentage of married AYAs increased following cancer treatment. The proportion of unemployment increased following cancer treatment in all age groups and was greatest (12.6%) in those aged 20–24 years old. Compared with SEER data from the United States, the incidence of carcinoma was high among AYAs, particularly genitourinary tract carcinomas in females, while the incidence of melanoma and skin carcinomas was low. Therefore, AYAs with cancer requires social and economic support.

Chromosomal rearrangements in myoepithelial carcinoma of the breast that presented as metachronic double cancer with invasive ductal carcinoma in the ipsilateral breast

Myoepithelial carcinoma of the breast is an extremely rare tumor composed entirely of malignant spindle cells with myoepithelial differentiation. The majority of previously reported cases have mainly described the clinicopathological features of the disease, and few have presented cytogenetic data. We herein present the case of a 48-year-old woman who was admitted with a left-sided breast lump in the inner upper quadrant that was initially diagnosed as a myoepithelioma with potentially malignant disorder. At 12 months after resection, she complained about a newly developed solid mass in the subareolar region of the ipsilateral breast that was diagnosed as an invasive ductal carcinoma. In addition, 16 months after the initial admission, a re-growing remnant lesion recurred in the inner upper quadrant and was ultimately diagnosed as a myoepithelial carcinoma. Lymph node metastasis of the myoepithelial carcinoma was also observed in her left axillary region 11 months after local recurrence. A cytogenetic analysis showed recurring specific chromosomal alterations both in the locally recurrent and in the lymph-node metastatic lesion: 48, XX, t(5;18)(q13;q23),del(6)(q?),+14. + mar1. To our knowledge, this is the first published report of clonal chromosomal rearrangements in myoepithelial carcinoma of the breast that presented as metachronic double cancer with invasive ductal carcinoma in the ipsilateral breast.

Masked MLL gene rearrangement was disclosed in the clinical course and sequential development of chromosome abnormality in a patient with therapy related acute myelogeneous leukemia

Therapy related acute myelogenous leukemia in a 55-year-old Japanese woman is described. She had been treated for a diagnosis of non-Hodgkins lymphoma 2 years before the onset of the secondary leukemia. She was diagnosed as AML (FAB: M2) with monosomy 7, and successfully treated by an intensive combination chemotherapy followed by an autologous peripheral blood stem cell transplantation. The disease relapsed shortly after the treatment, and the karyotype analysis revealed a complex abnormality accompanied with t(9;11)(p22;q23), however, monosomy 7 was absent. Southern blotting analysis was performed, and MLL rearrangement was evident in both the bone marrow samples obtained at that time and the cryopreserved marrow cells obtained at the onset of the disease. The bone marrow sample stored in a Carnoy solution at the onset was further analyzed, and three karyotype panels showing 45,XX, -7, t(9;11)(p22;q23) were found. Like this situation, a masked MLL rearrangement may have existed in some cases with hematopoietic malignancies, and appear to be disclosed in the clinical course.