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Brentuximab vedotin (BV), an anti-CD30 antibody with monomethyl auristatin E conjugate, has shown clinical effects against relapsed/refractory classic Hodgkin lymphoma (cHL) and hence is widely used in the clinical setting. We report a special clinical case of successful pregnancy and fetal outcome in a patient with cHL who achieved long-term remission with BV for early relapse after an autologous stem cell transplant (auto-SCT). A 27-year-old woman with advanced cHL achieved complete response (CR) after six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) regimen. Embryos obtained from intracytoplasmic sperm injection were cryopreserved before the initiation of induction chemotherapy. Despite achieving a second CR following intensive salvage chemotherapy, auto-SCT, and radiotherapy, she relapsed again six months after transplantation. BV monotherapy was administered as salvage therapy. She completed 16 cycles of BV and achieved CR. Six months after BV completion, she expressed her desire to bear a child. She achieved pregnancy through third in vitro fertilization and embryo transfer and delivered a healthy baby. BV may provide a potentially curative treatment for patients with cHL relapsed after auto-SCT. Pregnancy should be avoided during BV administration up to a certain period after the end of administration. Fertility preservation is important for adolescent and young adult cancer survivors, and patients should be informed of cancer-related infertility and fertility preservation options prior to the initiation of cancer treatment.

DOI： 10.7759/cureus.57291

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OBJECTIVES: Intensive nutritional support during allogeneic hematopoietic stem cell transplantation (allo-HSCT) yields improved clinical outcomes. However, the clinical implications of early enteral nutrition (EN) in allo-HSCT remain unclear. This retrospective study was conducted to determine the significance of early EN in individuals who underwent allo-HSCT, and the association between early nutritional intervention and clinical outcomes, including the status of the intestinal microbiome. METHODS: Thirty-one participants received EN before conditioning. The intestinal microbiota was examined by meta 16S rRNA gene sequencing of fecal samples. RESULTS: The median body mass variation was only -0.35 kg on day 60. The probability of 2-y overall survival was 61.1%. The cumulative incidence of treatment-related mortality was 17.4%, and those of acute graft-versus-host disease were 32.3% (grades II-IV) and 3.2% (grades III-IV). Chronic graft-versus-host disease was observed in four participants. Dysbiosis of the intestines and acute graft-versus-host disease occurred simultaneously, and Enterococcus species were abundant. CONCLUSIONS: Our results suggest that early nutritional support can improve the outcomes for individuals who have undergone allo-HSCT and can maintain homeostasis of their intestinal microbiome. Future prospective clinical trials are required to elucidate the role of EN in allo-HSCT and the association between the intestinal microbiome and EN.

DOI： 10.1016/j.nut.2020.111093

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Brentuximab vedotin monotherapy for late-relapse CHL is a promising therapeutic with sustained CR benefit and avoiding potential toxicities caused by aPBSCT/HDT.

DOI： 10.1002/ccr3.2688

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Patients with HIV are at higher risk of developing thrombosis than the general population. We present a rare case of a 57-year-old Japanese man with HIV infection and a malignant lymphoma. He had fever with unknown origin and cervical lymph node swelling 2 months before his hospital visit. Because he was positive for the HIV antibody, he was referred to our HIV special outpatient section. HIV RNA level was found to be 846,680 copies/ml. Therefore, antiretroviral therapy of DTG/ABC/3TC was initiated. However, the high fever continued for 7 days after treatment initiation; moreover, renal dysfunction was progressive. After admission, antibiotic therapy was initiated, due to which the fever subsided. However, renal dysfunction continued to progress. Fourteen days later, he died due to acute renal failure with hyperkalemia. An autopsy revealed a large mass in the spleen, and histological findings revealed a diffuse large B cell lymphoma (DLBCL). Furthermore, thrombi were detected in the right and left ventricles, right atrium, iliac artery, and renal artery. Pathological findings revealed that the thrombus induced the renal failure. These thrombi contained fibrin with inflammatory cell infiltration but not tumor cells. Patients with HIV and malignant lymphoma are at a higher risk of thrombosis. It is important to consider thrombosis during the treatment of patients with HIV.

DOI： 10.11406/rinketsu.61.1595

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Recently, a new erythroid regulator, erythroferrone (ERFE), which downregulates hepatic hepcidin production, has been identified. However, the relationship between ERFE and abnormal iron metabolism in MDS is unclear. In this study, we examined the level of ERFE mRNA during ex vivo erythroid differentiation using cord blood CD34+ cells and we further analyzed whether ERFE could be produced by MDS cells using a public database (GSE58831). ERFE mRNA was increased during normal erythroid differentiation. An analysis of GSE58831 indicated that ERFE expression in bone marrow (BM) MDS cells was higher than that in healthy volunteer (HV)-derived BM cells. ERFE expression significantly and positively correlated with the expression of erythropoietin (EPO) receptors (EPO-R), ALAS2 (5'-Aminolevulinate Synthase 2), STEAP3 (STEAP family member 3) and the presence of ring sideroblasts or the SF3B1 mutation. These results suggest that EPO-R+ MDS cells with ring sideroblasts or an SF3B1 mutation produce high levels of ERFE that may be associated with a reduction in hepcidin.

DOI： 10.1016/j.bcmd.2019.04.014

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We and others have demonstrated that various abnormalities of the bone marrow (BM) mesenchymal stromal cells (MSCs) such as aberrant cytokine expression, abnormal hedgehog signaling, and impaired miRNA biogenesis are observed in patients with acute myeloid leukemia (AML). However, underlying mechanisms to induce the dysfunction of BM MSCs have not yet been clarified. We previously showed that AML cells release abundant exosomal miR-7977, which, in turn, enters BM mesenchymal stromal cells (MSCs). However, the precise function of miR-7977 is not known. In this study, we performed transduction of a miR-7977 mimic into MSCs, compared transcriptomes between control-transduced (n = 3) and miR-7977-transduced MSCs (n = 3), and conducted pathway analysis. The array data revealed that the expression of 0.05% of genes was reduced 2-fold and the expression of 0.01% of genes was increased 2-fold. Interestingly, approximately half of these genes possessed a miR-7977 target site, while the other genes did not, suggesting that miR-7977 regulates the gene expression level directly and indirectly. Gene set enrichment analysis showed that the gene sets of Yes-associated protein 1 (YAP1) _up were significantly enriched (p<0.001, q<0.25), suggesting that miR-7977 modulates the Hippo-YAP signaling pathway. Visualization of pathway and network showed that miR-7977 significantly reduced the expression of Hippo core kinase, STK4. miR-7977 inactivated the Hippo-YAP signaling pathway as proven by GFP-tagged YAP nuclear trans localization and TEAD reporter assay. The miR-7977-transduced MSC cell line, HTS-5, showed elevated saturation density and enhanced entry into the cell cycle. These results suggest that miR-7977 is a critical factor that regulates the Hippo-YAP signaling pathway in BM-MSCs and may be involved in the upregulation of leukemia-supporting stroma growth.

DOI： 10.1371/journal.pone.0213220

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A 62-year-old man was referred to our hospital due to pancytopenia and abnormal leukocyte fraction in December 2016. Bone marrow aspiration showed a massive proliferation of blast cells (96%) with rich myeloperoxidase-negative basophilic granules. He was diagnosed with acute basophilic leukemia, and an appropriate treatment for acute myelogenous leukemia was initiated. Blast cells were positive for minor BCR-ABL mutations, and chemotherapy using imatinib was initiated on day 7. The treatment was effective and complete remission was achieved on day 30. The ultrastructural features of blast cells showed typical basophilic granules with high electron density structure on electron microscopy. However, immunohistochemical analysis were positive for CD79a, PAX5, and TdT expression. Rearrangements of immunoglobulin heavy chain and T-cell receptor genes were detected, prompting the diagnosis of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) with basophilic change. The patient continued to be treated with the imatinib combination regimen, as well as umbilical cord blood transplantation. The patient has currently achieved recurrence-free survival. This case represents a rare divergence between morphology and molecular condition.

DOI： 10.11406/rinketsu.60.773

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We report three cases of POEMS syndrome treated with lenalidomide and dexamethasone who presented with peripheral neuropathy. All of them had markedly elevated serum vascular endothelial growth factor (VEGF) levels treated with lenalidomide and dexamethasone for severe peripheral neuropathy, which normalized serum VEGF levels and improved peripheral neuropathy. The standard treatment of POEMS syndrome has not been established, but has been effectively treated with high-dose chemotherapy with autologous stem cell transplantation. Newer agents currently used for plasma cell dyscrasias include bortezomib and immunomodulatory drugs, such as thalidomide and lenalidomide. A randomized controlled trial on thalidomide plus dexamethasone for POEMS syndrome showed reduced serum VEGF levels after therapy; however, the incidence of peripheral neuropathy, a well-known side effect of both thalidomide and bortezomib, increased. Lenalidomide is associated with lower incidence of peripheral neuropathy compared to thalidomide and bortezomib, making it a reasonable treatment option for POEMS syndrome.

DOI： 10.11406/rinketsu.60.308

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PURPOSE: Consolidation/maintenance therapy induces deep remission in patients with multiple myeloma (MM); however, the most suitable regimen has been under investigation. The combination therapy with bortezomib, lenalidomide and dexamethasone (VRD) is a powerful regimen for relapsed/refractory as well as newly diagnosed MM as an induction therapy. However, severe adverse events (AEs) may become a problem when VRD is introduced without dose reduction as a consolidation/maintenance therapy. METHODS: In this single-arm phase II study, we evaluated the efficacy of small-dose VRD regimen (sVRD) in the consolidation/maintenance setting. Sixteen patients who had partial response (PR) or better after any induction therapy were enrolled. Patients received at least six 28-day cycles of subcutaneous bortezomib (1.3 mg/m2 on days 1 and 15), lenalidomide (10 mg on days 1-21) and dexamethasone (40 mg on days 1, 8, 15 and 22). RESULTS: The overall response rate and the complete response (CR) rate were 100 and 43.8 %, respectively. In particular, one patient with CR and two patients with very good PR at enrollment achieved stringent CR during 6 courses of sVRD. With a median follow-up time of 29.4 months, the median progression-free survival (PFS) and overall survival (OS) were not reached, while the PFS and OS rates at 2.5 years were 66.6 and 77.3 %, respectively. Univariate analysis demonstrated that disease progression as a reason for discontinuation of sVRD had a negative impact on OS. There were no grade 3 or 4 hematologic or nonhematologic AEs. CONCLUSION: Our sVRD regimen as a consolidation/maintenance therapy was highly effective and well tolerable.

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UNLABELLED: We report the treatment outcomes of 5 cases of adult-onset Ewing sarcoma(ES)managed between 2011 and 2014. We examined prognostic factors including the primary lesion, tumor size, metastatic status, and serum LDH levels. RESULTS: The locations of the primary lesions included the limbs in 1 case and the trunk in 4; the cases in the trunk had a worse prognosis than that in the limbs. Tumor size was greater than 8 cm in only 1 patient, who also displayed evidence of metastases at presentation and high LDH levels. All the patients received chemotherapy consisting of alternating vincristine, doxorubicin, and cyclophosphamide(VDC)and etoposide and ifosfamide(IE). Surgery was selected for the treatment of 4 patients, and radiotherapy was administered to 1 patient for local treatment of the tumor. A median follow-up duration of 31.6 months revealed the 2-year overall survival rate and progression-free survival rate to be 80.0%. CONCLUSIONS: The prognosis of patients with adult-onset ES is poor; however, combined modality therapy, including VDC-IE, was demonstrated to improve the outcome of patients in the present study. Nevertheless, the patient with tumor size exceeding 8 cm, metastasis, and high LDH levels, relapsed 1 year after treatment, as reported previously. Further investigation is required to clarify the factors affecting prognosis in adults, and to develop effective therapies for patients with a poor prognosis.

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BACKGROUND: Systemic capillary leak syndrome is a rare condition characterized by episodic attacks of hypovolemia due to systemic capillary hyperpermeability, which results in profound hypotension and edema. Although the implication of vascular endothelial growth factor, angiopoietin-2, and C-X-C motif chemokine 10 has been suggested, the pathogenesis of systemic capillary leak syndrome remains unclear. In this report, we describe a case of systemic capillary leak syndrome in which serum isoform D of vascular endothelial growth factor was elevated. To the best of our knowledge, this is the first reported case of systemic capillary leak syndrome in which isoform D of vascular endothelial growth factor is suggested as the plausible biomarker. CASE PRESENTATION: A 41-year-old Japanese man was transferred to our emergency department. He was hypotensive, tachycardic, and edematous over the trunk and all four limbs. He received aggressive intravenous fluid therapy and underwent fasciotomy of the right forearm to prevent muscle necrosis. A diagnosis of systemic capillary leak syndrome was suspected. The presence of serum monoclonal immunoglobulin G and κ light chain supported this diagnosis. Prevention of hypotensive crises was unsuccessfully attempted with theophylline, intravenous immunoglobulin, high-dose dexamethasone, bortezomib, melphalan, and prednisolone; however, the patient's attacks dramatically disappeared after the introduction of thalidomide. The serum of the patient was stored soon after the onset of hypotensive crisis and analyzed to profile possible mediators responsible for the capillary leak. The concentration of vascular endothelial growth factor, angiopoietin-2, and C-X-C motif chemokine 10 were all within normal ranges. Meanwhile, we found that isoform D of vascular endothelial growth factor was elevated, which was normalized after the introduction of thalidomide. CONCLUSIONS: In our patient, isoform D of vascular endothelial growth factor (instead of vascular endothelial growth factor) may have been a causative factor of hypotensive crises, since isoform D contributes to vascular endothelial growth factor receptor-2 signaling, which is the major mediator of the permeability-enhancing effects of vascular endothelial growth factor. We suggest the measurement of isoform D of vascular endothelial growth factor in patients with systemic capillary leak syndrome in whose serum vascular endothelial growth factor is not elevated.

DOI： 10.1186/s13256-016-0894-7

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The failure of normal hematopoiesis is observed in myeloid neoplasms. However, the precise mechanisms governing the replacement of normal hematopoietic stem cells in their niche by myeloid neoplasm stem cells have not yet been clarified. Primary acute myeloid leukemia and myelodysplastic syndrome cells induced aberrant expression of multiple hematopoietic factors including Jagged-1, stem cell factor and angiopoietin-1 in mesenchymal stem cells even in non-contact conditions, and this abnormality was reverted by extracellular vesicle inhibition. Importantly, the transfer of myeloid neoplasm-derived extracellular vesicles reduced the hematopoietic supportive capacity of mesenchymal stem cells. Analysis of extracellular vesicle microRNA indicated that several species, including miR-7977 from acute myeloid leukemia cells, were higher than those from normal CD34(+)cells. Remarkably, the copy number of miR-7977 in bone marrow interstitial fluid was elevated not only in acute myeloid leukemia, but also in myelodysplastic syndrome, as compared with lymphoma without bone marrow localization. The transfection of the miR-7977 mimic reduced the expression of the posttranscriptional regulator, poly(rC) binding protein 1, in mesenchymal stem cells. Moreover, the miR-7977 mimic induced aberrant reduction of hematopoietic growth factors in mesenchymal stem cells, resulting in decreased hematopoietic-supporting capacity of bone marrow CD34(+)cells. Furthermore, the reduction of hematopoietic growth factors including Jagged-1, stem cell factor and angiopoietin-1 were reverted by target protection of poly(rC) binding protein 1, suggesting that poly(rC) binding protein 1 could be involved in the stabilization of several growth factors. Thus, miR-7977 in extracellular vesicles may be a critical factor that induces failure of normal hematopoiesis via poly(rC) binding protein 1 suppression.

DOI： 10.3324/haematol.2015.134932

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DOI： 10.1111/1346-8138.13150

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Neurolymphomatosis is a rare manifestation of malignant lymphoma. The involvement of peripheral nerves has mostly been described as dissemination of a systemic lymphoma. In contrast, primary peripheral nerve lymphoma is extremely rare. A 68-year-old man presented in January 2014 with a sensory disturbance in the left lower extremity. There were no obvious findings on MRI or CT that could account for his symptoms. After 1 year of symptomatic treatment, the patient was managed conservatively for an additional year. However, his symptoms worsened. FDG-PET/CT showed high FDG uptake in the left sciatic nerve. Biopsy of the lesion revealed diffuse large B cell lymphoma.

DOI： 10.11406/rinketsu.57.52

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Narrowband ultraviolet B (NB-UVB) has been widely used in dermatological phototherapy. As for the application of NB-UVB phototherapy to graft-versus-host disease (GVHD), we previously reported that it was highly efficacious for cutaneous lesions of acute GVHD (aGVHD) and that expansion of regulatory T (Treg) cells induced by NB-UVB might be one of the mechanisms. In order to examine whether NB-UVB irradiation through expansion of Treg cells is effective for the treatment of not only cutaneous aGVHD but also aGVHD of inner organs such as the intestine or liver, we conducted experiments in which a murine lethal aGVHD model, characterized by severe involvement of the intestine, was irradiated with NB-UVB. We found that NB-UVB irradiation improved the clinical score and survival rate. The pathological score of aGVHD was improved in all affected organs: intestine, liver, and skin. In the serum of mice irradiated with NB-UVB, the levels of Treg cells-associated cytokines such as transforming growth factor beta (TGFβ) and interleukin-10 (IL-10) were elevated. The numbers of infiltrating Treg cells in inflamed tissue of the intestine and those in spleen were increased in mice treated with NB-UVB. This is the first report demonstrating that NB-UVB phototherapy has the ability to ameliorate intestinal aGVHD through the expansion of Treg cells.

DOI： 10.1371/journal.pone.0152823

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A 61-year-old woman with rheumatoid arthritis who was undergoing hemodialysis for end-stage renal failure was transferred to our hospital due to severe thrombocytopenia and anemia. A bone marrow biopsy showed the complete absence of megakaryocytes and erythroblasts. Cyclosporine treatment resulted in the improvement of her megakaryocyte and erythroblast levels, and a decrease in her serum level of anti-c-Mpl (thrombopoietin receptor) antibodies. After this initial improvement, her anemia progressively worsened, despite the continuous administration of immunosuppressive therapy with cyclosporine. Her platelet and leukocyte counts remained stable. This is the first report of a probable case of anti-c-Mpl antibody-associated pure red cell aplasia and acquired amegakaryocytic thrombocytopenic purpura.

DOI： 10.2169/internalmedicine.55.5190

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An 86-year-old man presented with enlarged left submandibular, left inguinal, and superficial femoral lymph nodes. He was diagnosed with Langerhans cell sarcoma (LCS) on the basis of the histopathological findings of the left inguinal lymph node biopsy. In addition, laboratory examinations revealed normocytic normochromic anemia, and bone marrow aspiration and biopsy led to a diagnosis of idiopathic cytopenia of undetermined significance (ICUS). Because of the patient's age, he was administered a regimen of cyclophosphamide, pirarubicin, vincristine, and prednisolone (THP-COP), and achieved a partial response after six courses. However, he developed acute myeloid leukemia (AML) 11 months after completion of the THP-COP therapy, and received only supportive care until his death. LCS is an extremely rare and aggressive dendritic cell neoplasm. To the best of our knowledge, only 67 cases have been reported in the literature. There are case reports describing the concurrence of hematological malignancies. Herein, we report the first documented development of LCS in a patient with ICUS who progressed to AML, and summarize the published data on the epidemiology of and therapeutic options for LCS.

DOI： 10.11406/rinketsu.56.2456

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A 55-year-old female with stage IVA follicular lymphoma in third complete remission underwent allogeneic peripheral blood stem cell transplantation. Neutrophil engraftment was achieved on day +18; however, platelet counts remained below 10 × 10(3)/µL, necessitating transfusions twice a week for more than 3 months. Bone marrow showed a decreased number of megakaryocytes with hypolobulated nuclei. No graft versus host disease, viral infection, or disease relapse was observed. Furthermore, severe thrombocytopenia below 5.0 × 10(3)/µL refractory to transfusion appeared on day +240 after influenza virus infection. Treatments with intravenous immunoglobulin, romiplostim, and rituximab were administered without any recovery. Subsequently, eltrombopag was initiated on day +443, after which platelet counts rose gradually and continued to rise above 20 × 10(3)/µL after 10 weeks of administration. The serum thrombopoietin (TPO) level was markedly elevated, and anti-TPO receptor (TPOR) antibody was detected in the patient's serum. Anti-TPOR antibody may play an important role in some cases of prolonged thrombocytopenia after allogeneic hematopoietic stem cell transplantation with unknown etiology, and eltrombopag could be a novel therapeutic option for such cases.

DOI： 10.1007/s12185-015-1806-0

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Double- and triple-hit lymphomas (DHL/THL), high-grade B-cell lymphomas with an extremely poor prognosis, are defined by a chromosomal breakpoint affecting the MYC/8q24 locus in combination with another recurrent breakpoint. The successful use of dose-adjusted (DA) EPOCH-R in patients with MYC-positive lymphoma and Burkitt lymphoma (BL) was recently reported. A 74-year-old man with acute renal dysfunction and hyperkalemia was transferred to our emergency center by ambulance. PET-CT revealed a left renal hilar mass enveloping the abdominal para-aortic domain and bladder and hydronephrosis. High (18)F-FDG uptake revealed lymph node, peritoneum, and multiple bone metastases. Analysis of the bone marrow aspirate revealed abnormal lymphoid cells with deeply basophilic cytoplasm and numerous vacuoles resembling Burkitt cells. Chromosomal analysis revealed a complex chromosomal karyotype, including t(14;18)(q32;q21), and FISH analysis confirmed split BCL2, BCL6, and MYC signals. Bone marrow biopsy revealed diffusely infiltrating large abnormal lymphoid cells with a CD10⁺, CD20⁺, BCL2⁺, BCL6⁺, c-MYC⁺ and MUM1(-) immunophenotype. B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and BL, was diagnosed. The patient achieved a partial response after eight courses of DA-EPOCH-R chemotherapy. Our experience suggests that DA-EPOCH-R may be an effective treatment for DHL/THL.

DOI： 10.11406/rinketsu.56.905

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A 79-year-old female diagnosed with T cell/histiocyte-rich large B cell lymphoma in complete remission after six cycles of rituximab-combined chemotherapy developed severe anemia, reticulocytopenia, and bone marrow erythroid hypoplasia. She was diagnosed with pure red cell aplasia (PRCA) accompanied by Coombs-negative autoimmune hemolytic anemia evidenced by a lack of glycophorin-A-positive cells in the bone marrow, haptoglobin under the detection level, and a high titer of RBC-bound IgG. Anti-erythropoietin receptor (EPOR) antibody was detected in the serum, and oligoclonal α/β and γ/δ T cells were also detected in her peripheral blood by Southern blotting analysis. Parvovirus B19 DNA was not detected by PCR. Although the treatment with rituximab had limited efficacy (specifically, only for hemolysis), subsequent cyclosporine therapy led to prompt recovery of erythropoiesis with the disappearance of anti-EPOR antibody and oligoclonal T cells. This is the first case report of anti-EPOR antibody-associated PRCA in a patient with malignant lymphoma treated successfully with cyclosporine.

DOI： 10.1007/s12185-014-1652-5

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To date, intravenous drip infusion of zoledronic acid (ZA) has mainly been used for the treatment and prevention of skeletal-related events (SRE) in patients with multiple myeloma (MM). Recently, denosumab, a fully humanized monoclonal antibody against receptor activator of nuclear factor-κB ligand (RANKL), has also become available for the same purpose, but little is known about the impact of switching from ZA to denosumab. Herein, we present a retrospective study on bone metabolic markers in 10 MM patients initially treated with ZA and then switched to denosumab. Consequently, the levels of bone resorption markers, tartrate-resistant acid phosphatase 5b (TRACP-5b) and serum type-I collagen crosslinked N-telopeptide (sNTX), significantly decreased after denosumab treatment, while the levels of bone formation markers, osteocalcin (OC) and bone-specific alkaline phosphatase (BAP), showed no apparent changes. No patient developed severe hypocalcemia with denosumab treatment. In one patient not given chemotherapy, the M-protein level increased after switching from ZA to denosumab and plateaued when ZA was restarted. Based on this finding, we anticipate that switching from ZA to denosumab would exert a stronger suppressive effect on osteoclasts, but the anti-myeloma activity of ZA must be taken into consideration.

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The combination of glutamine, fiber and oligosaccharides (GFO) is thought to be beneficial for alleviating gastrointestinal mucosal damage caused by chemotherapy. A commercial enteral supplementation product (GFO) enriched with these 3 components is available in Japan. We performed a retrospective study to test whether oral GFO decreased the severity of mucosal injury following hematopoietic stem cell transplantation (HSCT). Of 44 HSCT patients, 22 received GFO and 22 did not. Severity of diarrhea/mucositis, overall survival, weight loss, febrile illness/documented infection, intravenous hyperalimentation days/hospital days, engraftment, acute and chronic GVHD, and cumulative incidence of relapse were studied. Sex, age, performance status, diagnosis, disease status, and treatment variables were similar in both groups. There were fewer days of diarrhea grade 3-4 in patients receiving GFO than in those who did not (0.86 vs. 3.27 days); the same was true for days of mucositis grade 3-4 (3.86 vs. 6.00 days). Survival at day 100 was 100% in the GFO group, but only 77.3% for the patients not receiving GFO (p = 0.0091, log-rank test). Weight loss and the number of days of intravenous hyperalimentation were better in the GFO group (p < 0.001 and p = 0.0014, respectively). Although not significant, less gut bacterial translocation with Enterococcus species developed in the GFO group (p = 0.0728) than in the non-GFO group. Other outcomes were not affected. To the best of our knowledge, this is the first comparative clinical study of GFO supplementation to alleviate mucosal injury after allo-HSCT. We conclude that glutamine, fiber and oligosaccharide supplementation is an effective supportive therapy to decrease the severity of mucosal damage in HSCT.

DOI： 10.1159/000368714

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Pazopanib, an oral tyrosine kinase inhibitor, is the first molecular-targeted agent approved for the treatment of advanced soft tissue sarcoma(STS). Rhabdomyosarcoma in adults is rare, accounting for less than 3%of all adult STS cases. A 57-year old woman presented with cervical lymphadenopathy. Computed tomography revealed a heterogeneous mass in the retroperitoneum, replacing the entire right kidney. On the basis of the above findings, the patient was diagnosed with alveolar rhabdomyosarcoma. She was first treated with 4 courses of vincristine, actinomycin D, and cyclophosphamide(VAC), which resulted in a partial response. Dose reduction and delay occurred owing to hematological toxicity and febrile neutropenia. As second-line chemotherapy, the patient was administered a single daily dose of 800 mg of pazopanib. Because of an episode of hand-foot syndrome and hepatic impairment, the 800-mg daily dose of pazopanib was reduced to a daily dose of 600 mg, which had to be further reduced to a daily dose of 400 mg owing to fatigue and anorexia. The patient maintained a partial response for a total of 4.3 months when treated with pazopanib. Therefore, this drug may be a new treatment option for patients showing metastatic STS after previous chemotherapy.

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Therapy-related leukemia (TRL) has been reported to occur after treatment with alkylating agents and/or topoisomerase II inhibitors. Oxaliplatin (OXP) is used as a key drug for the treatment of colorectal cancer (CRC). Cisplatin and carboplatin have been linked with TRL, but the involvement of OXP is questionable. A 74-year-old male was diagnosed with peritoneal metastasis from CRC in July 2011. The patient received nine cycles of 5-fluorouracil (5-FU), leucovorin (LV), and OXP (mFOLFOX-6 regimen) and three cycles of 5-FU and LV only, resulting in a clinical complete response. However, recurrence of CRC was detected by CT within 3 months after the last course of chemotherapy. In April 2013, laboratory tests showed pancytopenia and 15% blast cells. A bone marrow examination revealed multilineage dysplasia and 20.4% myeloblasts. Cytogenetic analysis indicated a complex karyotype that included chromosome 5 and 7 abnormalities. The patient was diagnosed with TRL and treated with a combination of azacitidine (AZA) and cetuximab (Cmab) for both cancers. AZA might be useful in TRL when a patient needs to be treated simultaneously for more than one primary cancer because of its low toxicity. Moreover, Cmab is an effective therapeutic tool in TRL patients with metastatic CRC with the wild-type K-ras gene.

DOI： 10.1159/000363100

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Narrowband ultraviolet B phototherapy (NB-UVB) is a therapeutic alternative for haematopoietic stem cell transplantation-related skin graft-versus-host disease (GVHD). The beneficial effects of this intervention may be induced by direct irradiation of inflammatory cells in the skin; however, the putative involvement of indirect effects on systemic immunity has not been elucidated. To address this issue, 11 acute skin GVHD patients refractory to standard corticosteroid treatment and with no gut/liver involvement were treated with NB-UVB irradiation. The median number of treatments was 10 times, with a mean cumulative exposure of 6.36 J/cm(2). No other immunosuppressive therapy was initiated during irradiation. Eight patients achieved an objective complete response, two had a partial response, and one showed no change. None of the patients experienced progressive skin GVHD or newly diagnosed gut/liver GVHD. NB-UVB was well tolerated, with no patients discontinuing irradiation due to toxicity. We additionally demonstrated by flow cytometry that NB-UVB irradiation induces the increment of the proportion of regulatory T cell (Tregs) in patients' peripheral blood. These results suggest that NB-UVB may exert beneficial effects on steroid-refractory skin GVHD through the expansion of Tregs.

DOI： 10.1007/s12185-014-1530-1

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DOI： 10.1038/bcj.2014.2

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Primary malignant lymphoma of the uterine cervix is a rare disease, and the therapeutic strategy has not been clearly established. A 45-year old woman presented with vaginal bleeding and hypermenorrhea in January 2012. Physical examination revealed a mass in the pelvic cavity approximately the size of a neonate's head. Pelvic magnetic resonance imaging(MRI) showed a solid mass 11 cm in size in the uterine cervix with homogeneous low intensity on T1-weighted images, iso-high intensity on T2-weighted images, and heterogeneous iso-high intensity on gadolinium-diethylenetriaminepentaacetate(Gd- DTPA)-enhanced images. Multiple lymphadenopathy were also detected in the pelvis. The Papanicolaou smear indicated class 5 cervical cytology, and a subsequent histological examination by a punch biopsy of the cervix showed diffuse infiltration of medium- to large-sized mononuclear cells that stained positive for CD20 and CD79a and negative for CD3, CD5, and EBER. Bone marrow biopsy revealed no abnormality. Positron emission tomography-computed tomography(PET-CT)showed strong fluorodeoxyglucose(FDG)accumulation in the uterine cervix mass, and in the pelvic and right inguinal lymphadenopathy. The patient was diagnosed with diffuse large B-cell lymphoma of the uterine cervix, Ann Arbor stage II AE. She was successfully treated with 8 courses of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone(R-CHOP) chemotherapy, and maintains a complete remission.

PubMed

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Language：Japanese   Publishing type：Research paper (scientific journal)  

The evidence that rituximab is effective therapy for refractory warm or cold autoimmune hemolytic anemia (AIHA) has been accumulating; however, the efficacy of rituximab for mixed-type AIHA is not evident. Herein, we report a case of mixed-type AIHA refractory to corticosteroids and splenectomy, but successfully treated with rituximab (375 mg/m(2)/day, once weekly, four times). She achieved a complete response, which has been maintained for 16 months, to date, despite steroid tapering. Our case suggests that rituximab therapy should be considered for refractory AIHA even of mixed-type.

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s12185-013-1376-y

PubMed

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare disorder characterized by severe thrombocytopenia associated with total absence or a selective decrease in bone marrow megakaryocytes. A 67-year-old male presented with a 2-month bleeding tendency. He was referred to our hospital because of severe thrombocytopenia. Bone marrow biopsy showed complete absence of megakaryocytes without dysplasia in cells of the myeloid and erythroid lineages. AATP was diagnosed. In addition, mild normocytic normochromic anemia and reticulocytosis were also observed and haptoglobin was below the detectable level. Coombs-negative autoimmune hemolytic anemia (AIHA) was diagnosed based on the high titer of RBC-bound IgG and negative direct and indirect coombs test results. He was first treated with cyclosporine 200 mg per day and subsequently with prednisolone but only slight temporary improvement was achieved. Administration of eight doses of rituximab 375 mg/m(2) per week ameliorated both thrombocytopenia and anemia. AATP should be considered in the differential diagnosis of thrombocytopenia, and immunosuppressive therapy is a potential first-line treatment. This is the first case report of AATP accompanied by AIHA successfully treated with rituximab.

PubMed

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Language：Japanese   Publishing type：Research paper (scientific journal)  

A 69-year-old male was referred to our hospital because of anemia, renal insufficiency, and a positive urine test for Bence-Jones protein. A bone marrow examination showed 73.7% of myeloma cells with lymphoplasmacytic morphology, the strong expressions of CD20 and CD23 by flow cytometry, and the chromosomal aberration of CCND1/IGH by FISH analysis. He was diagnosed with multiple myeloma, IgG-λ type. The initial treatment with bortezomib plus dexamethasone (BD) provided a rapid decrease in the level of IgG; however, he developed bortezomib-induced recurrent paralytic ileus accompanied by aspiration pneumonia during the second course. Interestingly, CD23 expression on myeloma cells decreased from 87.7% to 2.2% after 2 courses of BD. Negative CD23 expression was maintained following lenalidomide plus dexamethasone therapy. There are extremely few reports on CD23 expression on myeloma cells, and this is the first case report of multiple myeloma in which CD23 expression was lost after BD therapy.

PubMed

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J-GLOBAL

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J-GLOBAL

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Publishing type：Research paper (scientific journal)  

Permeability and gating properties of single, non-inactivating, K+ channel currents in cultured Drosophila neurons were studied using the gigaohm-seal patch-clamp technique. The non-inactivating K+ currents were activated by depolarizing the membrane to -30 mV or to more positive potentials. The slope conductance of the channel was estimated to be 17.6 +/- 3.70 pS when the cytoplasmic side of the inside-out membrane patch was perfused with solutions containing 145 mmoll-1 K+. The single-channel conductance was temperature-sensitive, with a Q10 of 1.44 between 10 and 20 degrees C. Single-channel currents could be recorded when the cytoplasmic K+ was replaced with NH4+, Rb+ or Na+, but not with Cs+. The conductance ratio of the channel for these cations was: K+ (1) greater than NH4+(0.53) greater than Rb+ (0.47) greater than Na+ (0.44). Tetraethylammonium (TEA+) ions applied at a concentration of 10 mmoll-1 to the cytoplasmic side of the membrane increased the frequency of 'blank' traces which contained no channel openings during repetitive depolarization. In addition, single-channel amplitude was reduced by about 20%. The open-time distribution was fitted by a single exponential function, whereas the closed-time distribution required a three-exponential fit. Permeability and gating properties of single, non-inactivating K+ channel currents in neurons of eag, a mutant which has defects in the delayed rectifier K+ channel, were indistinguishable from those recorded from wild-type neurons.

DOI： 10.1242/jeb.145.1.173

PubMed

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Language：Japanese   Publisher：(一社)日本エイズ学会  

Ichushi

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Language：English   Publisher：(一社)日本血液学会  

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Language：English   Publisher：(一社)日本血液学会  

Ichushi

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Language：English   Publisher：(一社)日本血液学会  

Ichushi

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Language：English   Publisher：(一社)日本血液学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本脳神経外科コングレス  

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Other Link:： https://search.jamas.or.jp/default/link?pub_year=2025&ichushi_jid=J01540&link_issn=&doc_id=20250709210001&doc_link_id=10.11406%2Frinketsu.66.405&url=https%3A%2F%2Fdoi.org%2F10.11406%2Frinketsu.66.405&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Ichushi

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Language：Japanese   Publisher：(一社)日本血栓止血学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本輸血・細胞治療学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本輸血・細胞治療学会  

Ichushi

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Ichushi

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Language：English   Publisher：(一社)日本血液学会  

Ichushi

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Language：English   Publisher：(一社)日本血液学会  

Ichushi

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Language：English   Publisher：(一社)日本血液学会  

Ichushi

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Language：English   Publisher：(一社)日本血液学会  

Ichushi

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Language：Japanese   Publisher：(株)医学書院  

Ichushi

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Ichushi

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Language：English   Publisher：(一社)日本血液学会  

Ichushi

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Language：English   Publisher：(一社)日本血液学会  

Ichushi

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Language：English   Publisher：(一社)日本血液学会  

Ichushi

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Ichushi

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Ichushi

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Language：Japanese   Publisher：(公社)日本医師会  

Ichushi

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J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Ichushi

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Language：English   Publisher：(一社)日本血液学会  

Ichushi

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Language：English   Publisher：(一社)日本血液学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Ichushi

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Language：English   Publishing type：Research paper, summary (international conference)  

DOI： 10.1182/blood-2020-134861

Web of Science

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Other Link:： https://search.jamas.or.jp/default/link?pub_year=2020&ichushi_jid=J01540&link_issn=&doc_id=20201130320007&doc_link_id=1391693801399657344&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1391693801399657344&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

Ichushi

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J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Ichushi

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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Language：English   Publisher：札幌医科大学  

Other Link:： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J00522&link_issn=&doc_id=20190416510003&doc_link_id=https%3A%2F%2Fsapmed.repo.nii.ac.jp%2Frecords%2F15486&url=https%3A%2F%2Fsapmed.repo.nii.ac.jp%2Frecords%2F15486&type=%E6%9C%AD%E5%B9%8C%E5%8C%BB%E7%A7%91%E5%A4%A7%E5%AD%A6%EF%BC%9A%E6%9C%AD%E5%B9%8C%E5%8C%BB%E7%A7%91%E5%A4%A7%E5%AD%A6%E5%AD%A6%E8%A1%93%E6%A9%9F%E9%96%A2%E3%83%AA%E3%83%9D%E3%82%B8%E3%83%88%E3%83%AA_ikor&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80183_3.gif

Ichushi

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Language：English   Publishing type：Research paper, summary (international conference)  

DOI： 10.1182/blood-2018-99-111124

Web of Science

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：金原出版(株)  

Other Link:： https://search.jamas.or.jp/default/link?pub_year=2017&ichushi_jid=J01266&link_issn=&doc_id=20171215080005&doc_link_id=10.18888%2Fhi.0000000391&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fhi.0000000391&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Ichushi

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J-GLOBAL

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Language：English   Publishing type：Research paper, summary (international conference)  

DOI： 10.1182/blood.V128.22.2863.2863

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)  

DOI： 10.1182/blood.V128.22.2455.2455

Web of Science

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Language：Japanese   Publisher：(株)癌と化学療法社  

Other Link:： https://search.jamas.or.jp/default/link?pub_year=2016&ichushi_jid=J00296&link_issn=&doc_id=20160826360018&doc_link_id=%2Fab8gtkrc%2F2016%2F004308%2F019%2F1015-1018%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2016%2F004308%2F019%2F1015-1018%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Ichushi

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Language：Japanese   Publisher：(医)王子総合病院  

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Other Link:： https://search.jamas.or.jp/default/link?pub_year=2016&ichushi_jid=J01540&link_issn=&doc_id=20160209310011&doc_link_id=1390001205035056640&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390001205035056640&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Other Link:： https://search.jamas.or.jp/default/link?pub_year=2015&ichushi_jid=J01540&link_issn=&doc_id=20160108350008&doc_link_id=1390282680013991808&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390282680013991808&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Ichushi

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Language：Japanese   Publisher：日臨技北日本支部医学検査学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Other Link:： https://search.jamas.or.jp/default/link?pub_year=2015&ichushi_jid=J01540&link_issn=&doc_id=20150810280022&doc_link_id=1390282680014232064&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390282680014232064&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

Ichushi

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

Other Link:： https://search.jamas.or.jp/default/link?pub_year=2015&ichushi_jid=J05953&link_issn=&doc_id=20150728200006&doc_link_id=%2Fci6respo%2F2015%2F000404%2F006%2F0298-0302%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fci6respo%2F2015%2F000404%2F006%2F0298-0302%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Ichushi

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Language：Japanese   Publisher：(一社)日本骨髄腫学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本骨髄腫学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本内科学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Other Link:： https://search.jamas.or.jp/default/link?pub_year=2014&ichushi_jid=J01540&link_issn=&doc_id=20141204280003&doc_link_id=1390001205034802560&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390001205034802560&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

Ichushi

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Language：Japanese   Publisher：(公社)日本皮膚科学会  

Ichushi

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Language：Japanese   Publisher：(株)癌と化学療法社  

Other Link:： https://search.jamas.or.jp/default/link?pub_year=2014&ichushi_jid=J00296&link_issn=&doc_id=20140822480024&doc_link_id=1010000782259951380&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1010000782259951380&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Ichushi

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Language：Japanese   Publisher：(一社)日本骨髄腫学会  

Ichushi

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Language：Japanese   Publisher：(株)ジェフコーポレーション  

Ichushi

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Language：Japanese   Publisher：(株)癌と化学療法社  

Other Link:： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J00296&link_issn=&doc_id=20131219480026&doc_link_id=%2Fab8gtkrc%2F2013%2F004013%2F027%2F2589-2592%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2013%2F004013%2F027%2F2589-2592%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Ichushi

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Language：English   Publishing type：Research paper, summary (international conference)  

DOI： 10.1182/blood.V122.21.1219.1219

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)  

DOI： 10.1182/blood.V122.21.959.959

Web of Science

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Other Link:： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J01540&link_issn=&doc_id=20131206430006&doc_link_id=1390282680011370496&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390282680011370496&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

Ichushi

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Language：Japanese   Publisher：(一社)日本癌治療学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本癌治療学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Other Link:： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J01540&link_issn=&doc_id=20130708240010&doc_link_id=1390282680013649664&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390282680013649664&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Other Link:： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J01540&link_issn=&doc_id=20130226280012&doc_link_id=1390001205036592512&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390001205036592512&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

Ichushi

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

Ichushi

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Language：Japanese   Publisher：(一社)日本癌治療学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本肝臓学会  

Ichushi

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