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Background: Progression of chronic liver fibrosis and related increased fibrotic markers are associated with functional liver reserves or patient prognosis as well as tumor factors in hepatocellular carcinoma (HCC) patients. The aim of this study was to newly clarify the relationship between fibrotic markers and HCC malignant behaviors or its long-term postoperative prognosis by the retrospective cohort study. Methods: We examined the relationship between tumor-related factors or six liver fibrosis-associated parameters, including platelet count, hyaluronic acid (HA), Mac-2 binding protein glycosylation isomer (M2BPGi), type IV collagen 7S (T4C7), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (Fib-4) index, and clinicopathological parameters, surgical records, and postoperative prognosis in 130 HCC who underwent curative hepatectomy. Results: Histological fibrosis stage 4 as cirrhosis was in 31%. The platelet count significantly decreased in stage 4 fibrosis and correlated with grade B liver damage (P<0.01). HA levels were significantly increased in multiple HCC, stage 4 fibrosis, and grade B liver damage (P<0.01). T4C7 was significantly increased in patients with post-hepatectomy tumor recurrence compared to those without (P<0.01). Additionally, M2BPGi was significantly higher in stage 4 fibrosis and liver damage grade B, and was significantly associated with poor prognosis (P<0.05). Fib-4 index was significantly higher in patients with liver damage B (P<0.05), and T4C7 alone did not correlate with other five fibrosis markers. Stage 4 fibrosis, higher T4C7, higher M2BPGi, and increased tumor size were significantly associated with shorter cancer-free, overall, and cancer-specific survivals. Higher T4C7, non-met Milan criteria, liver damage B, blood transfusion, and curability C were independently associated with cancer-specific survivals (P<0.05). Conclusions: Type IV collagen 7S (T4C7) may reflect not only impaired liver function but also HCC malignant behaviors and patient survivals.
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Hepatitis C virus (HCV) reactivation has been reported to be caused due to several anticancer drugs and immunosuppressive agents; however, HCV reactivation after steroid monotherapy has rarely been reported. Here, we report the case of a 65-year-old Japanese man with HCV infection who developed HCV reactivation after the administration of prednisolone (PSL) for 6 days for sudden deafness. In the patient history, the positivity for anti-HCV antibody was observed, but serum level of HCV RNA was not measured. Two months after PSL administration, the patient experienced an alanine aminotransferase (ALT) flare and the serum level of HCV RNA was observed to be 6.2 log IU/mL; then, the patient was admitted to our hospital for hepatitis treatment. Based on the clinical course and laboratory findings, the patient was diagnosed with HCV reactivation. Although the ALT levels decreased spontaneously during follow-up, they did not drop to normal range; subsequently, sofosbuvir and ledipasvir treatments were started. A sustained virological response 24 weeks after the end of treatment was achieved. This case study suggests that HCV reactivation with hepatitis flare can occur even after a steroid monotherapy, and doctors should pay attention to HCV reactivation when administering PSL for patients with HCV infection.
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Antivirais , Perda Auditiva Súbita , Hepacivirus , Prednisolona , Ativação Viral , Humanos , Masculino , Idoso , Prednisolona/uso terapêutico , Perda Auditiva Súbita/tratamento farmacológico , Perda Auditiva Súbita/etiologia , Perda Auditiva Súbita/virologia , Ativação Viral/efeitos dos fármacos , Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C/complicações , Sofosbuvir/uso terapêutico , Fluorenos/uso terapêutico , Fluorenos/efeitos adversos , Benzimidazóis/uso terapêutico , Benzimidazóis/efeitos adversos , Alanina Transaminase/sangue , RNA Viral/sangue , Glucocorticoides/uso terapêutico , Glucocorticoides/efeitos adversosRESUMO
Introduction: Although the incidence of hyperammonemia as an adverse event of tyrosine kinase inhibitors is quite low, several cases of tyrosine kinase inhibitor associated hyperammonemia have been reported. We report a case of hyperammonemia, that occurred during combined treatment with axitinib and pembrolizumab in a metastatic renal cell carcinoma patient without hepatic disorder or liver metastases. Case presentation: A 77-year-old Japanese woman was diagnosed with metastatic renal cell carcinoma and was treated with pembrolizumab and axitinib. Both agents were subsequently discontinued due to hyperammonemia with hypothyroidism. After recovery, the patient resumed single-agent therapy with axitinib. However, hyperammonemia and hypothyroidism occurred again, suggesting axitinib-inducible adverse event. After nephrectomy, a lower dose of axitinib was restarted and continued safely for residual metastases under prophylactic treatment with aminoleban, lactulose, and levothyroxine. Conclusion: The rare occurrence of hyperammonemia should be considered during treatment with VEGFR- targeted tyrosine kinase inhibitor including axitinib, and supportive prophylactic medication may be useful.
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An 82-year-old female patient was admitted to our hospital for visual acuity loss in both eyes. The patient was diagnosed with invasive liver abscess syndrome and bilateral endophthalmitis due to Klebsiella pneumoniae 4 days after the onset of ocular symptoms. The liver abscess improved by broad-spectrum antibiotics and intravitreal injection, but bilateral blindness occurred. Most literature reported fever as the first symptom of invasive abscess syndrome, but this case had no fever at the onset of ocular symptoms. Delayed invasive liver abscess syndrome diagnosis might cause poor visual acuity prognosis.
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Endoftalmite , Abscesso Hepático , Feminino , Humanos , Idoso de 80 Anos ou mais , Klebsiella pneumoniae , Cegueira , Endoftalmite/tratamento farmacológico , Endoftalmite/etiologia , Abscesso Hepático/complicações , Abscesso Hepático/diagnóstico por imagemRESUMO
We reported a notable case of inflammatory hepatocellular adenoma that grew during pregnancy, consequently changing its appearance on magnetic resonance imaging remarkably. A 5-months-pregnant 35-year-old woman presented with a 37-mm liver nodule that had been diagnosed as focal nodular hyperplasia 3 years earlier. She had never used oral contraceptives. After 2 months, the nodule grew to 57 mm. The patient delivered a full-term infant without complications. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging performed after delivery revealed markedly different findings compared with the first images. A liver biopsy was performed, and the tumor was diagnosed as inflammatory hepatocellular adenoma.
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Adenoma de Células Hepáticas , Carcinoma Hepatocelular , Hiperplasia Nodular Focal do Fígado , Neoplasias Hepáticas , Feminino , Humanos , Gravidez , Adenoma de Células Hepáticas/diagnóstico por imagem , Adenoma de Células Hepáticas/patologia , Carcinoma Hepatocelular/patologia , Meios de Contraste , Diagnóstico Diferencial , Hiperplasia Nodular Focal do Fígado/diagnóstico por imagem , Hiperplasia Nodular Focal do Fígado/patologia , Hiperplasia/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética , AdultoRESUMO
RATIONALE: Hepatocellular carcinoma (HCC) is the sixth most common type of cancer globally. Since 2020, combination treatment with atezolizumab and bevacizumab were approved in patients with unresectable HCC in Japan, and atezolizumab plus bevacizumab is the first-line treatment for unresectable HCC. PATIENT CONCERNS: A 73-year-old Japanese man diagnosed with a large HCC was treated with atezolizumab plus bevacizumab. After 2 cycles, he had fever and fatigue and was admitted to the hospital. DIAGNOSIS: Abdominal contrast-enhanced computed tomography revealed tumor necrosis in HCC with gas formation in the necrotic area. Laboratory examination revealed a white blood cell (WBC) count of 16,340/µL and C-reactive protein (CRP) level of 33.0 mg/dL. Based on the above findings, he was diagnosed with a liver abscess. INTERVENTIONS: Percutaneous transhepatic liver abscess drainage and broad-spectrum antibiotics treatment were performed. OUTCOMES: Despite liver abscess drainage, persistent fever and no improvement in the WBC count or CRP level was observed. The patient's respiratory condition and renal function gradually worsened; The patient's general condition did not improve despite the ventilator support and continuous hemodiafiltration, and he died on day 37. LESSONS: We report the first case of liver abscess after atezolizumab plus bevacizumab treatment for unresectable HCC.
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Carcinoma Hepatocelular , Abscesso Hepático , Neoplasias Hepáticas , Idoso , Antibacterianos , Anticorpos Monoclonais Humanizados , Bevacizumab/uso terapêutico , Proteína C-Reativa , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Abscesso Hepático/diagnóstico , Abscesso Hepático/tratamento farmacológico , Abscesso Hepático/etiologia , Neoplasias Hepáticas/terapia , MasculinoRESUMO
BACKGROUND: It is estimated that approximately 50% of patients with hepatitis C virus (HCV) infection in Japan are currently over 75 years old. However, patients aged ≥ 75 years are typically underrepresented in clinical trials of direct-acting antivirals. This study aimed to evaluate the efficacy and safety of glecaprevir and pibrentasvir (G/P) treatment in Japanese patients with HCV infection aged ≥ 75 years. METHODS: This multicenter, retrospective study included 271 Japanese patients with HCV infection from 12 centers in Miyazaki Prefecture, Japan. Demographic, clinical, virological, and adverse events (AEs) data obtained during and after G/P treatment were collected from medical records. The patients were divided into two groups: younger (n = 199, aged < 75 years) and older (n = 72, aged ≥ 75 years). Virological data and AEs were analyzed according to the age group. RESULTS: In intention-to-treat (ITT) and per-protocol analyses, the overall sustained virological response 12 (SVR12) rates were 93% and 98.8%, respectively. Two patients in the older group and 14 patients in the younger group dropped out before SVR12 assessment. Although patients in the older group tended to have liver cirrhosis, 95.8% in the older group and 92% in the younger group achieved SVR12 in the ITT analysis (P = 0.404). In total, 48 (17.7%) patients experienced treatment-related AEs. Common AEs during treatment included pruritus, headache, and fatigue. The AEs were not significantly different between the two groups. CONCLUSIONS: Compared with younger patients, older patients showed similar virological response and tolerance to G/P treatment.
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Hepacivirus , Hepatite C Crônica , Idoso , Antivirais/efeitos adversos , Benzimidazóis , Combinação de Medicamentos , Genótipo , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Humanos , Japão , Pirrolidinas , Quinoxalinas , Estudos Retrospectivos , SulfonamidasRESUMO
BACKGROUND/AIM: Direct-acting antiviral (DAA) therapies for patients with hepatitis C virus (HCV) infection deliver higher cure rates and lower frequencies of adverse events than existing therapies, though DAA treatment costs $45,000-64,000 in Japan. The prognosis of patients who require new long-term care insurance (LTCI) certification is inferior to that of patients who do not. Here, we clarify the factors associated with new LTCI certification in elderly patients with HCV infection who undergo DAA therapy. PATIENTS AND METHODS: We retrospectively surveyed 53 patients aged ≥70 years who were treated with DAAs, and evaluated the factors associated with new LTCI certification. RESULTS: Of 53 patients, 10 required new LTCI certification. Age ≥85 years and a modified Japanese Cardiovascular Health Study index ≥2 were independently associated with new LTCI certification. CONCLUSION: In elderly HCV patients, poor frailty status strongly predicted new LTCI certification after DAA therapy.
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Antivirais/uso terapêutico , Carbamatos/uso terapêutico , Fragilidade , Hepatite C/tratamento farmacológico , Imidazóis/uso terapêutico , Seguro de Assistência de Longo Prazo , Isoquinolinas/uso terapêutico , Pirrolidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Valina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Definição da Elegibilidade , Feminino , Hepatite C/mortalidade , Humanos , Japão , Masculino , Valina/uso terapêuticoRESUMO
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by clonal myeloproliferation, progressive bone marrow (BM) fibrosis, splenomegaly, and anemia. BM fibrosis was previously thought to be a reactive phenomenon induced by mesenchymal stromal cells that are stimulated by the overproduction of cytokines such as transforming growth factor (TGF)-ß1. However, the involvement of neoplastic fibrocytes in BM fibrosis was recently reported. In this study, we showed that the vast majority of collagen- and fibronectin-producing cells in the BM and spleens of Jak2V617F-induced myelofibrosis (MF) mice were fibrocytes derived from neoplastic hematopoietic cells. Neoplastic monocyte depletion eliminated collagen- and fibronectin-producing fibrocytes in BM and spleen, and ameliorated most characteristic MF features in Jak2V617F transgenic mice, including BM fibrosis, anemia, and splenomegaly, while had little effect on the elevated numbers of megakaryocytes and stem cells in BM, and leukothrombocytosis in peripheral blood. TGF-ß1, which was produced by hematopoietic cells including fibrocytes, promoted the differentiation of neoplastic monocytes to fibrocytes, and elevated plasma TGF-ß1 levels were normalized by monocyte depletion. Collectively, our data suggest that neoplastic fibrocytes are the major contributor to BM fibrosis in PMF, and TGF-ß1 is required for their differentiation.
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Fibroblastos/patologia , Janus Quinase 2/metabolismo , Megacariócitos/patologia , Mutação , Mielofibrose Primária/patologia , Animais , Diferenciação Celular , Proliferação de Células , Fibroblastos/metabolismo , Janus Quinase 2/genética , Megacariócitos/metabolismo , Camundongos , Camundongos Transgênicos , Mielofibrose Primária/genética , Mielofibrose Primária/metabolismo , Esplenomegalia , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Mutations in JAK2, myeloproliferative leukemia virus (MPL), or calreticulin (CALR) occur in hematopoietic stem cells (HSCs) and are detected in more than 80% of patients with myeloproliferative neoplasms (MPNs). They are thought to play a driver role in MPN pathogenesis via autosomal activation of the JAK-STAT signaling cascade. Mutant CALR binds to MPL, activates downstream MPL signaling cascades, and induces essential thrombocythemia in mice. However, embryonic lethality of Calr-deficient mice precludes determination of a role for CALR in hematopoiesis. To clarify the role of CALR in normal hematopoiesis and MPN pathogenesis, we generated hematopoietic cell-specific Calr-deficient mice. CALR deficiency had little effect on the leukocyte count, hemoglobin levels, or platelet count in peripheral blood. However, Calr-deficient mice showed some hematopoietic properties of MPN, including decreased erythropoiesis and increased myeloid progenitor cells in the bone marrow and extramedullary hematopoiesis in the spleen. Transplantation experiments revealed that Calr haploinsufficiency promoted the self-renewal capacity of HSCs. We generated CALRdel52 mutant transgenic mice with Calr haploinsufficiency as a model that mimics human MPN patients and found that Calr haploinsufficiency restored the self-renewal capacity of HSCs damaged by CALR mutations. Only recipient mice transplanted with Lineage-Sca1+c-kit+ cells harboring both CALR mutation and Calr haploinsufficiency developed MPN in competitive conditions, showing that CALR haploinsufficiency was necessary for the onset of CALR-mutated MPNs.
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Calreticulina/fisiologia , Transtornos Mieloproliferativos/etiologia , Células-Tronco/patologia , Animais , Medula Óssea/patologia , Calreticulina/deficiência , Calreticulina/genética , Autorrenovação Celular , Eritropoese , Genótipo , Hematopoese Extramedular , Células-Tronco Hematopoéticas/patologia , Camundongos , Camundongos Transgênicos , Transtornos Mieloproliferativos/patologia , Células-Tronco Neoplásicas/patologia , Deleção de Sequência , TranscriptomaRESUMO
A 72-year-old man was admitted to a general hospital with progressive liver dysfunction, hypokalemia, hyperglycemia, and nodules in the lung and liver and then transferred to our institution on the seventh hospital day. Plasma levels of adrenocorticotropic hormone (ACTH), cortisol, and neuron-specific enolase concentrations were extremely high. He developed acute liver failure, his consciousness and general condition deteriorated rapidly, and he died on Day 11. At the postmortem examination, he was found to have extensive metastases from small-cell lung cancer, including advanced hepatic metastases. This is the first reported case of acute liver failure caused by metastases derived from an ACTH-producing pulmonary small-cell carcinoma.
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Hormônio Adrenocorticotrópico/biossíntese , Síndrome de Cushing/complicações , Falência Hepática Aguda/etiologia , Neoplasias Hepáticas/secundário , Carcinoma de Pequenas Células do Pulmão/secundário , Síndrome de ACTH Ectópico/complicações , Idoso , Evolução Fatal , Humanos , Hidrocortisona/sangue , Hiperglicemia/etiologia , Hipopotassemia/etiologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
Calreticulin (CALR) exon 9 frameshift mutations, commonly detected in essential thrombocythemia (ET) and primary myelofibrosis patients, activate signal transducer and activator of transcription (STAT) proteins in the presence of Myeloproliferative Leukemia Virus (MPL) and induce ET in vivo. Loss of the KDEL motif, an endoplasmic reticulum retention signal, and generation of many positively charged amino acids (AAs) in the mutated C-terminus are thought to be important for disease induction. To test this hypothesis, we generated mice harboring a Calr frameshift mutation using the CRISPR/Cas9 system. Deletion of 19-base pairs in exon 9 (c.1099-1117del), designated the del19 mutation, induced loss of the KDEL motif and generated many positively charged AAs, similar to human mutants. Calr del19 mice exhibited mild thrombocytosis, slightly increased megakaryocytes, and mild splenomegaly. In vitro experiments revealed that the murine CALR del19 mutant had a weaker ability to combine with murine MPL than the human CALR del52 mutant. Consequently, STAT5 activation was also very weak downstream of the murine mutant and murine MPL, and may be the reason for the mild disease severity. In summary, loss of the KDEL motif and positively charged AAs in the C-terminus of CALR is insufficient for MPL binding and ET development.
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Calreticulina/genética , Trombocitose/etiologia , Animais , Humanos , Camundongos , MutaçãoRESUMO
BACKGROUND: Monocyte-derived fibrocytes play an important role in the progression of fibrosis in the skin, lungs, heart and kidney. However, the contribution of fibrocytes to liver fibrosis is unclear. The aim of this study was to investigate whether fibrocytes contributed to fibrosis progression in the livers of carbon tetrachloride (CCl4)-treated mice. METHODS: C57BL/6J mice were divided into 4 groups: normal control group, CCl4-treated group, CCl4â¯+â¯control liposome-treated group, and CCl4â¯+â¯clodronate liposome-treated group. For the elimination of systemic monocyte and monocyte-derived fibrocyte, one group was treated with clodronate liposome, and another group with control liposome as a control. After 4 weeks of treatment, hepatic mononuclear cells were subjected to immunofluorescent (IF) staining and fluorescence-activated cell sorter (FACS) analysis to detect fibrocytes. Measurement of collagen-positive Sirius red stained area and collagen-I mRNA expression in the liver were performed to evaluate the degree of liver fibrosis quantitatively. RESULTS: In the liver of the CCl4-treated and CCl4â¯+â¯control liposome-treated groups, the number of fibrocytes, the area positive for Sirius red staining and collagen-I mRNA expression significantly increased compared with those in the normal control group. In the liver of the CCl4â¯+â¯clodronate liposome-treated group, few fibrocytes was observed as in the normal control group, but Sirius red staining positive area and collagen-I mRNA expression were increased and equivalent to the CCl4-treated and CCl4â¯+â¯control liposome-treated groups. CONCLUSION: Monocyte-derived fibrocytes play a minimal role in CCl4-induced liver fibrosis. Cells other than fibrocytes such as hepatic stellate cells play a central role in liver fibrosis.
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Doença Hepática Induzida por Substâncias e Drogas/patologia , Cirrose Hepática Experimental/patologia , Fígado/patologia , Monócitos/patologia , Animais , Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Ácido Clodrônico/farmacologia , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Progressão da Doença , Feminino , Fígado/efeitos dos fármacos , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/genética , Cirrose Hepática Experimental/metabolismo , Camundongos Endogâmicos C57BL , Monócitos/efeitos dos fármacos , Fatores de Tempo , Regulação para CimaRESUMO
BACKGROUND/AIM: In myeloproliferative neoplasms (MPN), Janus kinase 2 (JAK2) is activated by mutations including JAK2V617F (JAK2VF). It is unclear whether JAK kinases [i.e. JAK1, JAK2, JAK3, or tyrosine kinase 2 (TYK2)] other than JAK2 have cooperative actions such as enhancement or suppression of JAK2. If other kinases enhance activation, therapies that co-target them could have a therapeutic efficacy. We examined the role of TYK2 in Jak2VF-induced murine MPN. MATERIALS AND METHODS: We crossed Jak2VF transgenic mice and Tyk2-knockout (Tyk2KO) mice to generate Jak2VF/Tyk2KO mice. The disease severity and treatment effect with a JAK2 inhibitor was compared between Jak2VF and Jak2VF/Tyk2KO mice. RESULTS: Both types of mice developed MPN, and there were no differences in peripheral blood counts, spleen weight, or survival period. Upon JAK2 inhibitor therapy, both types of mice had equally improved leukocytosis and splenomegaly. CONCLUSION: TYK2 does not have cooperative effects with JAK2VF upon MPN onset nor in the presence of a JAK2 inhibitor.
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Janus Quinase 2/genética , Mutação , Transtornos Mieloproliferativos/patologia , TYK2 Quinase/metabolismo , Animais , Janus Quinase 2/antagonistas & inibidores , Janus Quinase 2/metabolismo , Fígado/metabolismo , Pulmão/metabolismo , Camundongos , Camundongos Transgênicos , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/metabolismo , Transtornos Mieloproliferativos/veterinária , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacologia , Baço/metabolismoRESUMO
Ten-eleven translocation-2 (TET2) mutation is frequently observed in myeloid malignancies, and loss-of-function of TET2 is essential for the initiation of malignant hematopoiesis. TET2 mutation presents across disease entities and was reported in lymphoid malignancies. We investigated TET2 mutations in 27 diffuse large B-cell lymphoma (DLBCL) patients and found a frameshift mutation in 1 case (3.7%). TET2 mutation occurred in some populations of DLBCL patients and was likely involved in the pathogenesis of their malignancies.
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Proteínas de Ligação a DNA/genética , Mutação da Fase de Leitura , Linfoma Difuso de Grandes Células B/genética , Proteínas Proto-Oncogênicas/genética , Idoso , Dioxigenases , Feminino , Neoplasias Hematológicas/etiologia , Hematopoese , Humanos , Leucemia Mieloide/etiologia , Linfoma Difuso de Grandes Células B/epidemiologia , Masculino , Pessoa de Meia-IdadeAssuntos
Calreticulina/genética , Janus Quinase 2/genética , Trombocitemia Essencial/diagnóstico , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Criança , DNA/química , DNA/genética , DNA/metabolismo , Éxons , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Receptores de Trombopoetina/genética , Análise de Sequência de DNA , Fatores Sexuais , Trombocitemia Essencial/genética , Adulto JovemRESUMO
AIM: To evaluate the efficacy and safety of a regimen containing sofosbuvir (SOF) and ledipasvir (LDV) in Japanese patients aged ≥ 75 years with hepatitis C genotype 1. METHODS: This multicenter, retrospective study consisted of 246 Japanese patients with HCV genotype 1 at nine centers in Miyazaki prefecture in Japan. Demographic, clinical, virological, and adverse effects (AE)-related data obtained during and after SOF/LDV therapy were collected from medical records. These patients were divided into two groups, younger (aged < 75 years) and elderly (aged ≥ 75 years). Virological data and AEs were analyzed by age group. RESULTS: The sustained virological response (SVR) rates at 12 wk after treatment were 99.2%, 99.4%, and 98.7% in the overall population and in patients aged < 75 and ≥ 75 years, respectively. Common AEs during therapy were headache, pruritus, constipation, and insomnia. These occurred in fewer than 10% of patients, and their incidence was not significantly different between the younger and elderly groups. Two patients discontinued treatment, one due to a skin eruption and the other due to cerebral bleeding. CONCLUSION: Compared with younger patients, elderly patients had a similar virological response and tolerance to SOF/LDV therapy.
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Background and Aim. It is difficult to master the skill of discriminating gastric adenoma from early gastric cancer by conventional endoscopy or magnifying endoscopy combined with narrow-band imaging, because the colors and morphologies of these neoplasms are occasionally similar. We focused on the surrounding gastric mucosa findings in order to determine how to discriminate between early gastric cancer and gastric adenoma by analyzing the characteristics of the gastric background mucosa. Methods. We retrospectively examined 146 patients who underwent endoscopic submucosal dissection for gastric neoplasm between October 2009 and January 2015. The boundary of atrophic gastritis was classified endoscopically according to the Kimura-Takemoto classification system. Of 146 lesions, 63 early gastric cancers and 21 gastric adenomas were ultimately evaluated and assessed. Results. Almost all gastric adenomas were accompanied by open-type gastritis, whereas 47 and 16 early gastric cancers were accompanied by open-type and closed-type gastritis, respectively (p = 0.037). Conclusions. The evaluation of the boundary of atrophic gastritis associated with gastric neoplasms appears to be useful for discrimination between early gastric cancer and gastric adenoma. When gastric neoplasm is present in the context of surrounding localized gastric atrophy, gastric cancer is probable but not certain.
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Myeloproliferative neoplasms (MPNs) are clinically characterized by the chronic overproduction of differentiated peripheral blood cells and the gradual expansion of malignant intramedullary/extramedullary hematopoiesis. In MPNs mutations in JAK2 MPL or CALR are detected mutually exclusive in more than 90% of cases [1,2]. Mutations in them lead to the abnormal activation of JAK/STAT signaling and the autonomous growth of differentiated cells therefore they are considered as "driver" gene mutations. In addition to the above driver gene mutations mutations in epigenetic regulators such as TET2 DNMT3A ASXL1 EZH2 or IDH1/2 are detected in about 5%-30% of cases respectively [3]. Mutations in TET2 DNMT3A EZH2 or IDH1/2 commonly confer the increased self-renewal capacity on normal hematopoietic stem cells (HSCs) but they do not lead to the autonomous growth of differentiated cells and only exhibit subtle clinical phenotypes [4,6-8,5]. It was unclear how mutations in such epigenetic regulators influenced abnormal HSCs with driver gene mutations how they influenced the disease phenotype or whether a single driver gene mutation was sufficient for the initiation of human MPNs. Therefore we focused on JAK2V617F and loss of TET2-the former as a representative of driver gene mutations and the latter as a representative of mutations in epigenetic regulators-and examined the influence of single or double mutations on HSCs (Lineage(-)Sca-1(+)c-Kit(+) cells (LSKs)) by functional analyses and microarray whole-genome expression analyses [9]. Gene expression profiling showed that the HSC fingerprint genes [10] was statistically equally enriched in TET2-knockdown-LSKs but negatively enriched in JAK2V617F-LSKs compared to that in wild-type-LSKs. Double-mutant-LSKs showed the same tendency as JAK2V617F-LSKs in terms of their HSC fingerprint genes but the expression of individual genes differed between the two groups. Among 245 HSC fingerprint genes 100 were more highly expressed in double-mutant-LSKs than in JAK2V617F-LSKs. These altered gene expressions might partly explain the mechanisms of initiation and progression of MPNs which was observed in the functional analyses [9]. Here we describe gene expression profiles deposited at the Gene Expression Omnibus (GEO) under the accession number GSE62302 including experimental methods and quality control analyses.