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In the above article, we noticed that one female patient in the positive group (plasma lyso-Gb3 7.6 ng/ml, α-galactosidase A activity 4.9 nmol/h/ml) who presented at the neurology clinic was already diagnosed with Fabry disease before the current study. We excluded patients with a confirmed diagnosis of Fabry disease and those with relatives known to have Fabry disease. To accurately describe the information in the current study, we must exclude this patient from the analysis. We have accurately revised this information as follows.
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The PDF and HTML versions of the article have been updated to include the Creative Commons Attribution 4.0 International License information.
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The HTML version of this Article contained errors in Supplementary Figure S2 "Flowchart of the lyso-Gb3 screening and gene analysis in female patients", which have been detailed in the associated Correction.
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PURPOSE: Plasma globotriaosylsphingosine (lyso-Gb3) is a promising secondary screening biomarker for Fabry disease. Here, we examined its applicability as a primary screening biomarker for classic and late-onset Fabry disease in males and females. METHODS: Between 1 July 2014 and 31 December 2015, we screened 2,359 patients (1,324 males) referred from 168 Japanese specialty clinics (cardiology, nephrology, neurology, and pediatrics), based on clinical symptoms suggestive of Fabry disease. We used the plasma lyso-Gb3 concentration, α-galactosidase A (α-Gal A) activity, and analysis of the α-Gal A gene (GLA) for primary and secondary screens, respectively. RESULTS: Of 8 males with elevated lyso-Gb3 levels (≥2.0 ng ml-1) and low α-Gal A activity (≤4.0 nmol h-1 ml-1), 7 presented a GLA mutation (2 classic and 5 late-onset). Of 14 females with elevated lyso-Gb3, 7 displayed low α-Gal A activity (5 with GLA mutations; 4 classic and 1 late-onset) and 7 exhibited normal α-Gal A activity (1 with a classic GLA mutation and 3 with genetic variants of uncertain significance). CONCLUSION: Plasma lyso-Gb3 is a potential primary screening biomarker for classic and late-onset Fabry disease probands.
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Biomarcadores/sangue , Doença de Fabry/sangue , Testes Genéticos , Glicolipídeos/sangue , Esfingolipídeos/sangue , Idoso , Doença de Fabry/genética , Doença de Fabry/patologia , Feminino , Galactosidases/sangue , Galactosidases/genética , Glicolipídeos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Seleção de Pacientes , Fatores de Risco , Esfingolipídeos/genéticaRESUMO
BACKGROUND: Although previous studies have suggested a certain prevalence of Fabry disease (FD) in left ventricular hypertrophy (LVH) patients, the screening of FD is difficult because of its wide-ranging clinical phenotypes. We aimed to clarify the utility of combined measurement of plasma globotriaosylsphingosine (lyso-Gb3) concentration and α-galactosidase A activity (α-GAL) as a primary screening of FD in unexplained LVH patients.MethodsâandâResults:Between 2014 and 2016, both lyso-Gb3 and α-GAL were measured in 277 consecutive patients (male 215, female 62, age 25-79 years) with left ventricular wall thickness >12 mm on echocardiogram: 5 patients (1.8%) screened positive (2 (0.7%) showed high lyso-Gb3 and 4 (1.4%) had low α-GAL levels). Finally, 2 patients (0.7%) were diagnosed with clinically significant FD. In 1 case, a female heterozygote with normal α-GAL levels had genetic variants of unknown significance and was diagnosed as FD by endomyocardial biopsy. The other case was a male chronic renal failure patient requiring hemodialysis, and he had a p.R112H mutation. In both cases there were high lyso-Gb3 levels. CONCLUSIONS: The serum lyso-Gb3 level can be relevant for clinically significant FD, and combined measurement of lyso-Gb3 and α-GAL can provide better screening of FD in unexplained LVH patients.
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Doença de Fabry/sangue , Glicolipídeos/sangue , Hipertrofia Ventricular Esquerda/sangue , Esfingolipídeos/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Doença de Fabry/diagnóstico por imagem , Doença de Fabry/genética , Doença de Fabry/fisiopatologia , Feminino , Predisposição Genética para Doença , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/genética , Hipertrofia Ventricular Esquerda/fisiopatologia , Japão , Masculino , Pessoa de Meia-Idade , Mutação , Valor Preditivo dos Testes , Estudos Prospectivos , Função Ventricular Esquerda , Remodelação Ventricular , Adulto Jovem , alfa-Galactosidase/sangue , alfa-Galactosidase/genéticaRESUMO
BACKGROUND: Transcatheter arterial chemoembolization (TACE) is a widely used and well-established treatment for hepatocellular carcinoma (HCC). However, TACE loses its therapeutic efficacy when performed repeatedly, a phenomenon termed TACE refractoriness. c-Met is associated with malignant potential and with resistance to anti-tumor therapies in some kinds of cancers. AIMS: The aim of this study is to investigate the clinical impact of TACE on c-Met expression with the aim of understanding the mechanism underlying TACE refractoriness. METHODS: The effect of TACE on the c-Met expression level was investigated in vitro in HCC cell lines, and it was shown that c-Met expression is upregulated in HCC cell lines cultured under hypoxia and/or exposed to chemotherapeutic agents. The in vitro results were validated using 82 clinical samples of HCC with and without preoperative TACE treatment. RESULTS: c-Met upregulation was observed significantly more frequently in clinical samples of HCC that were treated with preoperative TACE than in samples with no TACE treatment. Increased c-Met expression was significantly associated with poor prognosis. Furthermore, the incidence of c-Met-positive expression was significantly higher in TACE-refractory HCC samples. CONCLUSIONS: TACE treatment upregulates c-Met expression in HCC and the upregulated c-Met expression may be responsible for TACE refractoriness.
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Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/terapia , Proteínas Proto-Oncogênicas c-met/metabolismo , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/metabolismo , Proteínas Proto-Oncogênicas c-met/genética , Regulação para CimaRESUMO
A 65-year-old woman presented to our department with a liver tumor. She had undergone subtotal colectomy and total hysterectomy for hereditary nonpolyposis colorectal cancer and uterine cancer 14 years prior to diagnosis. An abdominal CT scan revealed a ring-enhancing tumor with portal vein tumor thrombus on the left lobe. With a preoperative diagnosis of intrahepatic cholangiocarcinoma, combined hepatocellular and cholangiocarcinoma, or metastatic liver cancer; we performed an extended left hepatic lobectomy. The histopathological examination showed adenocarcinoma of the liver. The histopathological findings of the liver tumor resembled that of the previous uterine cancer. Immunohistochemical testing was positive for CK7 and negative for CK20, CDX2, PgR, vimentin, and CA125. However, PgR, vimentin, and CA125 were positively stained in the uterine cancer. Based on these findings, the final diagnosis of the liver tumor was primary intrahepatic cholangiocarcinoma.
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Neoplasias dos Ductos Biliares/diagnóstico , Colangiocarcinoma/diagnóstico , Neoplasias Hepáticas/diagnóstico , Idoso , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Hepáticas/secundário , Tomografia Computadorizada por Raios XRESUMO
An 82-year-old man without any complaint was shown to have a hypoechoic lesion, 2 cm in diameter, in segment 5 of the liver by ultrasonography. After 3 months, an abdominal computed tomographic (CT) scan revealed a tumor lesion, 5.5 cm in diameter, with irregular peripheral enhancement. Positron emission tomography (PET)-CT revealed abnormal accumulation of fluorodeoxyglucose in the liver tumor, but no accumulation in other lesions. Based on the diagnosis of primary malignant liver tumor, we performed S5 subsegmentectomy of the liver. Histopathological examination showed spindle tumor cells forming hemorrhagic and focal necrosis. On immunohistochemistry, the tumor cells weakly expressed CD31. We diagnosed the tumor as hepatic angiosarcoma. The patient was discharged from the hospital 17 days after the surgery and survived without evidence of recurrence for 12 postoperative months.
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Hemangiossarcoma/patologia , Neoplasias Hepáticas/patologia , Idoso de 80 Anos ou mais , Progressão da Doença , Hemangiossarcoma/cirurgia , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Serum uric acid-lowering therapy is associated with maintaining renal function. OBJECTIVE: We aimed to retrospectively evaluate renal function and serum uric acid in patients with hyperuricemia who received topiroxostat for over a year. METHODS: Medical records of patients from 1 January, 2015 to 31 October, 2019 in our hospital were used. From the medical records, data of 100 patients with hyperuricemia treated with topiroxostat were extracted (67:33 male:female). The primary endpoints were changes in serum creatinine level and estimated glomerular filtration rate at 12 months after topiroxostat administration. The secondary endpoints were changes in serum creatinine, serum uric acid, and estimated glomerular filtration rate before and after topiroxostat administration. RESULTS: The study mainly involved elderly individuals (77.2 ± 9.5 years). Forty-four patients administered uric acid-lowering drugs were switched to topiroxostat. After 12 months, the serum creatinine level and estimated glomerular filtration rate showed no significant changes from baseline; however, the serum uric acid level significantly decreased. The estimated glomerular filtration rate significantly decreased during the 6 months before topiroxostat administration (p < 0.001), but showed no significant change at 6 months after topiroxostat administration (p = 0.849). CONCLUSIONS: This study revealed that topiroxostat use not only reduced the serum uric acid level but also maintained renal function in elderly patients with hyperuricemia in daily clinical practice.
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Most cases of adult intussusception are caused by neoplastic lesions, and idiopathic adult intussusception is very rare. We present a case in which laparoscopic surgery was performed for idiopathic adult intussusception initially reduced by colonoscopy. A 53-year-old woman presented to the emergency department of our hospital with intermittent lower abdominal pain. Contrast-enhanced computed tomography and ultrasonography of the abdomen showed a concentric structure in the ascending colon. We diagnosed intussusception. Colonoscopy achieved successful reduction before surgery. Twelve days after this reduction, laparoscopic surgery was performed. Histopathological examination did not reveal any causative pathology; therefore, idiopathic adult intussusception was diagnosed. The postoperative course was uneventful, and the patient was discharged on postoperative day 14. Preoperative colonoscopy should be utilized to diagnose the main lesion and may be useful for reducing adult intussusception. Laparoscopic surgery is both minimally invasive and safe and can be performed following endoscopic reduction.
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INTRODUCTION: Synovial sarcoma is a malignant soft tissue sarcoma which arises near joints. The most frequent metastasis sites of synovial sarcoma are the lungs, lymph nodes, and bone. Pancreatic metastasis is quite rare; only 3 cases have been reported worldwide to date. We herein present the 4th case of pancreatic metastasis from synovial sarcoma. METHODS AND RESULTS: A 32-year-old man underwent extended excision of synovial sarcoma in the left pelvis and femur in 2009. In 2013, follow-up contrast-enhanced computed tomography revealed a 35-mm heterogeneously enhanced mass in the pancreas body. Endoscopic ultrasound-guided fine needle aspiration of the mass revealed a diffuse proliferation of atypical spindle cells in a fascicular arrangement. Because the histology was quite similar to the resected specimen of synovial sarcoma in 2009, the mass was suspected to be a metastasis from synovial sarcoma. Laparoscopic distal pancreatectomy with adjuvant adriamycin/ifosfamide chemotherapy was subsequently performed. Synovial sarcoma-specific SS18-SSX1 (synovial sarcoma translocation, chromosome 18-synovial sarcoma X1) or SS18-SSX2 chimera mRNA was detected in the resected specimen, confirming the diagnosis of metastasis from synovial sarcoma. The patient did well for 30 months without recurrence. CONCLUSION: This case suggests that pancreatic metastasis from synovial sarcoma can be successfully treated by metastasectomy with adjuvant chemotherapy.
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Neoplasias Ósseas/patologia , Metastasectomia/métodos , Neoplasias Pancreáticas/secundário , Neoplasias Pancreáticas/terapia , Sarcoma Sinovial/patologia , Adulto , Quimioterapia Adjuvante , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Humanos , Masculino , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgiaRESUMO
We investigated mutations of the iduronate-2-sulfatase (I2S) gene and structural characteristics of I2S to clarify genotype/phenotype relationships in 18 Japanese patients with mucopolysaccharidosis type II. The I2S gene was analyzed in five patients with a severe phenotype and in 13 patients with an attenuated phenotype. The tertiary structural model of the human I2S was constructed by homology modeling using the arylsulfatase structure as a template. We identified four missense mutations and a nonsense mutation in the severe phenotype; four missense, two nonsense, three frame shifts, and one each of splice and amino acid deletion in the attenuated phenotype. Seven of them (L73del, Q75X, G140R, C171R, V401 fs, C422 fs, and H441 fs) were novel mutations. Structural analysis indicated that the residues of the mutations found in the severe phenotype would have direct interactions with the active site residues or should break the hydrophobic core domain of I2S, whereas residues of the missense mutations found in the attenuated phenotype were located in the peripheral region. In addition, effects by deletion or frameshift mutations could also be interpreted by the structure. Structural analysis of mutant proteins would help in understanding the genotype/phenotype relationships of Hunter disease.