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The mortality of coronavirus disease 2019 (COVID-19) is strongly correlated with pulmonary vascular pathology accompanied by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-triggered immune dysregulation and aberrant activation of platelets. We combined histological analyses using field emission scanning electron microscopy with energy-dispersive X-ray spectroscopy analyses of the lungs from autopsy samples and single-cell RNA sequencing of peripheral blood mononuclear cells to investigate the pathogenesis of vasculitis and immunothrombosis in COVID-19. We found that SARS-CoV-2 accumulated in the pulmonary vessels, causing exudative vasculitis accompanied by the emergence of thrombospondin-1-expressing noncanonical monocytes and the formation of myosin light chain 9 (Myl9)-containing microthrombi in the lung of COVID-19 patients with fatal disease. The amount of plasma Myl9 in COVID-19 was correlated with the clinical severity, and measuring plasma Myl9 together with other markers allowed us to predict the severity of the disease more accurately. This study provides detailed insight into the pathogenesis of vasculitis and immunothrombosis, which may lead to optimal medical treatment for COVID-19.
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COVID-19 , Pulmão , Cadeias Leves de Miosina , SARS-CoV-2 , Índice de Gravidade de Doença , Tromboinflamação , Vasculite , COVID-19/sangue , COVID-19/complicações , COVID-19/patologia , Humanos , Leucócitos Mononucleares , Pulmão/irrigação sanguínea , Pulmão/metabolismo , Pulmão/patologia , Pulmão/virologia , Cadeias Leves de Miosina/sangue , RNA-Seq , SARS-CoV-2/isolamento & purificação , Análise de Célula Única , Espectrometria por Raios X , Tromboinflamação/patologia , Tromboinflamação/virologia , Vasculite/patologia , Vasculite/virologiaRESUMO
PURPOSE: Auto-antibodies (auto-abs) to type I interferons (IFNs) have been identified in patients with life-threatening coronavirus disease 2019 (COVID-19), suggesting that the presence of auto-abs may be a risk factor for disease severity. We therefore investigated the mechanism underlying COVID-19 exacerbation induced by auto-abs to type I IFNs. METHODS: We evaluated plasma from 123 patients with COVID-19 to measure auto-abs to type I IFNs. We performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells from the patients with auto-abs and conducted epitope mapping of the auto-abs. RESULTS: Three of 19 severe and 4 of 42 critical COVID-19 patients had neutralizing auto-abs to type I IFNs. Patients with auto-abs to type I IFNs showed no characteristic clinical features. scRNA-seq from 38 patients with COVID-19 revealed that IFN signaling in conventional dendritic cells and canonical monocytes was attenuated, and SARS-CoV-2-specific BCR repertoires were decreased in patients with auto-abs. Furthermore, auto-abs to IFN-α2 from COVID-19 patients with auto-abs recognized characteristic epitopes of IFN-α2, which binds to the receptor. CONCLUSION: Auto-abs to type I IFN found in COVID-19 patients inhibited IFN signaling in dendritic cells and monocytes by blocking the binding of type I IFN to its receptor. The failure to properly induce production of an antibody to SARS-CoV-2 may be a causative factor of COVID-19 severity.
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Autoanticorpos , COVID-19 , Interferon Tipo I , Células Mieloides , Feminino , Humanos , Masculino , Autoanticorpos/imunologia , Autoanticorpos/sangue , COVID-19/imunologia , Células Dendríticas/imunologia , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Células Mieloides/imunologia , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Transdução de Sinais/imunologiaRESUMO
BACKGROUND: We report a case of neuromyelitis optica spectrum disorders (NMOSD), who developed after the pembrolizumab treatment, an immune checkpoint inhibitor, against lung adenocarcinoma. The present case is discussed with the lung adenocarcinoma specimen which was stained by aquaporin-4 (AQP4) and with literature review of NMOSD linked to immune checkpoint inhibitors. CASE PRESENTATION: A 62-year-old Japanese man presented with acute diencephalic syndrome, left optic neuritis, and myelitis 5 months after initiation of pembrolizumab treatment for lung adenocarcinoma. He was diagnosed with NMOSD based on serum anti-aquaporin-4 (AQP4) antibody positivity. Immunohistochemistry of lung biopsy samples showed AQP4 expression on CD68+ cells. This is the fifth reported case of AQP4+ NMOSD triggered by an immune checkpoint inhibitor and the first with a brain lesion. Four out of five NMOSD cases, including the present case and one case with lung metastasis, had lung cancer. CONCLUSIONS: Immune checkpoint inhibitors may trigger AQP4+ NMOSD owing to their molecular similarity to AQP4 expressed in lung and glial tissues. Prompt brain/spinal cord imaging and anti-AQP4 antibody testing may facilitate early diagnosis of immune-mediated adverse event in central nervous system associated with immune checkpoint inhibitors.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Neuromielite Óptica , Masculino , Humanos , Pessoa de Meia-Idade , Neuromielite Óptica/diagnóstico , Inibidores de Checkpoint Imunológico/uso terapêutico , Aquaporina 4 , Autoanticorpos , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/complicações , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/complicaçõesRESUMO
Terahertz (THz) electromagnetic waves are attractive for use in nondestructive and biocompatible sensing applications. Thermal sensors are widely used for THz detection owing to the small photon energies of THz radiation, where this requires materials with low thermal conductivity and a small heat capacity to ensure the sensitive and fast operation of the sensors. In this study, we investigated the thermal and optical properties of porous nanomesh structures for sensitive THz bolometric detection. Nanometer (nm)-scale hole array structures were formed on gallium arsenide (GaAs) microelectromechanical system (MEMS) beams to improve their thermal properties. The thermal conductance of the porous MEMS beams was obtained by measuring their thermal bandwidths; it was found to decrease by as much as ~90% when the porosity (P) of the porous nanostructure was increased to ~0.69. We also measured the THz absorptance of the porous hole array structure. The results show that although the porous nanostructure has a much smaller area than the bulk material, it maintained a high coefficient of THz absorptance because the featured size was much smaller than the THz wavelength. The measured absorptance agreed well with that calculated by using the Drude model. These results demonstrate that the porous nanomesh structure is promising for developing highly sensitive THz thermal sensors.
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Nanoestruturas , Radiação Terahertz , Porosidade , PeleRESUMO
A 35-year-old man who previously underwent splenectomy for hereditary spherocytosis at age 29 visited our hospital complaining of fatigue that had started 7 days ago and right upper abdominal pain. Laboratory data showed increased white blood cell and eosinophil count accompanied by severe transaminitis and clotting abnormalities. Computed tomography scan showed multiple embolisms in the portal vein, superior mesenteric vein, right pulmonary artery, and inferior vena cava. Severe liver damage presumably caused by portal vein thrombosis was also observed. Anticoagulant therapies consisting of continuous arterial infusion of urokinase from the superior mesenteric artery and an intravenous infusion of recombinant human thrombomodulin and heparin dissolved the systemic thrombosis. Concurrently administered prednisone decreased the eosinophil count. With regard to eosinophilia, we were unable to find any connective tissue diseases, antibodies to parasites, or genetic anomalies including PDGFRA, PDGFRB, and FGFR1. Hence we diagnosed the patient with idiopathic hypereosinophilic syndrome (HES). Although thromboembolisms in patients with HES have been reported, the literature on portal vein thrombosis associated with HES is scarce. In the present case, the previous splenectomy may have contributed to the portal vein thrombosis.
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Síndrome Hipereosinofílica/complicações , Veia Porta , Trombose Venosa/etiologia , Adulto , Humanos , Hepatopatias/etiologia , Masculino , EsplenectomiaRESUMO
This report focuses on part 3 of a multicenter, open-label, phase 1 study (NCT03198650) assessing the safety, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of acalabrutinib plus obinutuzumab in Japanese patients with treatment-naive (TN) chronic lymphocytic leukemia (CLL). Ten patients were included; median age was 68 years. With a median treatment duration of 27.2 months, treatment-emergent adverse events (AEs) occurred in all patients (grade ≥3, 70%), and the most common AEs were anemia and headache (40% each). One patient had a grade 4 AE of neutropenia (the only dose-limiting toxicity). PK results suggested no marked effects of concomitant obinutuzumab treatment on the exposure of acalabrutinib. PD assessment indicated that combination therapy provided >98% Bruton tyrosine kinase (BTK) occupancy. Overall response rate (ORR) was 100% with median duration of response (DoR) and median progression-free survival (PFS) not reached. Treatment with acalabrutinib plus obinutuzumab was generally safe and efficacious in adult Japanese patients with TN CLL.
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PURPOSE: This study proposes a process for detecting slices with bone marrow edema (BME), a typical finding of axSpA, using MRI scans as the input. This process does not require manual input of ROIs and provides the results of the judgment of the presence or absence of BME on a slice and the location of edema as the rationale for the judgment. METHODS: First, the signal intensity of the MRI scans of the sacroiliac joint was normalized to reduce the variation in signal values between scans. Next, slices containing synovial joints were extracted using a slice selection network. Finally, the BME slice detection network determines the presence or absence of the BME in each slice and outputs the location of the BME. RESULTS: The proposed method was applied to 86 MRI scans collected from 15 hospitals in Japan. The results showed that the average absolute error of the slice selection process was 1.49 slices for the misalignment between the upper and lower slices of the synovial joint range. The accuracy, sensitivity, and specificity of the BME slice detection network were 0.905, 0.532, and 0.974, respectively. CONCLUSION: This paper proposes a process to detect the slice with BME and its location as the rationale of the judgment from an MRI scan and shows its effectiveness using 86 MRI scans. In the future, we plan to develop a process for detecting other findings such as bone erosion from MR scans, followed by the development of a diagnostic support system.
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BACKGROUND AND AIMS: The Japan Society for Dialysis Therapy established "Guidelines for the Treatment of Hepatitis C Virus Infection in Dialysis Patients." We evaluated the status of HCV infection and the treatment of hemodialysis patients in Gunma prefecture. METHODS: Questionnaires concerning the infection rate, recognition of the guidelines, and treatment status were sent to all 64 hospitals/clinics that had hemodialysis systems in Gunma prefecture. The hepatitis C virus-infected hemodialysis patients who received pegylated interferon (peg-IFN) were analyzed at Gunma University Hospital. RESULTS: The positive rate for hepatitis C virus antibody was 256/2582 hemodialysis patients (9.9%). The positive rate varied between institutions (range 0-40.0%; median 9.0%). All institutes recognized the establishment of the guidelines. Conventional or peg-IFN treatment was being given at 37.5% of the institutions. The other 62.5% institutions answered that they intended to provide the treatment in the future if collaboration with a hepatologist could be arranged. The most common answers regarding the indication for IFN treatment were as follows: few complications, under 60 years of age, more than 10 years of survival expected on hemodialysis. Eighteen patients received peg-IFN treatment. The sustained virological response rate of all patients was 33.3%, 0% in 1b/high viral titer, 50% in genotype 2, and 100% in genotype 2/low viral titer. The sustained virological response rate was worse in the patients with 1b/high viral load and diabetic nephropathy (P < 0.05). CONCLUSIONS: Recognition of the publication of the guidelines was high. However, the number of patients treated with peg-IFN was still low. Further enlightenment and cooperation between hemodialysis teams and hepatologists are therefore needed.
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Antivirais/uso terapêutico , Fidelidade a Diretrizes/estatística & dados numéricos , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Falência Renal Crônica/terapia , Polietilenoglicóis/uso terapêutico , Diálise Renal , Adulto , Idoso , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Inquéritos e Questionários , Resultado do Tratamento , Carga ViralRESUMO
A tomographic tactile sensor based on the contact resistance of conductors is a high sensitive pressure distribution imaging method and has advantages on the flexibility and scalability of device. While the addition of internal electrodes improves the sensor's spatial resolution, there still remain variations in resolution that depend on the contact position. In this study, we propose an optimization algorithm for electrode positions that improves entire spatial resolution by compensating for local variations in spatial resolution. Simulation results for sensors with 16 or 64 electrodes show that the proposed algorithm improves performance to 0.81 times and 0.93 times in the worst spatial resolution region of the detection area compared to equally spaced grid electrodes. The proposed methods enable tomographic tactile sensors to detect contact pressure distribution more accurately than the conventional methods, providing high-performance tactile sensing for many applications.
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Treatments for paraneoplastic optic neuropathy (PON), a tumor-related autoimmune disease, include immunosuppression, plasma exchange, and immunoglobulin therapies, as well as treatment of the underlying disease. Herein, we describe the clinical course of an older adult patient with PON whose loss of vision improved after switching between epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatments for cancer. A 76-year-old woman, who had been treated with gefitinib for lung adenocarcinoma for two years, presented with acute bilateral visual disturbances. Her decimal best-corrected visual acuity (BCVA) was 0.3 in the right eye (RE) and 0.7 in the left eye (LE). Slit-lamp examination and funduscopy showed no abnormal findings. Two weeks later, her BCVA decreased to 0.2 in the RE and 0.01 in the LE. Goldman's perimetry showed a defect in the lower nasal RE and extensive visual-field loss in the LE. Single-flash electroretinograms showed normal amplitudes. Magnetic resonance imaging revealed left optic neuritis and showed neither metastatic cancer nor multiple sclerosis. Pattern-reversal visual evoked potentials showed decreased P100 amplitudes in both eyes (BE). Based on a diagnosis of PON from clinical findings, methylprednisolone pulse treatment was administered. However, her BCVA became no light perception in BE two months after the first visit. Because the tumor tissue was found to be positive for the EGFR T790M resistance mutation by bronchoscopy, the EGFR-TKI treatment was changed to osimertinib, decreasing the size of the lung cancer lesions. Her BCVA improved to hand motion in BE. Her final BCVA was 0.01 in the RE, counting fingers 10 cm in the LE. She died at the age of 79 years. To our knowledge, no reports have shown improvement in BCVA in patients with PON after changing EGFR-TKI treatments. This report indicates that some patients may develop severe visual dysfunction without early treatment for the primary tumor.
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Achados Incidentais , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Ruptura Esplênica/etiologia , Abdome Agudo/diagnóstico , Abdome Agudo/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia por Agulha , Emergências , Seguimentos , Humanos , Imuno-Histoquímica , Linfoma Difuso de Grandes Células B/complicações , Masculino , Pessoa de Meia-Idade , Medição de Risco , Ruptura Espontânea/diagnóstico por imagem , Ruptura Espontânea/patologia , Esplenectomia/métodos , Ruptura Esplênica/diagnóstico por imagem , Ruptura Esplênica/patologia , Ruptura Esplênica/cirurgia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Respiratory failure can be the direct cause of death in patients with Leigh syndrome. Unfortunately, no effective treatment strategy is available. Here, we report successful treatment of a patient with Leigh syndrome using idebenone, a derivative of coenzyme Q-10. The patient's brainstem function, especially respiratory function, improved after idebenone treatment. Idebenone may be worth trying in patients with Leigh syndrome.
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Doença de Leigh/complicações , Insuficiência Respiratória/tratamento farmacológico , Ubiquinona/análogos & derivados , Adolescente , Tronco Encefálico/efeitos dos fármacos , Tronco Encefálico/fisiopatologia , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Seguimentos , Humanos , Ácido Láctico/líquido cefalorraquidiano , Masculino , Polissonografia , Respiração/efeitos dos fármacos , Insuficiência Respiratória/etiologia , Ubiquinona/uso terapêuticoRESUMO
A novel induction therapy, including intensive L-asparaginase, was designed in 2007 for patients aged <45 years with Philadelphia-negative acute lymphoblastic leukemia (ALL). We analyzed seven de novo cases and one case of recurrence who received this treatment. The median age was 21 years (range: 16-35 years). Four patients had T-ALL and the others had B-ALL. All the patients achieved complete remission and proceeded to cord blood transplantation. In the median 72-month follow-up, there were no cases of observed mortality or recurrence. Our results indicate scope for further development of both induction therapy and postremission therapy.
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Antineoplásicos/uso terapêutico , Asparaginase/uso terapêutico , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
Nine patients with hepatocellular carcinoma (HCC) in nonalcoholic steatohepatitis (NASH) (six men and three women, median age 71.5 years) and one patient with intrahepatic cholangiocarcinoma (ICC), a 50-year-old man, in NASH are described. Most patients were associated with obesity, diabetes, hypertension, hypercholesterolemia, or hypertriglyceridemia. Seven patients showed insulin resistance and hyperinsulinemia. All patients except one met the criteria for metabolic syndrome. An HCC or ICC diagnosis was confirmed by tumor biopsy, surgery or autopsy except in two patients, who were diagnosed by computed tomography or hepatic angiography. The underlying liver disease was liver cirrhosis in six patients and chronic liver disease including mild hepatic fibrosis in four patients. The treatment of liver cancers consisted of surgery, radio-frequency ablation (RFA), transcatheter arterial embolization and transcatheter arterial infusion. Although the follow-up period was relatively short (median 27.5 months, average 32.1 months), all postoperative and post-RFA patients have not had a recurrence of HCC to date, except for one patient who had a palliative operation with intra-arterial infusion of anticancer drugs through an implanted reservoir port. Older age and liver cirrhosis are considered risk factors for HCC in NASH, and regular screening of these patients is necessary. Diabetes may contribute to the development of ICC in NASH. Curative therapy (surgery or RFA) and weight loss by the active therapeutic intervention (nutritional care and exercise therapy) after curative therapy may help us improve the prognosis of HCC in NASH.
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Carcinoma Hepatocelular/etiologia , Fígado Gorduroso/complicações , Neoplasias Hepáticas/etiologia , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/etiologia , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/terapia , Ductos Biliares Intra-Hepáticos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Colangiocarcinoma/etiologia , Colangiocarcinoma/patologia , Colangiocarcinoma/terapia , Fígado Gorduroso/patologia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , PrognósticoRESUMO
BACKGROUND: Cardiac hypertrophy and failure are major complications of hypertension. OBJECTIVES: The beneficial effect of treatment with antihypertensive drugs on serum levels of brain natriuretic peptide (BNP) was examined in patients with essential hypertension. METHODS: Antihypertensive drugs were administered to 88 hypertensive patients (44 diabetic and 44 nondiabetic) whose systolic blood pressure was greater than 140 mmHg and/or diastolic blood pressure was greater than 90 mmHg. Other antihypertensive drugs were added every two months until the blood pressure fell below 130/85 mmHg. Candesartan, benidipine, bisoprolol or celiprolol, and bunazosin were administered in this order. RESULTS: The mean systolic blood pressure was reduced from 163.7+/-11.6 mmHg to 121.8+/-7.5 mmHg after 12 months in patients with diabetes and from 167.6+/-12.3 mmHg to 122.8+/-7.5 mmHg in patients without diabetes. The mean diastolic blood pressure was also significantly reduced in patients with and without diabetes. Serum BNP levels were reduced from 52.2+/-38.8 pg/mL to 38.8+/-30.9 pg/mL in patients with diabetes and from 47.1+/-34.2 pg/mL to 35.8+/-22.5 pg/mL in patients without diabetes. In patients older than 70 years of age, serum BNP levels were reduced from 56.3+/-39.3 pg/mL to 40.2+/-23.0 pg/mL in those with diabetes and from 54.6+/-32.9 pg/mL to 38.0+/-16.0 pg/mL in those without diabetes. CONCLUSIONS: These results indicate that combination therapy with antihypertensive drugs is usually necessary to reduce blood pressure to below 130/85 mmHg and to improve serum BNP levels.
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A 79-year-old woman with adenocarcinoma of the lung almost fully obstructing the right main bronchus and with multiple bone and brain metastases was admitted to our hospital in March 2005. Irradiation was considered to be successful. Since subsequent vinorelbine chemotherapy was futile, it was changed to gefitinib in June. A week after gefitinib therapy, serum alkaline phosphatase (ALP) began to increase from about 400 IU/l to 1247 IU/l, to 3470 IU/l after two weeks, and up to 3527 IU/l after three weeks. The levels then decreased to within the normal range after nine weeks. ALP isozyme showed a peak composed of ALP2 and ALP3, and the levels of other enzymes (GOT, GPT, gamma-GTP) were normal. Hence, increased ALP was thought to be derived from the bones. The patient's performance status and metastases improved during this phenomenon. Bone scintigraphy findings one month after beginning gefitinib therapy worsened, but improved after four months. Bone ALP represents osteoblastic activity. We believe that in this case bone formation became dominant because of the favorable response to gefitinib therapy.
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Adenocarcinoma/enzimologia , Fosfatase Alcalina/sangue , Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/enzimologia , Quinazolinas/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Idoso , Neoplasias Ósseas/secundário , Feminino , Gefitinibe , Humanos , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
AIM: To identify the clinical and prognostic features of patients with hepatocellular carcinoma (HCC) aged 80 years or more. METHODS: A total of 1310 patients with HCC were included in this study. Ninety-one patients aged 80 years or more at the time of diagnosis of HCC were defined as the extremely elderly group. Two hundred and thirty-four patients aged > or = 50 years but less than 60 years were regarded as the non-elderly group. RESULTS: The sex ratio (male to female) was significantly lower in the extremely elderly group (0.90:1) than in the non-elderly group (3.9:1, P < 0.001). The positive rate for HBsAg was significantly lower in the extremely elderly group and the proportion of patients negative for HBsAg and HCVAb obviously increased in the extremely elderly group (P < 0.001). There were no significant differences in the following parameters: diameter and number of tumors, Child-Pugh grading, tumor staging, presence of portal thrombosis or ascites, and positive rate for HCVAb. Extremely elderly patients did not often receive surgical treatment (P < 0.001) and they were more likely to receive conservative treatment (P < 0.01). There were no significant differences in survival curves based on the Kaplan-Meier methods in comparison with the overall patients between the two groups. However, the survival curves were significantly worse in the extremely elderly patients with stage I/II, stage I/II and Child-Pugh grade A cirrhosis in comparison with the non-elderly group. The causes of death did not differ among the patients, and most cases died of liver-related diseases even in the extremely elderly patients. CONCLUSION: In the patients with good liver functions and good performance status, aggressive treatment for HCC might improve the survival rate, even in the extremely elderly patients.
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Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/terapia , Causas de Morte , Feminino , Humanos , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
The term ectopic varices is used to describe dilated portosystemic collateral veins in unusual locations other than the gastroesophageal region. We recently experienced a rare case of ectopic varices that developed in the right diaphragm and ruptured into the pleural cavity. A 68-year-old female with hepatocellular carcinoma complicated with liver cirrhosis was admitted due to an acute onset of dyspnea and right bloody pleural effusion. Because of the patient's advanced hepatocellular carcinoma and poor condition, conservative therapies such as hemostats and blood transfusion were selected. Even though the bleeding to the pleural cavity stopped spontaneously, the patient died due to a progression of liver failure. Autopsy revealed a huge collateral vein in the right diaphragm. The etiology, prevalence, relationship with portal hypertension, and treatment of ectopic varices are discussed herein.
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Carcinoma Hepatocelular/complicações , Diafragma/lesões , Neoplasias Hepáticas/complicações , Cavidade Pleural/lesões , Idoso , Varizes Esofágicas e Gástricas/complicações , Varizes Esofágicas e Gástricas/terapia , Evolução Fatal , Feminino , Humanos , Ruptura/etiologiaRESUMO
PURPOSE: Small cell lung cancer (SCLC) is a rapidly growing neoplasm accounting for approximately 20% of patients with lung cancer. Progastrin-releasing peptide (proGRP) is produced in about two-thirds of SCLC tumors and is used as a specific marker for SCLC. Although GRP is known to have a variety of biological functions, only limited information is available concerning expression of proGRP mRNA and protein, and that of the receptor for GRP (GRPR) in SCLC tumors. METHODS: In individuals with SCLC, the levels of serum proGRP(31-98) were measured by enzyme-linked immunosorbent assay. Expression of proGRP as well as GRPR mRNA in SCLC tumor tissues was investigated by reverse transcription-nested polymerase chain reaction (PCR) amplification. The proportions of alternatively spliced proGRP mRNA transcripts were analyzed in proGRP-producing tumors by nested and competitive PCR amplification. Finally, production of proGRP protein in SCLC tumor was evaluated by using immunohistochemical staining with a polyclonal human anti-proGRP antibody. RESULTS: ProGRP mRNA transcripts could be detected only in tumor tissues recovered from individuals with high serum proGRP levels. The proportions of mRNA subtypes in each case were nearly the same, revealing type I of 55.4+/-7.6%, type II with 21-b deletion of 1.8+/-3.6%, and type III with 19-b deletion of 42.8+/-4.3%, respectively. ProGRP protein production was demonstrated in tumor tissues exclusively from individuals exhibiting high serum proGRP levels. In contrast, GRPR mRNA transcripts were detectable in cancer cells from two of five proGRP-expressing tumor tissues. CONCLUSIONS: ProGRP mRNA expression is closely related with the synthesis of proGRP protein which is eventually released into the blood. It is suggested GRP may function as an autocrine growth factor for cancer cells in a subgroup of SCLC patients through, at least in part, upregulation of GRPR expression.