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We conducted a multicenter retrospective study for evaluating the background of and diagnostic opportunity for 651 patients with primary hepatocellular carcinoma (HCC). The etiologies were hepatitis B virus (HBV) in 20.0% of patients, hepatitis C virus (HCV) in 36.3%, and non-B non-C (NBNC) in 43.5%. The characteristics of non-alcoholic NBNC HCC patients included low frequency of liver cirrhosis and high frequency of life style-related diseases. The mean diameter of HCC was approximately 4cm. Most patients were diagnosed using ultrasonography and dynamic computed tomography (CT). However, 18.6% of patients were diagnosed using conventional contrast-enhanced CT. Compliance with the surveillance program for HCC diagnosis was 35.4% in HBV carriers and 49.2% in HCV carriers. The main causes of deviation from the program included undiagnosed HBV and HCV carriers, non-compliance with the surveillance program by physicians, and no medical care for HBV and HCV carriers. For an early diagnosis of HCC, it is essential to improve the diagnoses of HBV and HCV carriers, promote the follow-ups of HBV and HCV carriers in hospitals, re-educate physicians, and identify the risk factors of NBNC HCC.
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Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Idoso , Carcinoma Hepatocelular/etiologia , Feminino , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
AIM: Acoustic radiation force impulse is a noninvasive method for evaluating tissue elasticity on ultrasound. Renal shear wave velocity measured by this technique has not been fully investigated in patients with renal disease. The aim of the present study was to compare renal shear wave velocity in end-stage renal disease patients and that in patients without chronic kidney disease and to investigate influencing factors. METHODS: Renal shear wave velocities were measured in 59 healthy young subjects (control group), 31 subjects without chronic kidney disease (non-CKD group), and 39 end-stage renal disease patients (ESRD group). Each measurement was performed 10 times at both kidneys, and the mean value of eight of 10 measurements, excluding the maximum and minimum values, was compared. RESULTS: Renal shear wave velocity could be measured in all subjects. Renal shear wave velocity in the control group was higher than in the non-CKD group and in the ESRD group, and no difference was found between the non-CKD group and the ESRD group. Age and depth were negatively correlated to the renal shear wave velocity. In multiple regression analysis, age and depth were independent factors for renal shear wave velocity, while renal impairment was not. There was no difference between the non-CKD group and the ESRD group, even when ages were matched and depth was adjusted. CONCLUSION: Renal shear wave velocity was not associated with advanced renal impairment. However, it reflected alteration of renal aging, and this technique may be useful to detect renal impairment in the earlier stages.
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Técnicas de Imagem por Elasticidade , Falência Renal Crônica/diagnóstico por imagem , Rim/diagnóstico por imagem , Insuficiência Renal Crônica/diagnóstico por imagem , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Elasticidade , Feminino , Humanos , Rim/patologia , Rim/fisiopatologia , Falência Renal Crônica/patologia , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/fisiopatologia , Reprodutibilidade dos Testes , Adulto JovemRESUMO
BACKGROUND & AIMS: The aim of this study was to investigate the feasibility of ablative margin (AM) grading by magnetic resonance imaging (MRI) with Gd-EOB-DTPA administered prior to radiofrequency ablation (RFA), and to identify factors for achieving a sufficient AM and predictors for local tumor progression. METHODS: A total of 124 hepatocellular carcinomas (HCCs) were treated by RFA after Gd-EOB-DTPA administration. MRI and enhanced CT were performed within seven hours and one month after RFA. The AM assessment was categorized using three grades: AM (+), low-intensity area with continuous high-intensity rim; AM zero, low-intensity area with discontinuous high-intensity rim; and AM (-), low-intensity area extends beyond the high-intensity rim. Patients were followed and local tumor progression was observed. RESULTS: AM (+), AM zero, AM (-), and indeterminate were found in 34, 33, 26, and 31 nodules, respectively. The overall agreement rate between MRI and enhanced CT for the diagnosis of AM was 56.8%. The κ coefficient was 0.326 (p<0.001), indicating moderate agreement. Multivariate logistic regression analysis showed that a significant factor for the achievement of AM (+) on MRI was no contiguous vessels. The cumulative local tumor progression rates (0% at 1, 2, and 3 years) in 33 AM (+) nodules were significantly lower than those (3.6%, 11.5%, and 18.3% at 1, 2, and 3 years respectively) in 32 AM zero nodules. A multivariate Cox proportional hazards model identified tumor size as an independent predictor for local tumor progression. CONCLUSION: Gd-EOB-DTPA-MRI enabled an early assessment of RFA effectiveness in the majority ofHCC nodules. Local tumor progression was not detected in AM (+) nodules during the follow-up.
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Carcinoma Hepatocelular/cirurgia , Ablação por Cateter , Neoplasias Hepáticas/cirurgia , Idoso , Carcinoma Hepatocelular/patologia , Meios de Contraste , Progressão da Doença , Feminino , Gadolínio DTPA , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
Background: Patients taking multiple drugs and various health foods often develop acute hepatitis. We hypothesized that the interaction between health foods and drug metabolism was the cause of severe liver injury in these patients. Therefore, we studied changes in the activity of the drug-metabolizing enzyme, cytochrome P450 (CYP), using slimming health food extracts and elucidated the molecular mechanism of liver injury onset through hepatotoxicity evaluation. Methods: For cytotoxicity testing, health food extract samples were added to HepG2 cells derived from hepatic parenchymal cells and culture medium, and cell viability was calculated 48 h after culture. To evaluate CYP3A4 induction, 3-1-10 cells constructed with a reporter linked to CYP3A4 gene were used, and reporter activity was measured 48 h after culture. Results: In the chronological order of the slimming health food intake history of the patient, niacinamide and Gymnema sylvestre extracts strongly inhibited HepG2 cell viability. In contrast, dietary supplements A and Coleus forskohlii extract strongly induced CYP3A4 reporter activity.To confirm CYP3A4 induction in humans, humanized CYP3A/pregnane X receptor (PXR) mice were treated with forskolin. CYP3A4 mRNA expression levels were elevated 3.9 times compared to that of the control group (P < 0.05). Conclusion: Coleus forskohlii extract showed the strongest transcriptional activation of CYP3A4 gene. In a mouse model of human-type drug metabolism, forskolin induced CYP3A4 transcription. Thus, we concluded that CYP3A4 induction by Coleus forskohlii is one of the causes of crucial hepatocellular injury, which is a type of liver injury caused by the active metabolite of acetaminophen produced by CYP3A4.
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BACKGROUND/AIMS: The purpose of this study was to investigate whether bubble images after radiofrequency ablation (RFA) can predict the ablated area. METHODOLOGY: The spread of bubbles 5 minutes after RFA were compared with the unenhanced area of virtual sonography with magnetic navigation in two RFA methods: expandable needle and cool-tip needle. RESULTS: Thirty-one hepatocellular carcinoma nodules were treated by RFA with either an expandable needle or cool-tip needle (n=14 and n=17, respectively) and examined. In the 14 nodules treated by expandable needle, bubble images (puncture direction; r=0.833, p=0.0002, perpendicular direction; r=0.803, p=0.0005) were closely correlated with the unenhanced area of virtual sonography. On the other hand, in 17 nodules treated by cool-tip needle, there was no correlation between the bubble images and virtual sonography (puncture direction; r=0.590, p=0.0127, perpendicular direction; r=0.342, p=0.180). CONCLUSIONS: The observation of bubbles with the expandable needle can accurately predict the ablated area and is helpful for assessing local control of RFA.
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Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Idoso , Feminino , Humanos , Modelos Lineares , Imageamento por Ressonância Magnética , Masculino , Microbolhas , Pessoa de Meia-Idade , Agulhas , Recidiva Local de Neoplasia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , UltrassonografiaRESUMO
A 45-year-old Philippine woman who came from Mindanao Island was admitted to our hospital with a complaint of epigastric discomfort. Abdominal ultrasonography and computed tomography demonstrated a network pattern and linear calcification in the liver. Laparoscopic examination showed numerous yellowish, small speckles over the liver surface. The liver surface was separated into many small blocks by groove-like depressions, demonstrating a so-called tortoise shell pattern. Conventional colonoscopy and narrow-band imaging showed irregular areas of yellowish mucosa, and diminished vascular network and increased irregular microvessels extending from the descending colon to the rectum. Liver biopsy showed many Schistosoma japonicum eggs in Glisson's capsule and colon biopsy showed many S. japonicum eggs in the submucosal layer. These findings established a diagnosis of schistosomiasis japonica. The present case is imported schistosomiasis japonica. Even though new cases have not occurred recently in Japan, we should remain aware of schistosomiasis japonica for patients who came from foreign epidemic areas.
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Colonoscopia , Laparoscopia , Esquistossomose Japônica/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Esquistossomose Japônica/etiologia , Esquistossomose Japônica/terapiaRESUMO
The essential trace element zinc maintains liver functions. Liver diseases can alter overall zinc concentrations, and hypozincemia is associated with various hepatic pathologies. Modulating systemic zinc through dietary supplementation is potentially useful for liver diseases. We evaluated the usefulness of zinc (NPC-02; acetate formulation) supplementation. We conducted two NPC-02 studies on zinc-deficient patients (serum zinc < 70 µg/dL). Study 1: double-blind, randomized, placebo-controlled trial on 57 subjects with chronic liver diseases comparing serum zinc in patients given NPC-02 (NPC-02 group) versus placebo (Placebo group). Study 2: dose adjustment study on 43 subjects with/without liver diseases to determine proportions maintaining serum zinc target (≥ 80 µg/dL but < 200 µg/dL). In study 1, NPC-02 subjects had higher serum zinc concentrations at week 8 than Placebo subjects (83.2 ± 20.2 and 61.3 ± 12.0, respectively; P < 0.0001), and more NPC-02 than Placebo subjects achieved the serum zinc target (15/27 vs. 1/26). In study 2, the NPC-02-induced serum zinc increase was dose-dependent in subjects both with and without liver diseases (r = 0.5143, P = 0.0022 and r = 0.5753, P = 0.0005, respectively). Interestingly, there was a marginally positive correlation between serum zinc and albumin levels in subjects with but not in those without liver diseases (r = 0.4028, P = 0.0631 and r = 0.1360, P = 0.5567, respectively). NPC-02 dose-dependently increases serum zinc in hypozincemic patients, regardless of liver disease. NPC-02 is a potentially effective therapy for liver cirrhosis, in which zinc deficiency is common. Clinical trial registry number: NCT02337569, NCT02321865.
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Hepatopatias/sangue , Acetato de Zinco/sangue , Zinco/sangue , Idoso , Doença Crônica , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Hepatopatias/patologia , Masculino , Pessoa de Meia-Idade , Acetato de Zinco/administração & dosagemRESUMO
BACKGROUND/AIMS: Recently, complementary alternative medicine is actively performed for cancer therapy. We investigated the effectiveness of supplementary food containing superfine dispersed lentinan (beta-1,3-glucan) in patients with unresectable or recurrent hepatocellular carcinoma in a multi-center study. METHODOLOGY: Peripheral blood was collected prior to the test food ingestion and was incubated with fluorescein-labeled lentinan. The rates of lentinan-binding CD14+ monocytes were determined by flow cytometry. Patient survival times were followed up for 3 years. RESULTS: Thirty-six patients were eligible among 40 enrolled patients. Median survival time of eligible patients was 13.6 months (95% confidence interval, 8.7-18.9 months). Survival times of patients who ingested test food for a mean period of 47 weeks (range, 26 to 145 weeks) were significantly longer than that of patients who ingested for 7 to 12 weeks (p < 0.05). The rates of lentinan-binding cells in CD14+ monocytes showed individual variations (0.1-19.7%; Median, 1.6%). Survival times (median survival time, 16.3 months) of lentinan-high-binding group were significantly longer than those (median survival time, 12.5 months) of lentinan-low-binding group (p < 0.05). CONCLUSIONS: A superfine dispersed lentinan-containing supplementary food is effective for hepatocellular carcinoma patients' survival. Long-time ingestion is preferable. Assessment of lentinan-binding CD14+ monocytes is a promising prognostic predictor.
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Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Lentinano/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Suplementos Nutricionais , Feminino , Humanos , Lentinano/administração & dosagem , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do TratamentoRESUMO
An eighty-six-year-old man was admitted to our hospital for bacterial septic shock due to splenic abscess. He had undergone percutaneous coronary intervention 3 weeks earlier. Percutaneous splenic abscess drainage was urgently performed under ultrasonography, and then the general state of the patient rapidly improved. Staphylococcus hemolyticus was isolated from the splenic abscess. We reported that percutaneous catheter drainage was effective for splenic abscess.
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Abscesso/cirurgia , Drenagem/métodos , Esplenopatias/cirurgia , Abscesso/etiologia , Idoso de 80 Anos ou mais , Humanos , Masculino , Infecções Estafilocócicas/complicações , Staphylococcus haemolyticusRESUMO
An 80-year-old woman with hepatic encephalopathy and esophagogastric varices was admitted. Doppler sonography and arteriography demonstrated an arterioportal fistula in the right anterior superior segment of the liver. Two attempts at transcatheter arterial embolization failed to manage the fistula and portacaval collaterals. We carried out hepatectomy and balloon-occluded retrograde transvenous obliteration, by which the portal flow changed from hepatofugal to hepatopetal. The resected specimen demonstrated multiple small holes in the right portal vein, which are arterioportal fistula. The underlying liver was normal. After treatment, esophagogastric varices and hepatic encephalopathy were markedly improved. Hepatectomy is useful as a reliable therapy for arterioportal fistula in case of failure of transarterial embolization.
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BACKGROUND: Vitamin B12 is stored primarily in the liver, and highly elevated serum vitamin B12 levels occur in acute hepatitis and severe alcoholic liver disease. We evaluated the relationship between vitamin B12 levels and liver disease severity and long term prognosis in patients with chronic viral hepatitis and cirrhosis. METHODS: We enrolled 90 patients (57 men, 33 women) with chronic viral hepatitis and cirrhosis who admitted to our hospital as a prospective cohort study. Overall, 37 patients had chronic hepatitis and 53 had cirrhosis (Child-Pugh A 33, B 13, and C 7); 57 patients had primary liver cancer. Serum vitamin B12 concentration and holotranscobalamin (holoTC) II (active form of vitamin B12) were determined and followed prospectively for at least 5 years. RESULTS: Mean total serum vitamin B12 concentration was significantly higher in Child-Pugh C (1308 ± 599 pg/mL) compared to those with chronic hepatitis (655 ± 551 pg/mL), Child-Pugh A (784 ± 559 pg/mL), and Child-Pugh B (660 ± 464 pg/mL) (P = 0.036) Presence of primary liver cancer also influenced serum vitamin B12 levels [657 (167-2956) vs. 432 (189-2956); P = 0.015]. Patients were divided into quartiles by vitamin B12 level. Patients without primary liver cancer in quartile 4 (≥ 880 pg/mL) demonstrated significantly poorer prognosis than those in quartiles 1-3 (< 880 pg/mL) (P = 0.023). The percentage of holohaptocorrin (holoHC) [(total vitamin B12 - holoTC II) × 100] was significantly higher in Child-Pugh B and C 86 (80-87)% than chronic hepatitis and Child-Pugh A 77 (31-89)% (P = 0.006) Multivariate analysis indicated serum vitamin B12 levels (HR = 1.001, P = 0.029) as a prognostic factor. CONCLUSION: Falsely elevated serum vitamin B12 levels mainly composed of increased holoHC were associated with severity (Child-Pugh C and primary liver cancer) and prognosis in chronic viral liver disease.
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BACKGROUND: Procalcitonin (PCT) is a known diagnostic marker of bacterial infection. There are no previous reports of PCT concerning acute liver failure (ALF). We evaluated the clinical value of serum PCT levels in patients with ALF. METHODS: Forty-four patients with acute hepatitis (19 men and 25 women; median age, 40 years; range, 20-79 years) were retrospectively enrolled from January 2001 and June 2015. PCT levels were measured by saved serum samples obtained within 3 days after admission. ALF was defined as prothrombin time (PT) < 40% regardless of hepatic encephalopathy. RESULTS: Serum PCT levels were significantly higher in the patients with ALF (n = 16) than in those with non-ALF (n = 28) [0.25 (0.13-2.66) ng/mL vs. 0.165 (0.03-1.08), P = 0.00967]. Creatinine, total bilirubin, and direct bilirubin were positively correlated, and PT was negatively correlated with PCT. Receiver operating characteristic curve analysis showed an area under the curve of 0.74 for detecting ALF. With a PCT cut-off value of 0.5 ng/mL, the presence of ALF could be demonstrated with low sensitivity (37.5%) and high specificity (96.5%) with high positive (85.7%) and negative (72.9%) predictive value. Multivariate analysis showed that PCT was an independent factor associated with the presence of ALF. The cumulative survival rate was also significantly lower in patients with PCT ≥ 0.5 ng/mL (P = 0.0314), but it was not an independent prognostic factor. CONCLUSION: Serum PCT level was significantly higher in patients with ALF.
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BACKGROUND: Diuretics are essential for treating acute decompensated heart failure (ADHF), but the response is inconsistent. This study aimed to clarify whether kidney volume as assessed by ultrasound (US) predicts diuretic resistance in patients with ADHF. METHODS: We enrolled 29 patients with ADHF and 32 controls. Height-adjusted kidney volume was assessed by US. We divided patients into two groups based on the median value of total daily use of furosemide (intravenous dose plus 0.5 × oral dose of furosemide equivalents) during 3 days from admission. RESULTS: Patients with ADHF had a significantly smaller left kidney volume than did control subjects (27.7 ± 10.0 vs. 32.8 ± 8.8 mL/m, P < 0.05). Patients in the high-dose furosemide group (≥ 51.7 mg/d) had a significantly lower estimated glomerular filtration rate (eGFR) and a significantly smaller kidney volume than did those in the low-dose furosemide group (eGFR: 43.9 ± 20.4 vs. 60.8 ± 21.6 mL/min/1.73 m2, left kidney volume: 23.2 ± 5.2 vs. 32.6 ± 11.0 mL/m, right kidney volume: 26.5 ± 7.5 vs. 32.6 ± 7.9 mL/m, all P < 0.05). Multivariate logistic analysis showed that left kidney volume, but not eGFR, was independently associated with the requirement of high-dose furosemide (odds ratio: 0.856, 95% confidence interval: 0.735-0.997, P < 0.05). CONCLUSION: Kidney volume as assessed by US is a useful predictor of diuretic resistance in patients with ADHF.
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A patient was diagnosed with chronic hepatitis C at the age of 63 years. He achieved eradication of HCV via interferon (IFN). Eight years after, a hepatocellular carcinoma (HCC) was detected and treated through transarterial embolization and percutaneous ethanol injection therapy. After about 1 year, a large hypovascular tumor was detected. This tumor was surgically resected and diagnosed as an HCC with sarcomatous change. This is the first case of an HCC with sarcomatous change arising after a sustained response to IFN therapy.
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Carcinoma Hepatocelular/etiologia , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Interferons/uso terapêutico , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/prevenção & controle , Neoplasias Vasculares/etiologia , Idoso , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/prevenção & controle , Hepatite C/diagnóstico , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Resultado do Tratamento , Neoplasias Vasculares/diagnósticoRESUMO
AIM: To examine the effects of the endothelin type A receptor antagonist ambrisentan on hepatic steatosis and fibrosis in a steatohepatitis mouse model. METHODS: Fatty liver shionogi (FLS) FLS-ob/ob mice (male, 12 wk old) received ambrisentan (2.5 mg/kg orally per day; n = 8) or water as a control (n = 5) for 4 wk. Factors were compared between the two groups, including steatosis, fibrosis, inflammation, and endothelin-related gene expression in the liver. RESULTS: In the ambrisentan group, hepatic hydroxyproline content was significantly lower than in the control group (18.0 µg/g ± 6.1 µg/g vs 33.9 µg/g ± 13.5 µg/g liver, respectively, P = 0.014). Hepatic fibrosis estimated by Sirius red staining and areas positive for α-smooth muscle actin, indicative of activated hepatic stellate cells, were also significantly lower in the ambrisentan group (0.46% ± 0.18% vs 1.11% ± 0.28%, respectively, P = 0.0003; and 0.12% ± 0.08% vs 0.25% ± 0.11%, respectively, P = 0.047). Moreover, hepatic RNA expression levels of procollagen-1 and tissue inhibitor of metalloproteinase-1 (TIMP-1) were significantly lower by 60% and 45%, respectively, in the ambrisentan group. Inflammation, steatosis, and endothelin-related mRNA expression in the liver were not significantly different between the groups. CONCLUSION: Ambrisentan attenuated the progression of hepatic fibrosis by inhibiting hepatic stellate cell activation and reducing procollagen-1 and TIMP-1 gene expression. Ambrisentan did not affect inflammation or steatosis.
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AIMS: The kidney becomes atrophic in advanced chronic kidney disease, and renal size and parenchymal volume correlate with renal function. However, alterations in renal parenchymal volume have not been adequately studied in terms of the renal cortex and medulla. We investigated the relationship between the changes in the renal cortex and medulla and renal function. METHODS: Renal ultrasound (US) parameters including renal length, parenchymal thickness, cortical thickness and medullary thickness were assessed in 176 subjects, who were categorized into 4 groups based on the estimated glomerular filtration rate (ml/min/1.73 m2): group 1, ≥ 90; group 2, ≥ 60 but < 90; group 3, ≥ 30 but < 60; and group 4, < 30. Renal US parameters in both kidneys were compared among the 4 groups. RESULTS: We found stepwise associations in renal length, cortical thickness and parenchymal thickness with decreased renal function. Medullary thickness showed no changes among groups 1-3. Multiple linear regression analysis including sex, age and renal US parameters showed that only renal length was an independent predictor of renal function. When analyzed in groups 1-3, cortical thickness was the strongest associated parameter. Lower cortical left/right ratio (left cortical thickness/right cortical thickness) showed a stepwise association with a decrease in renal function. CONCLUSION: Renal length and cortical thickness measured by US were correlated with renal function. In particular, left cortical thickness could help to detect early changes in renal function.
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Córtex Renal/diagnóstico por imagem , Insuficiência Renal Crônica/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Testes de Função Renal , Medula Renal/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Ultrassonografia , Adulto JovemRESUMO
The aim of the present study was to predict the effects of transarterial infusion (TAI) chemotherapy based on early changes in α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) in patients with advanced hepatocellular carcinoma (HCC). Seventy-four patients who underwent TAI with cisplatin, 5-fluorouracil, mitomycin C and epirubicin for advanced HCC were enrolled. Antitumor responses were evaluated 6 months after TAI. Rapid and early responses were defined as the ratio of AFP or DCP after 1 week and 1 month compared to baseline. A total of 5, 10, 17 and 42 patients had complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD), respectively. Early AFP response was significantly lower in the CR+PR compared to the SD+PD groups (P<0.01). The early DCP response was significantly lower in the CR+PR compared to the SD+PD. The sensitivity and specificity of rapid and early AFP responses in the CR+PR were 0.78 and 0.72, and 0.80 and 0.73, respectively, and those of rapid and early DCP responses were 0.67 and 0.65, and 0.77 and 0.71, respectively. The combination of AFP and DCP responses had higher specificity compared to AFP or DCP alone responses. Patients were divided into responder and non-responder groups to evaluate the prediction of survival outcome. Early responders of AFP, DCP and AFP+DCP, who were divided based on the cut-off values of CR+PR survived significantly longer than the non-responders (P<0.05). In conclusion, rapid or early responses of AFP and/or DCP levels 1 and 4 weeks after TAI chemotherapy helped to predict the treatment effects.
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Objectives: We investigated how radiofrequency ablation (RFA) alone or the combination with transcatheter arterial embolization (TAE-RFA) for hepatocellular carcinoma (HCC) affects the liver parenchymal function of underlying chronic liver disease to find a predictive factor for selecting appropriate candidates for RFA. Methods: In 53 HCC patients (RFA alone, 25; TAE-RFA, 28), liver laboratory tests and development of complications were monitored until 6 months after treatments. Serum albumin deteriorated within 1 month and recovered after 6 months in both groups, whereas the elevation of the Pugh score continued in RFA alone group and that of serum bilirubin continued in TAE-RFA group until 6 months. The elevation of Pugh score 6 months after RFA was significantly more frequent in patients with a high pre-treatment Pugh score (>/=8 points) than in those with a low pre-treatment Pugh score (<8 points). Complications after RFA were observed in 11 of the 53 patients: temporary complications in 5, refractory ascites in 6. Refractory ascites developed in only patients with a high pre-treatment Pugh score. Conclusion: Liver parenchymal functions in patients with a low pre-treatment Pugh score were transiently deteriorated by RFA or TAE-RFA. However, in patients with a high Pugh score, RFA or TAE-RFA induces long-term deterioration of the liver parenchymal functions and causes serious complications. Therefore, patients with a Pugh score >/=8 points would not be good candidates for RFA or TAE-RFA.
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The aim of this study was to clarify the clinical features of patients with isolated HCC metastases to the heart. A 66-year-old female hospitalized with a hepatocellular carcinoma (HCC) ranging from the right to the left lobe and with a tumor thrombus in the main portal vein, was treated with intraarterial cisplatin, 5-fluouracil, adriamycin and mitomycin. Computed tomography (CT) one month later revealed that the HCC had progressed with multiple lung metastases and moderate ascites. The patient had no symptoms. Magnetic resonance imaging (MRI) and echocardiography revealed a round, movable tumor with a diameter of 2 cm in the right atrium (RA). The patient succumbed to HCC five months later. An autopsy revealed HCC with portal tumor thrombi and metastases to the lungs, inferior vena cava (IVC) and RA. The metastases in the RA and IVC were not continous with the intrahepatic tumor and were histologically attached to the endocardium and endothelium, respectively. An isolated metastasis of a HCC of the RA and IVC is extremely rare. In conclusion, although the majority of isolated metastases of HCC to the heart were diagnosed by echocardiography and were treated with mainly surgery, they had poor prognosis. The echocardiography should be performed for patients with advanced HCC. A novel treatment including molecular targeted drugs is required.
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PURPOSE: Ras/Raf/mitogen-activated protein-extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signaling is critical for tumor cell proliferation and survival. Selumetinib is a potent, selective, and orally available MEK1/2 inhibitor. In this study, we evaluated the therapeutic efficacy of selumetinib alone or with cediranib, an orally available potent inhibitor of all three VEGF receptor (VEGFR) tyrosine kinases, in murine orthotopic non-small cell lung carcinoma (NSCLC) models. EXPERIMENTAL DESIGN: NCI-H441 or NCI-H460 KRAS-mutant human NSCLC cells were injected into the lungs of mice. Mice were randomly assigned to treatment with selumetinib, cediranib, paclitaxel, selumetinib plus cediranib, or control. When controls became moribund, all animals were sacrificed and assessed for lung tumor burden and locoregional metastasis. Lung tumors and adjacent normal tissues were subjected to immunohistochemical analyses. RESULTS: Selumetinib inhibited lung tumor growth and, particularly at higher dose, reduced locoregional metastasis, as did cediranib. Combining selumetinib and cediranib markedly enhanced their antitumor effects, with near complete suppression of metastasis. Immunohistochemistry of tumor tissues revealed that selumetinib alone or with cediranib reduced ERK phosphorylation, angiogenesis, and tumor cell proliferation and increased apoptosis. The antiangiogenic and apoptotic effects were substantially enhanced when the agents were combined. Selumetinib also inhibited lung tumor VEGF production and VEGFR signaling. CONCLUSIONS: In this study, we evaluated therapy directed against MEK combined with antiangiogenic therapy in distinct orthotopic NSCLC models. MEK inhibition resulted in potent antiangiogenic effects with decreased VEGF expression and signaling. Combining selumetinib with cediranib enhanced their antitumor and antiangiogenic effects. We conclude that combining selumetinib and cediranib represents a promising strategy for the treatment of NSCLC.