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INTRODUCTION: Atezolizumab, an immune checkpoint inhibitor, plus bevacizumab, a monoclonal antibody that binds to vascular endothelial growth factor (VEGF), is an approved first-line systemic treatment for unresectable hepatocellular carcinoma (HCC). Immune checkpoint inhibitors are more effective in patients with HCC when administered with anti-VEGF drugs; however, these drugs affect host immunity. Lenvatinib is an anti-VEGF agent used to treat HCC; therefore, this study evaluated the effect of treatment of HCC with lenvatinib on host immunity in patients with chronic liver disease (CLD). METHODS: We studied adult Japanese patients with CLD and unresectable HCC treated with lenvatinib at our hospital. Lenvatinib was administered for 4 weeks (8 mg/day for bodyweight <60 kg; 12 mg/day for bodyweight >60 kg). Blood samples were collected at baseline and at 4 weeks of treatment and examined for immune-related changes. RESULTS: Forty-three patients were enrolled in this study. We found a significant increase in T helper (Th) 1 cells following 4 weeks of lenvatinib treatment, although there was no significant difference in Th2 cells and regulatory T cells. We also found a significant increase in serum levels of TNF-alpha, soluble TNF-alpha receptor I, and endothelial growth factor following 4 weeks of lenvatinib treatment. Furthermore, an increase in Th1 cells and serum levels of TNF-alpha was found in patients with partial response. CONCLUSION: Lenvatinib might induce Th1-dominant host immunity in patients with CLD and unresectable HCC treatment in patients who showed a partial response. These changes in host immunity may be a biomarker in HCC patients treated with lenvatinib.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Adulto , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Antineoplásicos/uso terapéutico , Factor A de Crecimiento Endotelial Vascular , Factor de Necrosis Tumoral alfa/uso terapéutico , Compuestos de Fenilurea/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/uso terapéuticoRESUMEN
PURPOSE: The aim of this study was to clarify the adaptation of lenvatinib treatment in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT). METHOD: Fifty-three patients with HCC were treated with lenvatinib. Before and after treatment blood sampling, patients were examined by computed tomography and ultrasonography. In patients with portal trunk invasion (Vp4), the analysis focused on the degree of occlusion due to the tumor in the portal trunk. In patients without major PVTT {ie, invasion of the primary branch of the portal vein [Vp3] or Vp4}, portal blood flow volume was measured by Doppler analysis; however, Doppler analysis is difficult to perform in patients with major PVTT, so the time from administration of the contrast agent to when it reached the primary branch of the portal vein (portal vein arrival time) was evaluated with the contrast agent Sonazoid. RESULTS: Patients with Vp4 had a significantly worse prognosis than patients with Vp3 and a significant increase in Child-Pugh score at 2 months. Patients with major PVTT had a poor prognosis if the degree of occlusion of the portal trunk was 70% or more. In patients without major PVTT, portal blood flow was significantly decreased after administration of lenvatinib; and in patients with major PVTT, the hepatic artery and portal vein arrival times were significantly increased. CONCLUSION: Lenvatinib treatment should be avoided in patients with Vp4 with a high degree of portal trunk occlusion because of concerns about decreased portal blood flow.
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Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Hígado/irrigación sanguínea , Compuestos de Fenilurea/uso terapéutico , Quinolinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/mortalidad , Femenino , Humanos , Hígado/efectos de los fármacos , Hígado/patología , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Compuestos de Fenilurea/administración & dosificación , Vena Porta/efectos de los fármacos , Vena Porta/fisiopatología , Pronóstico , Quinolinas/administración & dosificación , Trombosis de la Vena/patologíaRESUMEN
Tivantinib, a mesenchymal-epithelial transition factor (cMET) inhibitor, is a molecular targeting drug that kills hepatocellular carcinoma (HCC) cells. Tivantinib alone does not affect the overall survival of patients with HCC, and combination treatment with tivantinib and other therapies has not been evaluated. This study was conducted to clarify the effect of the tivantinib in regulating breast cancer therapy-resistant protein (BCRP), a key transporter of 5-fluorouracil (5-FU), and dihydropyridine dehydrogenase (DPYD), a major metabolic enzyme of 5-FU. To this end, cMET gene expression was determined by RT-PCR in HepG2 (human hepatoma) cells. The transcriptional start sites of BCRP were determined by 5'-rapid amplification of cDNA ends (5'-RACE). BCRP and DPYD mRNA levels were determined by real-time RT-PCR, and promoter activities were measured by dual-luciferase assays. Results show that hepatocyte growth factor (HGF) upregulated the mRNA level of BCRP, but not DPYD, in HepG2 cells. The upregulation of BCRP expression by HGF was down-regulated by tivantinib. We also identified two transcriptional start sites (E1α, E1ß) in BCRP by 5'-RACE. The transcriptional activity of the region -287 to E1α of BCRP was upregulated by HGF, which was decreased by tivantinib, whereas activity of the region -297 to E1ßo f BCRP was not affected by tivantinib. Therefore, tivantinib regulates BCRP expression upstream of exon 1α. Combination treatment of tivantinib and 5-FU should be further evaluated for HCC therapy.
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Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Factor de Crecimiento de Hepatocito/antagonistas & inhibidores , Neoplasias Hepáticas/tratamiento farmacológico , Proteínas de Neoplasias/genética , Pirrolidinonas/farmacología , Quinolinas/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Dihidrouracilo Deshidrogenasa (NADP)/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células Hep G2 , Factor de Crecimiento de Hepatocito/metabolismo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Proteínas Proto-Oncogénicas c-met/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-met/metabolismo , Pirrolidinonas/uso terapéutico , Quinolinas/uso terapéutico , Activación Transcripcional/efectos de los fármacosRESUMEN
AIM: We previously reported that sorafenib induces Th1 [interferon-γ (IFNγ)-positive interleukin 4 (IL4)-negative] dominance which prevents tumor cells from escaping the host immune system in patients with liver cirrhosis (LC) and advanced hepatocellular carcinoma (aHCC). However, in that study we did not assess the influence of sorafenib on host immunity according to the etiology of LC. Therefore, this study was retrospectively performed to evaluate the impact of sorafenib therapy for aHCC on host immunity in patients stratified according to the etiology of LC: Patients and Methods: A total of 116 adult Japanese patients with LC and aHCC received sorafenib therapy at our hospital. Blood samples were collected before and after treatment for 4 weeks. RESULTS: Twenty-two patients had hepatitis B virus (HBV)-related LC, 62 patients had hepatitis C virus (HCV)-related LC, 22 patients had alcoholic LC, and 10 patients had LC without these causative factors. In patients receiving sorafenib at a dose of 400 mg/day, patients in Child-Pugh class A, and patients with stage IVA aHCC, Th2 (IFNγ-negative/IL4-positive) cells decreased significantly after treatment, although there was no significant impact on the tumor response. In addition, Th2 cells decreased significantly in patients with HCV-related LC after treatment, while there were no significant changes in the other groups. CONCLUSION: Sorafenib might prevent tumor cells from escaping the host immune system in patients with aHCC and HCV-related LC, although it does not seem to do so in those with LC of other etiologies.
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Antineoplásicos/farmacología , Carcinoma Hepatocelular/inmunología , Cirrosis Hepática/inmunología , Neoplasias Hepáticas/inmunología , Inhibidores de Proteínas Quinasas/farmacología , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/etiología , Femenino , Hepatitis B/complicaciones , Hepatitis C/complicaciones , Humanos , Interferón gamma/inmunología , Interleucina-4/inmunología , Cirrosis Hepática/etiología , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/uso terapéutico , Sorafenib , Células Th2/inmunologíaRESUMEN
Sonazoid is a commonly used contrast agent for characterizing liver tumors in ultrasonography (US). We performed flash imaging in the post-vascular phase of contrast-enhanced US (CEUS) to investigate associations between collapse of Sonazoid microbubbles (MB) and progression of liver disease. This study enrolled 409 patients (205 men, 204 women) with hepatitis C virus-related liver disease (CLD) between 2007 and 2017 (mean age 60 ± 14 y; range 20-90 y). In the post-vascular phase, 10 min after administering Sonazoid, flash imaging was performed to burst MB in the liver parenchyma; the range of bubble destruction was measured from the surface of the liver. The range of bubble destruction, stage of fibrosis, shear wave velocity (Vs), serologic markers and fibrosis-4 (FIB4) index were analyzed in 259 patients who underwent liver biopsy. Fibrosis stage was F0-1 in 108 patients, F2 in 73, F3 in 38 and F4 in 40. In 150 patients with cirrhosis, diagnosis was made based on imaging findings. The range of bubble destruction was 42.0 ± 10.4 mm in F0-1 patients, 42.9 ± 13.2 mm in F2, 51.5 ± 15.9 mm in F3 and 55.4 ± 17.3 mm in F4 and was significantly increased according to progression of fibrosis staging. The range of bubble destruction was positively correlated with Vs (râ¯=â¯0.34; p < 0.01), total bilirubin (râ¯=â¯0.25; p < 0.01) and FIB4 index (râ¯=â¯0.38; p < 0.01). In contrast, the range of bubble destruction was negatively correlated with serum levels of albumin (râ¯=â¯-0.34; p < 0.01), platelet count (râ¯=â¯-0.35; p < 0.01) and prothrombin time (râ¯=â¯-0.36; p < 0.01). The results indicated that flash imaging in the post-vascular phase of CEUS was a non-invasive assessment and could predict disease progression in patients with CLD.
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Medios de Contraste , Progresión de la Enfermedad , Hepatitis C Crónica/complicaciones , Aumento de la Imagen/métodos , Cirrosis Hepática/diagnóstico por imagen , Ultrasonografía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Compuestos Férricos , Humanos , Hierro , Hígado/diagnóstico por imagen , Cirrosis Hepática/etnología , Masculino , Microburbujas , Persona de Mediana Edad , Óxidos , Curva ROC , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
PURPOSE: Arrival time parametric imaging (At-PI) using contrast-enhanced ultrasonography (CEUS) is a procedure for evaluating liver disease progression in chronic hepatitis C infection (CHC). We investigated At-PI diagnostic efficacy in predicting development of collateral veins. METHODS: In total, 171 CHC patients underwent CEUS and upper gastrointestinal (UGI) endoscopy before liver biopsy. Conventional US was performed before CEUS to identify paraumbilical veins (PV) or splenorenal shunts (SRS). After intravenous perflubutane, contrast dynamics of liver segments 5-6 and the right kidney were saved as raw data. At-PI image ratio of red (ROR) pixels to the entire liver was analyzed. Receiver operating characteristic (ROC) curves were generated to investigate the utility of At-PI for collateral vein identification. RESULTS: Conventional US revealed PV in two patients and SRS in five patients; UGI endoscopy detected esophageal varices (EV) in eight patients. Diagnostic capability of At-PI for detecting PV, SRS, and EV was satisfactory, and high for PV and SRS [PV; area under the ROC curve (AUROC) 0.929, cutoff value 77.9%, SRS; AUROC 0.970, cutoff value 82.0%, EV; AUROC 0.883, cutoff value 66.9%]. CONCLUSIONS: Evaluation of hepatic arterialization by At-PI was useful for predicting collateral vein development in CHC patients.
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Circulación Colateral , Hepatitis C Crónica/diagnóstico por imagen , Cirrosis Hepática/diagnóstico por imagen , Hígado/irrigación sanguínea , Hígado/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Arterias/diagnóstico por imagen , Medios de Contraste , Progresión de la Enfermedad , Endoscopía Gastrointestinal , Esófago/irrigación sanguínea , Esófago/diagnóstico por imagen , Femenino , Fibrosis/diagnóstico por imagen , Fibrosis/etiología , Fibrosis/fisiopatología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/fisiopatología , Humanos , Cirrosis Hepática/etiología , Cirrosis Hepática/fisiopatología , Masculino , Persona de Mediana Edad , Pronóstico , Ultrasonografía/métodos , Venas/diagnóstico por imagen , Adulto JovenRESUMEN
Arrival time parametric imaging (At-PI) in contrast-enhanced ultrasonography is useful for assessing liver fibrosis in chronic hepatitis C (CHC) infection. The study aimed to elucidate the effect of hepatic inflammation on At-PI efficiency. Subjects were 159 CHC patients who underwent contrast-enhanced ultrasonography immediately before liver biopsy. Ultrasound contrast agent was injected, and contrast dynamics of the S5 to S6 region of the liver and right kidney were recorded for 40 seconds. The At-PI of liver parenchyma blood flow was generated using saved video clips. Hepatic blood flow during the first 5 seconds after starting contrast injection was displayed in red and that after another 5 seconds was displayed in yellow. The ratio of red (ROR) in At-PI images of the entire liver was measured with ImageJ. Ratio of red values of livers with different activity grades (0-3) were compared for each fibrosis (F) stage as determined by biopsy. Correlations of ROR with alanine aminotransferase (ALT) levels were analyzed using a linear regression line from the distribution map. Comparison of ROR for different activity grades in each F stage revealed no significant differences. Correlation coefficient R (P value) for ALT and ROR was R = -0.0094 (P = 0.43) at F0 to F1, R = -0.186 (P = 0.21) at F2, R = -0.233 (P = 0.27) at F3, and R = 0.041 (P = 0.89) at F4, with no significant correlation between ALT and ROR in any F stage. Hepatic inflammation in CHC infection does not affect At-PI diagnostic accuracy.
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Medios de Contraste , Hepatitis C Crónica/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador , Cirrosis Hepática/diagnóstico por imagen , Ultrasonografía Doppler/métodos , Adulto , Anciano , Biopsia con Aguja , Estudios de Cohortes , Progresión de la Enfermedad , Diagnóstico por Imagen de Elasticidad/métodos , Femenino , Hepatitis C Crónica/patología , Humanos , Inmunohistoquímica , Inflamación/diagnóstico por imagen , Inflamación/patología , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
AIM: Vascular endothelial growth factor (VEGF) is a primary driving force for both physiological and pathological angiogenesis and over-expression of VEGF has been detected in hepatocellular carcinoma (HCC). The aim of the present study was to clarify the usefulness of VEGF for monitoring the response to intra-arterial chemotherapy in patients with HCC. PATIENTS AND METHODS: Seventy-three patients with liver cirrhosis (LC) and advanced HCC (aHCC) received hepatic arterial infusion chemotherapy (HAIC: leucovorin (LV) at 12 mg/h, cisplatin (CDDP) at 10 mg/h and 5-fluorouracil (5-FU) at 250 mg/22 h) via the proper hepatic artery every 5 days for 4 weeks using a catheter connected to a subcutaneous drug delivery system. RESULTS: i) Serum VEGF levels were higher in patients with progressive disease than those in patients with a partial response or stable disease. ii) VEGF levels were higher in patients with alcoholic LC than those in patients with hepatitis C-related or hepatitis B-related LC. iii) VEGF levels were higher in stage IVB patients than those in patients with stage III or IVA disease. iv) VEGF levels were significantly higher in patients with giant or confluent multinodular tumors than those in patients with multiple discrete nodules. v) Serum VEGF levels were higher in patients with vascular invasion than in patients without vascular invasion. CONCLUSION: Monitoring the serum VEGF level is useful for predicting the response of aHCC to HAIC, as well as for predicting metastasis, tumor type and vascular invasion.
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Carcinoma Hepatocelular/sangre , Cirrosis Hepática/sangre , Neoplasias Hepáticas/sangre , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Anciano , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Cisplatino/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Leucovorina/administración & dosificación , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/genética , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/sangreRESUMEN
BACKGROUND: Patients with advanced hepatocellular carcinoma (aHCC) and portal vein tumor thrombus (PVTT) still have a very poor prognosis, even though the oral multikinase inhibitor sorafenib has revolutionized treatment of aHCC in patients with liver cirrhosis (LC). Standardization of multimodal therapy for aHCC with PVTT has not yet been achieved. AIM: This retrospective study was performed to clarify the usefulness of combined treatment with sorafenib and hepatic arterial infusion chemotherapy (HAIC) for patients with LC, aHCC and PVTT. PATIENTS AND METHODS: Twenty adult Japanese patients with LC underwent HAIC (HAIC group) between 2002 and 2009, while 18 patients received HAIC after treatment with sorafenib between 2009 and 2014 (SF-HAIC group). RESULTS: Among patients with Child-Pugh class A disease, the median survival time of the SF-HAIC group (315 days) was significantly longer than that of the HAIC group (197 days), while there was no significant difference between the two groups (234 and 228 days) among patients with Child-Pugh class B disease. HAIC led to a partial response (PR) in 16.7% of patients with class A disease and 21.4% of patients with class B disease. With SF-HAIC, PR was obtained in 63.8% and 42.9% of patients respectively, although the PR rate was only 9.1% and 0.0%, respectively, after treatment with sorafenib alone for four weeks. CONCLUSION: When multimodal therapy is employed for patients with LC in Child-Pugh class A disease with aHCC and PVTT, performing HAIC after four weeks of sorafenib treatment might improve both the tumor response and patient survival.
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Carcinoma Hepatocelular/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Pronóstico , Trombosis/tratamiento farmacológico , Anciano , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/patología , Femenino , Arteria Hepática , Humanos , Infusiones Intraarteriales , Cirrosis Hepática/complicaciones , Cirrosis Hepática/patología , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Vena Porta/patología , Estudios Retrospectivos , Sorafenib , Trombosis/patología , Resultado del TratamientoRESUMEN
PURPOSE: We have previously reported that continuous hepatic arterial infusion chemotherapy (HAIC) might be more effective for advanced hepatocellular carcinoma (aHCC) in patients with liver cirrhosis (LC) related to HCV infection (C-LC) or alcohol abuse (A-LC) than in patients who had LC related to HBV infection (B-LC). The aim of the present study was to retrospectively assess the efficacy of lamivudine therapy for B-LC patients with aHCC undergoing HAIC. METHODS: Seventeen adult Japanese B-LC patients with aHCC were treated by HAIC with or without lamivudine (100 mg/day) between 2002 and 2008 at our hospital. Their tumors were inoperable according to computed tomography findings. HAIC (LV at 12 mg/hr, CDDP at 10 mg/hr, and 5-FU at 250 mg/22 hr) was given via the proper hepatic artery every 5 days for 4 weeks using a catheter connected to a subcutaneously implanted drug delivery system. RESULTS: Nine of the 17 patients received lamivudine at a dose of 100 mg/day together with HAIC (LAM group), while 8 patients did not receive lamivudine and only had HAIC (non-LAM group). The response rate was 12.5 in the non-LAM group and 0.0% in the LAM group. However, the survival of the LAM group was better than that of the non-LAM group, although there was no significant difference between them. The median survival time of the LAM and non-LAM groups was 310 and 157 days, respectively. HBV-DNA levels were significantly lower after chemotherapy compared with that before chemotherapy in the LAM group. In the non-LAM group, the percentage of Th2 cells before HAIC and after HAIC was significantly higher than in the control group. However, the percentage of Th2 cells in the LAM group after HAIC was not different from that in the control group, although it was significantly higher in the LAM group than in the control group before chemotherapy. CONCLUSIONS: These results indicate that lamivudine therapy may prolong the survival of B-LC patients receiving HAIC for aHCC by reducing HBV-DNA level and inhibiting the increase of Th2 cells in host immunity.
RESUMEN
PURPOSE: Recently, the oral multikinase inhibitor sorafenib has been used to treat advanced hepatocellular carcinoma (aHCC). Tumor necrosis factor (TNF) induces apoptosis of tumor cells by binding to TNF-related apoptosis-inducing ligand, while binding of the Fas ligand on cytotoxic T lymphocytes to the Fas receptor on hepatocytes also causes apoptosis. The aim of this study was to retrospectively evaluate changes of cytokines in patients with liver cirrhosis (LC) and aHCC receiving sorafenib therapy. METHODS: Fifty-seven adult Japanese LC patients received sorafenib for aHCC (200-800 mg/day for 4 weeks) between 2009 and 2012 at our hospital. Blood samples were collected in the early morning before and after treatment, and the serum levels of soluble TNF-alpha (sTNF-alpha), soluble TNF receptor (sTNF-R), soluble Fas ligand (sFas L), and soluble Fas (sFas) were evaluated. RESULTS: Ten patients were treated with sorafenib at 200 mg/day (200 mg group), 37 patients were given 400 mg/day (400 mg group), and 10 patients received 800 mg/day (800 mg group). The serum level of sTNF-alpha was significantly increased after treatment compared with before treatment in the 400 and 800 mg groups. The serum level of sTNF-R also showed a significant increase after treatment in the 400 mg group, although there was no significant difference of sTNF-R between before and after treatment in the 200 and 800 mg groups. sFas showed a significant decrease after treatment compared with before treatment in the 400 and 800 mg groups, although the serum level of sFas L never exceeded 0.15 ng/ml. CONCLUSIONS: These findings suggest that treatment with sorafenib at doses ≥400 mg/day might promote TNF-related or Fas-related apoptosis by increasing the circulating level of TNF-alpha or decreasing that of sFas.
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Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Citocinas/sangre , Cirrosis Hepática/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Anciano , Anciano de 80 o más Años , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/patología , Femenino , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/patología , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Niacinamida/uso terapéutico , Estudios Retrospectivos , SorafenibRESUMEN
Bile duct hamartomas (BDH), which are also known as von Meyenburg complexes, are benign neoplasms that involve cystic dilatation of the bile duct surrounded by fibrous stroma. However, multiple lesions develop in most cases of BDH, whereas a solitary lesion, as seen in our case, is relatively rare. We report here the co-existence of gastric carcinoma and BDH mimicking metastasis in a 30-year-old woman. A lesion measuring 13 × 9 mm with the appearance of a hyperechoic nodule with no pulsatile blood flow signals was observed on US and Doppler US in S4 of the liver. On contrast-enhanced ultrasonography (CEUS), the septum-like structure in the tumor was weakly enhanced at 17 s after administration of Sonazoid. There has been no description of solitary BDH findings on CEUS in the literature. We present the US findings of BDH, including those yielded by CEUS using Sonazoid, along with the microscopic pathological correlation.
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BACKGROUND/AIMS: It has been reported that Th2 cytokines down-regulate antitumor immunity, while activation of Th1 cells promotes such immunity. The aim of this study was to assess changes of host immunity in relation to efficacy in patients with liver cirrhosis (LC) and advanced hepatocellular carcinoma (aHCC) treated by combined intra-arterial chemotherapy (CIAC). METHODOLOGY: Forty-three adult Japanese LC patients who had aHCC received CIAC. Blood samples were collected before and after CIAC. RESULTS: Eleven of the 43 patients showed a partial response (group PR) and 21 patients had stable disease (group SD), but 11 patients showed no response (group PD). There were no significant differences of Th1 or Th2 cells between before and after CIAC in each group. However, groups SD and PD had higher levels of Th2 cells than in group PR before and after CIAC. The percentage of regulatory T (Treg) cells in group PD was significantly increased after CIAC compared with before CIAC, whereas groups PR and SD showed significant decrease after CIAC. CONCLUSIONS: The percentage of Th2 cells is useful for predicting the response to CIAC and the percentage of Treg cells is useful for assessment of efficacy in LC patients with aHCC receiving CIAC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Cirrosis Hepática/inmunología , Neoplasias Hepáticas/tratamiento farmacológico , Linfocitos Infiltrantes de Tumor/inmunología , Anciano , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Cisplatino/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Infusiones Intraarteriales , Japón , Leucovorina/administración & dosificación , Cirrosis Hepática/diagnóstico , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Recuento de Linfocitos , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Células TH1/efectos de los fármacos , Células TH1/inmunología , Células Th2/efectos de los fármacos , Células Th2/inmunología , Resultado del TratamientoRESUMEN
It is considered difficult to make a definitive diagnosis of focal nodular hyperplasia (FNH) of <3 cm when using conventional diagnostic imaging modalities. Typical FNH imaging findings are: i) central scar formation, ii) nutrient vessels extending radially from the center and iii) the presence of Kupffer cells. In a clinical setting, identification of a spoke-wheel pattern formed by nutrient vessels extending radially is a key feature in the diagnosis of FNH. In this study, we investigated the detection rate of spoke-wheel patterns of FNH <3 cm using arrival time parametric imaging (At-PI) technology with Sonazoid-enhanced ultrasonography (US). Five patients with FNH <3 cm who had undergone Sonazoid-enhanced US at the Toho University Omori Medical Center between February 2008 and March 2009 were included in the study. The mean tumor diameter was 20.2±7.2 mm. Lesions were enhanced with 0.5 ml Sonazoid US contrast agent and a video of the procedure was saved and used for At-PI analysis of contrast agent dynamics in FNH. Three ultrasonographic specialists examined the images and made a diagnosis of FNH based on the findings of spoke-wheel patterns. Similarly, micro-flow imaging (MFI) was performed to evaluate the contrast agent dynamics in FNH. Using MFI, FNH was diagnosed in 3 of the 5 cases by the three specialists, whereas At-PI enabled the identification of spoke-wheel patterns in all 5 cases. At-PI using Sonazoid-enhanced US is superior for detecting spoke-wheel patterns of FNH <3 cm.
RESUMEN
AIM: Vascular endothelial growth factor (VEGF) is a primary driving force for both physiological and pathological angiogenesis, and its overexpression has been found in hepatocellular carcinoma (HCC). The aim of this study was to retrospectively clarify the usefulness of serum VEGF levels as a tumor marker in patients with hepatitis C virus (HCV)-related liver cirrhosis (CLC) and HCC. MATERIALS AND METHODS: The patients with CLC were divided into three groups: 28 patients without HCC (CLC group), 11 patients with HCC (HCC group), and 48 patients with advanced HCC (aHCC group). The control group consisted of 37 patients with chronic HCV. RESULTS: When the relation of serum VEGF to liver function was assessed, there was no significant difference of VEGF levels between the control group and the CLC group. When serum VEGF levels were assessed in relation to the presence of HCC, the VEGF levels of the HCC group and aHCC group were found to be significantly higher than that of the control group, while there was no significant difference between the control group and the CLC group. For the detection of cancer, serum VEGF had the largest area under the curve (AUC) and the highest accuracy when we employed the cut-off value obtained by receiver operating characteristic (ROC) analysis using the Youden index. Evaluation of various tumor markers in the aHCC group showed that the serum levels of α-fetoprotein (AFP) were higher in patients with infiltrating tumors than in patients with multiple discrete nodules or confluent multinodular tumors, while there were no significant differences in the serum levels of VEGF, Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-γ-carboxy prothrombin. There were no significant differences on the serum levels of all four markers between tumor stages, but serum VEGF was higher in patients with vascular invasion than in those without vascular invasion. CONCLUSION: The present findings suggest that the serum levels of VEGF might be a useful predictor of the presence of HCC in patients with CLC, while serum levels of AFP and VEGF can predict the tumor type and vascular invasion, respectively.
Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/diagnóstico , Hepatitis C/complicaciones , Cirrosis Hepática/diagnóstico , Neoplasias Hepáticas/diagnóstico , Factor A de Crecimiento Endotelial Vascular/sangre , Adulto , Anciano , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/patología , Femenino , Humanos , Cirrosis Hepática/sangre , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Curva ROC , alfa-Fetoproteínas/análisisRESUMEN
PURPOSE: It has been reported that Th2 cytokines downregulate antitumor immunity, while activation of type T cells promotes antitumor immunity. The aim of this paper was to evaluate host immunity in liver cirrhosis (LC) patients with advanced hepatocellular carcinoma (aHCC) receiving sorafenib therapy. METHODS: Forty-five adult Japanese LC patients received sorafenib for aHCC between 2009 and 2011 at our hospital. Sorafenib was administered at a dose of 200-800 mg/day for 4 weeks. Blood samples were collected before and after treatment. RESULTS: Eleven patients were treated with sorafenib at 200 mg/day (200 group), 27 patients received sorafenib at 400 mg/day (400 group), and 7 patients were given sorafenib at 800 mg/day (800 group). There was no significant change in the percentage of Th1 cells after treatment in any group. However, the percentages of Th2 cells and regulatory T cells were significantly decreased after treatment in the 400 group and 800 group compared with before treatment, although there was no significant change after treatment in the 200 group. CONCLUSIONS: These results indicate that treatment with sorafenib might induce Th1 dominance and prevent the escape of tumor cells from the host immune system in LC patients with aHCC.
Asunto(s)
Antineoplásicos/administración & dosificación , Bencenosulfonatos/administración & dosificación , Carcinoma Hepatocelular/tratamiento farmacológico , Cirrosis Hepática/inmunología , Neoplasias Hepáticas/tratamiento farmacológico , Piridinas/administración & dosificación , Linfocitos T Reguladores/patología , Células Th2/patología , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Bencenosulfonatos/efectos adversos , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Recuento de Células , Femenino , Humanos , Inmunidad/efectos de los fármacos , Japón , Cirrosis Hepática/complicaciones , Cirrosis Hepática/patología , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Piridinas/efectos adversos , Sorafenib , Linfocitos T Reguladores/efectos de los fármacos , Células TH1/efectos de los fármacos , Células TH1/patología , Células Th2/efectos de los fármacos , Resultado del TratamientoRESUMEN
Urolith, which consists of dirty yellow-colored attachments on the toilet bowl, is associated with a variety of odorous chemicals, including ammonia, and causes disadvantages in daily life. Although largely it is derived from microorganisms, little is known about the microbial processes underlying the formation of urolith. In order to gain insight into the types and the activities of microorganisms present in urolith, culturable bacteria were isolated, identified, and physiologically characterized. One of the isolates exhibited higher ability to produce ammonia when it was grown in artificial urine medium. Phylogenetic and physiological analyses indicated that this strain (T-02) belonged to a new group of Staphylococcus species, showing combined phenotypes as between S. lentus and S. xylosus. T-02 exhibited high urease activity and was capable of growing in the urinary condition by forming robust biofilms. The results of this study indicate that T-02 has successfully adapted itself to the environment of urolith.
Asunto(s)
Biopelículas , Staphylococcus/fisiología , Cuartos de Baño , Ureasa/fisiología , Amoníaco/metabolismo , Filogenia , Staphylococcus/enzimología , Staphylococcus/aislamiento & purificación , Orina/microbiologíaRESUMEN
Five new phenolic compounds, 4-(beta-D-glucopyranosyloxy)-3,5-dimethoxyphenyl-propanone (8), 3-[5-[(threo) 2,3-dihydro-2-(4-hydroxy-3-methoxyphenyl)-3-hydroxymethyl-7-methoxybenzofuranyl]-propanoic acid (12), 2-[4-(3-hydroxy-1-propenyl)-2,6-dimethoxyphenoxy]-3-hydroxy-3-(4-hydroxy-3,5-dimethoxyphenyl)propyl-beta-D-glucopyranoside (13), 4-[(erythro) 2,3-dihydro-3(hydroxymethyl)-5-(3-hydropropyl)-7-methoxy-2-benzofuranyl]-2,6-dimethoxyphenyl-beta-D-glucopyranoside (14), 9-O-beta-D-xylopyranoside of icariol A2 (15), and known phenolic compounds were isolated from Kokuto, non-centrifuged cane sugar (Saccharum officinarum L.). Their structures were determined by a spectral investigation.
Asunto(s)
Carbohidratos/química , Fenoles/química , Fenoles/aislamiento & purificación , Saccharum/química , Estructura Molecular , Análisis Espectral/métodosRESUMEN
Nine compounds, 3-hydroxy-4,5-dimethoxyphenyl-beta-D-glucopyranoside (1), beta-D-fructfuranosyl-alpha-D-(6-vanilloyl)-glucopyranoside (2), beta-D-fructfuranosyl-alpha-D-(6-syringyl)-glucopyranoside (3), 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxy-1-(E)-propenyl)-2-methoxyphenoxy]propyl-beta-D-glucopyranoside (4), 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxy-1-(E)-propenyl)-2,6-dimethoxyphenoxy] propyl-beta-D-glucopyranoside (5), dehydrodiconiferyl alcohol-9'-beta-D-glucopyranoside (6), 4-[ethane-2-[3-(4-hydroxy-3-methoxyphenyl)-2-propen]oxy]-2,6-dimethoxyphenyl-beta-D-glucopyranoside (7), 4-[ethane-2-[3-(4-hydroxy-3-methoxyphenyl)-2-propen]oxy]-2-methoxyphenyl-beta-D-glucopyranoside (8), and 3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-2-[4-(3-hydroxy-1-(E)-propenyl)-2,6-dimethoxyphenoxy]propyl-beta-D-glucopyranoside (9), were isolated from Kokuto non-centrifuged cane sugar. Their structures were elucidated by spectroscopic evidence, mainly based on the NMR technique. Among them, seven new glycosides were identified. The 2-deoxyribose oxidation method was used to measure their antioxidative activity. All of these compounds showed antioxidative activities.