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AIM: To establish a prognostic formula that distinguishes non-hypervascular hepatic nodules (NHNs) with higher aggressiveness from less hazardous one. METHODS: Seventy-three NHNs were detected in gadolinium ethoxybenzyl diethylene-triamine-pentaacetic-acid magnetic resonance imaging (Gd-EOB-DTPA-MRI) study and confirmed to change 2 mm or more in size and/or to gain hypervascularity. All images were interpreted independently by an experienced, board-certified abdominal radiologist and hepatologist; both knew that the patients were at risk for hepatocellular carcinoma development but were blinded to the clinical information. A formula predicting NHN destiny was developed using a generalized estimating equation model with thirteen explanatory variables: age, gender, background liver diseases, Child-Pugh class, NHN diameter, T1-weighted imaging/T2-weighted imaging detectability, fat deposition, lower signal intensity in arterial phase, lower signal intensity in equilibrium phase, α-fetoprotein, des-γ-carboxy prothrombin, α-fetoprotein-L3, and coexistence of classical hepatocellular carcinoma. The accuracy of the formula was validated in bootstrap samples that were created by resampling of 1000 iterations. RESULTS: During a median follow-up period of 504 d, 73 NHNs with a median diameter of 9 mm (interquartile range: 8-12 mm) grew or shrank by 68.5% (fifty nodules) or 20.5% (fifteen nodules), respectively, whereas hypervascularity developed in 38.4% (twenty eight nodules). In the fifteen shrank nodules, twelve nodules disappeared, while 11.0% (eight nodules) were stable in size but acquired vascularity. A generalized estimating equation analysis selected five explanatories from the thirteen variables as significant factors to predict NHN progression. The estimated regression coefficients were 0.36 for age, 6.51 for lower signal intensity in arterial phase, 8.70 or 6.03 for positivity of hepatitis B virus or hepatitis C virus, 9.37 for des-γ-carboxy prothrombin, and -4.05 for fat deposition. A formula incorporating the five coefficients revealed sensitivity, specificity, and accuracy of 88.0%, 86.7%, and 87.7% in the formulating cohort, whereas these of 87.2% ± 5.7%, 83.8% ± 13.6%, and 87.3% ± 4.5% in the bootstrap samples. CONCLUSION: These data suggest that the formula helps Gd-EOB-DTPA-MRI detect a trend toward hepatocyte transformation by predicting NHN destiny.
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Carcinoma Hepatocelular/patologia , Transformação Celular Neoplásica/patologia , Meios de Contraste , Detecção Precoce de Câncer/métodos , Gadolínio DTPA , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética/métodos , Idoso , Distribuição de Qui-Quadrado , Técnicas de Apoio para a Decisão , Diagnóstico Diferencial , Progressão da Doença , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Carga TumoralRESUMO
Hepatic lymphoma is a rare disease with poor prognosis because of delayed diagnosis. The disease comprises primary, metastatic, and intravascular hepatic lymphomas. The pathological characteristics of lymphomas differ contributing to difficulty in early diagnosis. Early diagnosis and appropriate treatment result in improved prognosis; therefore, diagnostic radiology and its development with various contrast agents are critical for improving disease outcomes. Herein, we review hepatic lymphomas and summarize the results of imaging studies in correlation with pathological characteristics. The information provided will help physicians in early diagnosis and thereby improving prognosis.
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Diagnóstico por Imagem/métodos , Neoplasias Hepáticas/diagnóstico , Linfoma/diagnóstico , Humanos , Neoplasias Hepáticas/classificação , Linfoma/classificaçãoRESUMO
Hepatic intravascular large B-cell lymphoma (IVL) is a rare disease entity that involves invasion into various organs. Due to the aggressive behavior and poor prognosis of the disease and the difficulty in making an early diagnosis, some cases are diagnosed at autopsy. Early suspicion and the use of imaging studies and liver biopsies are key for diagnosing IVL; however, no reports have described the results of imaging studies due to the limited number of cases. We herein report the results of imaging studies of hepatic IVL, including the findings PET-CT, dynamic-CT, EOB-MRI and CEUS. These results may help physicians to make an early diagnosis and improve the prognosis.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Hepáticas/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Neoplasias Vasculares/diagnóstico , Idoso , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Diagnóstico Precoce , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Prednisolona/administração & dosagem , Prognóstico , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Neoplasias Vasculares/tratamento farmacológico , Neoplasias Vasculares/patologia , Vincristina/administração & dosagemRESUMO
PURPOSE: To evaluate the value of measuring shear wave velocity evoked by acoustic radiation force impulse (VTTQ) for the risk assessment of hepatocellular carcinoma (HCC) development in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: VTTQ was measured three times in each of the four liver segments in 163 NAFLD patients, including 14 HCC cases; the results were statistically evaluated. RESULTS: The VTTQ was 3.04 ± 0.17 m/s (median ± median absolute deviation) and 1.27 ± 0.25 m/s in patients with and without HCC, respectively, and was significantly higher in HCC cases (p < 0.001). When the patients were classified as F0-F4 based on VTTQ cutoff values, VTTQ was significantly higher in the left lobe than in the right lobe for F0 (p < 0.0001) and for F1 and F2 combined (p < 0.0001), but not significantly higher for F3 and F4 combined (p = 0.070). The robust coefficient of variation was significantly higher in the left than in the right (p = 0.018) and significantly increased as VTTQ increased (p = 0.0002). Multivariate analysis showed that total bilirubin concentration {p = 0.014, 38.9 (2.08-727) [odds ratio (95 % confidence interval)]} and VTTQ [p = 0.006, 113 (3.91-3245)] were the only independent explanatory factors for HCC presence among the seven variables identified by univariate analysis. The area under the receiver-operating characteristic curve in the differentiation of HCC from non-HCC was 0.943 for VTTQ and was comparable to that for other noninvasive markers such as Fib-4 (0.964) or higher than that in BARD (0.838). CONCLUSIONS: These results suggest that fibrosis occurs heterogeneously throughout the liver and that VTTQ measurements are useful in HCC risk evaluation in a NAFLD cohort.
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AIM: To determine whether an active intervention is beneficial for the survival of elderly patients with hepatocellular carcinoma (HCC). METHODS: The survival of 740 patients who received various treatments for HCC between 1983 and 2011 was compared among different age groups using Cox regression analysis. Therapeutic options were principally selected according to the clinical practice guidelines for HCC from the Japanese Society of Hepatology. The treatment most likely to achieve regional control capability was chosen, as far as possible, in the following order: resection, radiofrequency ablation, percutaneous ethanol injection, transcatheter arterial chemoembolization, transarterial oily chemoembolization, hepatic arterial infusion chemotherapy, systemic chemotherapy including molecular targeting, or best supportive care. Each treatment was used alone, or in combination, with a clinical goal of striking the best balance between functional hepatic reserve and the volume of the targeted area, irrespective of their age. The percent survival to life expectancy was calculated based on a Japanese national population survey. RESULTS: The median ages of the subjects during each 5-year period from 1986 were 61, 64, 67, 68 and 71 years and increased significantly with time (P < 0.0001). The Child-Pugh score was comparable among younger (59 years of age or younger), middle-aged (60-79 years of age), and older (80 years of age or older) groups (P = 0.34), whereas the tumor-node-metastasis stage tended to be more advanced in the younger group (P = 0.060). Advanced disease was significantly more frequent in the younger group compared with the middle-aged group (P = 0.010), whereas there was no difference between the middle-aged and elderly groups (P = 0.75). The median survival times were 2593, 2011, 1643, 1278 and 1195 d for 49 years of age or younger, 50-59 years of age, 60-69 years of age, 70-79 years of age, or 80 years of age or older age groups, respectively, whereas the median percent survival to life expectancy were 13.9%, 21.9%, 24.7%, 25.7% and 37.6% for each group, respectively. The impact of age on actual survival time was significant (P = 0.020) with a hazard ratio of 1.021, suggesting that a 10-year-older patient has a 1.23-fold higher risk for death, and the overall survival was the worst in the oldest group. On the other hand, when the survival benefit was evaluated on the basis of percent survival to life expectancy, age was again found to be a significant explanatory factor (P = 0.022); however, the oldest group showed the best survival among the five different age groups. The youngest group revealed the worst outcomes in this analysis, and the hazard ratio of the oldest against the youngest was 0.35 for death. The survival trends did not differ substantially between the survival time and percent survival to life expectancy, when survival was compared overall or among various therapeutic interventions. CONCLUSION: These results suggest that a therapeutic approach for HCC should not be restricted due to patient age.
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Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Gerenciamento Clínico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Ablação por Cateter , Quimioembolização Terapêutica , Terapia Combinada , Tratamento Farmacológico , Feminino , Hepatectomia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Hepatic angiomyolipoma (AML) is notoriously difficult to diagnose without an invasive surgery even with the recent development of the various imaging modalities. Additionally, recent reports showed its malignant behavior after the surgery; it is important to diagnose the character of each tumor including the possible malignant potential and determine the postoperative management for each case. For this purpose, we have reviewed reports and focused on the immunohistochemical staining with p53 and ki67 of the tumors showing the representative case of 60-year-old female. The imaging study of her tumor showed the character similar to the hepatocellular carcinoma, and she underwent the hepatectomy. The resected tumor stained positive for HMB-45 that is a marker of the AML, and 30-50% of the tumor cells were positively stained with Ki67 that is a mitotic marker. Also, the atypical epithelioid cells displayed p53 immunoreactivity. These results suggest the malignant potential of our tumor based on the previous reports; therefore the careful followup for this case is necessary for a long period whether it shows metastasis, sizing up, and so forth.
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Patent ductus venosus (PDV) is a rare condition of a congenital portosystemic shunt from the umbilical vein to the inferior vena cava. This report presents the case of an adult patient with PDV, who was successfully treated with laparoscopic shunt division. A 69-year-old male was referred with hepatic encephalopathy. Contrast-enhanced CT revealed a large connection between the left portal vein and the inferior vena cava, which was diagnosed as PDV. The safety of a shunt disconnection was confirmed using a temporary balloon occlusion test for the shunt, and the shunt division was performed laparoscopically. The shunt was carefully separated from the liver parenchyma with relative ease, and then divided using a vascular stapler. Portal flow was markedly increased after the operation, and the liver function of the patient improved over the 3-month period after surgery. Although careful interventional evaluation for portal flow is absolutely imperative prior to surgery, a minimally invasive laparoscopic approach can be safely used for treating PDV.
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Laparoscopia , Malformações Vasculares/cirurgia , Idoso , Humanos , Masculino , Veia Porta/anormalidades , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgia , Tomografia Computadorizada por Raios X , Malformações Vasculares/diagnóstico por imagemRESUMO
BACKGROUND: There is no standard therapeutic procedure for the hepatocellular carcinoma (HCC) in patients with poor hepatic reserve function. With the approval of newly developed chemotherapeutic agent of miriplatin, we have firstly conducted the phase I study of CDDP powder (DDP-H) and miriplatin combination therapy and reported its safety and efficacy for treating unresectable HCC in such cases. To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) for the combination of transarterial oily chemoembolization (TOCE) and transarterial chemotherapy (TAC) using miriplatin and DDP-H for treating unresectable hepatocellular carcinoma (HCC). METHODS: Transarterial chemotherapy using DDP-H was performed through the proper hepatic artery targeting the HCC nodules by increasing the dose of DDP-H (35-65 mg/m(2)) followed by targeting the HCC nodules by transarterial oily chemoembolization with miriplatin. RESULTS: A total of nine patients were enrolled in this study and no DLT was observed with any dose of DDP-H in all cases in whom 80 mg (median, 18-120) miriplatin was administered. An anti-tumour efficacy rating for partial response was obtained in one patient, while a total of four patients (among eight evaluated) showed stable disease response, leading to 62.5% of disease control rate. The pharmacokinetic results showed no further increase in plasma platinum concentration following miriplatin administration. CONCLUSION: Our results suggest that a combination of DDP-H and miriplatin can be safely administered up to their respective MTD for treating HCC. TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR000003541).
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Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Cisplatino/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Compostos Organoplatínicos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Cisplatino/farmacocinética , Feminino , Artéria Hepática , Humanos , Injeções Intra-Arteriais , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Compostos Organoplatínicos/farmacocinética , PósRESUMO
We report a case of primary malignant mesothelioma of the appendix. A 35-year-old man without any history of asbestos exposure was admitted to our hospital for further examination following the discovery of multiple liver tumors, an ileocecal tumor, and abdominal lymph node swelling. An ultrasound-guided liver tumor biopsy revealed malignant mesothelioma. Despite receiving systemic chemotherapy, he died 3 months after the initial diagnosis. At autopsy, a diagnosis of multiple organ metastases from a malignant biphasic mesothelioma of the appendix was made. To our knowledge, this is only the second reported case of primary malignant mesothelioma of the appendix.
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Neoplasias do Apêndice/diagnóstico , Mesotelioma/diagnóstico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Apêndice/tratamento farmacológico , Evolução Fatal , Humanos , Masculino , Mesotelioma/tratamento farmacológicoRESUMO
Erythropoietin (EPO) has long been utilized for the treatment of renal anemia. The erythropoietin receptor (EPOR) is also expressed in the cardiovascular and central nervous systems in addition to an erythroid lineage, to provide an organoprotective role against several types of cellular stress. Pulmonary hypertension (PH) is a poor prognostic disease caused by primary and secondary pulmonary vascular injury. We observed the effects of EPO derivatives on monocrotaline-induced PH in rats on the supposition that EPO may protect small arteries from injury. Asialoerythropoietin (AEPO) lacks sialic acids in the termini of carbohydrate chains that results in rapid clearance from blood. Carbamyl-erythropoietin (CEPO) interacts with EPOR/ßc heterodimers, but not with EPOR homodimers expressed in erythroid cells. Monocrotaline-injected rats were treated with continuous intravenous injection of 2500 ng/kg/day of EPO, AEPO, or CEPO for 21 days, and lung histology, cardiac function, and mRNA expression in the lungs were examined. Wall thickening of small arteries in the lungs and PH were improved by administration of EPO, but not by its non-hematopoietic derivatives, AEPO, or CEPO. Erythropoietin administration increased mRNA expression of the anti-apoptotic molecule, Bcl-xL, and maintained expression of the CD31 antigen. We conclude that lungs may express EPOR homoreceptors, but not heteroreceptors. Adequate serum erythropoietin levels may be essential for pulmonary protective effects.
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Assialoglicoproteínas , Eritropoetina/análogos & derivados , Eritropoetina/farmacologia , Hipertensão Pulmonar/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Animais , Assialoglicoproteínas/farmacologia , Modelos Animais de Doenças , Masculino , Monocrotalina , RNA Mensageiro/efeitos dos fármacos , Ratos , Ratos Wistar , Receptores da Eritropoetina/efeitos dos fármacos , Resultado do TratamentoRESUMO
A 22-year-old Japanese woman was found to have severe esophageal varices and then suffered from hepatic encephalopathy. She was diagnosed with Budd-Chiari syndrome (BCS) due to hepatic vein (HV) thrombosis accompanied by portal vein thrombosis without inferior vena cava (IVC) obstruction. Latent myeloproliferative neoplasm (MPN) lacking the JAK2-V617F mutation was considered to be the underlying disease. Liver transplantation was strikingly effective for treating the clinical symptoms attributable to portal hypertension. Although thrombosis of the internal jugular vein occurred due to thrombocythemia, which manifested after transplantation despite anticoagulation therapy with warfarin, the thrombus immediately disappeared with the addition of aspirin. Neither thrombosis nor BCS has recurred in more than 4 years since the amelioration of the last thrombotic event, and post-transplant immunosuppression with tacrolimus has not accelerated the progression of MPN. In Japan, IVC obstruction, which was a predominant type of BCS, is suggested to have decreased in incidence with recent improvements in hygiene. The precise diagnosis of BCS and causative underlying diseases should be made with attention to the current trend of the disease spectrum, which fluctuates with environmental sanitation levels. Because the stepwise strategy, including liver transplantation, has been proven effective for patients with pure HV obstruction in Western countries, this strategy should also be validated for utilization in Japan and in developing countries where HV obstruction potentially predominates.
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Angiomyolipoma (AML) is a benign mesenchymal tumor that is frequently found in the kidney and, rarely, in the liver. The natural history of hepatic AML has not been clarified, and, because of the similar patterns in imaging studies, such as ultrasonography, computed tomography, and magnetic resonance imaging, some of these tumors have been overdiagnosed as hepatocellular carcinoma in the past. With an increase in the number of case reports showing detailed imaging studies and immunohistochemical staining of the tumor with human melanoma black-45, the diagnostic accuracy is also increasing. In this paper, we focused on the role of noninvasive imaging studies and histological diagnosis showing distinctive characteristics of this tumor. In addition, because several reports have described tumor progression in terms of size, recurrence after surgical resection, metastasis to other organs, and portal thrombosis, we summarized these cases for the management and discussed the indications for the surgical treatment of this tumor.
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BACKGROUND & AIMS: The activating receptor natural killer group 2, member D (NKG2D) and its ligands play a crucial role in immune response to tumors. NKG2D ligand expression in tumors has been shown to be associated with tumor eradication and superior patient survival, but the involvement of NKG2D ligands in the immune response against hepatocellular carcinoma (HCC) still remains to be elucidated. METHODS: We investigated the expression of NKG2D ligands in HCC tissues collected from 54 patients and HCC cell lines. We also examined the proteasome expression and the effect of inhibition of proteasome activity on NKG2D ligand expression in HCC tissues and cell lines. RESULTS: In dysplastic nodules (DN), well-differentiated (well-HCC), and moderately-differentiated HCCs (mod-HCC), UL16-binding protein (ULBP) 1 was expressed predominantly in tumor cells, but not in poorly-differentiated HCCs (poor-HCC). Remarkably, recurrence-free survival of patients with ULBP1-negative HCC was significantly shorter than that of patients with ULBP1-positive HCC (p=0.006). Cox regression analysis revealed that loss of ULBP1 expression was an independent predictor of early recurrence (p=0.008). We confirmed that ULBP1 was expressed in the well- and mod-HCC cell lines, but not in the poor-HCC cell line KYN-2. However, inhibition of proteasome activity resulted in significant up-regulation of ULBP1 expression in KYN-2. Moreover, we found that 20S proteasome expression was more abundant in KYN-2 than that in the well- and mod-HCC cell lines. CONCLUSIONS: ULBP1 is prevalently expressed in DN to mod-HCC, but loss of its expression correlates with tumor progression and early recurrence.
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Carcinoma Hepatocelular/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Hepáticas/imunologia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Idoso , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Diferenciação Celular , Linhagem Celular Tumoral , Inibidores de Cisteína Proteinase/farmacologia , Intervalo Livre de Doença , Feminino , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Células Matadoras Naturais/imunologia , Leupeptinas/farmacologia , Ligantes , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Complexo de Endopeptidases do Proteassoma/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismoRESUMO
We analyzed hepatocellular carcinoma (HCC) with progenitor cell features using hepatic stem/progenitor cell marker neural cell adhesion molecule (NCAM). Approximately 8.3% of the operated HCC cases expressed NCAM, and 22.3% of the HCC patients had soluble NCAM levels >1000ng/ml (the "highly soluble" NCAM group). Soluble NCAM status was a significant independent factor predictive of long-term survival in patients with HCC, and high levels of soluble NCAM were significantly related to intrahepatic metastasis. The 140-kDa NCAM isoform was specifically detected in the "highly soluble" NCAM group of HCC patients andits related signals are potential drug targets for NCAM+ HCC.
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Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Moléculas de Adesão de Célula Nervosa/biossíntese , Idoso , Biomarcadores Tumorais/biossíntese , Carcinoma Hepatocelular/metabolismo , Feminino , Humanos , Fígado/patologia , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Moléculas de Adesão de Célula Nervosa/sangue , Valor Preditivo dos Testes , Prognóstico , Isoformas de Proteínas/metabolismo , Células-Tronco/metabolismo , Células-Tronco/patologiaRESUMO
UNLABELLED: Hepatocellular carcinoma (HCC) is characterized by frequent recurrence, even after curative treatment. Vitamin K2, which has been reported to reduce HCC development, may be effective in preventing HCC recurrence. Patients who underwent curative ablation or resection of HCC were randomly assigned to receive placebo, 45 mg/day, or 90 mg/day vitamin K2 in double-blind fashion. HCC recurrence was surveyed every 12 weeks with dynamic computed tomography/magnetic resonance imaging, with HCC-specific tumor markers monitored every 4 weeks. The primary aim was to confirm the superiority of active drug to placebo concerning disease-free survival (DFS), and the secondary aim was to evaluate dose-response relationship. Disease occurrence and death from any cause were treated as events. Hazard ratios (HRs) for disease occurrence and death were calculated using a Cox proportional hazards model. Enrollment was commenced in March 2004. DFS was assessed in 548 patients, including 181 in the placebo group, 182 in the 45-mg/day group, and 185 in the 90-mg/day group. Disease occurrence or death was diagnosed in 58, 52, and 76 patients in the respective groups. The second interim analysis indicated that vitamin K2 did not prevent disease occurrence or death, with an HR of 1.150 (95% confidence interval: 0.843-1.570, one-sided; P=0.811) between the placebo and combined active-drug groups, and the study was discontinued in March 2007. CONCLUSION: Efficacy of vitamin K2 in suppressing HCC recurrence was not confirmed in this double-blind, randomized, placebo-controlled study.
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Carcinoma Hepatocelular/prevenção & controle , Neoplasias Hepáticas/prevenção & controle , Recidiva Local de Neoplasia/prevenção & controle , Vitamina K 2/uso terapêutico , Vitaminas/uso terapêutico , Idoso , Carcinoma Hepatocelular/cirurgia , Método Duplo-Cego , Feminino , Humanos , Neoplasias Hepáticas/cirurgia , MasculinoRESUMO
We report a case of chronic hepatitis C in whom liver cirrhosis was later diagnosed following abnormality of ALT levels during pegylated interferon α2a and ribavirin treatment. A 62-year-old woman with chronic hepatitis C was treated with pegylated interferon α2a plus ribavirin for 72 weeks. Her HCV RNA became negative 16 weeks after the start of treatment and continued to be negative for most of the treatment duration. Her AST/ALT, ALP/γ-GTP levels became elevated soon after the initiation of treatment and thereafter remained unchanged. However, most of these levels normalized after the end of treatment. Post-treatment liver biopsy showed liver cirrhosis, probably due to the interferon treatment itself. This unusual therapeutic outcome should be considered if the levels of hepatic dysfunction during interferon treatment are severe.
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Doença Hepática Induzida por Substâncias e Drogas/etiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Cirrose Hepática/induzido quimicamente , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Ribavirina/administração & dosagem , Ribavirina/efeitos adversos , Quimioterapia Combinada , Feminino , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Pessoa de Meia-Idade , RNA Viral/sangue , Proteínas RecombinantesRESUMO
AIM: To reveal the manner of hepatocellular carcinoma (HCC) development in patients with nonalcoholic steatohepatitis (NASH) focusing on multicentric occurrence (MO) of HCC. METHODS: We compared clinicopathological characteristics between patients with and without MO of HCC arising from NASH background. The clinical features were implicated with reference to the literature available. RESULTS: MO of HCC was identified with histological proof in 4 out of 12 patients with NASH-related HCC (2 males and 2 females). One patient had synchronous MO; an advanced HCC, two well-differentiated HCCs and a dysplastic nodule, followed by the development of metachronous MO of HCC. The other three patients had multiple advanced HCCs accompanied by a well-differentiated HCC or a dysplastic nodule. Of these three patients, one had synchronous MO, one had metachronous MO and the other had both synchronous and metachronous MO. There were no obvious differences between the patients with or without MO in terms of liver function tests, tumor markers and anatomical extent of HCC. On the other hand, all four patients with MO of HCC were older than 70 years old and had the comorbidities of obesity, type 2 diabetes mellitus (T2DM), hypertension and cirrhosis. Although these conditions were not limited to MO of HCC, all the conditions were met in only one of eight patients without MO of HCC. Thus, concurrence of these conditions may be a predisposing situation to synchronous MO of HCC. In particular, old age, T2DM and cirrhosis were suggested to be prerequisite for MO because these factors were depicted in common among two other cases with MO of HCC under NASH in the literature. CONCLUSION: The putative predisposing factors and necessary preconditions for synchronous MO of HCC in NASH were suggested in this study. Further investigations are required to clarify the accurate prevalence and predictors of MO to establish better strategies for treatment and prevention leading to the prognostic improvement in NASH.
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Alpha-fetoprotein (AFP)-producing adenocarcinoma is known for its rapid progression and poor prognosis, and chemotherapy regimens are yet to be standardized. Here we describe the first report of AFP-producing adenocarcinoma with calcification. The metastatic route was visualized from the calcification, and combination chemotherapy was performed. A 77-year-old Japanese man was transferred to our hospital for treatment of liver tumors. Computed tomography (CT) revealed multiple liver tumors with portal vein tumor thrombosis. The tumors were highly attenuated before enhancement, suggesting various degrees of calcification. Serum levels of carcinoembryonic antigen (CEA), AFP, and the proportion of fucosylated AFP were considerably elevated. Gastroduodenoscopy revealed an elevated tumor occupying the duodenal bulb with an ulcerative lesion in the vicinity of the gastroduodenal junction, and biopsy specimens from the duodenum and liver revealed medullary adenocarcinoma with calcification. Three-dimensional reconstruction of CT images clearly showed that the calcified lesions had spread from the gastroduodenal junction to the liver via a route comprising the corresponding local vein, the superior mesenteric vein, and portal vein. The patient was accordingly diagnosed with calcified AFP-producing adenocarcinoma with multiple liver metastases. Combination chemotherapy using TS-1 and cisplatin (CDDP) resulted in a striking response for the initial 4 months in terms of tumor markers and CT findings. This is the first report of AFP-producing adenocarcinoma with calcification. A metastatic route from the primary tumor to the liver was clearly visualized by tracing the calcified lesions. Combination chemotherapy based on 5-fluorouracil and CDDP may have the potential to prolong survival.
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Recently the authors proposed a new staging and grading system for primary biliary cirrhosis (PBC) that takes into account necroinflammatory activity and histological heterogeneity. Herein is proposed a convenient version of this system. Scores for fibrosis, bile duct loss, and chronic cholestasis were combined for staging: stage 1, total score of 0; stage 2, score 1-3; stage 3, score 4-6; and stage 4, score 7-9. Cholangitis activity (CA) and hepatitis activity (HA) were graded as CA0-3, and HA0-3, respectively. Analysis of interobserver agreement was then conducted. Digital images of 62 needle liver biopsy specimens of PBC were recorded as virtual slides on DVDs that were sent to 28 pathologists, including five located overseas. All participants were able to apply this version in all 62 cases. For staging, kappa was 0.385 (fair agreement) and the concordance rate was 63.9%. For necroinflammatory activity, the kappa and concordance rate were 0.110 (slight agreement) and 36.9% for CA, and 0.197 (slight agreement) and 47% for HA, respectively. In conclusion, this new staging and grading system for PBC seems to be more convenient and practical than those used at present, but more instruction and guidance are recommended for the grading of necroinflammatory activity in practice.
Assuntos
Ductos Biliares/patologia , Colestase/patologia , Cirrose Hepática Biliar/classificação , Cirrose Hepática Biliar/patologia , Fígado/patologia , Idoso , Colestase/classificação , Progressão da Doença , Feminino , Fibrose/patologia , Hepatite C/classificação , Hepatite C/patologia , Humanos , Inflamação/classificação , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do ObservadorRESUMO
Hepatic angiomyolipoma (AML) is known as a rare benign tumor with invasive growth. In the past, some of these tumors were misdiagnosed as hepatocellular carcinomas, because of the similar pattern on imaging studies. Recently, correct diagnoses have been increasing, with the development of HMB-45 immunohistochemical staining, and it appears that the majority of these tumors behave as benign tumors. However, there are not a few cases which have resulted in fatal courses because of recurrence and metastasis of the tumor. The clinical features and signs of the malignant potential of this tumor are unknown; thus, the management and treatment of the tumor are still controversial. Here in this article, we report a case of hepatic AML which showed a size increase of 175% in 1 year, and portal vein thrombosis detected by angiography. During a follow up of 3 years after a curative hepatic lobectomy, no metastasis or recurrence was seen. Review of the literature suggests that portal vein thrombosis could be one of the markers of the malignant potential and transformation of this tumor. Therefore, in this paper, we recommend surgical treatment of hepatic AML in which there is a strong suspicion of portal vein thrombosis.