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Background: To examine the incidence of cirrhosis patients with high-risk esophageal varices (EV) who show hepatic venous pressure gradient (HVPG) < 10 mmHg and to identify their hemodynamic features. Methods: This prospective study consisted of 110 cirrhosis patients with EV, all with the candidate for primary or secondary prophylaxis. Sixty-one patients had red sign, and 49 patients were bleeders. All patients underwent both Doppler ultrasound and HVPG measurement. Results: There were 18 patients (16.4%) with HVPG < 10 mmHg. The presence of venous-venous communication (VVC) was more frequent in patients with HVPG < 10 mmHg (10/18) than in those with HVPG ≥ 10 mmHg (19/92; p = 0.0021). The flow volume in the left gastric vein (LGV) and the incidence of red sign were higher in the former (251.9 ± 150.6 mL/min; 16/18) than in the latter (181 ± 100.5 mL/min, p = 0.02; 45/92; p = 0.0018). The patients with red sign had lower HVPG (13.3 ± 4.5) but advanced LGV hemodynamics (velocity 13.2 ± 3.8 cm/s; flow volume 217.5 ± 126.6 mL/min), whereas those without red sign had higher HVPG (16.2 ± 4.6, p = 0.001) but poorer LGV hemodynamics (10.9 ± 2.3, p = 0.002; 160.1 ± 83.1, p = 0.02). Conclusion: Patients with high-risk EV with HVPG < 10 mmHg showed 16.4% incidence. Although low HVPG may be underestimated by the presence of VVC, the increased LGV hemodynamics compensates for the severity of portal hypertension, which may contribute to the development of red sign.
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Várices Esofágicas y Gástricas/fisiopatología , Fibrosis/fisiopatología , Venas Hepáticas/fisiopatología , Hígado/irrigación sanguínea , Adulto , Anciano , Anciano de 80 o más Años , Cateterismo/métodos , Endoscopía/métodos , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/diagnóstico por imagen , Femenino , Fibrosis/complicaciones , Fibrosis/diagnóstico por imagen , Hemodinámica , Venas Hepáticas/diagnóstico por imagen , Humanos , Hígado/diagnóstico por imagen , Hígado/fisiopatología , Masculino , Persona de Mediana Edad , Presión Portal/fisiología , Estómago/irrigación sanguínea , Estómago/diagnóstico por imagen , Estómago/fisiopatología , Ultrasonografía , Presión VenosaRESUMEN
BACKGROUND: Sorafenib, an oral multikinase inhibitor, was approved for the treatment of advanced hepatocellular carcinoma (HCC), but has not been adequately evaluated for safety and effectiveness in Japanese patients with advanced HCC. AIMS: The purpose of this study was to prospectively assess the efficacy, safety, and risk factors for survival in patients with advanced HCC treated with sorafenib. METHODS: Between May 2009 and December 2010, 96 Japanese patients with advanced HCC (76 male, 20 female, mean age: 70.4 years) were treated with sorafenib. Eighty-eight patients had Child-Pugh class A, and 8 patients had Child-Pugh class B liver cirrhosis. Barcelona Clinic Liver Cancer stage B and C were found in 64 and 32 patients, respectively. RESULTS: Twelve patients demonstrated partial response to sorafenib therapy, 43 patients had stable disease, and 33 patients had progressive disease at the first radiologic assessment. The most frequent adverse events leading to discontinuation of sorafenib treatment were liver dysfunction (n = 8), hand-foot skin reaction (n = 7), and diarrhea (n = 4). The median survival time and time to progression were 11.6 and 3.2 months, respectively. By multivariate analysis, des-γ-carboxy prothrombin serum levels and duration of treatment were identified as independent risk factors for survival. CONCLUSIONS: This study showed that sorafenib was safe and useful in Japanese patients with advanced HCC. In addition, this study demonstrated that sorafenib should be administered as a long-term treatment for advanced HCC regardless of therapeutic effect and dosage.
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Bencenosulfonatos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Piridinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/secundario , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Seguridad , Sorafenib , Tasa de Supervivencia , Quinasas raf/antagonistas & inhibidoresRESUMEN
Percutaneous ablation under imaging guidance is a curative treatment that can induce complete tumor necrosis with advantages of minimal invasiveness and a low risk of complications. Thermal ablation, which includes radiofrequency ablation and microwave ablation, is a representative technique that has sufficient antitumor effects in cases of hepatocellular carcinoma with ≤3 lesions measuring ≤3 cm and preserved liver function. The short- and long-term outcomes of patients are comparable with those achieved with surgical resection. Despite their nonmalignant nature, some benign liver tumors require treatment for symptoms caused by the presence of the tumor and/or continuous enlargement. Ablation may be the treatment of choice because it has lower burden on patients than surgical treatment. This review describes the recent concepts, progress, and limitations of ablation-based treatment for benign liver tumors.
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Portal hypertension is a major pathophysiological condition in patients with cirrhosis. This accounts for the occurrence and severity of the various manifestations. The degree is determined by the portal pressure or hepatic venous pressure gradients, both of which are obtained by invasive interventional radiological procedures. Ultrasound (US) is a simple and minimally invasive imaging modality for the diagnosis of liver diseases. Owing to the availability of microbubble-based contrast agents and the development of imaging modes corresponding to contrast effects, contrast-enhanced US (CEUS) has become popular worldwide for the detailed evaluation of hepatic hemodynamics, diffuse liver disease, and focal hepatic lesions. Recent advancements in digital technology have enabled contrast-based demonstrations with improved resolution, leading to a wider range of applications. This review article describes the current role, benefits, and limitations of CEUS in the management of portal hypertension.
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BACKGROUND: Invasion beyond inferior vena cava (IVC) to right atrium (RA) is a rare complication in patients with advanced hepatocellular carcinoma (HCC), and results in fatal oncologic emergencies, including pulmonary embolism and right heart failure. AIM: As there is no gold standard treatment for unresectable HCC with tumor thrombi involving IVC and RA, we considered it valuable to assess safety and efficacy of a combination of hepatic arterial infusion chemoembolization (HAIC) therapy and external-beam radiation therapy (EBRT). METHODS AND RESULTS: The "New FP" was chosen as the HAIC therapy, in which the enhanced permeation and retention effect was achieved using a cisplatin-Lipiodol suspension combined with continuous infusion of 5-fluorouracil (5-FU). Sixteen patients with HCC with tumor thrombi in IVC, RA, and pulmonary arteries were enrolled. modified response evaluation criteria in solid tumors-based evaluation of response to the combination treatment was as follows: complete response, 6.2% (1 patient); partial response, 81.3% (13 patients); stable disease, 12.5% (2 patients); progressive disease, 0%. The median overall survival time (MST) was 19.0 months. Notably, MST of patients receiving sequential sorafenib monotherapy (39.0 months) was significantly longer than that of the rest (15.3 months). CONCLUSION: The combination of New FP and EBRT is an efficacious treatment option for unresectable HCC involving IVC and RA, complicated with pulmonary embolism. Sequential administration of molecular-targeted drugs may prolong survival in such patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Embolia Pulmonar , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/terapia , Fluorouracilo , Atrios Cardíacos/patología , Humanos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/terapia , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/etiología , Embolia Pulmonar/terapia , Vena Cava Inferior/patologíaRESUMEN
Background: Systemic treatments are recommended for advanced hepatocellular carcinoma (HCC) in preserved liver function. However, their effects are unsatisfactory in some tumor conditions, particularly macrovascular invasion (MVI) including major portal vein tumor thrombus (PVTT). We compared the efficacy of hepatic arterial infusion chemotherapy (HAIC) regimens New-FP and sorafenib for various tumor conditions in preserved liver function. Methods: We retrospectively collected the data of 1709 patients with HCC who were treated with New-FP or sorafenib. Survival was assessed after propensity score matching. Subgroup analyses were conducted: cohort 1 (no MVI or extrahepatic spread (EHS)), cohort 2 (MVI only), cohort 3 (EHS only), cohort 4 (MVI and EHS), and cohort 5 (major PVTT). Results: The New-FP group had a longer median survival time (MST) than the sorafenib in the whole analysis (18 vs. 9 months; p < 0.0001). New-FP demonstrated a longer MST compared with sorafenib in cohort 2 and cohort 4. In cohort 5, the MST of the New-FP group was 16 months, while that of sorafenib was 6 months (p < 0.0001). For major PVTT-HCC, the response rate of New-FP was 73.0%. The MST of patients who achieved complete response with New-FP was 59 months. Conclusions: HAIC using New-FP is promising for patients with MVI- and major PVTT-HCC in preserved liver function.
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Hepatocellular carcinoma (HCC) is a common cancer worldwide. Recent international guidelines request an identification of the stage and patient background/condition for an appropriate decision for the management direction. Radiomics is a technology based on the quantitative extraction of image characteristics from radiological imaging modalities. Artificial intelligence (AI) algorithms are the principal axis of the radiomics procedure and may provide various results from large data sets beyond conventional techniques. This review article focused on the application of the radiomics-related diagnosis of HCC using radiological imaging (computed tomography, magnetic resonance imaging, and ultrasound (B-mode, contrast-enhanced ultrasound, and elastography)), and discussed the current role, limitation and future of ultrasound. Although the evidence has shown the positive effect of AI-based ultrasound in the prediction of tumor characteristics and malignant potential, posttreatment response and prognosis, there are still a number of issues in the practical management of patients with HCC. It is highly expected that the wide range of applications of AI for ultrasound will support the further improvement of the diagnostic ability of HCC and provide a great benefit to the patients.
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BACKROUND: Not all patients with hepatocellular carcinoma (HCC) benefit from treatment with molecular targeted agents such as sorafenib. We investigated whether New-FP (fine-powder cisplatin and 5-fluorouracil), a hepatic arterial infusion chemotherapy regimen, is more favorable than sorafenib as an initial treatment for locally progressed HCC. METHODS: To avoid selection bias, we corrected the data from different facilities that did or did not perform New-FP therapy. In total, 1709 consecutive patients with HCC initially treated with New-FP or sorafenib; 1624 (New-FP, n = 644; sorafenib n = 980) were assessed. After propensity score matching (PSM), overall survival (OS) and prognostic factors were assessed (n = 344 each). Additionally, the patients were categorized into four groups: cohort-1 [(without macrovascular invasion (MVI) and extrahepatic spread (EHS)], cohort-2 (with MVI), cohort-3 (with EHS), and cohort-4 (with MVI and EHS) to clarify the efficacy of each treatment. RESULTS: New-FP prolonged OS than sorafenib after PSM (New-FP, 12 months; sorafenib, 7.9 months; p < 0.001). Sorafenib treatment, and severe MVI and EHS were poor prognostic factors. In the subgroup analyses, the OS was significantly longer the New-FP group in cohort-2. CONCLUSIONS: Local treatment using New-FP is a potentially superior initial treatment compared with sorafenib as a multidisciplinary treatment in locally progressed HCC without EHS.
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BACKGROUND: COVID-19 has been giving the devastating impact on the current medical care system. There are quite many guidelines on COVID-19, but only a few on the management of hepatocellular carcinoma (HCC) during COVID-19 pandemic. AIMS: We develop these recommendations to preserve adequate clinical practice for the management of HCC. METHODS: Experts of HCC in the Asia-Pacific region exchanged opinions via webinar, and these recommendations were formed. RESULTS: Close contact should be minimized to reduce possible exposure of both medical staff and patients to the novel coronavirus. To prevent transmission of the virus, meticulous hygiene measures are important. With the decrease in regular medical service, the medical staff may be mobilized to provide COVID-19-related patient care. However, diagnosis and treatment of HCC should not be delayed because of COVID-19 pandemic. The management of HCC should be the same as in non-pandemic circumstances. HCC is highly malignant, thus it is recommended not to delay curative treatment such as surgery and ablation. However, a kind of triage is necessary even among patients with HCC when resources are insufficient for all to be treated. Curative treatments should be periodized and cytoreductive or non-curative treatment such as vascular interventions and systemic therapy may be postponed until it can be performed safely with sufficient resources. For patients with confirmed or suspected to be infected with the novel coronavirus, diagnosis and treatment should be postponed until the virus is eliminated or they are confirmed as not being infected with it. CONCLUSIONS: These are collection of measures implemented by front-line medical professionals. We would evolve these recommendations over time as more real-world data becomes available.
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COVID-19 , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , COVID-19/complicaciones , Carcinoma Hepatocelular/complicaciones , Humanos , Neoplasias Hepáticas/complicacionesRESUMEN
INTRODUCTION: Radiofrequency ablation (RFA) has been accepted as safe and effective for treating early-stage hepatocellular carcinoma (HCC). However, it often causes severe pain. Therefore, in this study, we performed RFA under deep sedation and investigated its efficacy and safety. METHODS: We conducted a retrospective study including 511 HCC patients who received approximately 886 RFA treatments between December 2014 and November 2016 at our institution. Respiratory depression was defined as oxygen saturation of below 90%; and severe body movement was defined as movement caused by pain, which was managed by lowering the power of the generator. Factors associated with respiratory depression and severe body movement were examined via univariate and multivariate regression analyses. RESULTS: Respiratory depression occurred in 15.3% of the patients and severe body movement in 26.5% of the patients. In the multivariate analysis, BMI (≥ 25 kg/m2, odds ratio [OR] = 1.75, P = 0.035) and longer ablation (≥ 10 min, OR = 2.59, P = 0.002) were significant respiratory depression-related factors. Male sex (OR = 2.02, P = 0.005), Child-Pugh class A (odds ratio = 1.96, P = 0.018), and longer ablation (≥ 10 min, OR = 3.03, P < 0.001) were significant factors related to severe body movement. CONCLUSION: Deep sedation for RFA can be performed safely and effectively. Higher BMI and longer ablation were risk factors for respiratory depression and male sex, Child-Pugh class A, and longer ablation were independent predictors of severe body movement during RFA under deep sedation.
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Carcinoma Hepatocelular/cirugía , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , Sedación Profunda/métodos , Neoplasias Hepáticas/cirugía , Dolor Asociado a Procedimientos Médicos/terapia , Adulto , Anciano , Carcinoma Hepatocelular/terapia , Femenino , Humanos , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
We herein report the first case of immune-mediated drug-induced liver injury that may have been caused by laninamivir. A 15-year-old girl was diagnosed with influenza and prescribed 40 mg laninamivir. Six weeks later, she was admitted to our hospital because of jaundice and fatigue. Laboratory examinations revealed elevated levels of hepatobiliary enzymes, and acute liver injury was suspected. Laboratory examinations and histological findings were characteristic of autoimmune hepatitis. Steroid treatment was ineffective, and azathioprine was added to the treatment. Twenty-two months after the onset, a second biopsy revealed the absence of inflammatory infiltrations, and the drugs were withdrawn. Liver function tests remained normal nine months after withdrawal.
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Antivirales/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Gripe Humana/tratamiento farmacológico , Zanamivir/análogos & derivados , Adolescente , Azatioprina/uso terapéutico , Femenino , Guanidinas , Hepatitis Autoinmune/tratamiento farmacológico , Hepatitis Autoinmune/etiología , Humanos , Inmunosupresores/uso terapéutico , Virus de la Influenza A , Ictericia/inducido químicamente , Piranos , Ácidos Siálicos , Zanamivir/efectos adversosRESUMEN
Image-guided percutaneous ablation is considered best in the treatment of early-stage hepatocellular carcinoma (HCC). Ablation is potentially curative, minimally invasive, and easily repeatable for recurrence. Ethanol injection used to be the standard in ablation. However, radiofrequency ablation has recently been the most prevailing ablation method for HCC. Many investigators have reported that radiofrequency ablation is superior to ethanol injection, from the viewpoints of treatment response, local tumor curativity, and overall survival. New-generation microwave ablation can create a larger ablation volume in a shorter time period. Further comparison studies are, however, mandatory between radiofrequency ablation and microwave ablation, especially in terms of complications and long-term survival. Irreversible electroporation, which is a non-thermal ablation method that delivers short electric pulses to induce cell death due to apoptosis, requires further studies, especially in terms of long-term outcomes. It is considerably difficult to compare outcomes in ablation with those in surgical resection. However, radiofrequency ablation seems to be a satisfactory alternative to resection for HCC 3 cm or smaller in Child-Pugh class A or B cirrhosis. Furthermore, radiofrequency ablation may be a first-line treatment in HCC 2 cm or smaller in Child-Pugh class A or B cirrhosis. Various innovations would further improve outcomes in ablation. Training programs may be effective in providing an excellent opportunity to understand basic concepts and learn cardinal skills for successful ablation. Sophisticated ablation would be more than an adequate alternative of surgery for small- and possibly middle-sized HCC.
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Técnicas de Ablación/métodos , Carcinoma Hepatocelular/cirugía , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Cirugía Asistida por Computador/métodos , Técnicas de Ablación/efectos adversos , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , Criocirugía/efectos adversos , Criocirugía/métodos , Femenino , Ultrasonido Enfocado de Alta Intensidad de Ablación/efectos adversos , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Cirugía Asistida por Computador/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: This prospective study investigated the superiority of transarterial chemoembolization (TACE) with miriplatin over TACE with epirubicin regarding overall survival (OS) in patients with unresectable hepatocellular carcinoma (HCC). METHODS: Patients with unresectable HCC were randomized 1:1 to receive TACE with miriplatin or epirubicin in lipiodol. The primary endpoint was OS; secondary endpoints were percentages of patients who achieved treatment effect (TE) 4 (100% necrotizing effect or tumor reduction), duration of time to TACE failure, and adverse events (AEs). OS was compared using a stratified log-rank test adjusted for clinical stage, Child-Pugh class, and institution. RESULTS: Of 257 patients enrolled from August 2008 to August 2010, 247 were analyzed for efficacy and toxicity (miriplatin, n = 124; epirubicin, n = 123). Baseline characteristics were well balanced between the two groups. Median OS times were 1111 days for miriplatin and 1127 days for epirubicin (adjusted hazard ratio 1.01, 95% confidence interval 0.73-1.40, P = 0.946). TE4 rates were 44.4% for miriplatin and 37.4% for epirubicin. Median times to TACE failure were 365.5 days for miriplatin and 414.0 days for epirubicin. AEs of grade 3 or higher, including elevated aspartate aminotransferase (miriplatin, 39.5%; epirubicin, 57.7%) and elevated alanine aminotransferase (miriplatin, 31.5%; epirubicin, 53.7%), were less frequent in the miriplatin than the epirubicin group. CONCLUSIONS: OS after TACE with miriplatin was not superior to that after TACE with epirubicin; however, hepatic AEs were less frequent with miriplatin. CLINICAL TRIAL REGISTRATION: JapicCTI-080632.
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Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Epirrubicina/administración & dosificación , Neoplasias Hepáticas/terapia , Compuestos Organoplatinos/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/efectos adversos , Antineoplásicos/efectos adversos , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica/efectos adversos , Epirrubicina/efectos adversos , Femenino , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Compuestos Organoplatinos/efectos adversos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVE: The purpose of our study was to evaluate retrospectively the usefulness and complications associated with a temporary indwelling catheter system through the brachial artery for patients with liver tumors. CONCLUSION: The temporary indwelling catheter system via the left brachial artery can be used not only for CO2-enhanced sonographically guided aspiration biopsy, radiofrequency ablation, and percutaneous ethanol injection, but also for short-term hepatic arterial infusion chemotherapy and transcatheter arterial chemoembolization.
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Arteria Braquial , Cateterismo Periférico/instrumentación , Cateterismo Periférico/métodos , Catéteres de Permanencia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Diseño de Equipo , Análisis de Falla de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Although sorafenib and hepatic arterial infusion chemotherapy (HAIC) have been proven to improve prognosis in hepatocellular carcinoma (HCC) patients with macroscopic vascular invasion (MVI), the most appropriate approach remains unclear. The present multicenter, non-randomized, prospective cohort study aimed to compare the efficacy and safety of HAIC and sorafenib in patients with advanced HCC and MVI, without extra-hepatic spread (EHS) and Child-Pugh class A disease. The present study was performed between April 2008 and March 2014, and 64 HCC patients with MVI, without EHS and Child-Pugh class A disease were registered. Of these patients, 44 were treated with HAIC and 20 with sorafenib. HAIC involved cisplatin (50 mg fine powder in 5-10 ml lipiodol) and a continuous infusion of 5-fluorouracil (FU) (1,500 mg/5 days), which is referred to as new 5-FU and cisplatin therapy (NFP). The primary outcome was progression-free survival, and the secondary outcome was overall survival (OS). Clinical factors influencing OS and the therapeutic effect were identified using univariate and multivariate analyses. There were no differences in clinical factors between the two groups. The median progression-free survival was 5.1 and 9.5 months in the sorafenib and NFP groups, respectively (P=0.001). The complete response (CR) or partial response (PR) rates were 10 and 71% in the sorafenib and NFP groups, respectively (P<0.001). The median OS in the sorafenib and NFP groups was 13.2 and 30.4 months, respectively (P=0.013). Multivariate analysis revealed that the independent predictors of survival were Child-Pugh score (5, P=0.022, 95% CI, 0.191-0.892), grade of portal vein invasion (brunch, P=0.009, 95% CI, 0.220-0.752), and therapeutic effect (CR or PR, P<0.001, 95% CI, 0.220-0.752), and the independent predictor of therapeutic effect was therapeutic regimen (NFP, P<0.001, 95% CI, 0.006-0.199). NFP should be the first choice for patients with advanced HCC and MVI, without EHS and Child-Pugh A disease.
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Sorafenib is an oral multikinase inhibitor that has been approved to treat advanced hepatocellular carcinoma (HCC), though it is unclear how much benefit advanced HCC patients with progressive disease (PD) derive from sorafenib treatment. This study aimed to assess survival risk factors and evaluate therapeutic strategies for advanced HCC patients with PD after sorafenib treatment. We analyzed the clinical data and treatment outcomes for 315 consecutive advanced HCC patients treated with sorafenib. Univariate analyses of overall survival identified therapeutic effect as an independent risk factor in all patients. Among all patients, 141 developed PD. Of those, 58 (41%) were treated with sorafenib monotherapy, 70 (50%) with agents other than sorafenib, and 13 (9%) were not treated at all. The median survival time was 6.1 months for PD patients with sorafenib monotherapy and 12.2 months for those administered alternative treatments (p < 0.0001). Our results indicated that sorafenib treatment may have negative long-term therapeutic effects in advanced HCC patients with PD, and that alternative treatments should be considered for these patients after sorafenib administration.
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Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Progresión de la Enfermedad , Sustitución de Medicamentos , Femenino , Humanos , Japón , Estimación de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Niacinamida/efectos adversos , Niacinamida/uso terapéutico , Compuestos de Fenilurea/efectos adversos , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Inhibidores de Proteínas Quinasas/efectos adversos , Retratamiento , Sorafenib , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: Portal vein tumor thrombosis is a critical complication in patients with hepatocellular carcinoma (HCC). This prospective multicenter trial assessed the efficacy of hepatic arterial infusion chemoembolization therapy with cisplatin suspended in lipiodol combined with 5-fluorouracil for HCC patients with portal vein tumor thrombosis. METHODS: We enrolled 52 HCC patients with portal vein tumor thrombosis. They received hepatic arterial infusion chemoembolization therapy with cisplatin suspension in lipiodol and 5-fluorouracil. The primary efficacy endpoint was progression-free survival (PFS), while the secondary endpoints were overall survival (OS), tumor response rate, safety, and tolerability. Independent factors for survival were also evaluated. RESULTS: The median PFS and OS were 8.6 and 27.0 months, respectively. Ten patients showed complete response, while 29 had partial response (response rate, 75.0 %). The median survival time of 10 patients with complete response and 29 with partial response was 32 months, while that of 15 patients with partial response who later showed disappearance of HCC following additional therapies was 50 months. Multivariate analysis identified response to treatment and disappearance of viable HCC as independent predictors of survival. The treatment was well tolerated, and the only encountered Grade 3 toxicities were thrombocytopenia and hyperbilirubinemia. CONCLUSIONS: Hepatic arterial infusion chemoembolization therapy with cisplatin suspension in lipiodol combined with 5-fluorouracil is effective treatment for unresectable HCC with portal vein tumor thrombosis.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica/métodos , Cisplatino/administración & dosificación , Aceite Etiodizado/administración & dosificación , Fluorouracilo/administración & dosificación , Neoplasias Hepáticas , Vena Porta/patología , Trombosis de la Vena , Adulto , Anciano , Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/fisiopatología , Carcinoma Hepatocelular/terapia , Supervivencia sin Enfermedad , Femenino , Humanos , Infusiones Intraarteriales/métodos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/fisiopatología , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Resultado del Tratamiento , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/etiología , Trombosis de la Vena/terapiaRESUMEN
Sorafenib, an oral multikinase inhibitor, is approved for advanced hepatocellular carcinoma (HCC) treatment. However, its therapeutic effect in advanced HCC patients with extrahepatic metastasis remains uncertain. This study aimed to prospectively assess the efficacy, safety, and survival risk factors and evaluate the prognostic impact of sorafenib treatment in advanced HCC patients with or without extrahepatic metastasis. Between May 2009 and March 2014, 312 consecutive advanced HCC patients who received sorafenib were enrolled in this study. We evaluated their characteristics and compared the clinical outcomes of those with and without extrahepatic metastasis. Of the enrolled patients, 245 (81%) received sorafenib treatment for more than 1 month, with a median duration of 3.6 months. Eighteen patients demonstrated partial response to sorafenib therapy, 127 had stable disease, and 134 had progressive disease at the first radiologic assessment. The median survival time (MST) and progression-free survival (PFS) were 10.3 and 3.6 months, respectively. Multivariate analysis identified gender, Child-Pugh class, baseline serum des-gamma-carboxy prothrombin level, and treatment duration as independent risk factors for survival. Extrahepatic metastasis was detected in 178 patients. However, the MST, PFS, and therapeutic effect were comparable between patients with and without extrahepatic metastasis. The independent risk factors for decreased overall survival in patients with extrahepatic metastasis were similar to those affecting all patients. Our results indicated that sorafenib could be administered for hepatic reserve and as long-term treatment for advanced HCC patients regardless of their extrahepatic metastasis status.
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Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Niacinamida/administración & dosificación , Niacinamida/efectos adversos , Niacinamida/uso terapéutico , Cooperación del Paciente , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/efectos adversos , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Sorafenib , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: Flare-up of hepatitis due to the reactivation of hepatitis B virus (HBV) is a well-known complication in patients with malignant disease who receive chemotherapy. Despite the widespread use of chemotherapy for patients with HBV-related hepatocellular carcinoma (HCC), there is little corresponding data on exacerbation of liver damage in these patients. In the present study, we investigated the associating factors in exacerbation of liver damage in patients with HBV-related HCC who were undergoing trans-hepatic arterial infusion chemotherapy (THAIC). PATIENTS AND METHODS: Thirty-three patients who received THAIC for HCC were investigated. All patients were hepatitis B surface antigen positive. Hepatitis e antigen and antibody were generally tested at baseline and within 1 month of final chemotherapy. Serum alanine aminotransferase, asparate aminotransferase, albumin, total bilirubin, and prothrombin time were estimated once a week or every 2 weeks. HBV-DNA levels were measured at baseline and once a month. Mutation in the regions of precore and core promoter in HBV DNA was generally estimated at baseline and within 1 month of final chemotherapy. RESULTS: Eight patients with hepatitis Be antigen positive and hepatitis Be antibody negative at baseline were found to have exacerbation of liver damage during or after chemotherapy. Of these, three patients died of progressive liver failure. There was no association between exacerbation of liver damage and age, sex, hepatic reserve function, HBV-DNA levels, precore and core promoter sequencing, therapeutic regimen, or tumor stage. The only associating factor was HBeAg positivity. CONCLUSIONS: These results suggest that hepatitis B e antigen positivity is a significant associating factor in exacerbation of liver damage during or after chemotherapy in patients with HBV-related HCC.
RESUMEN
PURPOSE: This paper describes the technical details of the new indwelling catheter system, which we refer to as System-i, and provides an overview of our experience with this system at our institution. MATERIALS AND METHODS: The system is implanted via the left brachial artery. The feeding artery of the tumor is catheterized at each treatment, and the system can be used for multiple treatments via more than one feeding artery. Between January 2004 and January 2013, System-i was used to administer 398 treatments in 30 patients with hepatocellular carcinoma (HCC). The technical aspects and outcomes of treatment procedures were evaluated. RESULTS: Implantation was successful in all cases. System-i was used for a median number of 11 treatments per patient over a median period of 5.7 months, and 71.6 % of all treatments were administered on an outpatient basis. CONCLUSION: System-i provides an effective and safe method for selective catheterization of feeding arteries for administration of transcatheter arterial chemoembolization or infusion in patients with HCC. Treatment regimens can be individualized without limiting the number of treatments or treatment locations, and patients can be treated on an outpatient basis.