Design and rationale for the non‐interventional Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib (GIDEON) study

Background: Hepatocellular carcinoma (HCC) is a complicated condition influenced by multiple confounding factors, making optimum patient management extremely challenging. Ethnicity, stage at diagnosis, comorbidities and tumour morphology affect outcomes and vary from region to region, and there is no common language to assess patient prognosis and make treatment recommendations. Despite recent efforts to reduce the incidence of HCC, most patients present with unresectable disease. Non‐surgical treatments include ablation, transarterial chemoembolisation and the multikinase inhibitor, sorafenib, but their effects in all patient subgroups are not known and further information is needed to optimise the use of these treatments. Aims: The Global Investigation of Therapeutic DEcisions in Hepatocellular Carcinoma and Of its Treatment with SorafeNib (GIDEON) study (ClinicalTrials.gov identifier NCT00812175; http://clinicaltrials.gov/ ) is an ongoing global, prospective, non‐interventional study of patients with unresectable HCC who are eligible for systemic therapy and for whom the decision has been taken to treat with sorafenib under real‐life practice conditions. The aim of this study is to evaluate the safety and efficacy of sorafenib in different subgroups, especially Child‐Pugh B where data are limited. Discussion: This study will recruit 3000 patients from > 40 countries and follow them for approximately 5 years to compile a large and robust database of information that will be used to analyse local, regional and global differences in baseline characteristics, disease aetiology, treatment practice patterns and treatment outcomes, with a view to improve the knowledge base used to guide physician treatment decisions and to improve patient outcomes.     

Aetiology of cirrhosis of the liver has an impact on survival predicted by the Model of End-stage Liver Disease score

Background Originally, aetiology of liver disease has been incorporated into the computation of the Model of End‐stage Liver Disease (MELD) score. Clinical observations prompted us to hypothesize that patients with viral and alcoholic cirrhosis may differ in predicted survival rates. Until now, no large representative studies evaluated the impact of aetiology on long‐term survival predicted by the Child–Pugh and MELD scores. Materials and methods Four hundred and ninety‐three patients who underwent transjugular intrahepatic portosystemic shunt implantation in Vienna, Austria, and Palermo, Italy, were included in this retrospective study. The main analyses were a logistic regression model and a Cox proportional hazards regression model calculating the interaction of the aetiology with the scores. Results Both groups had similar survival rates (median 1377 and 1721 days for viral and alcoholic cirrhosis, respectively; P = 0.58), but patients with viral cirrhosis had significantly lower MELD scores (P = 0.002). In the Cox analysis, aetiology had a significant impact on the prediction of overall survival by MELD score. For 3‐month survival, MELD score was adequately predictive for both groups. For 1‐year survival, aetiology had a significant impact on survival, indicating that patients with identical scores but different aetiologies differed in survival rates. When stratifying patients into high‐ and low‐risk patients (MELD < 16 vs. MELD ≥ 16), aetiology of cirrhosis had no impact on the predictive value for low‐risk patients; high‐risk‐patients (MELD ≥ 16) with viral cirrhosis had significantly lower survival rates than patients with alcoholic cirrhosis and identical scores. With regard to Child–Pugh Score, no significant differences between the two patient groups and in the prediction of 3‐month and 1‐year survival could be observed. Conclusions Our study suggests that aetiology of cirrhosis has an impact on 1‐year survival predicted by the MELD score. This becomes more apparent in patients with advanced stage of liver disease (MELD ≥ 16). Since MELD score is used for ranking patients for liver transplantation and waiting times are regularly longer than 3 months, our observations suggest that with increasing time on the waiting list and severity of disease, patients with viral cirrhosis may have a disadvantage in the current allocation policy.     

Strategies for assessing and managing the adverse events of sorafenib and other targeted therapies in the treatment of renal cell and hepatocellular carcinoma: Recommendations from a European nursing task group

PurposeAs a group of European nurses familiar with treating patients with renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) using targeted/chemo- therapies, we aimed to review strategies for managing adverse events (AEs) associated with one targeted therapy, sorafenib.MethodFocusing on the AEs we considered the most difficult to manage (hand–foot skin reaction [HFSR], diarrhoea, fatigue and mucositis/stomatitis), we reviewed the literature to identify strategies relevant to sorafenib. Given the paucity of published work, this included strategies concerning targeted agents in general. This information was supplemented by considering the wider literature relating to management of these AEs in other tumour types and similar toxicities experienced during conventional anti-cancer therapy. Together with our own experience, this information was used to compile an AE management guide to assist nurses caring for patients receiving sorafenib.ResultsOur collated experience suggests the most commonly reported AEs with sorafenib and other targeted agents are HFSR, diarrhoea, fatigue, rash and mucositis/stomatitis; these generally have an acute (appearing at ～0–1 months) or delayed onset (appearing at ～3 months). Most management strategies in the literature were experience-based rather than arising from controlled studies. However, strategies based on controlled studies are available for HFSR and mucositis/stomatitis.ConclusionsEvidence, especially from controlled studies, is sparse concerning management of AEs associated with sorafenib and other targeted agents in RCC/HCC. However, recommendations can be made based on the literature and clinical experience that encompasses targeted and conventional therapies, particularly in the case of non-specific toxicities e.g. diarrhoea and fatigue.     

原发性肝癌合并肝功能C级患者介入治疗临床观察

目的对部分原发性肝癌合并肝功能Child C级患者行TACE介入治疗及联合索拉菲尼分子靶向治疗进行疗效观察。方法收集兰州军区兰州总医院安宁分院及东方肝胆外科医院44例肝功能Child C级肝癌患者临床资料,分为A、B两组,A组22例为TACE+索拉非尼治疗,B组22例单用索拉非尼治疗。索拉非尼起始剂量400mg,2次/d,治疗过程中根据不良反应情况调整剂量。结果 A组和B组患者分别有81.82%和50.00%患者肿瘤面积明显缩小,生活质量得到了提高,延长了生存期。结论肝癌合并肝功能Child C级行TACE+索拉非尼治疗取得了较好的疗效,能够使患者生活质量提高,延长存活期。     

Increased anticoagulant response to low‐molecular‐weight heparin in plasma from patients with advanced cirrhosis

Summary. Introduction: Cirrhotic patients may present thrombotic complications that warrant anticoagulant therapy. However, the efficacy of low‐molecular‐weight heparin (LMWH) in this clinical setting is still unclear. Aims/methods: To evaluate the in vitro effect of LMWH on thrombin generation (TG) in cirrhotic patients at different stages of liver disease. Thirty cirrhotics (10 Child Pugh A, 10 Child Pugh B and 10 Child Pugh C), 10 subjects with inherited type 1 antithrombin (AT) defect and 10 healthy controls were studied. TG was determined at baseline and with anti‐Xa levels after the addition of enoxaparin at 0.35 and 0.7 U anti‐Xa mL. The endogenous thrombin potential (ETP) ratio at 0.35 and 0.7 U anti‐Xa mL was obtained by dividing ETP with LMWH by ETP at baseline. Results: Mean AT levels in all cirrhotic subgroups and in patients with AT deficiency were significantly lower than in controls. The 0.35 ETP ratio was significantly lower in cirrhotic patients than in controls (0.26 ± 0.1 vs. 0.48 ± 0.1, P < 0.001) and the reduction paralleled the severity of liver disease, in spite of the concomitant decrease in AT and anti‐Xa activity. AT‐deficient subjects showed a significantly increased 0.35 ETP ratio compared with both cirrhotic patients and controls (0.69 ± 1 vs. 0.26 ± 0.1, P < 0.001, and vs. 0.48 ± 0.1, P = 0.04 respectively). LMWH at 0.7 U anti‐Xa mL completely inhibited TG in 9/30 cirrhosis patients with more advanced liver disease (Child Pugh B and C), whereas complete TG abolition was seen in only 1/10 controls. Conclusions: Cirrhotic patients show an increased response to LMWH, which correlates with the severity of liver disease, in spite of reduced AT and anti‐Xa activity levels. Thrombin generation may be a useful tool to monitor the response to LMWH in cirrhotic patients.     

Hepatocellular carcinoma

One of the advances in recent years about the treatment of hepatocellular carcinoma is clinical evidence of the molecular target drug, sorafenib. Although sorafenib shows little anti-tumor effect indicated by tumor shrinkage, it has inhibitory effect of tumor development to be the first drug shown to extend survival in hepatocellular carcinoma. Because its side effects are different than the traditional cytotoxic drugs, to better understand the side effects and its treatment is necessary for sorafenib treatment. More appropriate use of sorafenib is recommended because of serious adverse events or deaths in Japan. Position of sorafenib in the treatment of hepatocellular carcinoma among hepatic arterial infusion chemotherapy and transcatheter arterial embolization is not yet clear. Many clinical trials of molecular target drugs against hepatocellular carcinoma are underway.     

肝癌切除患者术后并发症的原因分析及对策

目的分析肝癌切除术后影响并发症出现的危险因素。方法对110名肝癌切除患者术后出现的并发症进行回顾性总结,选取11个可能因素,分别进行单因素及logistics分析,分析各因素与术后并发症之间的关系。结果110例肝癌切除患者,术后出现并发症38例（34．5％）,对可能影响并发症的各因素行单因素统计分析,结果表明,术前HBV DNA水平、术前Child分级、前白蛋白水平、PT情况、肝门阻断与否、术中出血量等6个因素和术后出现并发症有显著相关,而年龄、性别、有无附加手术、有无基础疾病、BMI等因素则和术后出现主要并发症无明显相关。将上述单因素分析中与术后并发症显著相关的6个因素再进行logistic多因素回归分析,结果表明术前Child分级、前白蛋白水平、术中出血量是术后出现主要并发症的独立危险因素。结论肝癌手术的并发症情况主要受术前肝功能储备情况及术中出血量等因素影响。     

Treatment options for unresectable HCC with a focus on SIRT with Yttrium‐90 resin microspheres

Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is the second leading cause of cancer‐related deaths across the globe. Only a small percentage of HCC patients (~20%‐30%) are diagnosed at an early stage when first‐line treatment options may be effective. The majority of HCC patients (>70%) are diagnosed with unresectable disease and given a poor overall prognosis. Current treatment guidelines recommend locoregional therapy with transarterial chemoembolisation (TACE) and systemic therapy with sorafenib as first‐line treatment for patients with intermediate and advanced stage HCC. However, multiple factors including contraindications, technical considerations and treatment‐related toxicities pose significant challenges in achieving favourable treatment outcomes, underscoring the need for a paradigm shift in managing these patients. In 2002, yttrium‐90 (Y‐90) resin microspheres was approved by the U.S. Food and Drug Administration (FDA) for the treatment of unresectable metastatic colorectal cancer to the liver with adjuvant floxuridine chemotherapy. However, thousands of patients with unresectable HCC have also been treated with resin Y‐90. For over two decades, several small‐scale prospective trials and retrospective studies have investigated and reported on the efficacy of locoregional selective internal radiation therapy (SIRT) with Y‐90 microspheres in treating unresectable HCC. Although it is currently a treatment option for intermediate‐stage HCC patients, mainstream clinical application of resin Y‐90 has been largely limited because of the lack of sufficient clinical data from a randomised controlled trial. This could change with the imminent announcement of results from the phase 3 Sorafenib vs Radioembolization in Advanced Hepatocellular carcinoma (SARAH) trial. To provide the foundation and context for interpreting results from the SARAH trial, this article provides an overview of treatment modalities and current challenges in managing unresectable HCC. There is also a review of key prospective and retrospective studies evaluating the use of Y‐90 SIRT, specifically Y‐90 resin microspheres in unresectable HCC, which led to the development of the SARAH trial. Methods: To identify relevant publications, the PubMed database was queried using one or more of the following search terms alone or in combination with Boolean operators: epidemiology, hepatocellular, hepatocellular cancer, hepatocellular carcinoma, unresectable, radioembolisation, selective internal radiation therapy, SIR‐Spheres, yttrium 90, TACE, and sorafenib. The results were sorted or filtered by “Author”, “Publication dates” or “Article types” to identify articles relevant to each section of the review. To ensure that information on ongoing clinical trials involving Y‐90 resin was included, we conducted a search on “ClinicalTrials.gov”, by combining the search terms “HCC” OR “hepatocellular carcinoma” with “Y 90” OR “yttrium 90” OR “radioembo”, and screened for studies that involved treatment with Y‐90 resin microspheres.     

索拉菲尼联合肝动脉栓塞化疗和氩氦刀消融治疗晚期肝癌的效果观察

目的：对比索拉菲尼单药与联合应用肝动脉栓塞化疗术（ TACE）、经皮局部氩氦刀消融（PLCT）综合治疗失去手术机会的肝癌的治疗效果。方法回顾性分析64例无法手术切除的肝癌患者的临床资料,行索拉菲尼单药或索拉菲尼联合 TACE、PLCT 治疗。其中索拉菲尼单药治疗32例,联合介入和氩氦刀消融治疗32例,随访时间6～32个月,观察两组患者治疗效果和肿瘤进展时间。结果所有患者顺利完成治疗,无手术相关死亡及严重并发症。64例患者中,完全缓解（ CR）11例,部分缓解（PR）31例,稳定（SD）14例,进展（PD）8例,其中单药治疗组 CR 3例,PR 11例,SD 12例,PD 6例;联合介入和氩氦刀消融组 CR 8例,PR 20例,SD 2例,PD 2例,两组比较差异有统计学意义（χ^2=14.028,P=0.003）。中位肿瘤进展时间分别为20周和53周,两组比较差异有统计学意义（χ^2=14.773,P=0.000）。结论针对无法手术切除的肝癌,索拉菲尼联合 TACE 和 PLCT 治疗效果较好,可延长肿瘤进展时间。     

Cerebellar stroke in a low cardiovascular risk patient associated with sorafenib treatment for fibrolamellar hepatocellular carcinoma

Sorafenib is the standard treatment of hepatocellular carcinoma (HCC). However, fibrolamellar HCC was not included in sorafenib trials. The case is a 26‐year‐old man with fibrolamellar HCC, who had a cerebrovascular accident (CVA) while being treated with sorafenib. This illustrates a probable relationship between use of sorafenib and CVA in low cardiovascular risk patients.     

Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling

Although patients with advanced refractory solid tumors have poor prognosis, the clinical development of targeted protein kinase inhibitors offers hope for the future treatment of many cancers. In vivo and in vitro studies have shown that the oral multikinase inhibitor, sorafenib, inhibits tumor growth and disrupts tumor microvasculature through antiproliferative, antiangiogenic, and/or proapoptotic effects. Sorafenib has shown antitumor activity in phase II/III trials involving patients with advanced renal cell carcinoma and hepatocellular carcinoma. The multiple molecular targets of sorafenib (the serine/threonine kinase Raf and receptor tyrosine kinases) may explain its broad preclinical and clinical activity. This review highlights the antitumor activity of sorafenib across a variety of tumor types, including renal cell, hepatocellular, breast, and colorectal carcinomas in the preclinical setting. In particular, preclinical evidence that supports the different mechanisms of action of sorafenib is discussed.     

肝硬化患者凝血功能、血小板参数、网织红细胞参数的变化与Child-Pugh分级的关系

目的了解肝硬化患者凝血功能、血小板参数、网织红细胞参数的变化与Child-Pugh肝功能分级的关系。方法分别采用全自动血液分析仪和全自动血凝仪测定163例肝硬化患者和50例健康对照者的凝血功能指标(PT、APTT、Fig、TT),血小板参数(PLT、MPV、PDW、PCT)和网织红细胞参数(RET#、RET%、IRF)。比较肝硬化组与对照组、肝硬化Child-Pugh分级后组间凝血功能、血小板参数和网织红细胞参数的变化。结果与对照组比较,肝硬化患者Fig降低,PT、APTT、TT延长,PLT、PCT下降,MPV、PDW升高,RET计数、RET%、IRF升高,差异有统计学意义(P0.05);Fig随着Child-Pugh等级上升逐渐降低,PT、APTT、TT随着Child-Pugh等级上升逐渐延长,PLT、PCT随着Child-Pugh等级上升逐渐下降,MPV、PDW随着ChildPugh等级上升逐渐升高,RET计数、RET%、IRF随着Child-Pugh等级上升逐渐升高(P0.05)。结论肝硬化患者存在凝血功能、血小板参数及网织红细胞参数异常,其凝血功能,血小板参数及网织红细胞参数的变化与Child-Pugh肝功能分级有密切相关,是判定肝脏损害程度、出血倾向及骨髓造血功能的重要指标。     

Evidence for an enhanced fibrinolytic capacity in cirrhosis as measured with two different global fibrinolysis tests

Summary. Background and objectives: It has been known for a long time that cirrhosis is associated with hyperfibrinolysis, which might contribute to an increased risk and severity of bleeding. However, recent papers have questioned the presence of a hyperfibrinolytic state in cirrhotic patients and postulated a rebalanced system owing to concomitant changes in both pro‐ and anti‐fibrinolytic factors. Therefore we re‐investigated the fibrinolytic state of cirrhotic patients using two different overall tests including a recently developed test for global fibrinolytic capacity (GFC) using whole blood. Patients and methods: Blood was collected from 30 healthy controls and 75 patients with cirrhosis of varying severity (34 Child–Pugh A, 28 Child–Pugh B and 13 Child–Pugh C). The plasma clot lysis time (CLT), which is inversely correlated with fibrinolysis, was determined as well as the GFC. Results: The mean CLT was 74.5 min in the controls and decreased significantly to 66.9 min in Child–Pugh class A patients, 59.3 min in class B patients and 61.0 min in class C patients, and hyperfibrinolysis existed in 40% of the patients. The median GFC was 1.7 μg mL^?1 in the controls and increased significantly to 4.0 μg mL^?1 in Child–Pugh class A patients, 11.1 μg mL^?1 in class B patients and 22.5 μg mL^?1 in class C patients, and hyperfibrinolysis existed in 43% of the patients. Taken together, 60% of the patients showed hyperfibrinolysis in at least one of the two global assays. Conclusion: A rebalanced fibrinolytic system may occur, but hyperfibrinolysis is found in the majority of patients with cirrhosis.     

Elevated plasma osteopontin level is predictive of cirrhosis in patients with hepatitis B infection

Background: Osteopontin (OPN) was shown to play an important role in the pathogenesis of various inflammatory and fibrotic processes and elevated in fibrotic liver of mouse model. However, the significance of OPN in hepatitis B virus (HBV)‐induced liver cirrhosis (LC) remains unclear and is therefore evaluated in this study. Methods: Thirty‐nine patients with HBV‐induced LC, 30 patients with HBV infection but without cirrhosis, 11 patients with HBV‐related hepatocellular carcinoma (HCC) and 14 additional healthy controls were enrolled in this study. Plasma levels of OPN were measured with enzyme‐linked immunosorbent assay and the relationship between OPN and clinical parameters was evaluated. Results: When compared to HBV infection group (median 2.16 ng/ml), plasma levels of OPN were significantly increased in cirrhosis (4.52 ng/ml, p < 0.001) and cancer group (13.38 ng/ml, p < 0.001). The OPN level was correlated with the severity of liver damage according to Child–Pugh classification (p = 0.003). It showed at least comparable sensitivity and specificity to predict cirrhosis as aspartate aminotransferase to platelet ratio index, a previously established non‐invasive serum marker of cirrhosis. Conclusions: These data suggest that OPN could be used to evaluate the existence of LC, as OPN has previously been reported to be increased in the HCC; this unique feature makes OPN a promising candidate for prediction biomarker in the long‐time surveillance of patients with HBV infection to evaluate the risk of cirrhosis and cancer.     

肝癌患者肝部分切除术后认知功能障碍的危险因素分析与护理对策

目的：探讨肝癌患者肝部分切除术后认知功能障碍（POCD）的危险因素。方法：选择在我院行肝部分切除术的肝癌患者426例,分别在术前7d和术后7d采用中文版简易精神状态检查量表进行认知功能评估,按是否发生POCD分为POCD组和非POCD组。收集两组患者性别、年龄和体质指数等共14个相关因素,通过单因素和多因素Logistic回归分析,筛选肝癌患者肝部分切术后POCD的独立危险因素。结果：408例患者完成本研究,其中95例发生POCD,发生率为23．28％。单因素分析显示,年龄、文化程度、嗜酒、高血压、糖尿病、肝功能Child—Pugh分级、肿瘤大小、手术时间、术中低血压和术后持续镇痛在两组间比较差异有统计学意义（P〈0．05）。多因素Logistic回归分析显示,年龄、嗜酒、高血压、肝功能Child—Pugh分级、肿瘤大小和术中低血压是肝癌患者肝部分切除术后POCD的独立危险因素（P〈0．05）,文化程度是其保护因素（P〈0．05）。结论：POCD是肝癌患者肝部分切除术后常见并发症,通过积极的护理干预,可减少患者POCD的发生。     

索拉非尼联合TACE治疗中晚期肝癌的临床观察

目的探讨索拉非尼联合经皮肝动脉化疗栓塞术（TACE）治疗中晚期肝癌的疗效。方法选取30例中晚期肝癌患者,给予索拉非尼联合TACE治疗（试验组）,同时选取30例中晚期肝癌患者作为对照组仅行TACE;于1-2个治疗周期后比较临床疗效及生存质量卡氏评分。结果试验组与对照组,治疗3个月后临床获益率分别为83.3%、60.0%,差异有统计学意义（P〈0.05）,而生存质量卡氏评分2组差异无统计学意义（P〉0.05）;6个月生存率分别为93.3%、86.7%,差异无统计学意义（P〉0.05）,12个月生存率分别为86.4%、60.0%,差异有统计学意义（P〈0.05）。结论采用索拉非尼联合TACE治疗中晚期肝癌,可提高患者临床获益率及1年生存率。     

Symptoms from treatment with sunitinib or sorafenib: a multicenter explorative cohort study to explore the influence of patient-reported outcomes on therapy decisions

Purpose

Optimal long-lasting treatment with sunitinib and sorafenib is limited by dose modifications (DMs) due to adverse events (AEs). These AEs may be underrecognized and their influence on health-related quality of life (HRQL) underestimated. Improved insight into the relationship between AEs and therapy decisions is needed. To improve decision making around managing symptoms and reduce DMs, this study was set up to explore the influence of patient-reported symptoms on therapy decisions.

Methods

In this multicenter cohort study, patient characteristics, reasons for and different forms of used dose modifications, and AEs were prospectively obtained from cancer patients on sunitinib/sorafenib treatment. Used instruments to get insight into AEs were the patient-scored Utrecht Symptom Diary (USD) and the professional-scored Common Terminology Criteria for AEs version 3.0.

Results

Median total treatment duration in 42 patients was 16 weeks. Median time till dose modification was 10 weeks. DMs occurred mostly due to multiple mild AEs. By using the USD, a higher prevalence of most AEs was found compared to the literature. Sixty percent of the patients experienced a decreased HRQL due to multiple AEs.

Conclusions

Because severe AEs due to sunitinib/sorafenib treatment seldom occur, it is more important to focus on treating and preventing multiple mild AEs with higher impact on HRQL, when trying to avoid dose modifications. Using patient self-reported measurement methods helps to early recognize symptoms and to differentiate among symptom intensities. This systematic approach might help to achieve the optimal dosing, which might improve PFS and OS.     

索拉非尼治疗肝细胞肝癌不良反应的护理

目的探讨索拉非尼治疗中晚期肝细胞肝癌的不良反应及护理措施。方法回顾性分析26例中晚期肝细胞肝癌患者服用索拉非尼期间出现的不良反应。结果 26例患者发生的不良反应有手足综合征(57.7%)、腹泻(53.8%)、高血压(50.0%)、皮疹(46.2%)、疲乏(46.2%)等,一般为1～2级,仅1例患者出现3级手足综合征,予减半量治疗,所有患者经护理干预后不良反应均有所好转。结论索拉非尼作为分子靶向治疗新药,服药期间应严密观察患者的不良反应,及时采取有效的护理干预,从而提高治疗疗效和患者的生活质量。     

Analysis of factors affecting the prognosis of transcatheter arterial chemoembolization for hepatitis B-related hepatocellular carcinoma

ObjectivesThe purpose of this study was to investigate the prognostic factors for transcatheter arterial chemoembolization (TACE) for hepatitis B-related hepatocellular carcinoma (HCC).Materials and methodsThe variables that may affect overall survival (OS), such as age, gender, AFP, Child Pugh classification, body mass index, HBV-DNA, HbeAg, tumor number, tumor diameter, BCLC stage, embolization method, ablation therapy, and targeted therapy, were analyzed by single factor and many factor COX regression. In addition, predictive factors of OS were stratified and a Kaplan-Meier survival curve was drawn.ResultsAmong the 136 patients, the median follow-up time was 14.5 months (range: 2–72 months). HCC patients with the tumor diameter <3 ​cm had the highest survival rate, followed by patients with a tumor diameter of 3–5 ​cm; the survival rate of patients with the tumor diameter (greater than 5 ​cm) was the lowest. Among the BCLC stages, stage A patients had the highest survival rate, followed by stage B and stage C patients, which had the lowest survival rate.The survival rate of Child Pugh grade A patients was higher than those with Child Pugh grade B. Compared with patients who did not undergo ablation treatment, the survival rate of patients with combined ablation treatment was relatively high. The survival rate of patients receiving drug-eluting beads transarterial chemoembolization (DEB-TACE) treatment was higher than those receiving conventional transarterial chemoembolization (cTACE) treatment. Additionally, repeated TACE treatment improved the OS rate of patients. These six factors were related to patient prognosis and the differences were statistically significant (P ​< ​0.05).ConclusionsTumor diameter, BCLC stage, TACE repetition, and TACE combined with ablation were independent prognostic factors of OS.     

Perceived medication adverse effects and coping strategies reported by chronic heart failure patients

Background: Data on medication adverse effects (AEs) in chronic heart failure (CHF) are primarily based on results from clinical trials. Little is known about AEs perceived by CHF patients in daily practice and how patients deal with these subjective AEs. Aims: To describe the scope and nature of perceived AEs of CHF patients, their coping strategies and the relationship of perceived AEs to medication, patient characteristics and quality of life. Methods: This cross‐sectional observational study included a sample of 680 patients previously hospitalised for CHF. Perceived AEs and coping strategies were collected by interviews based on a structured questionnaire. Medication and clinical information were collected by chart review. Results: Of the 670 CHF patients completing the questionnaire, 17% reported at least one AE. In total, 186 AEs were reported of which 15% could not be linked to any medication. Nausea (4%), dizziness (4%), itches (3%) and rash (3%) were the most prevalent. The drug associated with the highest AE rate was pravastatin (27%). On average, more than five different drugs could be related to the AEs headache, dizziness and nausea. Patients reporting AEs had a lower general health perception, younger age and were more often using antiarrhythmic drugs. Of patients experiencing AEs, 69% conferred with their doctor, 24% reported having done nothing in reaction and 2% discontinued their medication without discussing it with the doctor. Conclusion: Adverse effects are frequently perceived by CHF patients, but they are difficult to recognise and manage in daily practice.