Surgical treatment of hepatocellular carcinoma in cirrhosis

Hepatocellular carcinoma is one of the most frequent forms of cancer worldwide and its diagnosis and treatment have changed substantially during the last few years. Recent advances in ultrasonography, spiral computed tomography scan and nuclear magnetic resonance have further simplified the diagnostic approach to hepatocellular carcinoma. Ultrasonography is the reference examination, giving a wide variety of information on tumour size, location, relationship with portal and hepatic veins and splanchnic haemodynamics. Surgical resection and liver transplantation can both be defined as curative treatment while other techniques such as percutaneous ethanol injection and chemoembolization must be considered as palliative. Therapeutic strategies for hepatocellular carcinoma are based upon data concerning the characteristics of the tumour the functional status of non-tumoural liver parenchyma and patients' general conditions. Surgery of hepatocellular carcinoma in cirrhotic liver is mainly restricted by lack of functional hepatic reserve and by the limited capacity of hepatic regeneration. The best surgical results are obtained in early tumoural stages which generally need limited resection. Nevertheless, major liver resections have a specific role in selected cases. Recurrence rate after surgical resection is high and is related to a large number of factors. For this reason, liver transplantation, removing at the same time, the tumour and the underlying disease, is considered, theoretically, the best treatment for hepatocellular carcinoma, but its role is still debated and limited by difficult organ sharing. Integration of present therapeutic schemes are under evaluation with promising preliminary results.     

肝硬化食管胃静脉曲张破裂出血的预防和治疗新进展

肝硬化患者门静脉系统血流受阻导致门静脉及其属支血管内静力压力升高并伴侧支循环形成,临床主要表现为腹水、脾大、肝性脑病以及食管胃静脉曲张破裂出血等.其中,食管胃静脉曲张破裂出血的病死率最高,是最常见的消化系统急症之一.肝硬化患者上消化道出血的原因中,70％是因为静脉曲张破裂出血.     

Endoscopic variceal ligation of patients with liver cirrhosis and cirrhosis accompanied by hepatocellular carcinoma

Background: Rupture of esophageal varices with severe gastrointestinal hemorrhage is one of the most serious complications of liver cirrhosis (LC) and hepatocellular carcinoma (HCC) complicating LC. The present study looks at the success of hemostasis in LC and LC accompanied by HCC, the success of breaking the varices cluster and the rate of rebleeding in patients of LC subject to emergency ligation and prophylactic ligation. Methods: Seventy‐five patients were divided into three groups. Group 1: 30 patients with LC accompanied by HCC with digestive bleeding; group 2: 30 patients with LC with digestive bleeding; and group 3: 15 patients with LC with high risk of digestive bleeding from esophageal varices (with no medical history of digestive bleeding). Success of hemostasis 72 h after endoscopic variceal ligation (EVL) was that patients did not vomit blood nor produce black feces. The effectiveness of EVL for iradication of the variceal cluster was classified into three levels: good, fairly good and poor. Results: The hemostasis success in group 1 (LC accompanied by HCC) and group 2 (LC with digestive bleeding due to esophageal varices) was 73.3% and 93.4%, respectively. The success of breaking the varix cluster in group 2 (LC) and group 3 (LC with high risk of digestive bleeding and treated by prophylactic ligation) was 73.3% and 80%, respectively. The rate of rebleeding in group 2 and group 3 after 1 year was 20% and 13.3%, respectively. Conclusion: Endoscopic variceal ligation is a good technique for variceal hemostasis and eradication of the esophageal varices cluster.     

肝硬化食管胃静脉曲张破裂出血的防治

食管胃静脉曲张破裂出血是肝硬化患者的严重并发症,病死率高,是最常见的消化系统急症之一。近年来,随着研究的深入,食管胃静脉曲张破裂出血的预防和治疗方法都有了一些新的进展,本文对此进行综述。     

Experience from a real-life cohort: outcome of 606 patients with hepatocellular carcinoma following transarterial chemoembolization

Background: Hepatocellular carcinoma (HCC) is one of the most lethal cancers. Transarterial chemoembolization (TACE) has been accepted as the standard care for intermediate stage disease.

Methods: In this study, we characterized 606 with HCC patients from Hannover Medical School treated with TACE.

Results: 606 with HCC patients treated with TACE were identified between 2000 and 2015. Most patients (59.8%) were at intermediate stage. Following TACE, most patients subsequently received systemic therapy or best supportive care (BSC), whereas 227 (37.5%) patients were bridged to potentially curative local treatments. Depending on subsequent therapies, median post-TACE survival ranged from 7 to 162 months. Ascites, cholinesterase, c-reactive and alpha-feto protein and tumor size were identified as prognostic factors. These factors as well as the HAP, mHAP-II and STATE score also determined post-TACE survival independent of subsequent therapies. Hepatic function progressively deteriorated with repeated TACE sessions. Despite that, post-TACE survival was not shortened in frequently treated patients (≥5 times) as compared to patients treated 4 times or less (p?=?not significant [n.s.]). Patients treated ≥5 times with TACE received significantly more often systemic therapy following TACE (37.3%) as compared to patients with 3–4 (30.1%), 2 (27.4%) and 1 (21.8%) sessions (p?<?.05).

Conclusion: TACE is performed in a heterogeneous population as bridging therapy to other local treatments and palliative therapy. The long-term survival following TACE is determined by baseline tumor, patient-related factors and by subsequent therapies. Post-TACE survival is not shorter in patients with frequent treatments (≥5), and the rate of subsequent systemic treatments is higher compared to less frequently treated patients.     

肝细胞癌合并食道静脉曲张破裂出血的联合手术治疗

目的探讨肝细胞癌（hepatocellular carcinoma,HCC）合并食道静脉曲张破裂出血联合手术治疗的方法、病理生理基础和治疗效果。方法选取1999年12月-2007年12月采用肝部分切除联合脾切除、门奇断流术治疗HCC合并食道静脉曲张破裂出血患者共23例（联合手术组）,观察术前、术后外周血白细胞和血小板计数的变化、食管静脉曲张缓解情况、生存率和肿瘤复发率;并与同期行单纯肝切除术的39例HCC患者（单纯肝切除组）进行比较分析。结果联合手术组手术并发症和手术死亡率与单纯肝切除组相比差异无统计学意义;联合手术组术后白细胞及血小板计数回升明显,显著高于单纯肝切除组;已随访14例患者中,13例食道静脉曲张改善;随访期间无凶险感染发生;5年生存率和3年肿瘤复发率2组间比较,差异无统计学意义。结论对于HCC合并食道静脉曲张破裂出血,采用肝部分切除联合脾切除、门奇断流术进行治疗是安全有效的,联合脾切除、门奇断流术并不增加肝切除手术的风险,不影响远期生存率和肿瘤复发率。     

Outcome of patients with hepatocellular carcinoma referred to a tertiary centre with availability of multiple treatment options including cadaveric liver transplantation.

Hepatocellular carcinoma (HCC) is a primary cancer of the liver with an established causal link to viral hepatitis and other forms of chronic liver disease. Aims: The aim of this study was to analyse the determinants of outcome in patients with HCC referred to a tertiary centre for management. Method: Two hundred and thirty-five prospective patients with HCC and minimum 12-month follow-up were studied. Results: The cohort was heterogeneous, with 52% Caucasian, 40% Asian and 5% of Middle-Eastern origin. Independent predictors of outcome included tumour size and number, the presence of ascites or portal vein thrombosis, alpha-foetoprotein >50 U/L and an impaired performance status. Treatment was determined on an individual case basis by a multidisciplinary tumour team. Surgical resection was primary treatment in 43 patients, liver transplantation in 40 patients, local ablation (percutaneous radiofrequency ablation or alcohol injection) in 33 patients, transarterial chemoembolisation in 33 patients, chemotherapy or other systemic therapy in 30 patients and no treatment in 56 patients. After adjustment for significant covariates, both liver transplantation (P<0.001) and surgical resection (P=0.029) had a significant effect on patient survival compared with no treatment, but local ablation (P=0.410) and chemoembolisation (P=0.831) did not. Liver transplantation resulted in superior overall and, in particular, disease-free survival compared with surgical resection (disease-free survival 84 vs 15% at 5 years). Conclusion: In conclusion, both surgical resection and liver transplantation significantly improve the survival of patients with HCC, but improvements need to be made to the delivery of loco-regional therapy to enhance its effectiveness.     

Decision curve analysis to identify optimal candidates of liver resection for intermediate-stage hepatocellular carcinoma with hepatitis B cirrhosis: A cohort study

The selection criterion for liver resection (LR) in intermediate-stage (IM) hepatocellular carcinoma (HCC) is still controversial. This study aims to compare LR and transarterial chemoembolization (TACE) in the range of predicted death risk The multivariable Cox regression model (MVR) was estimated to predict mortality at 5 year. The cutoff values were determined by a 2-piece-wise linear regression model, decision curve analysis with MVR model, and hazard ratio curve for treatment plotted against the predicted mortality. 825 IM-hepatocellular carcinoma (IM-HCC) with hepatitis B cirrhosis were included for analysis (TACE, n = 622; LR, n = 203). The 5-year overall survival (OS) rate of LR patients was higher than the TACE group (52.8% vs 20.8%; P < .0001). The line of LR and TACE were crossing with predicted death risk at 100% (P for interaction = .008). The benefit of LR versus TACE decreased progressively as predicted death risk > 0.55 (95%CI: 0.45, 0.62). When predicted death risk over 0.7, decision curve analysis suggested that LR and TACE did not increase net benefit. Patients were then divided into 4 subgroups by the cutoff values (<0.45, 0.45≥/<0.62, 0.62≥/<0.7, ≥0.7). The stratified analysis of treatment in different subgroups, hazard ratios were 0.39 (95%CI: 0.27, 0.56), 0.36 (95%CI: 0.23, 0.56), 0.51 (95%CI: 0.27, 0.98), and 0.46 (95%CI: 0.27, 0.80), respectively. LR reached the maximal relative utility in the interval of 0.45 to 0.62, and both LR and TACE did not increase net benefit at the 5-year death risk over 0.7.     

肝脏硬度检测对乙型肝炎肝硬化食管静脉曲张的预测

目的遴选乙型肝炎（乙肝）肝硬化食管静脉曲张（esophagealvarices,Ev）的无创性诊断指标,并建立相应诊断模型。方法回顾性分析280例乙肝肝硬化患者资料,统计分析血常规、生化指标、超声指标及肝脏硬度,建立诊断模型。结果20例（7．1％）肝脏硬度检测失败。肝脏硬度、肝脏超声指标、清蛋白、血小板与EV具有相关性（Kendallb〉0．20无EV患者的年龄、肝脏硬度、肝脏超声评分、脾厚度、清蛋白、球蛋白、白细胞、血小板等指标与Ev患者相比,差异有统计学意义。肝脏超声评分联合肝脏硬度预测Ev的受试者工作特征曲线下面积（area under receiver operating characteristic curve, AUROC ）为0．83,以食管静脉曲张指数（esophagealvaricesindex,EVI）：4．254为诊断界值,预测患者无Ev的可能性为92．6％,阴性似然比为0．11;以EVI=6．853为诊断界值,预测患者存在EV的可能性为81．8％。在ALT〉5×ULN者中,肝脏硬度与EV相关性有所提高（Kendallb：0．421）,肝脏硬度检测预测Ev的AUROC为0．90。应用肝脏硬度预测Ev,80％患者可免除胃镜检查。肝脏硬度〈32．7kPa,排除EV的可能性为96．3％;肝脏硬度〉46．0kPa,确定EV存在的可能性为83．3％,阳性似然比为17．8。结论肝脏超声评分联合肝脏硬度可有效筛选、预测EV状态;在ALT〉5×ULN者中,肝脏硬度检测可独立准确预测EV状态。     

Adjuvant transcatheter arterial chemoembolization after radical resection of hepatocellular carcinoma patients with tumor size less than 5 cm: a retrospective study

Objective: Our aim is to retrospectively compare the disease-free survival (DFS) of adjuvant TACE after surgical resection on patients with tumor less than 5?cm.

Methods: A total of 307 patients with HCC underwent hepatic resection between January 2014 to December 2016 were enrolled in this study. Among these, 172 patients underwent surgical treatment only (group A) and 135 patients received surgical resection followed by adjuvant TACE (group B). Propensity score matching (PSM) analysis is used to minimize baseline differences between two groups. DFS was compared between the two groups and Cox proportional hazard model was used to predict the factor for recurrence.

Results: Before PSM, the 1, 2, 3 year DFS rate of group A and B were 90.1%, 83.3%, 75.3% versus 85.2%, 73.9%, 68.1%, respectively (p?=?.286). After PSM, the 1, 2, 3 year DFS rate of group A and group B were 90.3%, 80.8%, 71.9% versus 89.2%, 77.8%, 71.3%, respectively (p?=?.791). In subgroup analysis where patients presented with microvascular invasion (MiVI), before PSM the 1, 2, 3 year DFS rate were 77.8%, 77.8%, 77.8% and 70%, 70%, 47.3%, for group A and B, respectively (p?=?.491). After PSM the 1, 2, 3 year DFS rate for group A and B were 71.4%, 71.4%, 71.4% and 100%, 100%, 50%, respectively (p?=?.440). Cox proportional hazard model identified tumor size ≥3?cm as factor related to recurrence.

Conclusions: Adjuvant TACE does not improve the DFS of HCC patients with tumor size less than 5?cm.     

Development of a nomogram to predict outcome after liver resection for hepatocellular carcinoma in Child-Pugh B cirrhosis

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Combination of repeated single-session percutaneous ethanol injection and transarterial chemoembolisation compared to repeated single-session percutaneous ethanol injection in patients with non-resectable hepatocellular carcinoma

AIM: To evaluate the treatment effect of percutaneous ethanol injection (PEI) for patients with advanced, non-resectable HCC compared with combination of transarterial chemoembolisation (TACE) and repeated single-session PEI, repeated single-session PEI alone, repeated TACE alone, or best supportive care. METHODS: All patients who received PEI treatment during the study period were included and stratified to one of the following treatment modalities according to physical status and tumor extent: combination of TACE and repeated single-session PEI, repeated single-session PEI alone, repeated TACE alone, or best supportive care. Prognostic value of clinical parameters including Okuda-classification, presence of portal vein thrombosis, presence of ascites, number of tumors, maximum tumor diameter, and serum cholinesterase (CHE), as well as Child-Pugh stage, a-fetoprotein (AFP), fever, incidence of complications were assessed and compared between the groups. Survival was determined using Kaplan-Meier and multivariate regression analyses. RESULTS: The 1- and 3-year survival of all patients was 73% and 47%. In the subgroup analyses, the combination of TACE and PEI (1) was associated with a longer survival (1-, 3-, 5-year survival: 90%, 52%, and 43%) compared to PEI treatment alone (2) (1-, 3-, 5-year survival: 65%, 50%, and 37%). Secondary PEI after initial stratification to TACE (3) yielded comparable results (1-, 3-, 5-year survival: 91%, 40%, and 30%) while PEI after stratification to best supportive care (4) was associated with decreased survival (1-, 3-, 5-year survival: 50%, 23%, 12%). Apart from the chosen treatment modalities, predictors for better survival were tumor number (n < 5), tumor size (< 5 cm), no ascites before PEI, and stable serum cholinesterase after PEI (P < 0.05). The mortality within 2 wk after PEI was 2.8% (n = 3). There were 24 (8.9%) major complications after PEI including segmental liver infarction, focal liver necrosis, and liver abscess. All complications could be managed non-surgically. CONCLUSION: Repeated single-session PEI is effective in patients with advanced HCC at an acceptable and manageable complication rate. Patients stratified to a combination of TACE and PEI can expect longer survival than those stratified to repeated PEI alone. Furthermore, patients with large or multiple tumors in good clinical status may also profit from a combination of TACE and reconsideration for secondary PEI.     

Diagnosis and treatment of hepatocellular carcinoma

The diagnosis and treatment of hepatocellular carcinoma (HCC) have witnessed major changes over the past decade. Until the early 1990s, HCC was a relatively rare malignancy, typically diagnosed at an advanced stage in a symptomatic patient, and there were no known effective palliative or therapeutic options. However, the rising incidence of HCC in several regions around the world coupled with emerging evidence for efficacy of screening in high-risk patients, liver transplantation as a curative option in select patients, ability to make definitive diagnosis using high-resolution imaging of the liver, less dependency on obtaining tissue diagnosis, and proven efficacy of transarterial chemoembolization and sorafenib as palliative therapy have improved the outlook for HCC patients. In this article, we present a summary of the most recent information on screening, diagnosis, staging, and different treatment modalities of HCC, as well as our recommended management approach.