Systematic review of the outcomes of surgical resection for intermediate and advanced Barcelona Clinic Liver Cancer stage hepatocellular carcinoma:A critical appraisal of the evidence

AIM To perform a systematic review to determine the survival outcomes after curative resection of intermediate and advanced hepatocellular carcinomas(HCC).METHODS A systematic review of the published literature was performed using the PubM ed database from 1 st January 1999 to 31 st Dec 2014 to identify studies that reported outcomes of liver resection as the primary curative treatment for Barcelona Clinic Liver Cancer(BCLC) stage B or C HCC. The primary end point was to determine the overall survival(OS) and disease free survival(DFS) of liver resection of HCC in BCLC stage B or C in patients with adequate liver reserve(i.e., Child's A or B status). The secondary end points were to assess the morbidity and mortality of liver resection in large HCC(defined as lesions larger than 10 cm in diameter) and to compare the OS and DFS after surgical resection of solitary vs multifocal HCC.RESULTS We identified 74 articles which met the inclusion criteria and were analyzed in this systematic review. Analysis of the resection outcomes of the included studies were grouped according to(1) BCLC stage B or C HCC,(2) Size of HCC and(3) multifocal tumors. The median 5-year OS of BCLC stage B was 38.7%(range 10.0-57.0); while the median 5-year OS of BCLC stage C was 20.0%(range 0.0-42.0). The collective median 5-year OS of both stages was 27.9%(0.0-57.0). In examining the morbidity and mortality following liver resection in large HCC, the pooled RR for morbidity [RR(95%CI) = 1.00(0.76-1.31)] and mortality [RR(95%CI) = 1.15(0.73-1.80)] were not significant. Within the spectrum of BCLC B and C lesions, tumors greater than 10 cm were reported to have median 5-year OS of 33.0% and multifocal lesions 54.0%.CONCLUSION Indication for surgical resection should be extended to BCLC stage B lesions in selected patients. Further studies are needed to stratify stage C lesions for resection.

三种心电图标准对疑似ACS合并完全性左束支传导阻滞时被视为STEMI等危征的诊断价值

目的 探讨使用三种心电图诊断标准对急诊科拟诊为急性冠脉综合征(ACS)患者合并完全性左束支传导阻滞(CLBBB)时被视为ST段抬高型心肌梗死(STEMI)等危征,最终经急诊冠脉造影证实发生急性心肌梗死的诊断能力。方法 回顾性分析41例在急诊科拟诊为ACS合并CLBBB的患者,均经急诊完善冠脉造影后收入心内科重症监护单元(CCU),最终诊断分为AMI组(n=15)和非AMI组(n=26),分别使用巴塞罗那标准、Sgarbossa标准和Smith标准对两组患者心电图进行评测,绘制各诊断标准受试者工作特征(ROC)曲线,并得出ROC曲线下面积(AUC),分别计算敏感度(SEN)、特异度(SPE)、阳性预测值(PPV)、阴性预测值(NPV)和准确度(CP),并进行解读。结果 巴塞罗那标准对在急诊科拟诊为ACS患者合并CLBBB时,经急诊冠脉造影证实诊断并治疗的AMI的AUC为0.947(P<0.001),其SEN、SPE、PPV、NPV、CP分别为92.9%、92.0%、86.7%、95.8%、92.3%;Sgarbossa≥3标准诊断AMI的AUC为0.647(P=0.120),其SEN、SPE、PPV、NPV、CP分别为35.7%、96.0%、83.3%、72.7%、74.4%;Sgarbossa≥2标准诊断AMI的AUC为0.604(P=0.273),其SEN、SPE、PPV、NPV、CP分别为42.9%、84.0%、60.0%、72.4%、69.2%;SmithⅢ标准诊断AMI的AUC为0.795(P=0.002),其SEN、SPE、PPV、NPV、CP分别为71.4%、92.0%、83.3%、85.2%、84.6%;SmithⅣ标准诊断AMI的AUC为0.656(P=0.099),其SEN、SPE、PPV、NPV、CP分别为50.0%、84.0%、63.6%、75.0%、71.8%;SmithⅤ标准诊断AMI的AUC为0.614(P=0.228),其SEN、SPE、PPV、NPV、CP分别为28.6%、96.0%、80.0%、70.6%、71.8%。巴塞罗那标准对在急诊科拟诊为ACS患者合并CLBBB时经急诊冠脉造影证实,诊断AMI的AUC、SEN、SPE、PPV、NPV、CP均高于Sgarbossa标准和Smith标准(P<0.001)。结论 急诊科拟诊为ACS合并CLBBB的患者中,应用心电图的巴塞罗那标准诊断AMI具有准确、简洁、实用的特点。

左束支阻滞时急性心肌梗死的诊断

左束支阻滞(left bundle branch block,LBBB)时心室激动顺序发生改变,左室除极位于QRS波后半部,因此,当LBBB合并急性心肌梗死(acute myocardial infarction,AMI)时,可干扰心电图诊断。本文介绍了Sgarbossa、Smith和巴塞罗那诊断标准,并比较其诊断敏感性及特异性。1996年提出的Sgarbossa标准根据ST段同向改变及过度反向抬高等指标诊断LBBB合并AMI,特异性高,但敏感性低。Smith标准将Sgarbossa标准中的"过度反向抬高≥0.5 m V"修订为考量ST段反向偏移幅度与S(R)波的比值,提高了诊断的敏感性。巴塞罗那标准提出,LBBB时任意导联ST段同向偏移≥0.1 m V,或低电压导联反向偏移≥0.1 m V时,即可诊断AMI,显著提高了诊断敏感性及特异性。Cabrera及Chapman征对LBBB合并AMI也具有辅助诊断价值。

Clinical outcome in patients with hepatocellular carcinoma after living-donor liver transplantation

AIM: To investigate risk factors for hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation (LDLT) and efficacy of various criteria. METHODS: From October 2000 to November 2011, 233 adult patients underwent LDLT for HCC at our institution. After excluding nine postoperative mortality cases, we analyzed retrospectively 224 patients. To identify risk factors for recurrence, we evaluated recurrence, disease-free survival (DFS) rate, survival rate, and various other factors which are based on the characteristics of both the patient and tumor. Additionally, we developed our own criteria based on our data. Next, we compared our selection criteria with various tumor-grading scales, such as the Milan criteria, University of California, San Francisco (UCSF) criteria, TNM stage, Barcelona Clinic Liver Cancer (BCLC) stage and Cancer of the Liver Italian Program (CLIP) scoring system. The median follow up was 68 (6-139) mo.RESULTS: In 224 patients who received LDLT for HCC, 37 (16.5%) experienced tumor recurrence during the follow-up period. The 5-year DFS and overall survival rates after LDLT in all patients with HCC were 80.9% and 76.4%, respectively. On multivariate analysis, the tumor diameter {5 cm; P < 0.001; exponentiation of the B coefficient [Exp(B)], 11.89; 95%CI: 3.784-37.368} and alpha fetoprotein level [AFP, 100 ng/mL; P = 0.021; Exp(B), 2.892; 95%CI: 1.172-7.132] had significant influences on HCC recurrence after LDLT. Therefore, these two factors were included in our criteria. Based on these data, we set our selection criteria as a tumor diameter ≤ 5 cm and AFP ≤ 100 ng/mL. Within our new criteria (140/214, 65.4%), the 5-year DFS and overall survival rates were 88.6% and 81.8%, respectively. Our criteria (P = 0.001), Milan criteria (P = 0.009), and UCSF criteria (P = 0.001) showed a significant difference in DFS rate. And our criteria (P = 0.006) and UCSF criteria (P = 0.009) showed a significant difference in overall survival rate. But Milan criteria did not show significant difference in overall survival rate (P = 0.137). Among stages 0, A, B and C of BCLC, stage C had a significantly higher recurrence rate (P = 0.001), lower DFS (P = 0.001), and overall survival rate (P = 0.005) compared with the other stages. Using the CLIP scoring system, the group with a score of 4 to 5 showed a high recurrence rate (P = 0.023) and lower DFS (P = 0.011); however, the overall survival rate did not differ from that of the lower scoring group. The TNM system showed a trend of increased recurrence rate, decreased DFS, or survival rate according to T stage, albeit without statistical significance. CONCLUSION: LDLT is considered the preferred therapeutic option in patients with an AFP level less than 100 ng/mL and a tumor diameter of less than 5 cm.

challenges of advanced hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is an aggressive malignancy,resulting as the third cause of death by cancer each year. The management of patients with HCC is complex,as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging,clinical and biochemical parameters is routinely performed,a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice,several phase Ⅲ clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Locoregional therapies have also been tested as first line treatment,but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally,robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials.

Advanced hepatocellular carcinoma and sorafenib: Diagnosis, indications, clinical and radiological follow-up

Advanced stage hepatocellular carcinoma(HCC) is a category of disease defined by radiological, clinical and hepatic function parameters, comprehending a wide range of patients with different general conditions. The main therapeutic option is represented by sorafenibtreatment, a multi-kinase inhibitor with anti-proliferative and anti-angiogenic effect. Trans-arterial Radio Embolization also represents a promising new approach to intermediate/advanced HCC. Post-marketing clinical studies showed that only a portion of patients actually benefits from sorafenib treatment, and an even smaller percentage of patients treated shows partial/complete response on follow-up examinations, up against relevant costs and an incidence of drug related adverse effects. Although the treatment with sorafenib has shown a significant increase in mean overall survival in different studies, only a part of patients actually shows real benefits, while the incidence of drug related significant adverse effects and the economic costs are relatively high. Moreover, only a small percentage of patients also shows a response in terms of lesion dimensions reduction. Being able to properly differentiate patients who are responding to the therapy from non-responders as early as possible is then still difficult and could be a pivotal challenge for the future; in fact it could spare several patients a therapy often difficult to bear, directing them to other second line treatments(many of which are at the moment still under investigation). For this reason, some supplemental criteria to be added to the standard modified Response Evaluation Criteria in Solid Tumors evaluation are being searched for. In particular, finding some parameters(cellular density, perfusion grade and enhancement rate) able to predict the sensitivity of the lesions to anti-angiogenic agents could help in stratifying patients in terms of treatment responsiveness before the beginning of the therapy itself, or in the first weeks of sorafenib treatment. This would bring a strongly desirable help in clinical managements of these patients.