经肝动脉介入治疗肝转移瘤的疗效影响因素

Objective To evaluate the efficacy in the patients with metastatic liver tumor treated with regional therapy of hepatic artery in Cox's regression multivariate analyses.Methods 115 patients with liver metastases were treated by regional therapy of hepatic artery in 274 times. Antitumor agents were selected according to the pathologic results of origin tumor,added embolization with lipiedol ultra-fluid(LUF) or/and gelatin sponge to the patients of hypervascular. Cox regression was used in proportional hazard analysis.Results Cox regression multivariable analyses showed that single lesion,without metastases to the other sites,lesion with hypervascularity, adjuvant chemotherapy after regional therapy of hepatic artery and origination of primary tumor significantly affected the survival time (P＜0.05).Conclusion Those of above mentioned are main influence factors in the patients with liver metastases treated by regional therapy of hepatic artery.     

Laparoscopic approach for hepatocellular carcinoma： where is the limit？

Hepatocellular cancer （HCC） is the sixth most common malignant tumor worldwide and the most common primary liver cancer （1）. Liver resection or liver transplantation is the therapeutic gold standards in patient with HCC. Due to advanced disease, extrahepatic metastases, or inadequate liver reserve, only 15% to 30% of patients with HCC can undergo to surgery （2）. Five-year risk of recurrence of HCC after resection is as high as 70% because the underlying chronic liver disease continues to put the patient at risk for the development of new cancer nodules （3）. Starting from the assumption that recurrence may be newly treated with surgery, laparoscopic approach is recommended,     

Radiological diagnosis and staging of hilar cholangiocarcinoma

Hilar cholangiocarcinoma is a rare malignant tumor arising from the epithelium of the bile ducts.Surgery is still the only chance of potentially curative treatment in patients with perihilar cholangiocarcinoma.However,radical resection requires aggressive surgical strategies that should be tailored optimally according to the location,size and vascular invasion of the tumors.Accurate diagnosis and staging of these tumors is therefore critical for optimal treatment planning and for determining a prognosis.Multidetector computed tomography(MDCT),magnetic resonance imaging(MRI) and MR cholangiography are useful tools,both to diagnose and stage hilar cholangiocarcinoma.Modern imaging techniques allow accurate detection of the level of obstruction and the longitudinal and radial spread of the tumor.In addition,high-resolution MDCT and MR provide specific radiographic features to determine vascular involvement of anatomic structures,such as the hepatic artery or the portal vein,which are critical to decide the surgical strategy.Finally,radiological staging allows detection of patients with distant metastasis in the liver or peritoneum who will not benefit from a surgical approach.     

Surgical treatment of hepatic metastases from colorectal cancer

Colorectal carcinoma is one of the most frequent cancers in Western societies with an incidence of around 700 per million people.About half of the patients develop metastases from the primary tumor and liver is the primary metastatic site.Improved survival rates after hepatectomy for metastatic colorectal cancer have been reported in the last few years and these may be the result of a variety of factors,such as advances in systemic chemotherapy,radiographic imaging techniques that permit more accurate determination of the extent and location of the metastatic burden,local ablation methods,and in surgical techniques of hepatic resection.These have led to a more aggressive approach towards liver metastatic disease,resulting in longer survival.The goal of this paper is to review the role of various forms of surgery in the treatment of hepatic metastases from colorectal cancer.     

肝细胞癌的血清标志物

Hepatocellular carcinoma (HCC) is one of the most common malignant tumor with increasing incidence worldwid.Most of patients with HCC are diagnosed at a late stage.Threrfore,the prognosis of HCC patients is generally poor with a 5-year survival rate of 20% if withoutoperration. Screening strategies including α-fetoprotein (AFP) and ultrasound every 6 months in patients with liver cirrhosis,the major risk factor for HCC development, have been recommended to detect HCC at earlier stages amenable to effective treatment strateges.AFP, however,is a marker with poor sensitivity and specificity and the ultrasound is highly dependent on the operator's experience.Apart from AFP, lens culinaris agglutinin-reactive AFP and des-gamma carbexyprothrombin and several other biomarkers(e.g., glypican-3,human hepatocyte growth factor,and insulin-like growth factor) have been proposed as markers for HCC detection.In addition,with recently employed techniques,such as gene-expressing microarrays and proteomics,it is to be expected that new HCC-specific markers will become available in the near future.For all such proposed markers,however,the clinical usefulness has to be carefully evaluated and validated.     

肝细胞癌的血清标志物

Hepatocellular carcinoma (HCC) is one of the most common malignant tumor with increasing incidence worldwid.Most of patients with HCC are diagnosed at a late stage.Threrfore,the prognosis of HCC patients is generally poor with a 5-year survival rate of 20% if withoutoperration. Screening strategies including α-fetoprotein (AFP) and ultrasound every 6 months in patients with liver cirrhosis,the major risk factor for HCC development, have been recommended to detect HCC at earlier stages amenable to effective treatment strateges.AFP, however,is a marker with poor sensitivity and specificity and the ultrasound is highly dependent on the operator's experience.Apart from AFP, lens culinaris agglutinin-reactive AFP and des-gamma carbexyprothrombin and several other biomarkers(e.g., glypican-3,human hepatocyte growth factor,and insulin-like growth factor) have been proposed as markers for HCC detection.In addition,with recently employed techniques,such as gene-expressing microarrays and proteomics,it is to be expected that new HCC-specific markers will become available in the near future.For all such proposed markers,however,the clinical usefulness has to be carefully evaluated and validated.     

Transcatheter embolization therapy in liver cancer:an update of clinical evidences

Transarterial chemoembolization(TACE) is a form of intra-arterial catheter-based chemotherapy that selectively delivers high doses of cytotoxic drug to the tumor bed combining with the effect of ischemic necrosis induced by arterial embolization.Chemoembolization and radioembolization are at the core of the treatment of liver hepatocellular carcinoma(HCC) patients who cannot receive potentially curative therapies such as transplantation,resection or percutaneous ablation.TACE for liver cancer has been proven to be useful in local tumor control,to prevent tumor progression,prolong patients’ life and control patient symptoms.Recent evidence showed in patients with single-nodule HCC of 3 cm or smaller without vascular invasion,the5-year overall survival(OS) with TACE was similar to that with hepatic resection and radiofrequency ablation.Although being used for decades,Lipiodol~(Lipiodol~ Ultra Fluid~,Guerbet,France) remains important as a tumor-seeking and radio-opaque drug delivery vector in interventional oncology.There have been efforts to improve the delivery of chemotherapeutic agents to tumors.Drug-eluting bead(DEB) is a relatively novel drug delivery embolization system which allows for fixed dosing and the ability to release the anticancer agents in a sustained manner.Three DEBs are available,i.e.,Tandem~(CeloNova Biosciences Inc.,USA),DC-Beads~(BTG,UK) and HepaSphere~(BioSphere Medical,Inc.,USA).Transarterial radioembolization(TARE) technique has been developed,and proven to be efficient and safe in advanced liver cancers and those with vascular complications.Two types of radioembolization microspheres are available i.e.,SIR-Spheres~(Sirtex Medical Limited,Australia) and TheraSphere~(BTG,UK).This review describes the basic procedure of TACE,properties and efficacy of some chemoembolization systems and radioembolization agents which are commercially available and/or currendy under clinical evaluation.The key clinical trials of transcatheter arterial therapy for liver cancer are summarized.     

Primary hepatocellular carcinoma and metabolic syndrome: An update

Hepatocellular carcinoma(HCC) is the most common primary liver malignancy. The incidence of hepatocellular carcinoma has increased dramatically by 80% over the past two decades in the United States. Numerous basic science and clinical studies have documented a strong association between hepatocellular carcinoma and the metabolic syndrome. These studies have documented that, in most patients, non-alcoholic fatty liver disease is the hepatic manifestation of the metabolic syndrome, which may progress to hepatocellular carcinoma through the cirrhotic process. However, minority of patients with non-alcoholic fatty liver disease may progress to hepatocellular carcinoma without cirrhosis.This review summarizes the current literature of the link between hepatocellular carcinoma and metabolic syndrome with special emphasis on various components of the metabolic syndrome including risk of association with obesity, diabetes mellitus, hyperlipidemia,and hypertension. Current understanding of pathophysiology, clinical features, treatments, outcomes,and surveillance of hepatocellular carcinoma in the background of metabolic syndrome and non-alcoholic fatty liver disease is reviewed. With the current epidemic of metabolic syndrome, the number of patients with non-alcoholic fatty liver disease is increasing.Subsequently, it is expected that the incidence and prevalence of HCC will also increase. It is very important for the scientific community to shed more light on the pathogenesis of HCC with metabolic syndrome,both with and without cirrhosis. At the same time it is also important to quantify the risk of hepatocellular carcinoma associated with the metabolic syndrome in a prospective setting and develop surveillance recommendations for detection of hepatocellular carcinoma in patients with metabolic syndrome.     

Baseline radiologic features as predictors of efficacy in patients with pancreatic neuroendocrine tumors with liver metastases receiving surufatinib

Objective:Currently,pre-treatment prediction of patients with pancreatic neuroendocrine tumors with liver metastases (PNELM) receiving surufatinib treatment was unsatisfying.Our objective was to examine the association between radiological characteristics and efficacy/prognosis.Methods:We enrolled patients with liver metastases in the phase III,SANET-p trial (NCT02589821) and obtained contrast-enhanced computed tomography (CECT) images.Qualitative and quantitative parameters including hepatic tu...     

Clinical implications of microRNAs in liver cancer stem cells

The prognosis of patients diagnosed with hepatocellular carcinoma (HCC) is often dismal, mainly due to late presentation, high recurrence rate, and frequent resistance to chemotherapy and radiotherapy. Accumulating evidence on the differential microRNA (miRNA) expression patterns between non-tumor and HCC tissues or between liver cancer stem cells (CSCs) and non-CSC subsets and the significant clinical implications of these differences suggest that miRNAs are a promising, non-invasive marker for the prognosis and diagnosis of the disease. This perspective article summarizes the current knowledge of miRNAs in liver CSCs and highlights the need for further investigations of the role of miRNAs in regulating liver CSC subsets for possible future clinical applications.     

Multicenter analysis of soluble Axl reveals diagnostic value for very early stage hepatocellular carcinoma

If diagnosed at early stages, patients with hepatocellular carcinoma (HCC) can receive curative therapies, whereas therapeutic options at later stages are very limited. Here, we addressed the potential of soluble Axl (sAxl) as a biomarker of early HCC by analyzing levels of sAxl in 311 HCC and 237 control serum samples from centers in Europe and China. Serum concentrations of sAxl were significantly increased in HCC (18.575 ng/mL) as compared to healthy (13.388 ng/mL) or cirrhotic (12.169 ng/mL) controls. Receiver operating characteristic curve analysis of sAxl in very early stage HCC patients (BCLC 0) showed an area under the curve (AUC) of 0.848, with a sensitivity of 76.9% and a specificity of 69.2%. α‐Fetoprotein (AFP)‐negative HCC patients displayed an AUC of 0.803, with sensitivity and specificity of 73% and 70.8%. Combination of sAxl and AFP improved diagnostic accuracy to 0.936 in very early HCC patients and to 0.937 in all HCC. Differential diagnosis of very early HCC versus liver cirrhosis showed a combined performance for sAxl and AFP of 0.901 with a sensitivity of 88.5% and a specificity of 76.7%. Furthermore, sAxl levels failed to be elevated in primary ovarian, colorectal and breast carcinomas as well as in secondary hepatic malignancies derived from colon. In summary, sAxl outperforms AFP in detecting very early HCC as compared to healthy or cirrhotic controls and shows high diagnostic accuracy for AFP‐negative patients. sAxl is specific for HCC and suggested as a biomarker for routine clinical use.     

Localization of small liver tumors.

Thirty-six patients with small liver tumor were diagnosed by alpha-fetoprotein (AFP); sonography, and computed tomography (CT), and underwent hepatectomy. The pathological types included 23 hepatocelluler carcinoma (HCC), 11 hepatic cavernous hemangioma, and 2 secondary liver cancer. In 22 patients, the tumor nodules were located in the right lobe and 14 cases in the left lobe. The diagnostic accuracy rate of CT was 100% for HCC and secondary liver cancer, but for hepatic cavernous hemangioma it was only 72.2%. However, the accuracy rate of sonography was as high as 81.8% for hepatic cavernous hemangioma and only 60.4% for liver malignancies. The positive rate of AFP for the HCC patients of this series was only 66.6%. The method of intraoperative detection of small liver tumor is introduced, if the tumor was invisible grossly or nonpalpable during exploratory laparotomy. In the series, 7 cases in whom the right lobe lesion was too small to be located by routine manual examination during exploratory laparotomy were detected by this method, and all small liver tumors were resected successfully.     

外周血AFP mRNA表达与原发性肝癌转移的关系

目的 通过检测手术或介入治疗前后的肝癌患者外周血甲胎蛋白信使核糖核酸（ＡＦＰ ｍＲＮＡ）的表达,了解原发生性肝癌的血行播散情况及肝癌综合治疗的病理生理基础。方法 采用巢式逆转录－聚合酶链式反应（ＲＴ－ＰＣＲ）检测技术,对５４例原发性吕患者外周血样本ＡＦＰｍＲＮＡ的表达进行了研究。结果 ５４例样本中,２６例（４８．１％）ＡＦＰ ｍＲＮＡ阳性,２０例正常人及１０例良性肝病患者分别只有１例阳性。１６例伴     

富血供肝转移瘤的MRI表现和特点

背景与目的：肝脏是血源性转移癌最好发的器官，正确判断富血供肝转移瘤具有重要的临床价值，本研究探讨富血供肝转移瘤的MRI特征。方法：回顾性分析122例有明确原发肿瘤病史并伴有肝脏转移的病例。根据强化程度，当病灶显示出明显的早期强化（强化程度与胰腺或肾皮质相仿）时，肝转移瘤被认为是富血供的，据此，共有31例符合人选标准，其中男性8例，女性23例，年龄29～77岁，平均年龄51．9岁。所有31例均行上腹部MRI检查（采用1．5T超导MR扫描仪），扫描序列包括T2WIFSE序列，T1WISPGR序列（用于增强前后扫描）。对比剂为钆喷酸葡胺注射液（Gd—DTPA），注射剂量为0．1mmol/kg，注射速率为2ml／s，注射后行Ⅲ期扫描，扫描时间分别为：20、45、90S。所有MR图像由两位有经验的放射科高年主治医师分析并达成一致。结果：31例患者共发现239个肝转移灶，分布于两叶，无特别好发肝段。其中21例转移灶为多发，其余10例为单发转移灶。病灶小于9．5cm。MR图像显示所有病灶于T1WI均为低信号。在T2WI图像上，127个病灶（53％）显示为中等高信号，65个病灶（27％）为中等高信号伴病灶中央更高信号区。增强动脉期显示183个病灶（77％）呈明显的边缘强化，41个病灶（17％）呈弥漫均匀的结节样强化，15个病灶（6％）呈弥漫不均匀强化。增强门脉期，131个病灶表现为与动脉期相仿的强化方式与程度，其中33个病灶表现为较动脉期稍增厚的强化环。结论：根据富血供肝转移瘤的主要特征．大多数病灶可以和肝脏其他富血供病变（如HCC．血管瘤，FNH等）能正确鉴别。     

500例原发性肝癌的磁共振表现

背景与目的:磁共振成像(magneticresonanceimaging,MRI)是肝内恶性肿瘤的主要影像学诊断方法之一。本文总结了500例原发性肝癌的MRI表现,以评价钆-二乙烯三胺五乙酸(gadolinium-diethylenetriaminepentaacetic,Gd-DTPA)增强及超顺磁氧化铁(superparamagneticironoxideparticles,SPIO)增强扫描对小肝癌的诊断价值。资料与方法:收集我院行MR检查并经病理确诊为原发性肝癌的患者500例,分别行平扫、平扫+Gd-DTPA增强T1加权扫描、平扫+Gd-DTPA增强T1加权+SPIO增强重T2加权扫描。结果:500例原发性肝癌中,小肝癌有65例(13%),结节型肝癌81例(16.2%),块状型肝癌325例(65%),弥漫型肝癌29例(5.8%);单发310例(62%),多发190例(38%)。全组淋巴结转移率为12%;静脉癌栓率为31.4%。非弥漫型肝癌的肿块最大直径与子灶、异叶转移、淋巴结转移、癌栓之间存在正相关(P<0.05)。65例小肝癌的病灶总数为71个,平扫和增强、Gd-DTPA+SPIO增强和Gd-DTPA增强所发现病灶的平均数之间均存在显著差异(P<0.05)。结论:非弥漫型肝癌的肿块直径越大越容易发生子灶、异叶转移,淋巴结转移及癌栓。MRI诊断小肝癌,增强扫描比平扫有利于发现较多的病灶,而SPIO+Gd-DTPA增强比单纯Gd-DTPA增强发现的病灶多。     

高强度聚焦超声治疗肝癌的近期疗效分析

目的探讨高强度聚焦超声(HIFU)治疗肝癌的近期疗效。方法44例肝癌患者通过全身麻醉、超声肿瘤定位进行HIFU治疗,观察HIFU治疗前后临床症状以及肝功能、AFP、MRI的变化。结果HIFU治疗后患者的临床症状缓解率为87.5％(28/32),其中3例患者少量腹水自行消失。治疗前患者的ALT为(79.73±12.31)U/L,AST为(103.47±24.55)U/L;治疗后ALT、AST降至正常水平者分别占84.6％(22/26)和73.5％(25/34),AFP降低超过原数值50％者占64.3％(18/28),MRI显示肿瘤治疗区已凝固性坏死,肿瘤血供减少或消失。结论HIFU对肝癌患者的治疗是确切有效的,可成为肝癌无创局部治疗的新方法。     

Alpha-fetoprotein synthesis in human hepatocellular carcinoma: correlation with hepatitis B surface antigen expression.

We analyzed the pattern of alpha-fetoprotein (AFP) synthesis in 40 consecutive human hepatocarcinomas (HCC) in relation to hepatitis B viral (HBV) infection. In addition, histopathological characteristics of liver parenchyma and the tumor itself were examined. Elevated AFP (> 20 ng/ml) were found in 90% of HCC patients and in none of the controls. In 35% of HCC cases, serum AFP was above 100,000 ng/ml. AFP levels were significantly higher in patients seropositive for hepatitis B surface antigen (HBsAg) compared with their negative counterparts (mean log[AFP]: 4.28 +/- 1.67 vs. 3.28 +/- 1.96, respectively; geometric mean (GM): 19,322.6 ng/ml and 1939.5 ng/ml, respectively; p < 0.05). Furthermore, serum AFP levels were higher in HCC patients with liver cirrhosis than in those without (log[AFP]: 4.43 +/- 1.58 vs. 3.23 +/- 1.98, respectively; p < 0.05). However, the relationship of cirrhosis with AFP was confounded by the high prevalence of HBsAg in cirrhotic HCC patients. There was no correlation of AFP with either liver necrosis (abnormal AFP in 45% of cases; mean log[AFP]: 3.99 +/- 1.91 vs. 3.75 +/- 1.85 for HCC with and without necrosis, respectively; 0.05 < p < 0.68, not significant (NS)), or inflammation (abnormal AFP in 25%; mean log[AFP]: 4.33 +/- 1.62 vs. 3.70 +/- 1.93 for HCC with and without inflammation, respectively; 0.05 < p < 0.39, NS). A vast majority of HCC (75%) were moderately (grade 2-3) or poorly differentiated tumors (grade 3, grade 4, or combined grade 3-4). Serum AFP did not correlate with tumor grade. Immunohistochemical analysis of HBsAg and AFP confirmed the serological findings, and confirmed earlier observations of elevated AFP in HBsAg-positive patients. These results may reflect pathogenic and biological differences between HBsAG-secreting and nonsecreting HCC.     

多针双电极射频适形消融治疗肝癌16例报告

目的 探讨多针双电极射频适形消融治疗肝癌的原理和近期疗效。方法 采用多针双电极射频消融肝肿瘤16例,全部采用超声引导下经皮穿剌,单纯射频消融治疗15例,射频消融联合瘤内无水酒精注射术治疗1例。结果 全组有12例患者治疗1次后影像学检查见肿瘤完全消融,4例首次射频治疗后1个月影像学检查见肿瘤消融不完全,2例再次行射频消融后肿瘤完全消融。甲胎蛋白阳性者6例治疗后全部转为阴性。结论 多针双电极射频不仅能增大消融范围,而且可以根据肿瘤形态适形消融肿瘤,是1种新的有效射频消融技术。     

Pilot study of albendazole in patients with advanced malignancy. Effect on serum tumor markers/high incidence of neutropenia

Our preclinical studies have shown that the widely used antiparasitic drug albendazole has potent antiproliferative activity against colorectal cancer (CRC) and hepatocellular carcinoma (HCC). This trial was designed to evaluate albendazole in a small number of patients (n = 7) with either HCC or CRC and hepatic metastases refractory to other forms of therapy. Albendazole was given at 10 mg/kg/day orally in two divided doses for a period of 28 days. To follow the effect of treatment, tumor markers, carcinoembryonic antigen (CEA) or alpha-feto protein (AFP), were measured routinely in these patients. A range of hematological and biochemical indices were also serially measured to monitor bone marrow, kidney or liver toxicity. Albendazole therapy resulted in a decrease in CEA in 2 patients. In the remaining 5 with measurable tumor markers, serum CEA or AFP was stabilized in 3 patients, while in the other 2, after an initial stabilization (5-10 days), the markers began to increase. In the 7 patients completing the trial, albendazole was well tolerated and there were no significant changes in any hematological, kidney or liver function tests, but 3 patients were withdrawn for severe neutropenia which was probably contributory to the death of 1 patient. These data support our previous experimental results demonstrating that albendazole has antitumor effects.     

Do CA 19-9 and TPA play a minor role as compared to AFP in diagnosing primary hepatocellular carcinoma?

This study was undertaken in order to compare the ability of 4 tumour markers to discriminate between liver cirrhosis patients with or without hepatocellular carcinoma (HCC). Serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), CA 19-9 and tissue polypeptide antigen (TPA) were determined in 63 patients with liver cirrhosis and in 25 patients with HCC in liver cirrhosis. All 4 serum markers were found to be increased in a number of liver cirrhosis patients, regardless of the presence of HCC. AFP was found to be more elevated in HCC patients as compared to the other group; no difference was observed for CA 19-9, CEA and TPA. A significant correlation was detected in HCC patients between AFP and TPA. Significant correlation were detected in all except HCC patients between liver function tests and TPA. We can conclude that AFP determination remains as yet the only suitable marker able to detect HCC in liver cirrhosis. The newly introduced serum marker CA 19-9 is, as previously reported, unhelpful for CEA. TPA can in some instances (i.e. in the absence of an important hepatic cell necrosis or cholestasis) provide a clue to neoplastic growth.