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1.

Background and Aim

To investigate the value of changes in alpha-fetoprotein (AFP) levels for the prediction of radiologic response and survival outcomes in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) who received combined treatment of 3-dimensional conformal radiotherapy (3D-CRT) and transarterial chemoembolization (TACE).

Methods

A database of 154 HCC patients with PVTT and elevated AFP levels (>20 ng/mL) treated with 3D-CRT and TACE as an initial treatment between August 2002 and August 2008 was retrospectively reviewed. AFP levels were determined 1 month after radiotherapy, and AFP response was defined as an AFP level reduction of >20% from the initial level. Radiologic response, overall survival (OS), and progression-free survival (PFS) rates were compared between AFP responders and non-responders. Propensity-score based matching analysis was performed to minimize the effect of potential confounding bias.

Results

The median follow-up period was 11.1 months (range, 3.1–82.7 months). In the propensity-score matching cohort (92 pairs), a best radiologic response of CR or PR occurred in more AFP responders than AFP non-responders (41.3% vs. 10.9%, p < 0.001). OS and PFS were also longer in AFP responders than in non-responders (median OS 13.2 months vs. 5.6 months, p < 0.001; median PFS 8.7 months vs. 3.5 months, p < 0.001).

Conclusions

AFP response is a significant predictive factor for radiologic response. Furthermore, AFP response is significant for OS and PFS outcomes. AFP evaluation after combined radiotherapy and TACE appears to be a useful predictor of clinical outcomes in HCC patients with PVTT.  相似文献   

2.
Hepatocellular carcinoma is one of the most common malignancies worldwide, with a high risk of portal vein tumor thrombus (PVTT). Some promising results have been achieved for venous metastases of hepatocellular carcinoma; however, the etiology of PVTT is largely unknown, and it is unclear why the incidence of PVTT is not proportional to its distance from the carcinoma. We attempted to address this issue using physical concepts and mathematical tools. Finally, we discuss the relationship between the probability of a collision event and the microenvironment of the PVTT. Our formulae suggest that the collision probability can alter the tumor microenvironment by increasing the number of tumor cells.  相似文献   

3.
4.
肝癌是世界范围内恶性程度最高的恶性肿瘤之一。门静脉癌栓的出现加速了肝功衰竭以及门静脉高压的发生概率,严重影响了肝癌患者的预后,临床上对于肝癌合并门静脉癌栓的诊疗尤为棘手。传统的治疗手段对于肝癌合并门静脉癌栓的疗效欠佳,且创伤大、住院时间长、并发症多。介入治疗因其创伤小、住院时间短、并发症少,疗效确切等优势逐渐被人们认可。以往单独应用经导管肝动脉化疗栓塞术(Transcatheter Arterial Chemoembolization,TACE)治疗肝癌取得了可喜的成果,随着介入治疗的发展,TACE联合其他介入手段治疗肝癌伴门静脉癌栓引起了越来越多的学者重视。本文回顾了近几年来国内外的相关文献,对TACE联合其他介入手段治疗肝癌合并门静脉癌栓的方式及疗效做一综述,以期对肝癌的临床诊疗工作提供一些帮助。  相似文献   

5.

Background and Purpose

Liver cancer is the third leading cause of cancer mortality worldwide. The aim of this study was to investigate the frequency and characteristics of cerebral lipiodol embolism (CLE) in patients with hepatocellular carcinoma (HCC) receiving transarterial embolization/chemoembolization (TAE/TACE).

Methods

We reviewed all HCC patients who received TAE/TACE during the period of 2007 and 2013 at a university medical center. The frequency of CLE per procedure and the clinical manifestations of CLE, including the review of previous reported cases (n = 24), were analyzed.

Results

During the study period, a total of 7855 TAE/TACE procedures were conducted on 3277 patients. There were 8 patients (mean age 59±11 years; 5 males and 3 females) who developed CLE. The frequency of TAE/TACE-related CLE was 1.02 (95% CI, 0.44–2.01) per 1000 procedures. Acute disturbance of consciousness and respiratory distress after TAE/TACE were the most common presentations of CLE. All patients had disseminated infarcts involving both the anterior and posterior cerebral circulations. For 3 patients with shunting between the tumor feeding artery and the pulmonary vein, a specific imaging pattern of coexisting scattered hyperdense spots was found. Furthermore, combined with our 8 cases, the total of 32 cases indicated that old age and female sex were the two risk factors for poor outcome after CLE.

Conclusions

CLE is a rare but potentially serious complication in HCC patients receiving TAE/TACE. The clinical characteristics of CLE summarized in our study would help facilitate the ability of clinicians to provide timely diagnosis and management.  相似文献   

6.

Background

Intermediate-stage hepatocellular carcinoma (HCC), defined according to the Barcelona Clinic Liver Cancer (BCLC) staging system, is a heterogeneous condition with variable clinical benefits from transarterial chemoembolization (TACE). This study aimed to develop a simple validated prognostic score based on the predictive factors for survival in patients with intermediate-stage HCC treated with TACE.

Methods

Three-hundred and fifty patients with intermediate-stage HCC undergoing initial TACE at Chiba University Hospital (training cohort; n = 187) and two affiliated hospitals (validation cohort; n = 163) were included. Following variables were entered into univariate and multivariate Cox regression models to develop a points-based clinical scoring system: gender, age, etiology, pretreatment, Child–Pugh score, aspartate aminotransferase, creatinine, C-reactive protein, alfa-fetoprotein, size of the largest lesion, and number and location of lesions.

Results

The number of lesions and the Child–Pugh score were identified as independent prognostic factors in the training cohort. The development of a 0–7-point prognostic score, named the Chiba HCC in intermediate-stage prognostic (CHIP) score, was based on the sum of three subscale scores (Child–Pugh score = 0, 1, 2, or 3, respectively, number of lesions = 0, 2, or 3, respectively, HCV-RNA positivity = 0 or 1, respectively). The generated scores were then differentiated into five groups (0–2 points, 3 points, 4 points, 5 points, and 6–7 points) by the median survival time (65.2, 29.2, 24.3, 13.1, and 8.4 months, respectively; p < 0.0001). These results were confirmed in the external validation cohort (p < 0.0001).

Conclusions

The CHIP score is easy-to-use and may assist in finding an appropriate treatment strategy for intermediate-stage HCC.  相似文献   

7.

Background

Portal/hepatic vein tumor thrombosis (PVTT/HVTT) in hepatocellular carcinoma (HCC) is a sign of advanced stage disease and is associated with poor prognosis. This study investigated the surgical outcomes of patients with HCC and PVTT/HVTT to determine the most appropriate surgical treatment strategy for these patients.

Materials and Methods

The study population included 77 HCC patients from January 2004 to June 2009 who underwent hepatectomy in our department and were diagnosed with PVTT/HVTT based on pathological examination. The patients were divided into two groups: in group 1, PVTT/HVTT was located in the hepatic resection area and removed with the tumor en bloc (38 cases); in group 2, PVTT/HVTT was beyond the resection line and removed by suction or thrombectomy (39 cases). Concerning the factor of surgical margins, the patients were further divided into four subgroups: group 1A: patients in group 1 with surgical margins ≤1 cm (28 cases); group 1B: patients in group 1 with surgical margins >1 cm (9 cases); group 2A: patients in group 2 with surgical margins ≤1 cm (28 cases); and group 2B: patients in group 2 with surgical margins >1 cm (9 cases).

Results

Most of the characteristics of groups 1 and 2 were similar. Patients in group 2 had significantly higher median blood loss (p=0.002) and higher blood transfusion rate (p=0.002) during the operation, which were not considered prognostic factors (p=0.323 and 0.571, respectively). The median overall survival (OS) duration in group 1 was significantly longer than that in group 2 (14.3 vs. 10.4 months, p=0.047). The median OS durations in groups 1A, 1B, 2A, and 2B were 14.3, 42.7, 7.5, and 18.0 months, respectively, which were significantly different(p=0.018).

Conclusions

When PVTT/HVTT is located in the hepatic resection area and removed with the tumor en bloc, the median OS duration is longer. Based on this finding, widening the surgical margins when technically possible may increase OS.  相似文献   

8.

Background

In previous randomized trials, transarterial chemoembolization (TACE) has shown an improvement of survival rate in hepatocellular carcinoma (HCC) when combined with radiofrequency ablation (RFA), percutaneous ethanol injection (PEI) or other therapies. The aim of this meta-analysis was to evaluate the effectiveness of combination therapy of TACE with RFA, PEI, radiotherapy (RT), three-dimensional conformal radiation therapy (3D-CRT) or High-Intensity Focused Ultrasound (HIFU).

Methods

Randomized or nonrandomized studies comparing TACE combined with RFA, PEI, RT, 3D-CRT or HIFU with TACE alone for HCC were included. Meta-analysis was performed using a fix-effects model in RCTs and a random-effects model among the observational studies.

Results

10 randomized trials and 18 observational studies matched the selection criteria, including 2497 patients (682 in RCTs, 1815 in non-RCTs). Meta-analysis of RCTs showed that the combination of TACE and PEI ((RR)1 -year=1.10, 95%CI=0.99-1.22, p=0.073; (RR)3 -year=2.32, 95%CI=1.52-3.53, p<0.001), TACE+RT ((RR)1 -year=1.37, 95%CI=1.11-1.70, p=0.004; (RR)3 -year=2.32, 95%CI=1.44-3.75, p=0.001) were associated with higher survival rates. The results of observational studies were in good consistency with that of RCTs. Furthermore, TACE plus 3D-CRT ((RR)1 -year=1.22, 95%CI=1.06-1.41, p=0.005; (RR)3 -year=2.05, 95%CI=1.48-2.84, p<0.001) and TACE plus HIFU ((RR)1 -year=1.16, 95%CI=1.01-1.33, p=0.033; (RR)3 -year=1.66, 95%CI=1.12-2.45, p=0.011) have introduced marked survival benefit when pooling results from observational studies.

Conclusions

This meta-analysis demonstrated that TACE combined with local treatments, especially PEI, HIFU or 3D-CRT could improve the overall survival status than performing TACE alone. Importantly, these results need to be validated in further high-quality clinical trials.  相似文献   

9.

Background

Nodal, a TGF-β-related embryonic morphogen, is involved in multiple biologic processes. However, the expression of Nodal in hepatocellular carcinoma (HCC) and its correlation with tumor angiogenesis, epithelial-mesenchymal transition, and prognosis is unclear.

Methods

We used real-time PCR and Western blotting to investigate Nodal expression in 6 HCC cell lines and 1 normal liver cell line, 16 pairs of tumor and corresponding paracarcinomatous tissues from HCC patients. Immunohistochemistry was performed to examine Nodal expression in HCC and corresponding paracarcinomatous tissues from 96 patients. CD34 and Vimentin were only examined in HCC tissues of patients mentioned above. Nodal gene was silenced by shRNA in MHCC97H and HCCLM3 cell lines, and cell migration and invasion were detected. Statistical analyses were applied to evaluate the prognostic value and associations of Nodal expression with clinical parameters.

Results

Nodal expression was detected in HCC cell lines with high metastatic potential alone. Nodal expression is up-regulated in HCC tissues compared with paracarcinomatous and normal liver tissues. Nodal protein was expressed in 70 of the 96 (72.9%) HCC tumors, and was associated with vascular invasion (P = 0.000), status of metastasis (P = 0.004), AFP (P = 0.049), ICGR15 (indocyanine green retention rate at 15 min) (P = 0.010) and tumor size (P = 0.000). High Nodal expression was positively correlated with high MVD (microvessal density) (P = 0.006), but not with Vimentin expression (P = 0.053). Significantly fewer migrated and invaded cells were seen in shRNA group compared with blank group and negative control group (P<0.05). High Nodal expression was found to be an independent factor for predicting overall survival of HCC.

Conclusions

Our study demonstrated that Nodal expression is associated with aggressive characteristics of HCC. Its aberrant expression may be a predictive factor of unfavorable prognosis for HCC after surgery.  相似文献   

10.
Tumor biomarkers commonly used for the detection of hepatocellular carcinoma (HCC) complicated with portal vein tumor thrombosis (PVTT) do not show satisfactory sensitivity and specificity. This study assesses the diagnostic value of the tumor biomarkers for the diagnosis of HCC with PVTT. A retrospective study was conducted on 475 patients diagnosed as HCC with PVTT and 977 patients diagnosed with HCC by imaging and requiring surgery at our hospital from January 1993 to January 2011. Serum alpha-fetoprotein AFP, carcinoembryonic antigen, and cancer antigen 125 (Ca125) of the patients were studied. No significant differences were observed in the patients’ general characteristics. The receiver operating characteristic (ROC) analysis showed that the cut-off of AFP and Ca125 was 32.91 ng/ml and 113.65 U/ml, respectively (AUC = 0.814 and 0.783). The parallel testing with AFP and Ca125 has a sensitivity of 0.909 and a specificity of 0.410; the serial testing has a sensitivity of 0.520 and a specificity of 0.97. The condition of AFP ≥ 20,000 ng/ml can detect HCC with PVTT with a sensitivity of 0.24, a specificity of 0.96, and an accuracy of 0.73 and positive screening of 0.76. The standard of both AFP > 32.91 ng/ml and Ca125 > 113.65 U/ml or AFP ≥ 20,000 ng/ml can detect HCC with PVTT with a specificity of 0.97 and 0.96, respectively, providing important guidance for clinical practice.  相似文献   

11.
12.

Background and Aim

Hepatocellular carcinoma (HCC) is one of the most deadly tumors. Transarterial chemoembolization (TACE) is effective for unresectable HCC. In recent years, miRNAs have been proposed as novel diagnostic and prognostic tools for HCC. This study aimed to identify whether microRNAs (miRNAs) can serve as biomarkers to reliably predict outcome before HCC patients are treated with TACE.

Methods

Eleven miRNAs (miR-, miR-19a, miR-101-3p, miR-199a-5p, miR-200a, miR-21, miR-214, miR-221, miR-222, miR-223 and miR-, -5p) were quantified by quantitative real-time PCR (qRT-PCR) in 136 HCC patients’ serum before they received TACE therapy. Univariate and multivariate analysis were used to identify the prognostic value of clinical parameters and miRNAs. Area under the receiver operating characteristic curve (AUC) was used to evaluate the prediction potency.

Results

The levels of some miRNAs were dramatically associated with clinicopathologic features regarding Child-Puge class, AFP, tumor size and satellite nodules. Univariate analysis revealed that miR-200a, miR-21, miR-122 and miR-224-5p were significantly associated with patients’ survival. Multivariate analysis demonstrated that AFP, satellite nodules and miR-200a were the independent prognostic factors associated with survival in this cohort (p = 0.000, 0.001, 0.000, respectively). The probability of the prognostic accuracy of miR-200a was 81.64% (74.47% specificity and 88.76% sensitivity), which was higher than the classifier established by combination of AFP and satellite nodules (76.87% probability, 70.21% specificity and 69.66% sensitivity). Furthermore, the combination of AFP, satellite nodules and miR-200a demonstrated as a classifier for HCC prognosis, yielding a ROC curve area of 88.19% (93.62% specificity and 68.54% sensitivity).

Conclusions

Our study indicated that serum miR-200a may prognosticate disease outcome in HCC patients with TACE therapy. Therefore, miR-200a can potentially guide individualized treatment for HCC patients with a high risk of TACE treatment failures.  相似文献   

13.

Background

The flotillin family member flotillin-1 (FLOT1) encodes a caveolae-associated, integral membrane protein that belongs to lipid raft family and involves in vesicular trafficking and signal transduction. However, the role of FLOT1 in development and progression of cancer remains largely unknown. The present study was aimed to investigate the clinical and prognostic significance of FLOT1 in hepatocellular carcinoma (HCC).

Methods

Real-time PCR and western blot analyses were applied to examine FLOT1 expression in fourteen HCC cell lines and one normal hepatic cell line, ten pairs of primary HCC and matched adjacent noncancerous liver tissues from the same patient. Immunohistochemistry (IHC) was performed to examine FLOT1 protein expression in paraffin-embedded tissues from 196 HCC patients. Statistical analyses were applied to evaluate the diagnostic value and associations of FLOT1 expression with clinical parameters.

Results

FLOT1 expression was evidently up-regulated in HCC tissues compared with that in the matched adjacent noncancerous liver tissues. In the 196 cases of tested HCC samples, FLOT1 protein level was positively correlated with Tumor size (P = 0.025), clinical stage (P<0.002), CLIP stage (P<0.001), vascular invasion (P<0.001), relapse (P<0.001), and serum AFP levels (P = 0.025). Patients with higher FLOT1 expression had shorter overall survival time, whereas those with lower FLOT1 expression had longer survival time.

Conclusions

Our study demonstrated FLOT1 is associated with aggressive characteristics of HCC, and suggested the possibility of its use as a prognostic marker in patients with HCC.  相似文献   

14.
目的:对不同方式治疗原发性肝癌(HCC)合并门静脉癌栓(PVTT)的治疗效果进行比较。方法:收取我院2010年2月至2013年3月收治的HCC合并PVTT患者83例进行回顾性分析,按照治疗方法的不同分为A组(手术+经导管动脉化疗栓塞TACE)26例、B组(手术+门静脉化疗PVC)25例以及C组(手术+TACE+PVC)32例。对三组患者不良反应发生情况、生存率、生存质量进行考察与比较,并对可能影响生存率的因素进行分析。结果:三组患者均行手术切除,切除率为100%。三组患者化疗后不良反应发生率方面比较差异无统计学意义(P0.05)。C组患者生存质量提高总有效率及改善率分别为78.13%和50.00%,均显著高于其他两组,差异有统计学意义(P0.05)。C组患者中位生存时间及半年、1年、2年、3年生存率均显著高于A组和B组,差异具有统计学意义(P0.05)。影响HCC合并PVTT患者的主要因素包括肿瘤大小、肿瘤数目、病理分级及癌栓类型(P0.05)。结论:HCC合并PVTT患者术后使用TACE+PVC联合治疗可有效提高患者生存率,改善生活质量。  相似文献   

15.
目的:探讨原发性肝癌合并下腔静脉癌栓的手术治疗方法.方法:采用肝切除加下腔静脉取栓治疗2例肝癌合并下腔静脉癌栓患者,取栓方法包括经荷栓肝静脉取栓(1例)和下腔静脉切开取栓(1例),又分在全肝血流阻断下取栓和在萨氏钳局部血管阻断下取栓.结果:2例肝癌及下腔静脉癌栓均得到成功切除,术中无明显并发症发生;术后无死亡;随访中一例存活11月;另1例已生存8个月.结论:肝癌合并下腔静脉癌栓的手术治疗安全可行,其基本术式为肝切除加下腔静脉切开取检.  相似文献   

16.
目的:探讨原发性肝癌合并下腔静脉癌栓的手术治疗方法。方法:采用肝切除加下腔静脉取栓治疗2例肝癌合并下腔静脉癌栓患者,取栓方法包括经荷栓肝静脉取栓(1例)和下腔静脉切开取栓(1例),又分在全肝血流阻断下取栓和在萨氏钳局部血管阻断下取栓。结果:2例肝癌及下腔静脉癌栓均得到成功切除,术中无明显并发症发生;术后无死亡;随访中一例存活11月;另1例已生存8个月。结论:肝癌合并下腔静脉癌栓的手术治疗安全可行,其基本术式为肝切除加下腔静脉切开取栓。  相似文献   

17.
张振  张海涛  张琪坤  卢实春 《生物磁学》2013,(35):6907-6912
目的:探讨两种不同方案治疗直径小于10cm肝细胞癌合并门静脉癌栓患者影响生存率。方法:将我院100例直径小于10cm肝细胞癌合并门静脉癌栓患者按照抽签法随机地均分为A、B两组,A组行单纯肝动脉插管化疗栓撒(TACE)治疗,B组肝癌手术切除联合癌栓切除+TACE术,比较两组患者治疗前后DLIA蛋白与VEGF蛋白阳性表达率、五年生存率以及影响患者生存率的因素。结果:(1)A组治疗前后DLL4蛋白与VEGF蛋白阳性表达率差异无统计学意义(P〉0.05),B组治疗前后上述蛋白阳性表达率差异具有统计学意义(P〈0.05,P〈0.01);(2)根据Kaplan—Meir计算方法,B组五年生存率均明显大于A组(P〈0.001);(3)经Pearson单因素与COX多因素分析,影响患者预后的危险独立因素为肿瘤大小与手术方式。结论:综合治疗方案用于治疗直径小于10cm肝细胞癌合并门静脉癌栓患者之中,疗效显著,患者五年生存率明显提高。  相似文献   

18.
Recent genome-wide association studies (GWAS) have identified several common susceptibility loci associated with the risk of hepatocellular carcinoma (HCC) or chronic hepatitis B infection (CHB). However, the relationship between these genetic variants and survival of patients with hepatitis B virus (HBV)-related HCC is still unknown. In this study, 22 single nucleotide polymorphisms (SNPs) were genotyped among 330 HBV-related HCC patients using the MassARRAY system from Sequenom. Cox proportional hazards regression was used to examine the effects of genotype on survival time under an additive model with age, sex, smoking status and clinical stage as covariates. We identified four SNPs on 6p21 (rs1419881 T>C, rs7453920 G>A,rs3997872 G>A and rs7768538 T>C), and two SNPs on 8p12 (rs2275959 C>T and rs7821974 C>T) significantly associated with survival time of HBV-related HCC patients. Our results suggest that HCC or CHB susceptibility loci might also affect the prognosis of patients with HBV-related HCC.  相似文献   

19.

Background and Aims

Treatment of patients with Barcelona Clinic Liver Cancer Stage B hepatocellular carcinoma (BCLC-B HCC) is controversial. This study compared the long-term survival of patients with BCLC-B HCC who received liver resection (LR) or transarterial chemoembolization (TACE).

Methods

A total of 257 and 135 BCLC-B HCC patients undergoing LR and TACE, respectively, were retrospectively evaluated. Kaplan–Meier method was used for long-term survival analysis. Independent prognostic predictors were determined by the Cox proportional hazards model.

Results

The hospital mortality rate was similar between groups (3.1% vs. 3.7%; P = 0.76). However, the LR group showed a significantly higher postoperative complication rate than the TACE group (28 vs. 18.5%; P = 0.04). At the same time, the LR group showed significantly higher overall survival rates (1 year, 84 vs. 69%; 3 years, 59 vs. 29%; 5 years, 37 vs. 14%; P<0.001). Moreover, similar results were observed in the propensity score model. Three independent prognostic factors were associated with worse overall survival: serum AFP level (≥400 ng/ml), serum ALT level, and TACE.

Conclusions

LR appears to be as safe as TACE for patients with BCLC-B HCC, and it provides better long-term overall survival. However, prospective studies are needed to disclose if LR may be regarded as the preferred treatment for these patients as long as liver function is preserved.  相似文献   

20.

Purpose

To investigate the prognostic value of intratumoral invariant natural killer T (iNKT) cells and interferon-gamma (IFN-γ) in hepatocellular carcinoma (HCC) after curative resection.

Experimental Design

Expression of TRAV10, encoding the Vα24 domain of iNKT cells, and IFN-γ mRNA were assessed by quantitative real-time polymerase chain reaction in tumor from 224 HCC patients undergoing curative resection. The prognostic value of these two and other clinicopathologic factors was evaluated.

Results

Either intratumoral iNKT cells and IFN-γ alone or their combination was an independent prognostic factor for OS (P = 0.001) and RFS (P = 0.001) by multivariate Cox proportional hazards analysis. Patients with concurrent low levels of iNKT cells and IFN-γ had a hazard ratio (HR) of 2.784 for OS and 2.673 for RFS. The areas under the curve of iNKT cells, IFN-γand their combination were 0.618 vs 0.608 vs 0.654 for death and 0.591 vs 0.604 vs 0.633 for recurrence respectively by receiver operating characteristic curve analysis. The prognosis was the worst for HCC patients with concurrent low levels of iNKT cells and IFN-γ, which might be related with more advanced pTNM stage and more vascular invasion.

Conclusions

Combination of intratumoral iNKT cells and IFN-γ is a promising independent predictor for recurrence and survival in HCC, which has a better power to predict HCC patients’ outcome compared with intratumoral iNKT cells or IFN-γ alone.  相似文献   

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