Efficacy comparison of optimal treatments for hepatocellular carcinoma patients with portal vein tumor thrombus

Introduction and objectivesOptimal treatment of hepatocellular carcinoma (HCC) involving portal vein tumor thrombus (PVTT) remains controversial.Materials and methodsA total of 627 HCC patients with PVTT after initial treatment with one of the following at Affiliated Tumor Hospital of Guangxi Medical University: liver resection (LR, n = 225), transarterial chemoembolization (TACE, n = 298) or sorafenib (n = 104) were recruited and randomly divided into the training cohort (n = 314) and internal validation cohort (n = 313). Survival analysis were repeated after stratifying patients by Cheng PVTT type.ResultsResection led to significantly higher OS than the other two treatments among patients with type I or II PVTT. TACE worked significantly better than the other two treatments for patients with type III. All three treatments were associated with similar OS among patients with type IV. These findings were supported by the internal validation cohort.ConclusionsOur results suggest that the optimal treatment for HCC involving PVTT depends on the type of PVTT. LR may be more appropriate for type I or II PVTT; TACE, for type III Sorafenib may be more appropriate than invasive treatments for patients with type IV PVTT.     

Chemoembolization for Hepatocellular Carcinoma in Patients with Extrahepatic Spread: Prognostic Determinants and Appropriate Candidates

Purpose

To investigate treatment outcome, prognostic factors for overall survival, and appropriate candidates for transarterial chemoembolization among patients with hepatocellular carcinoma (HCC) and extrahepatic spread (EHS).

Clinical significance of removal of tumor thrombi in the main portal vein in patients with hepatocellular carcinoma

Twenty-two patients with portal vein tumor thrombi secondary to hepatocellular carcinoma were studied to evaluate the effectiveness of diagnostic and treatment procedures. B-mode ultrasonography is a simple and accurate means for the detection of tumor thrombus in the portal vein. All of the 22 patients were correctly diagnosed by this method, which should be used as the initial screening procedure in such patients. Fourteen of the 22 patients underwent surgical procedures, including embolectomy from the portal trunk; removal of the tumor thrombi combined with hepatectomy or through the rechanneled umbilical vein; and operative transcatheter arterial chemotherapy. The other 8 patients were treated by transcatheter arterial embolization or were not treated. The surgical treatment effectively prevented acute variceal bleeding in the patients who underwent the procedures successfully. The mean value of the portal venous pressure was reduced from 46 cmH₂O to 32 cmH₂O after the surgery. As a result of the effective portal decompression, the patients in the surgical group had a better prognosis and longer mean survival than the others. Our study suggests that portal vein tumor thrombus is not an absolute contraindication for surgery, and that accurate detection and prompt treatment are the keys to the achievement of better clinical results.     

肝细胞癌门静脉主干癌栓uPA和uPAR基因表达

目的：探讨uPA,uPAR基因表达和肝癌转移，肝细胞癌门静脉主干癌栓（Tumor thrombosid of the main trunk of the portal vein,PVTT)形成的关系。方法：采用原位杂交等技术检测uPA,uPAR表达。结果：癌栓（A1组）和其原发癌（A2组）uPA,uPAR mRNA阳性表达率均高于无转移肝癌（B组）（P均＜0．01），A1组表达强度均高于A2组（P＜0．01），A2组小血管内可见癌细胞群落，A1组多见，B组无此现象，A1组、A2组uPAR和uPA蛋白质阳性表达率均高于B组（P均＜0．01），A1组表达强度均高于A2组（P＜0．01），uPA,uPAR mRNA和其蛋白质表达存在良好相关性（P均＜0．01），结论：uPA,uPAR在肝癌的侵袭和转移中起重要作用。其过度表达是PVTT形成和肝癌转移的重要因素。     

Efficacy of preoperative radiotherapy to portal vein tumor thrombus in the main trunk or first branch in patients with hepatocellular carcinoma

Background The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) in the main trunk or the first branch is very poor. Methods Radiotherapy (RT) to PVTT was followed by hepatectomy within 2 weeks. The dose used was 30–36 Gy, in 10–12 fractions, for 15–20 days. The efficacy of preoperative RT to PVTT in the main trunk or first branch was evaluated by comparing results in patients who underwent hepatectomy (group R; n = 15) with preoperative RT and those without preoperative RT (group N; n = 28). Results The 1-, 3-, and 5-year survival rates in group R were 86.2%, 43.5%, and 34.8%, respectively, while these values in group N were 39.0%, 13.1%, and 13.1%, respectively. The survival curve of group R was significantly better than that of group N (P = 0.0359). In group R, five (83.3%) of six patients whose tumor thrombus was completely necrosed (based on pathological examination) and whose follow-up period was over 2 years survived for more than 2 years. Female sex (P = 0.0066), multiple tumors (P = 0.0369), and absence of preoperative RT (P = 0.0359) were ranked as significant factors for a poor prognosis by univariate analysis. Multivariate analysis revealed absence of preoperative RT and female sex to be significant factors for a poor prognosis. Conclusion Preoperative RT to PVTT in the main trunk or first branch improved the prognosis of patients with HCC with PVTT, and could be a promising new modality in the treatment of these patients.     

A new staging system for hepatocellular carcinoma associated with portal vein tumor thrombus

BackgroundA new staging system for patients with hepatocellular carcinoma (HCC) associated with portal vein tumor thrombus (PVTT) was developed by incorporating the good points of the BCLC classification of HCC, and by improving on the currently existing classifications of HCC associated with PVTT.MethodsUnivariate and multivariate analysis with Wald χ² test were used to determinate the clinical prognostic factors for overall survival (OS) in patients with HCC and PVTT in the training cohort. Then the conditional inference trees analysis was applied to establish a new staging system.ResultsA training cohort of 2,179 patients from the Eastern Hepatobiliary Surgery Hospital and a validation cohort of 1,550 patients from four major liver centers in China were enrolled into establishing and validating a new staging system. The system was established by incorporating liver function, general health status, tumor resectability, extrahepatic metastasis and extent of PVTT. This staging system had a good discriminatory ability to separate patients into different stages and substages. The median OS for the two cohorts were 57.1 (37.2–76.9), 12.1 (11.0–13.2), 5.7 (5.1–6.2), 4.0 (3.3–4.6) and 2.5 (1.7–3.3) months for the stages 0 to IV, respectively (P<0.001) in the training cohort. The corresponding figures for the validation cohort were 6.4 (4.9–7.9), 2.8 (1.3–4.4), 10.8 (9.3–12.4), and 1.5 (1.3–1.7) months for the stages II to IV, respectively (P<0.001). The mean survival for stage 0 to 1 were 37.6 (35.9–39.2) and 30.4 (27.4–33.4), respectively (P<0.001).ConclusionsA new staging system was established which provided a good discriminatory ability to separate patients into different stages and substages after treatment. It can be used to supplement the other HCC staging systems.     

伽玛刀序贯ＴＡＣＥ治疗肝癌伴门静脉癌栓的临床观察

目的　探讨伽玛刀和经皮肝动脉化疗栓塞（ＴＡＣＥ）序贯治疗原发性肝癌伴门静脉癌栓的临床疗效和不良反应。方法　将２００４年２月至２００８年３月收治的１０１例原发性肝癌伴门脉癌栓患者随机分为３组,Ａ组３４例,先给予伽玛刀治疗,之后予ＴＡＣＥ治疗;Ｂ组３７例,先给予ＴＡＣＥ治疗,之后予伽玛刀治疗;Ｃ组３０例,单纯行伽玛刀治疗。结果　１０１例患者治疗３个月的有效率为８７.１％（８８／１０１）。Ａ、Ｂ两组之间的有效率、中位生存期、局部控制率、生存率、门脉癌栓有效率、ＡＦＰ改善率及腹胀、腹部不适改善率比较,差异均无统计学意义（Ｐ＞０.０５）,但均优于Ｃ组（Ｐ＜０.０５）。Ｂ组肝功能恶化率高于Ａ组（Ｐ＜０.０５）,而Ａ组和Ｃ组比较差异无统计学意义（Ｐ＞０.０５）。全组患者随访５～３６个月,未见严重并发症。结论　对伴门静脉癌栓的原发性肝癌采用伽玛刀联合ＴＡＣＥ治疗的疗效较好,先给予伽玛刀治疗再行ＴＡＣＥ对肝功能影响较小。     

Experimental study on enhancement of the metastatic potential of portal vein tumor thrombus-originated hepatocellular carcinoma cells using portal vein serum

Objective： Portal vein metastasis of hepatocellular carcinoma（HCC） results in a poor prognosis and seriously affects the survival rate of patients. The mechanism underlying the formation of portal vein tumor thrombus（PVTT） is complex and is not yet fully understood. This study was conducted to investigate the impact of portal vein blood on the proliferation, metastasis, invasion and apoptosis of PVTT cells and to explore its possible mechanisms, which was expected to lay a foundation for ascertaining the mechanism underlying the portal vein metastasis of HCC.
Methods： Peripheral blood and portal vein blood were collected from patients with HCC, and the sera from these two sources were used to culture the PVTT-originated HCC cell line CSQT-2. The cells were collected after 24 h, and flow cytometry was performed to detect cell proliferation, cell cycle stages and apoptosis. Transwell migration and invasion assays were applied to detect the metastasis and invasion of the cells in each group. The changes in the expression of MMP-2 and MMP-9 in cells were detected via Western blotting. The contents of IL-12, IFN-γ, IL-1β, IL-2 and TNF-α in the two groups of sera were quantified using corresponding kits.
Results： Compared with the group of cells cultured with peripheral serum, the cells cultured with portal vein serum showed significantly lower apoptosis（P〈0.01）, significantly enhanced cell metastasis and invasion（P〈0.01）, whereas cell proliferation and the stages of the cell cycle did not differ significantly（P〉0.05）. A significantly increased expression level of MMP-2 has been observed in tumor cells treated portal vein serum. In addition, compared with peripheral serum, the content of IL-12 was significantly decreased in portal vein serum（P〈0.05）, while the contents of IFN-γ, IL-1β, IL-2, and TNF-α did not differ significantly（P〈0.05）.
Conclusions： Portal vein serum from HCC patients could inhibit the apoptosis of PVTT-originated HCC cells and promote cell met