There were many progressions of hepatocellular carcinoma (HCC) in the 2017 annual meeting of the American Society of Clinical Oncology (ASCO).(1) Sorafenib has been at the heart of treatment for advanced HCC,meanwhile,it has been confirmed to effectively prolong the life time of patients and improve the clinical efficacies combined with other therapies.A variety of molecular and clinical indicators also help screening out peoples.(2) New molecular targeted drugs have sprung up,and Lenvatinib (multiple receptor tyrosine kinases inhibitor) is expected to become the next first-line drug.The second-line Regorafenib has obtained supporting evidence from evidencebased medicine,and a combination therapy of Sorafenib and Regorafenib promises to be a new model of targeted therapy for HCC.However,the phase Ⅲ study (METIV-HCC) of which Tivatinib (ARQ 197) becomes the second-line drug for HCC has failed.(3) Immunization therapy remains a hotspot for HCC.The monoclonal antibodies of immunological checkpoint and adoptive immunotherapy have better safety and clinical efficacy.(4) Primary lesions resection of HCC and drug control of metastatic lesions are expected to be the therapy model for metastatic HCC.The liver transplantation for primary HCC will be further developed.(5) The combination and sequential application of multiple therapies will become an inevitable choice,and efficacy of stereotactic body radiation therapy is expected.The combination and sequential application of transcatheter arterial chemoembolization (TACE) and other therapies is still a main therapy for unresectable HCC.(6) The new predictors and models of prognosis have been popping up,nevertheless,its therapy effects should be further proven.

Mutations detection of circulating tumor DNA can be divided into quantitative and qualitative classifications:the forumer mainly detects the total amount of circulating DNA (serum or plasma),whereas the latter mainly detects the specific genetic variations in serum or plasma DNA,such as gene mutations,methylations of tumor suppressor genes,and microsatellite alterations,etc.Both of them may reflect the tumor presence and disease severity.In this paper,mutations detection and its clinical significance of circulating tumor DNA in patients with hepatocellular carcinoma are reviewed.

Objective:To identify the signature of tumor-infiltrating lymphocyte (TIL) subtypes that may affect cytokine expres-sion between different outcomes of hepatocellular carcinoma (HCC) patients by analyzing the CD molecular expression profiles of non-cancerous hepatic tissues. Methods:Surface markers of TIL in noncancerous hepatic tissues from 146 HCC patients were determined by using immunohistochemical method and flow cytometry. Univariate and multivariate Cox proportional hazards models and Kaplan-Meier method were used to analyze the association of their expression levels with tumor recurrence and survival. Results:More than 86.4%of TILs in patients were quiescent, as measured via CD4+or Foxp3 expression. Meanwhile, more than 90%of CD3+T cells ex-pressed CD8+. The proportion of T cells was low compared with CD8+T cells. The proportion of CD19 and CD20 in distant nontumor tissues almost was zero. The proportion of T cell subgroups isolated from HCC circulating whole blood did not show a significant shift compared with the normal control, as follows:CD4+T/CD8+T=1.167 ± 1.04, CD8+T/CD3+T=0.288 ± 0.116, and CD4+T/CD3+T=0.429 ± 0.178. The proportion of CD8+T cells in noncancerous hepatic tissues was higher than that in blood (P<0.001).Conclusion:TILs in HCC noncancerous hepatic tissues are increased and contain a subpopulation of CD3+CD8+T cells. CD8+T cells in cancerous tissues, rather than noncancerous tissues, show significant differences between different prognostic groups.

Objective To establish an in vitro isolation and culture system for hepatocellular carcinoma (HCC)-associated fibroblast (CAF) and identify based on its specific markers of CAF. Methods CAF was isolated from the tumor tissue of the HCC patients after hepatectomy, by digesting with collagenase enzyme, centrifugation and resuspension. The morphology of CAF was observed by electron microscopy. Immunofluorescence staining was performed for detecting α-SMA and fibronectin as well as other specific markers such as AFP on the surface of HCC cells and CD31 on the surface of vascular endothelial cells. On the basis of the study, the function work between CAF and HCC cell line Huh7, HepG2 was detected under co-culture system. Meanwhile, CCK-8 was used to observe the effect of CAF on the proliferation of Huh7 and HepG2 cells, and Transwell assay was used to analyze CAF effect on the invasion of Huh7 and HepG2 cells. Results Compared with the other cells, the morphological analysis showed that CAF was more elongated or spindle-shaped. Moreover, the cell size and the nucleus were larger than normal epithelial cells. Immunofluorescence staining revealed that the CAF surface specific markers including α-SMA and fibronectin were positive, and mainly were the cell membrane staining. The proliferation and invasion of Huh7 and HepG2 were significantly increased by CAF. The results show that the increasing percentage of cells in 24 hours between blank group and the experimental group was (63 ± 4) %, (78 ± 5) % and (69 ± 5) %, (81 ± 3) %respectively after co-culture with CAF, the difference was statistically significant (P<0.05). In transwell model, the number of cells in the blank group and the experimental group was (59.4 ± 3.1), (162.9 ± 3.9) and (104.8 ± 2.6), (166.4 ± 4.2), and the difference was also statistically significant (P< 0.05). Conclusion The isolated CAF from HCC enhances the ability of tumor's proliferation and invasion.

Objective To explore the effect of hepatocyte growth factor (HGF)/c-Met signaling in doxorubicin (DOX) treatment of hepatocellular carcinoma (HCC). Methods Different biologic and genetic characteristics human HCC cell lines, Huh7, HepG2, MHCC97-L and MHCC97H were used in this experiment. Variation in c-Met mRNA expression level among different HCC cell lines was analyzed by RT-PCR. Western blot analysis was performed to detect c-Met and p-Met expression levels in these cell lines. CCK-8 experiment was carried to analyze the DOX sensitivity in various cell lines. t test and repeated measure analysis of variance were used for statistical analysis. Results Both c-Met and p-Met were overexpressed in MHCC97-L and MHCC97-H cell lines and these cell lines were resistant to DOX compared to Huh7 and HepG2. However, treatment of HGF in Huh7 and HepG2 cells activated c-Met signaling pathway and decreased the sensitivity of these two cell lines to DOX [inhibition rate: Huh7 (34.848 ±5.370) vs. (66.409±5.792)%, HepG2 (34.351±3.305) %vs. (62.308±5.453) %, both P=0.002]. Whereas administration of c-Met inhibitor in MHCC97-L and MHCC97-H cell lines significantly increased the sensitivity to DOX [inhibition rate: MHCC97-L (73.106 ±3.472) % vs. (13.636 ±4.097) %; MHCC97-H (64.444 ±4.006) % vs. (6.296 ±2.796) %, both P< 0.001]. Conclusion HGF/c-Met signaling pathway is related the treatment efficacy of DOX in HCC.

Objective To evaluate the prognosis and management of recurrent primary clear cell carcinoma of liver (PCCCL).Methods 214 patients with PCCCL treated by curative resection from January 1996 to March 2006 were retrospectively studied.Tumour recurrences were classified into early (≤1 year) and late (＞1 year) recurrences.Results Of 99 patients who developed recurrences,28 developed early recurrence while 71 developed late recurrence.The patients with recurrences were treated with re-resection (n=33),percutaneous ethanol injection (PEI,n=7),radiofrequency ablation (RFA,n=10),transcatheter arterial chemoembolization (TACE,n =27),systemic chemotherapy (n=1),Chinese medicine (n=1),and conservative management (n=20).The re-resection rate was higher in the late than in the early recurrence group (P=0.04).In this study,reresection,PEI,and RFA were considered as curative therapies.There was no significant difference in the overall survival (OS) for patients who received these different curative therapeutic procedures (P=0.68).The 1,3-,and 5-year OS of patients with recurrences who were treated with curative treatment were comparable to those patients who did not develop recurrences (100％,86.0％,63.5％ vs 85.2％,72.2％,64.3％,P=0.71).The 1-,3-,and 5-year OS of patients who received TACE for recurrences were 100％,66.7％,and 44.4％ respectively.The results were poorer than patients who received curative treatment for recurrences (P=0.03),but were better than those who received conservative management after recurrences (80.0 ％,25.0 ％,and 10.0 ％,P＜ 0.01).Conclusions Reresection,PEI and RFA are optimal curative methods for recurrent PCCCL.TACE plays an important role in the management of patients with recurrent PCCCL who cannot be treated with curative methods.

Objective To summarize the techniques of anatomical liver resection for the treatment of hepatocellular carcinoma(HCC).Methods The clinical data of 125 patients with solitary HCC who underwent anatomical liver resection at the Zhongshan Hospital from January 2005 to December 2006 were retrospectively analysed.The inflow and outflow of hepatic segments to be resected were selectively clamped,then the main branches of portal vein and hepatic artery were ligated,and the ischemic hepatic segments were resected en bloc.Kelly forceps were used to crash and clamp the liver cut surface.The stumps of left and right hepatic ducts were continuously sutured with Prolene sutures.For tumors with the size above 10 cm in diameter,hepatectomy with anterior approach and liver hanging maneuver were adopted.Bile leakage was checked by injecting methylene blue or covering a gauze on the liver cut surface.Results The mean blood loss of all patients was 250 ml(100-6000 ml),and 32 of them needed blood transfusion.The morbidity was 23%(29/125).No patient died within 30 days after the operation,and 6%(5/83)of patients were found with residual tumor by postoperative arteriography.Conclusion Anatomical liver resection may improve the safety of operation,prevent the injury of great vessels and thus improve the efficacy.

Objective To summarize the clinical experienee in surgical treatment for hepatocellular carcinoma (HCC). Methods The clinical data of 7566 HCC patients who had been admitted to Research Institute of Liver Cancer of Fudan University from January 1988 to Deeember 2007 were retrospectively analyzed. The overall survival and recurrence free survival (RFS) rates were eaeulated with Kaplan-Meier survival curve. All the data were analyzed using Log-rank test and Cox regression model. Results The 3-, 5-, 10-year overall survival and RFS rates of 7164 patients with HCC resection were 56.29%, 41.76%, 26.70%, and 63.92%, 56.12%, 42.97%, respectively, and the perioperative mortality was 1.54%. The 5- and 10-year overall survival rates of patients with small HCC (diameter<5 era) were 58.20% and 38.47%, which were significantly higher than 31.42% and 20.43% of patients with large HCC (diameter >5 cm) (X2 =535. 568, P <0.01). The 5-year overall survival rotes of HCC patients with resection after down-staging (n = 110), re-resection after recurrence (n = 515), and tumor thrombus in portal vein (n = 168) were 51.26%, 67.28% and 26.81%, respectively; nd the 5-year DFS rotes were 77.44%, 13.01% (calculated from the first operation) and 34.90%, respectively. The 3- and 5-year overall survival and DFS rates of 402 patients who had undergone liver transplantation were 60.81%, 55.63% and 64.47%, 58.52%. The independent prognostic factors influencing the overall survival and DFS rates were the size, number and differentiation of HCC and intrahepatic vessel invasion (X2 = 200.539, 27. 536, 96.964,216. 156, P <0.01). Conclusions Early screening, improved safety of surgery, combined therapy and breakthrough in the reseaeh of preventing HCC metastasis and reeurrenee will significantly improve the treatment outcome of HCC.

Objective To investigate the risk factors influencing early and late recurrences after resection of primary clear cell carcinoma of the liver (PCCCL).Methods 214 PCCCL patients treated by curative resection from January 1996 to March 2006 were retrospectively analyzed.Recurrences were classified into early (≤1 year) and late (＞1 year) recurrences.Results 99 patients developed recurrences,with early recurrence in 28 patients and late recurrence in 71 patients.The 3-and 5-year overall survival (OS) rates for recurrent PCCCL were significantly worse than those with no recurrence (68.7％ and 46.2％ vs 72.2％ and 64.3％,P=0.003).The 1-,3-and 5-year OS rates for late recurrence were 100％,80.3％ and 54.6％,which were significantly better than those with early recurrence (85.7％,39.3％ and 25.0％,P=0.001).On multivariate analysis,aminoleucine transferase (ALT) level and vascular invasion were independent risk factors for early recurrence,while age was the only significant risk factor for late recurrence.Conclusions The time to recurrence was the main determinant for prognosis of recurrent PCCCL,Clarifying the different risk factors for early and late recurrences will help postoperative follow-up,early detection of recurrence,and hopefully will improve survival.

Objective To investigate the clinicopathologic characteristics and prognostic factors of primary clear cell carcinoma of the liver(PCCCL). Methods A total of 214 PCCCL patients treated by curative resection from January 1996 to March 2006 were retrospectively analyzed. Results The 1-,3-,and 5-year overall survival (OS) rates for PCCCL patients were significantly better than those of non-clear cell hepatocellular carcinoma ( NHCC ) patients ( 90.2％,70.6％,and 55.9％ vs 82.8％,62.7％ and 47.7％,P =0.001 ).Tumor size was significantly smaller in PCCCL group than in NHCC group ( x2 =4.37,P =0.04 ).Tumors of PCCCL group had a lower incidence of vascular invasion ( x2 =9.42,P =0.002) and a better differentiation than those of NHCC group ( x2 =4.30,P =0.04).Serum a-fetoprotein (AFP) level,tumor size,liver cirrhosis,and vascular invasion were independent risk factors impacting OS and disease-free survival (DFS) of PCCCL. Conclusions PCCCL is an uncommon subtype of HCC and has different clinicopathologic characteristics from NHCC. Complete surgical resection is the optimal treatment for PCCCL and its prognosis is much better than that of NHCC.