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Sorafenib (Sor) is clinical standard therapy for advanced hepatocellular carcinoma (HCC). However, detailed molecular mechanism behind Sor-exerted pharmacological effect remains unknown. In this study, sera samples, staged hepatic cancer tissues from Sor-treated patients with advanced HCC were harvested for a group of biochemical tests and immunoassays. Compared to non-treated control, blood contents of alanine transaminase (ALT), aspartate transaminase (AST), alphafetoprotein (AFP), fibroblast growth factor 21 (FGF21) were decreased in Sor-treated HCC patients, while the level of interleukin 10 (IL-10) were increased. As well, reduced triglyceride (TG), total cholesterol (T-CHOL), interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α) levels in sera were checked in Sor-treated HCC patients. In comparison with non-treated cancer sections, Sor-treated HCC cells showed decreased positive cells of proliferative marker for proliferating cell nuclear antigen (PCNA) and metastasized biomarker for cytokeratin 19 (CK19). In addition, elevated immunofluorescence-labeled cells of endoplasmic reticulum (ER)-stress markers of activating transcription factor 6 (ATF6), eukaryotic initiation factor 2α kinase (eIF2α), glucose-regulated protein (GRP-78), X-box binding protein 1 (XBP1) were observed in Sor-treated HCC livers. Further, validated data from Western blot assay exhibited that hepatocellular expressions of ATF6, eIF2α, GRP78, XBP1 in Sor-treated HCC liver cells were up-regulated. Briefly, our present clinicopathologic findings indicate that Sor-induced ER stress may be responsible for therapeutic mechanism against advanced HCC. In addition, induction of intracellular ER stress functions as a promising strategy for treating advanced HCC.

Objective: To investigate the effects of long non-coding RNA HULC on downstream related targets regulating the migration and invasion of hepatoma cells and theirs mechanism of action. Methods: The expression of highly upregulated in liver cancer (HULC) in hepatocellular carcinoma, and adjacent normal liver tissues and different hepatocellular carcinoma cells were detected by qPCR. The correlation between clinicopathological data of HULC and liver cancer patients were analyzed. Dual-luciferase reporter gene detected the interaction between HULC and miR-186. CCK-8 assay was used to detect the effect of HULC on proliferation of hepatocellular carcinoma cells. The change in hepatocellular carcinoma cell invasions ability after HULC inhibition was detected by transwell invasion assay and migration ability after inhibition of HULC was assessed by scratch assay. Differences between groups were compared using one-way ANOVA. P < 0.05 was considered statistically significant. Results: Compared with adjacent normal liver tissue, the expression of HULC in hepatocellular carcinoma was significantly higher [(1.79 ± 0.25) vs. (0.23 ± 0.05), P < 0.05]. The expression level of HULC was highest in hepatocellular carcinoma HepG3 cells. HULC specifically banded to the 3'UTR of miR-186 and regulated the expressional activity of miR-186. After inhibiting the expression of HULC, the proliferation of hepatocellular carcinoma cells was 72 h (0.35 ± 0.09) vs. (0.82 ± 0.16), P < 0.05; 96 h (0.42 ± 0.08) vs.(1.28 ± 0.19), P < 0.05), and the ability of migration and invasion was relatively decreased in 24 h (11.2% ± 1.6%) vs. (23.5% ± 3.6%), P < 0.05; 48 h (18.6% ± 3.0%) vs. (38.6% ± 5.6%), P < 0.05; 72 h (43.6% ± 5.3% ) vs. (69.6% ± 7.6%), P < 0.05]. After inhibiting the expression of HULC, the tumor volume and body weight of tumor-bearing mice were significantly reduced [volume (2.89 ± 0.29) cm(3) vs. (0.89 ± 0.18) cm(3), P < 0.05, body weight (3.18 ± 0.41) g vs. (0.45 ± 0.09) g, P < 0.05]. Conclusion: HULC plays an important role in the occurrence and development of hepatocellular carcinoma and can influence the biological behavior of hepatoma cells by regulating the expression of downstream-related targets.

Purpose: To develop a motion correction for Positron-Emission-Tomography (PET) using simultaneously acquired magnetic-resonance (MR) images within 90 s., Methods: A 90 s MR acquisition allows the generation of a cardiac and respiratory motion model of the body trunk. Thereafter, further diagnostic MR sequences can be recorded during the PET examination without any limitation. To provide full PET scan time coverage, a sensor fusion approach maps external motion signals (respiratory belt, ECG-derived respiration signal) to a complete surrogate signal on which the retrospective data binning is performed. A joint Compressed Sensing reconstruction and motion estimation of the subsampled data provides motion-resolved MR images (respiratory + cardiac). A 1-POINT DIXON method is applied to these MR images to derive a motion-resolved attenuation map. The motion model and the attenuation map are fed to the Customizable and Advanced Software for Tomographic Reconstruction (CASToR) PET reconstruction system in which the motion correction is incorporated. All reconstruction steps are performed online on the scanner via Gadgetron to provide a clinically feasible setup for improved general applicability. The method was evaluated on 36 patients with suspected liver or lung metastasis in terms of lesion quantification (SUVmax, SNR, contrast), delineation (FWHM, slope steepness) and diagnostic confidence level (3-point Likert-scale)., Results: A motion correction could be conducted for all patients, however, only in 30 patients moving lesions could be observed. For the examined 134 malignant lesions, an average improvement in lesion quantification of 22%, delineation of 64% and diagnostic confidence level of 23% was achieved., Conclusion: The proposed method provides a clinically feasible setup for respiratory and cardiac motion correction of PET data by simultaneous short-term MRI. The acquisition sequence and all reconstruction steps are publicly available to foster multi-center studies and various motion correction scenarios., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Autophagy is a pathophysiological phenomenon in liver cirrhosis that can further progress into hepatocarcinoma. Liver cancer stem cells (CSCs) are believed to initiate hepatocarcinogenesis. To investigate the precise mechanism related to the origin of CSCs in liver cirrhosis and hepatocarcinogenesis, we labeled Axin2+ hepatic cells with EGFP in Axin2Cre;Rosa26EGFP transgenic rats, and then stratified clinical and rat liver cirrhosis samples by autophagy flux. Clinical follow-up and lineage tracing in transgenic rat liver cirrhosis revealed that while Axin2/EGFP+ hepatic cells were present in normal livers and cirrhotic livers without aberrant autophagy, hepatic Axin2/EGFP+CD90+ cells were generated exclusively in cirrhotic livers with aberrant autophagy and promoted hepatocarcinogenesis. Aberrant autophagy in liver cirrhosis resulted in hepatocyte growth factor (HGF) expression, leading to activation of Met/JNK and Met/STAT3 signaling in sorted hepatic Axin2/EGFP+ cells and their transition into Axin2/EGFP+CD90+ cells that possess CSC properties. In a transgenic rat liver cirrhosis model, induction or inhibition of autophagy in cirrhotic livers by systemic administration of rapamycin or chloroquine or transfection with Atg3- and Atg7-shRNAs significantly induced or suppressed HGF expression, which in turn increased or reduced generation of EGFP+CD90+ hepatic cells by activating or inactivating Met/JNK and Met/STAT3 signaling, thereby promoting or preventing hepatocarcinogenesis. Systemic treatment with HGF-shRNA, SP600125 or stattic also reduced generation of EGFP(Axin2)+ hepatic cell-originated CD90+ CSCs in aberrant autophagic cirrhotic livers by inactivating HGF/Met/JNK or HGF/Met/STAT3 signaling, further preventing hepatocarcinogenesis. These data suggest that activation of Met/JNK and Met/STAT3 signaling in Axin2+ hepatic cells via autophagy-dependent HGF expression and the resultant generation of Axin2+CD90+ CSCs is a major mechanism of hepatocarcinogenesis in cirrhotic livers.

Angiomotin-like 2 (AMOTL2) is a member of Angiomotin family proteins, which are potent inhibitors for the Hippo pathway effector YAP. However, additional cellular functions of AMOTL2 besides YAP inhibition are largely unknown. Here, we reported that AMOTL2 associates with and negatively regulates AKT. Mechanistically, AMOTL2 binds to AKT pleckstrin homology domain and interrupts AKT's membrane localization. Liver-specific depletion of AMOTL2 enlarged mouse liver and activated both YAP and AKT. Downregulation of AMOTL2 is found in human liver cancers, correlating with the concomitant activation of YAP and AKT. Together, our results provide novel insights into a dual tumor suppressive function of AMOTL2 by targeting both YAP and AKT in liver size control and cancer prevention.

New tools for diagnostic of HCC remain to further investigate. We have evaluated the expression of SCCA1, 2 mRNA and their prognostic value in hepatocellular carcinoma (HCC). Reverse transcription polymerase chain reaction (RT-PCR) and direct sequencing were performed to evaluate the mRNA expression of SCCA1 and SCCA2 in 93 HCCs, and 93 paired adjacent non-cancerous tissues (PNT), 16 cirrhosis livers and 9 normal livers. The correlation of SCCA variants expression with the clinical parameters and the factors affecting survival were analyzed statistically.Total SCCA was detected in 33.3% of HCCs (31/93), in 9.68% of PNT (9/93) and 22.2% of normal livers (2/9). No expression was found in cirrhosis livers (0/16). The frequencies of total SCCA expression were significantly higher in HCCs than that in PNT and liver cirrhosis (p = 0.000, 0.006). From mRNA sequencing of HCCs, a new SCCA1 variant (presenting a T357A mutation) was identified in 16 specimens, while wild type SCCA1 was identified in 11 specimens and SCCA2 in 27 specimens. Clinicopathological analysis showed that the frequency of SCCA1 was significantly higher in poorly differentiated HCC, compared with moderately and well differentiated tumors (p = 0.021). T357A variant has a significantly higher frequency in nonencapsulated tumors than wild type SCCA1 (p = 0.034).The SCCA1, 2 mRNA is effective for detecting HCC and could be potentially applied in HCC diagnosis.

The hepatocellular carcinoma-associated antigen HAb18G/CD147, a member of CD147 family, could promote tumour invasion and metastasis via inducing the secretion of matrix metalloproteinases (MMP). Anti-CD147 monoclonal antibodies (MoAb) have exhibited obvious inhibitory effect on MMP induction. However, none of the epitopes of these MoAb has been reported. We previously prepared five MoAb against HAb18G/CD147, named HAb18, 3B3, 1B3, 5A5 and 4D2. To map the epitopes of these MoAb, a series of truncated fragments of extracellular region of HAb18G/CD147 was expressed in Escherichia coli and the MoAb-binding affinity to these fragments was examined with an enzyme-linked immunosorbent assay and Western blot. The residues (39)LTCSLNDSATEV(50), (36)KILLTCS(42) and (22)AAGTVFTTVEDL(33) were determined to be the epitopes of HAb18, 3B3 and 1B3, respectively, which were further proved by a dot-blot analysis with synthesized peptides and bioinformatics epitope prediction. The binding regions of MoAb 5A5 and 4D2 were located at residues E(120)-R(203). Then we constructed and expressed full-length HAb18G/CD147 and truncated HAb18G/CD147 without residues A(22)-V(50) in COS-7 cells. Gelatin zymography and Boyden chamber assay showed that the COS-7 cells expressing truncated HAb18G/CD147 failed to induce MMP production and enhance the cells' invasive potential, compared with the cells expressing full-length HAb18G/CD147. Taken together with the obviously inhibitory effects of HAb18 on the function of full-length HAb18G/CD147, these findings suggest that residues (22)AAGTVFTTVEDLGSKILLTCSLNDSATEV(50) may play a critical role in the functions of HAb18G/CD147 on MMP secretion and tumour invasion. These key residues can be used as potential drug target in cancer therapy.

Transarterial embolization (TAE) using various thrombotic substances for unresectable hepatocellular carcinoma (HCC) performed on many patients has resulted in a better survival rate. We evaluated the efficacy and clinical safety of using an Ethiodol-ethanol mixture as the embolizer for treatment of HCC and the possibility of a surgical approach for inoperable tumors after TAE. Twenty patients with HCC who underwent TAE and tumor resection were included in the study. Initially, eight had increased retention rate of indocyanine green dye via intravenous injection (0.5 mg/kg) at 15 minutes (ICGR15), and six had an insufficient residual volume that precluded them from undergoing tumor resection. TAE was performed by slowly infusing the mixture of Ethiodol and ethanol into the artery supplying the tumor until dual hepatic artery and portal vein embolization was achieved. Serum levels of alanine aminotransferase increased after embolization, but all biochemistry studies reverted to normal within 2 weeks. A decreased tumor size (n = 15), improved ICG (n = 8), and increased volume of the nonembolized lobe (n = 10) were noted. The operations performed were right lobectomy (n = 11), extended right lobectomy (n = 3), left lobectomy (n = 2), extended left lobectomy (n = 2), and wedge resection (n = 2), which included patients who did not want to undergo major hepatectomy. Complete tumor necrosis was found in seven cases. All patients survived with no associated complications. The 1-year survival rate was 95%. Transarterial Ethiodol and ethanol administration creating dual hepatic artery and portal vein embolization was a safe and efficacious method for treating HCC. It effectively decreases tumor size, causes compensatory hepatic hypertrophy, and improves the ICGR15, which allows a wider range of patients to undergo liver surgery and achieve better survival.

Objective: To evaluated the effectiveness of secondary prevention for primary liver cancer (PLC)., Methods: This is a randomized controlled study. 18,816 Shanghai urban residents, aged 35-55, with serum evidence of HBV infection or chronic hepatitis were randomly assigned into the screening group (9,373) or the control group (9,443). In the screening group, participants were tested with serum AFP and real time ultrasound every 6 months, while in the control group, participants were not informed about the study and received no screening. Participants with positive results underwent a diagnostic evaluation, and all patients diagnosed as PLC were treated appropriately and followed up., Results: After 5 years of study, there were 22,631.5 person-years screened. 86 patients with PLC were detected. 51 patients were detected in the control group within 32,944 person-years. In the screened group, 60.5% (52/86) of patients were in stage I, and 45.3% (40/86) with small liver cancer. However, there were no patients in stage I or with small liver cancer in the control group. The resection rates were 46.5% in the screened group, and 7.8% in the control group. The 1 to 5 years survival rates of PLC patients in the screening group were 65.0%, 65.0%, 52.7%, 52.7% and 52.7%, respectively, and in the control group were 30.0%, 6.5%, 0%, 0% and 0%, respectively., Conclusion: Screening can detect PLC in the early stage, and improve the prognosis of PLC, indicating that secondary prevention can decrease the mortality of PLC.

Objective: To summarize the progress of surgical treatment of hepatocellular carcinoma (HCC) and related basic research at the Liver Cancer Institute of Shanghai Medical University in the recent years, with special reference to recurrence and metastasis., Methods: Published and unpublished update clinical and experimental data in the above-mentioned areas are summarized., Results: Surgical resection has played an important role in improving prognosis of HCC, the 5-year survival were 63.4% for small HCC resection (n = 806), 39.6% for large HCC resection (n = 1061), 64.7% for cytoreduction (using hepatic artery cannulation and ligation) and sequential resection of initially unresectable HCC (n = 93), 56.0% for cytoreduction using transcatheter arterial chemoembolization (TACE) and followed by resection (n = 65), and 22.4% for hepatic resection with removal of tumor thrombi in portal vein (n = 103). Unfortunately, the 5-year recurrent rate after curative resection of HCC was up to 61.5%, which was mainly a result of intrahepatic "metastasis" and multicentric origin of HCC. Clinically, re-resection of subclinical recurrence yielded 56% of 5-year survival (n = 202); prevention of recurrence by transcatheter arterial chemoembolization (TACE) + Interferon, or LAK/IL-2 therapy have decreased 3-year recurrent rate from 33% to 11%-18%. In experimental aspect, metastatic human HCC model in nude mice (LCI-D20) and HCC cell line with metastatic potential (MHCC97) have been established; studies on HCC invasiveness in the molecular level revealed similar results that reported in other solid cancers, and small HCC showed slightly better biological characteristics as compared with large HCC; microvessel density (MVD) that reflecting angiogenesis adversely correlated with 5-year survival of small HCC; experimental interventions using antisense H-ras, bispecific antibody, BB94, as well as anti-angiogenic agents (TNP470, suramin, CAI, heparin, antisense VEGF, etc.) have been demonstrated to inhibit tumor growth and lung metastasis in nude mice model., Conclusions: Recurrence and metastasis are the major obstacle to further improve prognosis of HCC, studies should be conducted both in clinical and experimental aspects, "HCC invasiveness" will be the major target to be studied, particularly in the molecular level, and anti-angiogenesis will be one of the important approach.

Objective: To investigate the value of screening for early diagnosis of primary liver cancer (PLC)., Methods: A total of 18,816 persons, who were high-risk population of PLC, were divided randomly to allocated screening group and control group. In the screening group every individual was checked up by serum AFP test and ultrasound every 6 months but those in the control group were not., Results: Eighty-six patients with PLC were detected in the screening group, while 51 patients with PLC occurred in the control group. In patients from the screening group 60.5% were in the early stage, 45.3% of them were with small liver cancer. However, in the control group the figures were 0 and 0 respectively. In the screening group, 57 patients with PLC were detected by follow-up screening every 6 months, 77.2% patients of this series were in the early stage. However in the screening group the other 29 patients with PLC were detected by screening but they were not followed up every 6 months. Early-stage patients were only 27.6% in this series., Conclusion: This suggests mass screening, especially continual screening every 6 months in fixed population can diagnose PLC early.

Objective: To study the expression of T beta R I in HCC tissues and its clinical significance., Methods: Expressions of T beta R I in HCC tissues (HT, n = 30) and surrounding liver tissues(HST, n = 30) as well as four normal control liver tissues (CIT, n = 4) were determined by radioligand binding assay with 125I TGF beta 1 as the ligand. Relationships between some clinicopathological parameters of HCC and the relative expression rates of T beta R I in HCC were studied., Results: Compared with that in HST, the expression of T beta R I HT was significantly lower than in HST and CIT (P < 0.01). The expression of T beta R I in HST is similar to that in CIT. T beta R I relative expression rates in the group of no capsule or capsule invaded and in the group of tumor embolus were markedly decreased (P < 0.05). No close relationships were found between the T beta R I relative expression rate and age, sex, HBV infection, liver cirrhosis, AFP concentration, tumor diameter, tumor number, tumor differentiation as well as tumor embolus., Conclusions: The low expression of T beta R I in HT may be one of the key event which promote the HCC malignant growth by protecting them against the growth inhibition effect of active TGF beta. The T beta R I relative expression rate may be related to the prognosis of HCC.

Objective: To assess the validity and cost of a screening test for primary liver cancer using combined serum alpha fetoprotein testing and ultrasonography., Setting: An urban community in Shanghai, China., Methods: 9373 subjects aged 35 to 59 with positive hepatitis B surface antigen (HBsAg) or chronic hepatitis were studied. Outcome measures were detection rate, false positive rate, and positive predictive value, the cost for each primary liver cancer detected, and the average cost of detecting each additional primary liver cancer by the combined method. The number of small primary liver cancers detected was used for the economic evaluation., Results: 20,294 screening examinations were carried out. Primary liver cancer was detected in 51 subjects, 36 of whom had small primary liver cancer. When alpha fetoprotein and ultrasonography were used in parallel the detection rate, false positive rate, and positive predictive value were 92%, 7.5%, and 3.0%, respectively; the cost for each primary liver cancer detected was 30,206 RMB (Chinese currency, $3639). When ultrasonography was used alone the detection rate, false positive rate, and positive predictive value were 84%, 2.9%, and 6.6%, respectively; the cost for each primary liver cancer detected was 16,451 RMB ($1982). When the alpha fetoprotein test was used alone the detection rate, false positive rate, and positive predictive value were 69%, 5.0%, and 3.3%, respectively; the cost for each primary liver cancer detected was 25,139 RMB ($3029)., Conclusion: The combination of both screening methods results in a relatively small increase in detection but a considerably higher false positive rate, increasing the costs. The combined test may be the best choice for primary liver cancer screening in developed areas of China, but otherwise, ultrasonography alone is the method of choice.

Objective: To evulate the clinico-pathological singnificance of intratumoral microvessel density (MVD) and VEGF expression in primary liver cancer (PLC)., Methods: A retrospective study including 63 postoperative small PLC (diameter < 5 cm) patients was done. One group of 29 patients developed recurrence or metastasis within 2 years. The other group of 34 patients had no evidence of recurrence or metastasis within 2 years. Three PLC sections were taken from each patient, one for H. E. staining, the other two for VEGF and vascular endothelial cell immunohistochemical staining, respectively. MVD was counted by endothelial cells which were highlighted by Bio-UEA-I., Results: The MVD in patients with cancer recurrence or metastasis was (49.6 +/- 29.7) significantly greater than the other group (22.7 +/- 28.2) (P < 0.01). The positive rate of VEGF in cancer recurrence group was 86.2% (25/29), being significantly higher than the other group (47.1%) (P < 0.01). The stage of the tumor, the positive rate of satellite nodules and portal vein embolus were all significantly different between the 2 groups., Conclusion: Besides tumor stage, satellite nodules and portal vein embolus, the MVD and VEGF expression are also of prognostic significance.

Objective: To detect the expression of three TGF beta isoforms and its clinicopathologic significance in hepatocellular carcinoma(HCC)., Methods: Surgical specimens of 52 patients with small HCC resection during 1992-1995 were used to determine the immunoreactivity of TGF beta protein by ABC immunohistochemistry. These specimens were divided into recurrence group(G1) and recurrence group(G2) according to whether HCC recurred two years after resection. The relations with recurrence of HCC were analyzed., Results: The positive rates in G1 and G2 were 85% (17/20) versus 47% (15/32) for TGF beta 1, 90% (18/20) vs. 78% (25/32) for TGF beta 2, and 45% (9/20) vs. 63% (20/32) for TGF beta 3. Significant difference was found in TGF beta 1 and TGF beta 2, but not in TGF beta 3., Conclusion: The high immunoreactivity to TGF beta 1 or TGF beta 2 is positively related to the recurrence of HCC.

This paper summarizes the "study on small hepatocellular carcinoma and its extension" in Liver Cancer Institute, Zhongshan Hospital of Shanghai Medical University during the past 25 years. The results indicated that it was an important approach to obtain long-term HCC survivors, of the 239 patients with 5-year survival, small HCC resection accounted for 51.4%. It was an effective approach to improve the prognosis of HCC in the entire series, the 5-year survival of inpatients treated in authors' institution was 4.8% in 1958-1970, 12.2% in 1971-1983, and 46.7% in 1984-1995; which were correlated to the increase proportion of small HCC resection in the series; it was more effective as compared to large HCC resection, the 5 year survival was 61.3% (n = 645) versus 33.6% (n = 950). Extensions of small HCC study included early detection and treatment of small recurrent HCC, of the 147 patients with re-resection, the 5-year survival was 48.9% calculated from the time of first resection. Another extension was conversion of large HCC into small HCC, using multimodality combination treatment, 72 out of the 663 patients with surgically verified unresectable HCCs have been converted to resectable, 5-year survival being 62.1%, which was comparable to that of small HCC resection. Studies on related basic aspect of small HCC such as cell origin of recurrence, and molecular aspect of small HCC, indicated that biological characteristics, particularly the tumor invasiveness, remained the key link for further prolong survival after small HCC resection. Recently, a "patient-like" human HCC metastatic model in nude mice has been established. Experimental interventions have also been tried. Clinical trials for prevention of recurrence after small HCC resection have shown preliminary encouraging results. However, the "cost-effectiveness" of screening, the invasiveness of HCC, the multicentric origin, the coexisted Child C cirrhosis, etc., remained great challenge.

Purpose: To determine whether repeated screening can lead to early detection of primary liver cancer (PLC) and in turn to an improved clinical result., Methods: In this randomized controlled study, Shanghai urban residents aged 35-55 years and with serum evidence of HBV infection or chronic liver disease were eligible for recruitment. Using cluster sampling, these subjects were allocated into two groups-the screening group and the control group: there were 8109 subjects in the screening group and 9711 in the control group. Subjects in the screening group were tested with serum AFP and real-time ultrasound every 6 months. One to four rounds of screening were completed. Liver cancer was treated according to stage at diagnosis., Results: All subjects enrolled were followed up and classed at the end-point as alive without liver cancer, alive with liver cancer, dead from liver cancer, or dead from another cause. The mean follow-up was 1.2 years; total follow-up was 12,038 person-years in the screening group and 9,573 person-years in the control group. We detected 38 patients with PLC in the screening group and 18 patients with PLC in the control group. In the patients in the screening group 76.8% of patients were at a subclinical stage, and 70.6% of them underwent resection, the 1- and 2-year survival rates being 88.1% and 77.5%, respectively. However, in the control group, none of the patients was at a subclinical stage when diagnosed, none of them underwent resection, and none of them survived over 1 year. The lead time was estimated at 0.45 years. The cost of detecting PLC at an early stage was RMB 12,600 (US$1,500)., Conclusion: The study proved that screening the high-risk population for PLC with a serum AFP test and real-time ultrasound examination can detect patients in the early stages, increase the resection rate and prolong the survival time. It is therefore recommended that screening for PLC be advocated in any high-risk area.

Objective: For understanding the clinicopathologic significance of estrogen receptor (ER) in hepatocellular carcinoma (HCC) ER of the surgical resected species was detected and its relation to biologic feature was analysis., Methods: ER was detected in 62 HCC species with Dextran coated charcoal method. Some pathologic characteristics were studied with gross and microscopic examination and proliferating cell nuclear antigen (PCNA) was determined with immunohistochemistry using monoclonal antibody PC-10., Results: ER positive HCC had higher incidence of single nodule (83.3%) and complete encapsulation (58.3%) compared to ER negative HCC (42.1% and 21.0%). The difference was significant (P < 0.05). In small liver cancer ER positive rate was 62.5% which was higher than 30.4% in large liver cancer (P < 0.05). The PCNA labeled index was (26.2 +/- 18.7)% in ER positive HCC and (43.6 +/- 32.0)% in ER negative HCC. The difference was significant (P < 0.05)., Conclusion: The results suggest that ER positive HCC has less malignant biologic behavior and better prognosis than ER negative HCC.

In order to evaluate the effectiveness of early detection for primary liver cancer (PLC), a randomized, prospective study was performed in Shanghai from 1992 to 1995. The study population was 35 through 55 years of age, with serum evidence of HBV infection or tory of chronic hepatitis. Seventeen thousand nine hundred and twenty individuals were randomly to allocated screening group and control group. In the screening group, every individual was checked up by serum AFP test and ultrasound every 6 months and in the control group, they were unchecked. After a mean time of 1.2 years, 38 patients with PLC in the screening group were detected while 18 patients with PLC occur in the control group. In patients from the screening group, 76.8% were in subclinical stage, 70.6% of them were treated by surgical resection with 1-, 2-year survival rate of 88.1% and 77.5%, respectively. However, in the control group, none of patients was in subclinical stage, none of the tumors resected, and none of patients survived over 1 year. The lead time was estimated to be 0.45 years. The cost for detecting an early stage PLC patient is RMB 12,600 (US$1,500). The study indicates that screening in the high risk population of PLC can detect patients in early stage, increase the resection rate and the survival rate. Screening program for PLC carried out in high risk populations is thus recommended.