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The multiplicity of hepatocellular carcinoma (HCC) recurrence patterns is the most important determinant of patients' postsurgical survival. A systematic HCC recurrence classification is needed to help prevent and treat postoperative HCC recurrence in the era of precision medicine.A total of 1319 patients with recurrent HCC from four hospitals were enrolled and divided into a development cohort (n = 916), internal validation cohort (n = 225) and external validation cohort (n = 178). A comprehensive study of patients' clinicopathological factors and biological features was conducted.Four subtypes of recurrence were identified, which integrated recurrence features, survival, effects on systemic and liver function and potential therapeutics after recurrence: type I (solitary-intrahepatic oligorecurrence); type II (multi-intrahepatic oligorecurrence); type III (progression recurrence) and type IV (hyper-progression recurrence). Type III~IV recurrence indicated exceptionally poor prognosis. Subsequently, two nomogram models were established for type III~IV recurrence prediction, and both demonstrated excellent predictive performance and applicability of pre and postoperative strategy formulation. Multiple biological analyses revealed that HCC cases with type III~IV recurrence were characterized by enrichment in p53 mutations, CCND1 amplification, high proliferation/metastasis potential, inactive metabolism and immune exhaustion features. Over-expression of high mobility group protein 2 (HMGA2) enhanced the highly malignant behaviour of HCC through multiple molecular pathways, making it a potential prognostic predictor and therapeutic target.This 'recurrent HCC classification' has important potential value in identifying patients with surgical benefit, predicting postsurgical survival and guiding treatment strategies. Multidimensional biological insights also increased knowledge of factors associated with HCC recurrence.

Dysregulation of genes involved in alternative splicing contributes to hepatocarcinogenesis. SNRPB, a component of spliceosome, is implicated in human cancers, yet its clinical significance and biological function in hepatocellular carcinoma (HCC) remains unknown. Here, we show that SNRPB expression is increased in HCC tissues, compared with the nontumorous tissues, at both messenger RNA and protein levels in two independent cohorts. High expression of SNRPB is significantly associated with higher pathological grade, vascular invasion, serum alpha-fetoprotein level, tumor metastasis, and poor disease-free and overall survivals. Luciferase reporter and chromatin immunoprecipitation assays demonstrate that SNRPB upregulation in HCC is mediated by c-Myc. Positive correlation is found between SNRPB and c-Myc expression in clinical samples. In vitro studies show that ectopic expression of SNRPB promotes HCC cell proliferation and migration, whereas knockdown of SNRPB results in the opposite phenotypes. Collectively, our data suggest SNRPB function as an oncogene and serve as a potential prognostic factor in HCC.

Accurate preoperative assessment of hepatic functional reserve is essential for conducting a safe hepatectomy. In recent years, aspartate aminotransferase-to-platelet ratio index (APRI) has been used as a noninvasive model for assessing fibrosis stage, hepatic functional reserve, and prognosis after hepatectomy with a high level of accuracy. The purpose of this research was to evaluate the clinical value of combining APRI with standardized future liver remnant (sFLR) for predicting severe post-hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC). Six hundred thirty-seven HCC patients who had undergone hepatectomy were enrolled in this study. The performance of the Child-Pugh (CP) grade, model for end-stage liver disease (MELD), APRI, sFLR, and APRI-sFLR in predicting severe PHLF was assessed using the area under the ROC curve (AUC). Severe PHLF was found to have developed in 101 (15.9%) patients. Multivariate logistic analyses identified that prealbumin, cirrhosis, APRI score, sFLR, and major resection were significantly associated with severe PHLF. The AUC values of the CP, MELD, APRI, and sFLR were 0.626, 0.604, 0.725, and 0.787, respectively, indicating that the APRI and sFLR showed significantly greater discriminatory abilities than CP and MELD (P

Posthepatectomy liver failure (PHLF) is a serious complication after hepatectomy, and its effective methods for preoperative prediction are lacking. Here, we aim to identify predictive factors and build a nomogram to evaluate patients' risk of developing PHLF.A retrospective review of a training cohort, including 199 patients who underwent hepatectomy at the Shanghai Eastern Hepatobiliary Surgery Hospital, was conducted. Independent risk variables for PHLF were identified using multivariate analysis of perioperative variables, and a nomogram was used to build a predictive model. To test the predictive power, a prospective study in which a validation cohort of 71 patients was evaluated using the nomogram. The prognostic value of this nomogram was evaluated by the C-index.Independent risk variables for PHLF were identified from perioperative variables. In multivariate analysis of the training cohort, tumor number, Pringle maneuver, blood loss, preoperative platelet count, postoperative ascites and use of anticoagulant medications were determined to be key risk factors for the development of PHLF, and they were selected for inclusion in our nomogram. The nomogram showed a 0.911 C-index for the training cohort. In the validation cohort, the nomogram also showed good prognostic value for predicting PHLF. The validation cohort was used with similarly successful results to evaluate risk in two previously published study models with calculated C-indexes of 0.718 and 0.711.Our study establishes for the first time a novel nomogram that can be used to identify patients at risk of developing PHLF.

Portal vein tumor thrombus (PVTT) and microvascular invasion (MVI) are types of intrahepatic vascular metastasis of hepatocellular carcinoma (HCC) and are highly correlated with poor prognosis. However, the underlying biomarkers of PVTT and MVI are unclear.We identified a PVTT/MVI-associated gene S100P by cDNA microarray analysis, and assess the potential value of serum S100P measurement in the differential diagnosis of HCC and prediction of MVI status with large retrospective and perspective cohort studies.The mRNA and protein of S100P was increased in HCCs with PVTT or MVI. High S100P immunostaining in tumors was correlated with inferior tumor-free survival. Serum S100P values discriminated patients with HCCs from those with benign liver tumors, and it showed predictive potential of MVI status in both retrospective and perspective cohorts. S100P may regulate HCC tumorigenicity and invasive ability; S100P also was associated with up-regulation of CD44, which may mediate HCC cell adhesion to form PVTT/MVI.Serum S100P may be a novel differential diagnostic marker for HCC and a potential predictor of MVI status pre-surgery for HCC patients. S100P overexpression in HCC is highly correlated with the formation of PVTT and MVI, which may make S100P as a potential therapeutic target for HCC metastasis.

To clarify the significance of circulating tumor cells (CTC) undergoing epithelial–mesenchymal transition (EMT) in patients with hepatocellular carcinoma (HCC), we used an advanced CanPatrol CTC-enrichment technique and in situ hybridization to enrich and classify CTC from blood samples. One hundred and one of 112 (90.18%) patients with HCC were CTC positive, even with early-stage disease. CTCs were also detected in 2 of 12 patients with hepatitis B virus (HBV), both of whom had small HCC tumors detected within 5 months. CTC count ≥16 and mesenchymal–CTC (M-CTC) percentage ≥2% prior to resection were significantly associated with early recurrence, multi-intrahepatic recurrence, and lung metastasis. Postoperative CTC monitoring in 10 patients found that most had an increased CTC count and M-CTC percentage before clinically detectable recurrence nodules appeared. Analysis of HCC with high CTC count and high M-CTC percentage identified 67 differentially expressed cancer-related genes involved in cancer-related biological pathways (e.g., cell adhesion and migration, tumor angiogenesis, and apoptosis). One of the identified genes, BCAT1, was significantly upregulated, and knockdown in Hepg2, Hep3B, and Huh7 cells reduced cell proliferation, migration, and invasion while promoting apoptosis. A concomitant increase in epithelial marker expression (EpCAM and E-cadherin) and reduced mesenchymal marker expression (vimentin and Twist) suggest that BCAT1 may trigger the EMT process. Overall, CTCs were highly correlated with HCC characteristics, representing a novel marker for early diagnosis and a prognostic factor for early recurrence. BCAT1 overexpression may induce CTC release by triggering EMT and may be an important biomarker of HCC metastasis. Significance: In liver cancer, CTC examination may represent an important “liquid biopsy” tool to detect both early disease and recurrent or metastatic disease, providing cues for early intervention or adjuvant therapy. Cancer Res; 78(16); 4731–44. ©2018 AACR.

AIM To investigate the efficacy and safety of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) in preventing tumor recurrence and improving survival in Barcelona Clinic Liver Cancer (BCLC) early (A) and intermediate (B) stage hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). METHODS A total of 519 BCLC A or B HCC patients treated by liver resection alone or followed by PA-TACE between January 2012 and December 2015 were studied retrospectively. Univariate and multivariate analyses were performed to investigate the risk factors for recurrence-free survival (RFS) and overall survival (OS). Multiple logistic regression was used to identify the clinicopathological characteristics associated with MVI. The rates of RFS and OS were compared among patients with or without MVI treated with liver resection alone or followed by PA-TACE. RESULTS Univariate and multivariate analyses demonstrated that serum AFP level > 400 ng/mL, tumor size > 5 cm, tumor capsule invasion, MVI, and major hepatectomy were risk factors for poor OS. Tumor capsule invasion, MVI, tumor size > 5 cm, HBV-DNA copies > 1 x 104 IU/mL, and multinodularity were risk factors for poor RFS. Multiple logistic regression identified serum AFP level > 400 ng/mL, tumor size > 5 cm, and tumor capsule invasion as independent predictors of MVI. Both OS and DFS were significantly improved in patients with MVI who received PA-TACE as compared to those who underwent liver resection alone. Patients without MVI did not show a significant difference in OS and RFS between those treated by liver resection alone or followed by PA-TACE. CONCLUSION PA-TACE is a safe adjuvant intervention and can efficiently prevent tumor recurrence and improve the survival of BCLC early- and intermediate-stage HCC patients with MVI.

AIM To develop and validate a risk estimation of tumor recurrence following curative resection of operable hepatocellular carcinoma (HCC). METHODS Data for 128 patients with operable HCC (according to Barcelona Clinic Liver Cancer imaging criteria) who underwent preoperative computed tomography (CT) evaluation at our hospital from May 1, 2013 through May 30, 2014 were included in this study. Follow-up data were obtained from hospital medical records. Follow-up data through May 30, 2016 were used to retrospectively analyze preoperative multiphasic CT findings, surgical histopathology results, and serum α-fetoprotein and thymidine kinase-1 levels. The χ2 test, independent t-test, and Mann-Whitney U test were used to analyze data. A P-value of < 0.05 was considered statistically significant. RESULTS During the follow-up period, 38 of 128 patients (29.7%) had a postoperative HCC recurrence. Microvascular invasion (MVI) was associated with HCC recurrence (χ2 = 13.253, P < 0.001). Despite postoperative antiviral therapy and chemotherapy, 22 of 44 patients with MVI experienced recurrence after surgical resection. The presence of MVI was 57.9% sensitive, 75.6% specific and 70.3% accurate in predicting postoperative recurrence. Of 84 tumors without MVI, univariate analysis confirmed that tumor margins, tumor margin grade, and tumor capsule detection on multiphasic CT were associated with HCC recurrence (P < 0.05). Univariate analyses showed no difference between groups with respect to hepatic capsular invasion, Ki-67 proliferation marker value, Edmondson-Steiner grade, largest tumor diameter, necrosis, arterial phase enhanced ratio, portovenous phase enhanced ratio, peritumoral enhancement, or serum α-fetoprotein level. CONCLUSION Non-smooth tumor margins, incomplete tumor capsules and missing tumor capsules correlated with postoperative HCC recurrence. HCC recurrence following curative resection may be predicted using CT.

// Jian-Hong Zhong 1, 2, * , Ning-Fu Peng 1, 2, * , Xue-Mei You 1, 2, * , Liang Ma 1, 2, * , Xiao Xiang 1 , Yan-Yan Wang 1 , Wen-Feng Gong 1, 2 , Fei-Xiang Wu 1, 2 , Bang-De Xiang 1, 2 , Le-Qun Li 1, 2 1 Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China 2 Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning 530021, China * These authors have contributed equally to this work Correspondence to: Le-Qun Li, email: xitongpingjia@163.com Bang-De Xiang, email: xiangbangde@gmail.com Keywords: hepatic resection, hepatocellular carcinoma, transarterial chemoembolization, treatment selection, tumor stage Received: December 01, 2016 Accepted: January 18, 2017 Published: February 17, 2017 ABSTRACT The current clinical reality of tumor stages and primary treatments of hepatocellular carcinoma (HCC) is poorly understood. This study reviewed the distribution of tumor stages and primary treatment modalities among a large population of patients with primary HCC. Medical records of patients treated between January 2003 and October 2013 for primary HCC at our tertiary hospital in China were retrospectively reviewed. A total of 6241 patients were analyzed. The distribution of Barcelona Clinic Liver Cancer (BCLC) stages was as follows: stage 0/A, 28.9%; stage B, 16.2%; stage C, 53.6%; stage D, 1.3%. The distribution of Hong Kong Liver Cancer (HKLC) stages was as follows: stage I, 8.4%; stage IIa, 1.5%; stage IIb, 29.0%; stage IIIa, 10.0%; stage IIIb, 33.6%; stage IVa, 3.4%; stage IVb, 2.5%; stage Va, 0.2%; stage Vb, 11.4%. The most frequent therapy was hepatic resection for patients with BCLC-0/A/B disease, and transarterial chemoembolization for patients with BCLC-C disease. Both these treatments were the most frequent for patients with HKLC I to IIIb disease, while systemic chemotherapy was the most frequent first-line therapy for patients with HKLC IVa or IVb disease. The most frequent treatment for patients with HKLC Va/Vb disease was traditional Chinese medicine. In conclusion, Prevalences of BCLC-B and -C disease, and of HKLC I to IIIb disease, were relatively high in our patient population. Hepatic resection and transarterial chemoembolization were frequent first-line therapies.

Background Postoperative hepatitis B virus (HBV) reactivation (PHR) is associated with resection-induced immunosuppression in patients with HBV-related hepatocellular carcinoma (HCC). Controlling Nutritional Status (CONUT) score is an effective index for evaluating immune-nutrition function. However, the value of COUNT in predicting PHR in HBV-HCC patients remains unknown. Methods Totally, 209 HCC patients were enrolled. Results Preoperative immune function (CD3+CD4+, CD3+CD8+, IgG and IgM) in patients with high CONUT score was significantly worse than that in patients with low CONUT score (P Conclusion CONUT score is an effective indicator predicting survival and PHR in HBV-HCC patients, especially in those with HBV-DNA levels

Background Misregulation of the p53-mdm2 loop function is a major mechanism to promote hepatocellular carcinoma (HCC). RBM38, a member of the RNA recognition motif (RRM) family of RNA binding proteins (RBPs), plays a fundamental role in the posttranscriptional control of gene expression and regulatory functions in human tumors. A novel RBM38-p53-mdm2 autoregulatory feedback loop has been demonstrated. However, its mechanistic role in HCC remains unclear. Methods In the present study, we investigated the role and molecular mechanism of misregulation in the p53-mdm2 loop function by RBM38 in HCC. First we investigated the correlation of RBM38 activity and p53-mdm2 loop function in liver cancer cells and HCC tissues by western blot and quantitative RT-PCR. We then conducted functional assays to investigate the molecular roles of RBM38 in inhibiting liver cancer cells aggressiveness in vitro and suppressing tumorigenicity in vivo. Results We observed RBM38 protein expression was commonly silenced coupled with increased mdm2 and decreased wild type (wt) p53 in liver cancer cells and HCC tissues compared to the corresponding normal liver cells and adjacent liver tissues. RBM38 mRNA level was significantly lower in HCC than adjacent liver tissues, whereas mdm2 and wtp53 mRNA levels were similar between HCC and adjacent liver tissues. This implied that deactivation of RBM38 could disrupt the p53-mdm2 loop and promote HCC, even though p53 and mdm2 transcript amounts were stable. Then, we generated stable liver cancer cell lines with overexpressed RBM38 (RBM38-OE) and found that up-regulation of RBM38 could inhibit mdm2 and restore wtp53 expression. Luciferase assay shown that RBM38 destabilized the mdm2 transcript through binding to multiple AU-/U-rich elements in mdm2 3’-UTR. Furthermore, functional assays showed that ectopic expression of RBM38 could induce liver cancer cell apoptosis and senescence, inhibit proliferation and colony growth, and suppress migration and invasion in vitro. Lastly, RBM38 could suppress HCC tumorigenicity in vivo. Conclusion Our findings suggested that RBM38 may be a core contributor in stabilizing the p53-mdm2 loop function to prevent HCC, and a potential novel target to provide a therapeutic strategy for HCC by inhibiting mdm2 and rescuing p53 from inactivation. Electronic supplementary material The online version of this article (10.1186/s13046-018-0852-x) contains supplementary material, which is available to authorized users.

Background Assessing hepatic functional reserve before hepatectomy is beneficial to reduce the incidence of posthepatectomy liver failure (PHLF). This study aimed to compare the ability of the Child-Pugh score, model for end-stage liver disease (MELD) score, and retention test at 15 minutes (indocyanine green [ICG]-R15) to assess hepatic functional reserve. Methods A total of 185 patients with hepatocellular carcinoma (HCC) undergoing hepatectomy were enrolled in this study. The ability of Child-Pugh score, MELD score, and ICG-R15 predicting severe PHLF were compared. Results A total of 23 patients (12.4%) developed severe PHLF. Multivariate analyses identified that platelet count, ICG-R15, clinically significant portal hypertension, and major resection were independent factors for predicting severe PHLF. The area under the receiver operating characteristic curve of ICG-R15 for predicting severe PHLF was higher than that of both Child-Pugh score and MELD score. With an optimal cutoff value of 7.1%, the sensitivity and specificity of ICG-R15 for predicting severe PHLF were 52.2% and 89.5%, respectively. Both the incidence of severe PHLF and mortality in patients with ICG-R15 >7.1% were significantly higher than the figures for patients with ICG-R15 ≤7.1%. Conclusion ICG-R15 is more accurate than the Child-Pugh score and MELD score in predicting hepatic functional reserve before hepatectomy.

Background/Aims: Increasing evidence suggests that T-UCRs are involved in the development of cancer. In this study, we evaluated the role of a macrophage-derived T-UCR, uc.306, in the prognosis of hepatitis B (HBV)-related hepatocellular carcinoma (HCC). Methods: The uc.306 was obtained by screening microassay data obtained during the polarization of U937 cells from the M2 to M1 phenotype. Uc.306 and macrophage molecule markers were detected by qPCR. Immunohistochemical (IHC) assays were used to examine the M1/M2 status of 90 paired HCC tissues. Kaplan-Meier tests and multivariable Cox regression models were used to analyze predictive confidences, survival, and risk factors. Results: In total, 2,977 differentially expressed T-UCRs were obtained, of which 257 showed fold changes >1.5. The uc.306 was upregulated in M1 cells and was predicted to be involved in the Wnt pathway. The IHC results showed that M1 macrophages (CD68+) were present in the para-tumor tissues, while the M2 phenotype (CD163+) was mainly in the HCC tissues. Uc.306 had a lower expression in the HCC tissues than in that of the para-tumor tissues in 30 paired HCC training sets (P < 0.0001), and 252 paired HCC testing sets (P < 0.0001). Low expression of uc.306 was significantly associated with a shorter overall survival (P < 0.05). Conclusions: The uc.306 may be a promising biomarkerfor HBV-related HCC, providing a novel marker for the prognosis of HCC.

As the sixth most common cancer and the third leading cause of cancer-related deaths worldwide, hepatocellular carcinoma (HCC) imposes a significant burden on health care [1]. The geographical distribution of HCC is extremely uneven. Despite the increased frequency of surveillance programs, the majority of patients have an intermediate or advanced stage HCC at diagnosis due to no significant symptoms in early stage. Of these, quite a number of them are with multinodular HCC (≥2). It is therefore vital to choose the most effective and appropriate therapy for these patients. Hepatic resection (HR) is the standard therapy for early stage HCC in non-cirrhotics with a well-preserved liver function [2]. However, the role of HR in the treatment of multinodular HCC remains controversial. According to the widely used Barcelona Clinic liver cancer (BCLC) staging system [3] and its updated review [4], HR should not be recommended to the patients with multinodular HCC [3]. Although the recommendations of BCLC staging system are endorsed by the American Association for the Study of Liver Diseases (AASLD) [5] and the European Association for the Study of the Liver (EASL) [6], many large and qualified liver centers in treating HCC especially those in Asia do not subscribe to these guidelines. Some retrospective studies have demonstrated that HR is superior to palliative treatments for multinodular HCC [7–10]. Although these retrospective studies may have some unintentional selection bias, the first randomized controlled trial (RCT) by Yin and coworkers definitely support this conclusion [11]. These studies highlight one of the ongoing controversies that surround the BCLC system. The fact that AASLD/EASL guidelines do not recommend HR for patients with intermediate or advanced stage HCC reflects primarily concerns over high recurrence and perioperative mortality, rather than direct prospective clinical evidence. However, recent advances in perioperative management and surgical techniques, as well as more restrictive selection of patients for HR, have rapidly reduced perioperative mortality, which was only 1.1 % in the RCT [11]. Moreover, HR can achieve satisfactory overall survival [12] in patients with recurrent HCC. Aggressive treatment of recurrence by repeat HR, radiofrequency ablation (RFA), and adjuvant therapies, such as transarterial chemoembolization (TACE), can offer satisfactory overall survival (OS) [13–15]. Therefore, this trial and other retrospective studies concluding HR superior to TACE makes sense [7–9, 11]. RCTs directly comparing TACE and HR in such patients have been lacking because clinicians are loathe to treat them exclusively with TACE, given the demonstrated survival benefit of HR inmany retrospective studies [7–9]. For this reason, this RCT [11] stands out as providing clear, direct evidence against current guidelines. Therefore, it is a very valuable study. This RCT was conducted on 173 patients with multinodular HCC outside of Milan criteria who were treated in a big liver center in eastern China. The patients were included in a short time period from 2008 to 2010 and underwent intention-to-treat analysis. Most of the included patients (91.3 %) were positive for hepatitis B surface antigen and with cirrhosis (82.7 %). There were no significant differences in the 30-day and in the 90-day mortality between the Jian-Hong Zhong and Fei-Xiang Wu contributed equally to this work. J.

Background & Aims p53 is one of the most frequently mutated human tumour suppressor genes. Chronic infection with hepatitis B virus (HBV) and exposure to aflatoxin B1 (AFB1) induces p53 mutations in hepatocellular carcinoma (HCC) tissue. The aims of present study are to investigate the p53 mutation spectrum in HBV- and AFB1-related hepatocarcinogenesis in patients with hepatocellular carcinoma (HCC) in Guangxi, China. Methods Tumour and adjacent liver tissue were collected from 397 HCC patients who were subdivided into HBV(+)/AFB1(+), HBV(+)/AFB1(−), HBV(−)/AFB1(+) and HBV(−)/AFB1(−) four groups. All 11 exons of the p53 gene were PCR-amplified and sequenced. Immunohistochemistry was used to evaluate the effect of mutations on the expression of p53 protein. Results and Conclusions P53 mutations were detected in 223 HCC samples, 13 adjacent liver tissue samples and only 1 of 68 normal liver tissue samples. The mutation sites concentrated at exon 4, 5, 6, 7, 8, 9 and no mutation was detected in exon 1, 2, 3, 10 and 11. The most frequently occurring mutation was in codon 249 (R249S) in exon 7. Patients in the HBV(+)/AFB1(+) and HBV(−)/AFB1(+) groups had significantly higher mutation rates compared with patients in the HBV(+)/AFB1(−) and HBV(−)/AFB1(−) groups. P53 mutation status and HBV/AFB1 status were independent predictors of tumour recurrence after surgery. Immunohistochemical analysis revealed that p53 gene mutations were correlated with the p53 expression. In Guangxi area, the significant association between AFB1-induced p53 mutations and the expression of p53 protein suggest an important role for p53 mutations in carcinogenesis of HCC.

The present study compared the efficacy of hepatic resection (HR) in patients with large hepatocellular carcinoma (HCC) and those with multinodular tumor and examined how that efficacy has changed over time in a large medical center. The intermediate stage of HCC comprises a highly heterogeneous patient population. Moreover, official guidelines have different views on the suitability of HR to treat such patients. A consecutive sample of 927 patients with preserved liver function and large and/or multinodular HCC who were treated by initial HR were divided into 3 groups: those with a single tumor ≥5 cm in diameter (n = 588), 2 to 3 tumors with a maximum diameter >3 cm (n = 225), or >3 tumors of any diameter (n = 114). Hospital mortality and overall survival (OS) in each group were compared for the years 2000 to 2007 and 2008 to 2013. Patients with >3 tumors showed the highest incidence of hospital mortality of all groups (P 2 to 3 tumors > 3+ tumors (all P 3 tumors show the highest hospital mortality and lowest OS after HR. OS has been improving for all 3 types of HCC at our medical center as a consequence of improvements in surgical technique and perioperative management.

Many evidences show that epidermal growth factor receptor variant type III (EGFRvIII) plays an important role in initiation and progression of various cancers. But the relationship between EGFRvIII and hepatocellular carcinoma (HCC) is unclear. This study was to explore the expression and significance of EGFRvIII in human HCC tissues.Immunohistochemical staining (IHC) was used to detect the expression of EGFRvIII in 55 specimens of HCC tissues and their adjacent non-cancerous liver tissues.Positive rate of EGFRvIII in HCC tissue was significantly higher than that in adjacent non-cancerous liver tissue [61.8% (34/55) vs. 38.2% (21/55), P0.05]. Positive rate of EGFRvIII in HCC tissue was significantly correlated with clinical stage,portal vein tumor thrombus,presence of extrahepatic metastasis, tumor recurrence, and the diameter of tumor, but not correlated with the number of foci, serum alpha-fetoprotein (AFP) level, serum HBsAg status, tumor differentiation, and cirrhosis in adjacent liver tissue.EGFRvIII is over-expressed in human HCC tissues, and relates to progression and recurrence of HCC.

Many evidences demonstrated that the epidermal growth factor receptor (EGFR) subfamily played an important role in they initiation and progression of various cancers. But it is not clear whether there is a relationship between EGFR and hepatocellular carcinoma (HCC). The aims of the present study were to explore the expression and significance of the epidermal growth factor (EGF) mRNA and EGFR mRNA in human HCC tissues.Reverse transcription polymerase chain reaction (RT-PCR) was employed to determine the expression of EGF mRNA and EGFR mRNA in 60 HCC tissues and their adjacent liver tissues.The positive rate of EGF mRNA was significantly lower in the HCC tissue (60%, 36/60) than in the adjacent liver tissue (80%, 48/60) (P0.05). The positive rate of EGFR mRNA in the HCC tissue (60%, 36/60) was markedly higher than in the adjacent liver tissue (41.67%, 25/60) (P0.05). The expression of EGFR mRNA in the HCC tissue was significantly correlated with the clinical stage, the portal vein tumor thrombus, the presence of extrahepatic metastasis, and the recurrence of tumor, the number of tumor, but not correlated with the diameter of tumor, the level of serum alpha-fetoprotein (AFP), the differentiation of tumor and the liver cirrhosis in the adjacent tissue. The detectable rate of EGF mRNA was correlated with the diameter of tumor but not correlated with the clinical stage, the portal vein tumor thrombus, the presence of extrahepatic metastasis, the recurrence of tumor, the number of tumor, the level of serum AFP, the differentiation of tumor and the liver cirrhosis in the adjacent tissue.EGF may not be involved in the initiation and progression of HCC, whereas, EGFR relates to the initiation and progression and the recurrence of HCC. EGFR can be considered as a marker for predicting the metastasis and recurrence of HCC.

This study aims to refine the designation for single hepatocellular carcinoma (HCC) >5 cm by comparing the postresection prognosis of these patients with those who have a single-tumor ≤5 cm and those with stage B. Patients with a single-tumor were classified into subgroups based on diameter. Of the 1132 patients analyzed, 426 had a single-tumor >2 and ≤5 cm; 229, a single-tumor >5 and ≤8 cm; 52, a single-tumor >8 and < 10 cm; 150, a single-tumor ≥10 cm; and 275, stage B. Hospital mortality and complications increased with tumor size among the single-tumor subgroups and median survival decreased with increasing of tumor size. Overall survival (OS) among patients with a single-tumor >5 cm was significantly lower than among patients with a single-tumor >2 and ≤5 cm (P ≤ .001), but significantly higher than among patients with clearly stage B (P ≤ .001). Patients with a single-tumor >5 and ≤8 cm showed lower OS than patients with a single-tumor >2 and ≤5 cm (P < .001). Patients with a single-tumor >8 and 5 and ≤8 cm (P = .033 and.006), and similar OS to patients with stage B (P = .323). Patients with a single-tumor >5 and ≤8 cm may be assigned to a new stage between early and intermediate. Patients with a single-tumor >8 cm may be assigned to intermediate stage.