Combining bulk and scRNA-seq to explore the molecular mechanisms governing the distinct efferocytosis activities of a macrophage subpopulation in PDAC.

Pancreatic ductal adenocarcinoma (PDAC), a very aggressive tumour, is currently the third leading cause of cancer-related deaths. Unfortunately, many patients face the issue of inoperability at the diagnostic phase leading to a quite dismal prognosis. The onset of metastatic processes has a crucial role in the elevated mortality rates linked to PDAC. Individuals with metastatic advances receive only palliative therapy and have a grim prognosis. It is essential to carefully analyse the intricacies of the metastatic process to enhance the prognosis for individuals with PDAC. Malignancy development is greatly impacted by the process of macrophage efferocytosis. Our current knowledge about the complete range of macrophage efferocytosis activities in PDAC and their intricate interactions with tumour cells is still restricted. This work aims to resolve communication gaps and pinpoint the essential transcription factor that is vital in the immunological response of macrophage populations. We analysed eight PDAC tissue samples sourced from the gene expression omnibus. We utilized several software packages such as Seurat, DoubletFinder, Harmony, Pi, GSVA, CellChat and Monocle from R software together with pySCENIC from Python, to analyse the single-cell RNA sequencing (scRNA-seq) data collected from the PDAC samples. This study involved the analysis of a comprehensive sample of 22,124 cells, which were classified into distinct cell types. These cell types encompassed endothelial and epithelial cells, PDAC cells, as well as various immune cells, including CD4+ T cells, CD8+ T cells, NK cells, B cells, plasma cells, mast cells, monocytes, DC cells and different subtypes of macrophages, namely C0 macrophage TGM2+, C1 macrophage PFN1+, C2 macrophage GAS6+ and C3 macrophage APOC3+. The differentiation between tumour cells and epithelial cells was achieved by the implementation of CopyKat analysis, resulting in the detection and categorization of 1941 PDAC cells. The amplification/deletion patterns observed in PDAC cells on many chromosomes differ significantly from those observed in epithelial cells. The study of Pseudotime Trajectories demonstrated that the C0 macrophage subtype expressing TGM2+ had the lowest level of differentiation. Additionally, the examination of gene set scores related to efferocytosis suggested that this subtype displayed higher activity during the efferocytosis process compared to other subtypes. The most active transcription factors for each macrophage subtype were identified as BACH1, NFE2, TEAD4 and ARID3A. In conclusion, the examination of human PDAC tissue samples using immunofluorescence analysis demonstrated the co-localization of CD68 and CD11b within regions exhibiting the presence of keratin (KRT) and alpha-smooth muscle actin (α-SMA). This observation implies a spatial association between macrophages, fibroblasts, and epithelial cells. There is variation in the expression of efferocytosis-associated genes between C0 macrophage TGM2+ and other macrophage cell types. This observation implies that the diversity of macrophage cells might potentially influence the metastatic advancement of PDAC. Moreover, the central transcription factor of different macrophage subtypes offers a promising opportunity for targeted immunotherapy in the treatment of PDAC.

The potential mechanism of miR-130b on promotion of the invasion and metastasis of hepatocellular carcinoma by inhibiting Notch-Dll1.

Introduction: This study aimed to elucidate the regulatory role and molecular regulation mechanism of miR-130b gene in the process of invasion and metastasis of hepatocarcinoma, and provide a theoretical basis for seeking of effective prevention and treatment of new targets for hepatocellular carcinoma.Materials and methods: The expression level of miR-130b gene in hepatocarcinoma tissues was determined by qRT-PCR. The biological function and mechanism of miR-130b gene were verified by cell and animal models, and the target gene was verified by double luciferase assay.Results: In the liver cancer tissues of patients with metastasis, the expression level of miR-130b gene was increased, and the difference was significantly significant (p < 0.05). Evaluation of independent risk factors for overall survival showed significant difference (p < 0.01). Up-regulation of miR-130b in MHCC97L- subpopulation cells significantly enhanced the invasion and migration ability, and the difference was statistically significant (p < 0.05). The invasion and migration ability of MHCC97H + subpopulation cells with increased expression of miR-130b was significantly decreased, and the difference was notably significant (p < 0.05). When the expression of miR-130b in MHCC97H + subpopulation cells was inhibited, the expressions of Notch-Dll1 and SOX2, Nanog and E2F3 proteins in transplanted tumor tissues were significantly higher than those in other groups (p < 0.05). When miR-130b in MHCC97L- subpopulation cells was up-regulated, the expressions of Notch-Dll1 and Bcl-2, CCND1, Nanog and MET proteins in transplanted tumor tissues were significantly increased than those in other groups (p < 0.05). The prediction results of bioinformatics data suggest that the target gene of miR-130b may be Notch-Dll1 gene. The experiment of luciferase reporter gene confirmed that miR-130b gene can be inhibited and contains fluorescent reporter gene with complementary binding site, lost activity.Conclusion: The miR-130b gene can inhibit the protein expression of Notch-Dll1, and it can promote the invasion and metastasis of liver cancer cells.

Long noncoding RNA MALAT1 inhibits the apoptosis and autophagy of hepatocellular carcinoma cell by targeting the microRNA-146a/PI3K/Akt/mTOR axis.

BACKGROUND: Increased long noncoding RNA (lncRNA) expression is characteristic to hepatocellular carcinoma (HCC) and several other neoplasms. The present study aimed to identify the mechanism underlying modulation of HCC development by the lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). METHODS: Quantitative real-time polymerase chain reaction was used to determine MALAT1 and microRNA (miR)-146a expression in HCC tissues and cell lines. Western blotting was performed to measure PI3K, Akt, and mTOR levels. Dual-luciferase reporter assay was used to validate the direct targeting and negative regulatory interaction between miR-146a and MALAT1. Cell viability, proliferation, and apoptosis were analyzed using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, colony formation assay, and flow cytometry, respectively; autophagy was detected based on LC3B expression. RESULTS: MALAT1 expression was higher in HCC tissues than in normal tissues. MALAT1 upregulation promoted HCC cell proliferation, whereas MALAT1 downregulation promoted HCC apoptosis and autophagy. Moreover, effects of MALAT1 downregulation on HCC cells were abolished by miR-146a inhibition. miR-146a directly targeted the 3'-untranslated region of PI3K, and PI3K protein level was clearly decreased upon miR-146a mimic transfection. CONCLUSIONS: MALAT1 may modulate HCC cell proliferation, apoptosis, and autophagy via sponging miR-146a, which regulates HCC progression.

c-Myc-mediated SNRPB upregulation functions as an oncogene in hepatocellular carcinoma.

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.

Hepatectomy for liver metastases from gastric cancer: a systematic review.

BACKGROUND: Official guidelines recommend palliative treatments for patients with liver metastases from gastric cancer. However, many case series reported that hepatectomy for such cases is safe and effective. This systematic review compares the overall survival between hepatectomy and palliative therapy in patients with liver metastases from gastric cancer. METHODS: Two independent reviewers performed a systematic search of literature in EMBASE and PubMed, updated until 26 October 2016. The Newcastle-Ottawa score for cohort studies was used for quality assessment of included studies. RESULTS: A total of eight cohort studies involving 196 patients in the hepatectomy arm and 481 in the palliative arm were included. Median overall survival of patients in the two arms was 23.7 (range, 13.0 to 48.0) and 7.6 (range, 5.5 to 15.2), respectively. Median rates of overall survival of the two arms were 69, 40, 33 and 27, 8, 4% at 1, 2, and 3 years, respectively. Comparing with palliative therapy, hepatectomy was associated with significantly lower mortality at 1 year (odds ratio 0.17, P < 0.001) and 2 years (odds ratio 0.15, P < 0.001). Among the patients who underwent hepatectomy, Asian cohorts showed higher median rates of overall survival than Western cohorts at 1 year (76 vs. 60%), 2 years (47 vs. 30%) and 3 years (39 vs. 23%). CONCLUSIONS: Hepatectomy in the management of liver metastases from gastric cancer can be considered effective. In the elective setting, hepatectomy provides a potential alternative to palliative therapy.

Clinicopathological characteristics and liver stem cell marker expression in hepatocellular carcinoma involving bile duct tumor thrombi.

The aim of this study was to analyze the clinicopathological characteristics and expression of liver stem cell markers of hepatocellular carcinoma (HCC) involving bile duct tumor thrombi (BDTT). A total of 35 patients with HCC and BDTT in a consecutive series of HCC patients who underwent surgical treatment were studied retrospectively and compared with 916 patients without BDTT from the same series. Clinicopathological characteristics, overall survival (OS), and tumor expression of liver stem cell markers CD133, CD90, EpCAM, CK19, VEGF, and C-kit were compared between the two patient groups. Analysis was performed for the entire patient groups as well as for 35 pairs of patients with or without BDTT matched by propensity score. HCC patients with BDTT tended to have smaller tumors than those without BDTT, as well as a higher probability of having poorly differentiated tumor, Child-Pugh class B, liver cirrhosis, and microvascular invasion. Tumor tissue in patients with BDTT showed significantly higher expression rates of all liver stem cell markers examined. OS was significantly lower for patients with BDTT at 1 year (69 vs 84 %), 3 years (37 vs 64 %), and 5 years (20 vs 55 %) (P < 0.001). Patients with HCC and BDTT show lower OS than patients without BDTT. The higher frequency of liver stem cell marker expression in the presence of BDTT suggests that such stem cells may play a role in the pathogenesis of this form of HCC.

Combination of 5-fluorouracil and 2-morphilino-8-phenyl-4H-chromen-4-one may inhibit liver cancer stem cell activity.

This work aims to evaluate the impact of 2-morpholino-8-phenyl-4H-chromen-4-one (LY294002) combined 5-fluorouracil (5-FU) for the activity of CD90+ liver cancer cells derived from the human liver cancer cell line MHCC97H. MHCC97H sphere-forming cells (MSFCs) were amplified in serum-free medium and CD90+ cells were isolated from bulk MSFCs using flow cytometry. The phenotype of these CD90+ cells which show liver cancer stem cells (LCSCs) behavior was validated in vitro and in a xenograft model in nude mice. MSFCs, CD90+ liver cancer cells (CD90+ LCCs), and parental MHCC97H cells were treated with no drug, LY294002 alone, 5-FU alone, or both drugs together and then compared in terms of stem cell-related gene expression, proliferation, and invasion. Stem cell phenotype increased with increasing proportion of CD90+ cells, in ascending order: parental MHCC97H cells, MSFCs, and CD90+ liver cancer cells. LY294002 reduced the expression of CD90, Nanog, SALL4, and SHP2 in a concentration-dependent manner in CD90+ LCCs and MSFCs, but not in parental cells. LY294002 blocked AKT phosphorylation via the PI3K/AKT signaling pathway and inhibited CD90+ LCCs proliferation and tumorigenicity in vitro and in vivo. CD90+ liver cancer cells can express liver cancer stem cell phenotype. LY294002 inhibits the proliferation and invasion of MHCC97H-derived CD90+ LCCs and sensitized CD90+ LCCs-derived tumors to 5-FU in the current study which may provide insight into the association between the LY294002 combined 5-FU and liver cancer stem cell (LCSCs).

Association between age and overall survival of patients with hepatocellular carcinoma after hepatic resection.

AIM: The suitability of hepatic resection for older patients remains controversial. This study aimed to investigate whether age influences overall survival of patients with hepatocellular carcinoma (HCC) after resection. METHODS: Records of 1,132 patients with HCC after hepatic resection were retrospectively reviewed. Overall survival (OS) was compared between younger and older patients based on five cut-off ages (30, 40, 50, 60, and 70 years). RESULTS: Across all patients, OS was 89.7% at 1 year, 67.7% at 3 years, and 47.7% at 5 years. OS was similar between younger and older patients at all cut-off ages (all P > 0.1), but OS was marginally lower among patients >70 years old than those ≤70 (P = 0.090). Multivariate analyses identified several risk factors for lower OS: preoperative serum albumin <35 g/L, alanine aminotransferase >80 U/L, α-fetoprotein ≥400 ng/ml, presence of esophagogastric varices or macrovascular invasion, incomplete/absent tumor capsule, tumor size >10 cm, tumor number ≥3, and major hepatectomy. CONCLUSION: Age does not influence the prognosis of patients with HCC after hepatic resection. Older patients should be considered for curative resection if remnant liver volume and liver function are adequate. J. Surg. Oncol. 2016;114:966-970. © 2016 Wiley Periodicals, Inc.

Prognostic factors of regression and relapse of complex atypical hyperplasia and well-differentiated endometrioid carcinoma with conservative treatment.

OBJECTIVE: To evaluate possible prognostic factors regarding regression and relapse of complex atypical hyperplasia (CAH) and well-differentiated endometrioid adenocarcinoma (WDC) treated with conservative treatment. METHODS: The retrospective study reviewed clinicopathologic, treatment, regression and relapse data from patients diagnosed with CAH or WDC who were treated with conservative treatment at 4 institutions. Potential factor evaluation was performed. SPSS 16 was used for statistical analyses. RESULTS: Eighty-eight patients were included (51 had WDC, and 37 had CAH). Regression was evaluated in 88 patients, with a median follow-up of 61 (range 15-95) months. Seventy-seven (87.5%) patients regressed, and 11 (12.5%) had persistent or progressive disease. Univariate and multivariate analyses showed no factors associated with regression. Relapse was evaluated in 71 patients, with median follow-up of 54 (range 8-86) months. Twenty-five/71 (35.2%) patients experienced relapse. On univariate analysis, body mass index (BMI) 30 or higher (p=0.001), WCD at initial biopsy (p=0.017) and positive expression of post-treatment ki67 (p=0.033) were associated to a higher relapse probability. However, only BMI 30 or higher was significant on multivariate analysis (p=0.012). The Kaplan-Meier analysis revealed a higher relapse probability in the patients with BMI 30 or higher (p=0.001). CONCLUSION: Obesity seems to be a risk factor for relapse of CAH or WDC with conservative treatment.

A meta-analysis of the relationship between glutathione S-transferases gene polymorphism and hepatocellular carcinoma in Asian population.

The results from the published studies on the association between glutathione S-transferases (GST) gene polymorphism and hepatocellular carcinoma (HCC) in Asian population are still conflicting. GSTM1, GSTT1 and GSTP1 are the mainly mutant sites reported at present. This meta-analysis was performed to evaluate the relationship between GST gene polymorphism and HCC risk in Asians. Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) on February 1, 2012, and eligible investigations were synthesized using meta-analysis method. Results were expressed with odds ratios (OR) for dichotomous data, and 95 % confidence intervals (CI) were also calculated. Twenty-five investigations were identified for the analysis of association between polymorphic deletion of GSTM1 and HCC, consisting of 3,547 patients with HCC and 6,132 controls. There was a marked association between GSTM1 null genotype and HCC susceptibility (OR 1.48, 95 % CI 1.19-1.85, P = 0.0004). GSTM1 null genotype was associated with HCC risk in Chinese. Furthermore, null genotype of GSTT1 was associated with HCC susceptibility in Asians. For the GSTM1-GSTT1 interaction analysis, the dual null genotype of GSTM1/GSTT1 was significantly associated with HCC susceptibility in Asian population. However, GSTP1 ile105 val gene polymorphism was not associated with HCC risk in Asian population. In conclusion, GSTM1/GSTT1 null genotype is associated with the HCC susceptibility. However, GSTP1 gene polymorphism is not associated with HCC risk.

Artificial Intelligence Algorithm in Classification and Recognition of Primary Hepatic Carcinoma Images under Magnetic Resonance Imaging.

This study aimed to discuss the application value of the bias field correction algorithm in magnetic resonance imaging (MRI) images of patients with primary hepatic carcinoma (PHC). In total, 52 patients with PHC were selected as the experimental group and divided into three subgroups: mild (15 cases), moderate (19 cases), and severe (18 cases) according to pathological grading. Another 52 patients with hepatic nodules in the same period were included in the control group. All the patients underwent dynamic contrast-enhanced (DCE) MRI examination, and the image qualities of MRI before and after bias field correction were compared. The DCE-MRI perfusion parameters were measured, including the transport constant Ktrans, reverse rate constant Kep, extravascular extracellular volume fraction (Ve), plasma volume (Vp), microvascular density (MVD), hepatic artery perfusion index (HPI), mean transit time of contrast agent (MTT), time to peak (TTP), blood volume (BV), hepatic arterial perfusion (HAP), full perfusion (FP), and portal venous perfusion (PVP). It was found that the sensitivity (93.63%), specificity (71.62%), positive predictive value (95.63%), negative predictive value (71.62%), and accuracy (90.01%) of MRI examination processed by the bias field correction algorithm were all significantly greater than those before processing (P < 0.05). The Ktrans, Kep, Ve, Vp, and MVD of patients in the experimental group were significantly larger than those of the control group, and severe group> moderate group> mild group (P < 0.05). HPI, MTT, TTP, BV, and HAP of patients in the experimental group were also significantly greater than those of the control group, which was shown as severe group > moderate group > mild group (P < 0.05). FP and PVP of the experimental group were significantly lower than those of the control group, and severe group < moderate group < mild group (P < 0.05). It was suggested that in MRI images of patients with PHC, the bias field correction algorithm could significantly improve the diagnosis rate. Each perfusion parameter was related to the pathological grading, which could be used to evaluate the prognosis of patients.

Evaluation of risk factors and clinicopathologic features for intrahepatic cholangiocarcinoma in Southern China: a possible role of hepatitis B virus.

BACKGROUND: Recent efforts suggest an etiologic role of hepatitis B virus (HBV) infection in intrahepatic cholangiocarcinoma (ICC) and the involvement of hepatic progenitor cell in ICC development, without definitive conclusions. This case-control study was undertaken to investigate risk factors for ICC, and clinicopathological features of HBV-associated ICC were analyzed. METHODS: The report comprised 98 patients with pathologically confirmed ICC and 196 healthy control subjects. Logistic regression was used to determine odds ratios and 95% confidence intervals. The sex and age distributions of HBV-related and unrelated ICC patients were compared respectively with those of 882 HBV-associated hepatocellular carcinoma patients from a random selection, and the clinicopathological data of 62 ICC patients with or without HBV infection undergoing surgical resection were compared. RESULTS: There was an association between ICC and each of HBV infection, liver cirrhosis, hepatolithiasis, and liver fluke infestation with the odds ratios (95% confidence intervals) of 2.75 (1.27-5.95), 8.42 (2.50-28.37), 22.81 (7.16-72.68), and 3.55 (1.60-7.89), respectively, with a marked synergism of cirrhosis and HBV infection (20.67; 5.40-79.06). Compared with HBV-unrelated ICC patients, HBV-related ICC patients were more common in male and younger subjects, had a higher incidence of abnormal serum alfa-fetoprotein level, cirrhosis, and neutrophilic infiltration, and had a lower proportion of elevated carbohydrate antigen 19-9 (CA19-9) values. CONCLUSIONS: The independent association of HBV infection with ICC, synergy between cirrhosis and HBV infection, and some clinicopathological similarities between HBV-related ICC and hepatocellular carcinoma suggests that both may share similar or common tumorigenic process and may possibly originate from malignant transformation of hepatic progenitor cell.

Involvement of TRPC7-AS1 Expression in Hepatitis B Virus-Related Hepatocellular Carcinoma.

OBJECTIVE: To investigate the expression of transient receptor potential (TRP) superfamily genes, especially TRPC7-AS1 in hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC). METHODS: Three cancer samples of HBV-related HCC at phase IV and matched paracancerous liver tissues were included in the study. Total RNA was extracted, and differential expression of RNA was screened by high-throughput transcriptome sequencing. The expression of TRPC7-AS1 was detected by quantitative real-time PCR. The N6-adenosyl methylation RNA in MHCC97H, HepG2, and HL-7702 was enriched by coimmunoprecipitation with m6A antibody, and the relative level of N6-adenosyl methylation RNA in TRPC7-AS1 was detected. RESULTS: The expression of TRP family genes in cancer tissues was higher than that in paracancerous liver tissues, including TRPC7-AS1, TRPC4AP, PKD1P6, and PKD1P1. Moreover, the expression level of TRPC7-AS1 in MHCC97H and HepG2 was also significantly higher than that in L02, a normal liver cell. The methylation level of N6-adenosine of TRPC7-AS1 was lower in HepG2 cells than that in L02 cells. CONCLUSION: TRP superfamily genes, especially TRPC7-AS1, were highly expressed in HBV-related HCC. TRPC7-AS1 could be a potential therapeutic target or diagnostic marker for HCC.

[Synthesis of colon-specific prodrug of indomethacin and its inhibitory effect on liver metastasis from colon cancer].

OBJECTIVE: To develop a colon-specific prodrug of Indomethacin microbially triggered, carry out in vitro/in vivo evaluation of drug release, and appraise its inhibitory effect on liver metastasis from colon cancer. METHODS: Indomethacin prodrugs were synthesized and characterized by FTIR and NMR, and dissolution test simulating gastrointestinal tract was employed to screen the colon-specific prodrug. Then, the pharmacokinetic profile of portal vein and peripheral blood in Sprague-Dawley rats was studied. Lastly, the inhibitory effect on liver metastasis from colon cancer in nude mice was observed. RESULTS: The chemical structure characterized by FTIR and NMR demonstrated that six kinds of indomethacin-block-amylose with different drug loading (IDM-AM-1-6) were synthesized, among which IDM-AM-3 was degraded 1.3%, 9.3% and 95.3%, respectively, in simulated gastric fluid for 4 h, small intestine for 6 h, and colon for 36 h. The pharmacokinetic test of IDM-AM-3 showed that absorption was delayed significantly (P < 0.01), peak time [(11.35 + or - 2.45) h], elimination half-life [(16.74 + or - 4.04) h] and mean residence time [(22.27 + or - 0.52) h] were significantly prolonged (P < 0.01), as well as peak serum concentrations [(9.69 + or - 2.40) mg/L] and AUC(0-t) [(236.7 + or - 13.1) mg x L(-1) x h] were decreased markedly (P < 0.01) as compared with those of IDM regarding to portal vein. Additionally, its AUC(0-t) in peripheral blood was remarkably lower than that in Portal vein (P < 0.01). The tumor suppression observation showed that it could remarkably reduce the number of liver metastases in contrast to IDM (P < 0.05). CONCLUSION: Colon-specific IDM-AM-3 possesses advantage of sustained release in portal vein providing some experimental basis for colon-specific delivery system applied to sustained release in the portal vein.

Serum Prealbumin is Negatively Associated with Survival in Hepatocellular Carcinoma Patients after Hepatic Resection.

Objective: Low serum prealbumin levels are associated with poor prognoses in some type of cancers. However, the role of prealbumin in patients with hepatocellular carcinoma (HCC) is unknown. The present study aimed to investigate the role of serum prealbumin levels in long-term survival for HCC patients after hepatic resection. Methods: HCC patients who underwent hepatic resection from June 2007 to December 2015 were retrospectively analyzed in a tertiary liver center. Patients were classified as having normal or reduced serum prealbumin based on a cut-off value of 200 mg/L. Overall survival and recurrence rate were analyzed between groups. Propensity score analysis was used to reduce bias due to other patient differences at baseline. Results: A total of 1349 HCC patients who underwent hepatic resection were enrolled on this study, including 1168 (86.6%) male and 181 (13.4%) female. Patients with normal serum prealbumin had significantly higher overall survival than those with reduced serum prealbumin (P < 0.001). Similar findings were observed after propensity analysis and subgroup analysis based on liver cirrhosis. Moreover, patients with normal serum prealbumin had a significantly lower recurrence rate than those with reduced serum prealbumin (P < 0.001). Conclusions: Low preoperative level of serum prealbumin is associated with poor long-term survival in patients with HCC after hepatic resection. Low serum prealbumin may be a marker to identify patients at high risk of poor prognosis after hepatic resection.

Adjuvant transarterial chemoembolization to improve the prognosis of hepatocellular carcinoma following curative resection.

The present study aimed to investigate the prognostic factors for recurrence of hepatocellular carcinoma (HCC) following curative resection, and evaluate the efficacy of postoperative adjuvant transarterial chemoembolization (TACE) in improving prognosis. A total of 166 patients who underwent curative resection followed by adjuvant TACE, and 190 patients who underwent curative resection alone were studied retrospectively. Univariate and multivariate analyses were performed to investigate the risk factors of recurrence. Separated based on risk factors, subgroup studies were conducted and the association between TACE and recurrence rates was examined. Postoperative overall survival rates were determined using the Kaplan-Meier method and differences between the two therapeutic strategies were identified through log-rank analysis. Computerized tomography (CT)/magnetic resonance imaging (MRI) images were used to evaluate the function of postoperative adjuvant TACE for enhancing the efficacy of CT/MRI in detecting recurrence. The results of the univariate and multivariate analyses revealed that tumor capsule invasion, vascular invasion, and multiple nodules were risk factors of early recurrence. For patients with these risk factors, recurrence rates were markedly decreased at 6 and 12 months, but not at 18 and 24 months, if TACE was added to curative resection. The hepatitis B virus (HBV) was a risk factor for late recurrence. Postoperative TACE was not effective in reducing the recurrence rate in patients with HBV. Survival increased following curative resection with TACE compared with curative resection alone. Furthermore, adjuvant TACE enhanced the efficacy of CT/MRI in detecting recurrence. Postoperative adjuvant TACE may improve the prognosis of HCC following curative resection.

Preoperative evaluation with T-staging system for hilar cholangiocarcinoma.

AIM: To investigate the clinical value of T-staging system in the preoperative assessment of hilar cholangiocarcinoma. METHODS: From March 1993 to January 2006, 85 patients who had cholangiocarcinoma diagnosed by operative tissue-biopsy were placed into one of three stages based on the new T-staging system, and it was evaluated the resectability and survival correlated with T-staging. RESULTS: The likelihood of resection and achieving tumor-free margin decreased progressively with increasing T stage (P < 0.05). The cumulative 1-year survival rates of T1, T2 and T3 patients were 71.8%, 50.8% and 12.9% respectively, and the cumulative 3-year survival rate was 34.4%, 18.2% and 0% respectively; the survival of different stage patients differed markedly (P < 0.001). Median survival in the hepatic resection group was greater than in the group that did not undergo hepatic resection (28 mo vs 18 mo; P < 0.05). The overall accuracy for combined MRCP and color Doppler Ultrasonagraphy detecting disease was higher than that of combined using CT and color Doppler Ultrasonagraphy (91.4% vs 68%; P < 0.05 ). And it was also higher in detecting port vein involvement (90% vs 54.5%; P < 0.05). CONCLUSION: The proposed staging system for hilar cholangiocarcinoma can accurately predict resectability, the likelihood of metastatic disease, and survival. A concomitant partial hepatectomy would help to attain curative resection and the possibility of long-term survival. MRCP/MRA coupled with color Doppler Ultrasonagraphy was necessary for preoperative evaluation of hilar cholangiocarcinoma.