Trans-omics analysis of insulin action reveals a cell growth subnetwork which co-regulates anabolic processes.

Insulin signaling promotes anabolic metabolism to regulate cell growth through multi-omic interactions. To obtain a comprehensive view of the cellular responses to insulin, we constructed a trans-omic network of insulin action in Drosophila cells that involves the integration of multi-omic data sets. In this network, 14 transcription factors, including Myc, coordinately upregulate the gene expression of anabolic processes such as nucleotide synthesis, transcription, and translation, consistent with decreases in metabolites such as nucleotide triphosphates and proteinogenic amino acids required for transcription and translation. Next, as cell growth is required for cell proliferation and insulin can stimulate proliferation in a context-dependent manner, we integrated the trans-omic network with results from a CRISPR functional screen for cell proliferation. This analysis validates the role of a Myc-mediated subnetwork that coordinates the activation of genes involved in anabolic processes required for cell growth.

Prognostic Value of Serum Osteoprotegerin Level in Patients With Hepatocellular Carcinoma Following Surgical Resection.

BACKGROUND: Multiple studies have reported that tissue or serum osteoprotegerin (OPG) level is a prognostic factor for patients with cancer. However, little is known about the role of serum OPG in hepatocellular carcinoma (HCC). In this study, we aimed to investigate whether serum OPG concentration has an effect on HCC patients' prognosis. METHODS: A total of 386 eligible HCC patients undergoing radical hepatectomy were enrolled from Shanghai Ninth People's Hospital and Zhongshan Hospital between 2010 and 2018. Kaplan-Meier curves, Cox regression model, and the restricted mean survival time (RMST) were used to estimate the association of OPG and HCC patients' survival outcome. In addition, sensitivity analyses were carried out including subgroup analysis and propensity score matching (PSM). RESULTS: Patients were separated into two groups according to the cut-off value of OPG calculated by X-tile. Multivariate Cox analysis showed that patients with high OPG level had worse overall survival (OS) (HR: 1.93; 95% CI: 1.40-2.66, p<0.001) and disease-free survival (DFS) (HR: 1.85; 95% CI: 1.39-2.47, p<0.001) before matching. On average, RMST ratio between high and low OPG turned out to be 0.797 (95% CI: 0.716-0.887, p<0.001). In the matched population, we found that OPG level was negatively associated with OS (HR: 1.85; 95% CI: 1.25-2.74, p=0.002) and DFS (HR: 1.71; 95% CI: 1.20-2.44, p=0.003). In addition, a similar trend was further confirmed by subgroup analyses. CONCLUSION: In a word, HCC patients with high OPG level had poorer survival rates compared with HCC patients with low OPG level. This factor could act as a potential prognostic predictor for HCC patients who underwent radical resection in the future.

Serum GGT/ALT ratio predicts vascular invasion in HBV-related HCC.

BACKGROUND: The gamma-glutamyl transferase (GGT) to alanine aminotransferase (ALT) ratio has been reported as an effective predictor of the severity of hepatitis and HCC. The purpose of this study was to determine the role of the GGT/ALT ratio in the prediction of vascular invasion and survival outcomes in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: The risk factors for vascular invasion were determined by univariate/multivariate logistic analysis. The cut-off value of GGT/ALT in predicting vascular invasion was calculated using the receiver operating characteristic (ROC) curve. The prognostic value of GGT/ALT was examined by Cox analysis and Kaplan-Meier curves. Sensitivity analysis, such as subgroup analysis and propensity score matching (PSM), was performed to reduce potential confounding bias. RESULTS: A high GGT/ALT ratio was identified as an independent risk factor for vascular invasion (P = 0.03). The correlation analysis suggested that higher GGT/ALT was associated with more severe tumour burdens, including vascular invasion (P < 0.001), tumour volume > 5 cm (P < 0.001), poor pathological differentiation (P = 0.042), more severe BCLC (P < 0.001) and ALBI grade (P = 0.007). In the survival analysis, a high GGT/ALT ratio was associated with poor overall survival (OS) (HR: 1.38; 95% CI 1.03, 1.87; P < 0.0001) and disease-free survival (DFS) (HR: 1.32; 95% CI 1.03, 1.87; P < 0.0001). In the subgroup analysis, similar results were consistently observed across most subgroups. In PSM analysis, GGT/ALT remained independently associated with vascular invasion (OR, 186; 95% CI 1.23, 3.33). CONCLUSION: The GGT/ALT ratio was a potential effective factor in the prediction of vascular invasion and prognosis in patients with HBV-related HCC.

Down-regulation of EOMES drives T-cell exhaustion via abolishing EOMES-mediated repression of inhibitory receptors of T cells in liver cancer.

T-cell exhaustion is one of the hallmarks in cancer, but the mechanisms underlying T-cell dysregulation remains unclear. Here, we reported that down-regulation of transcription factor EOMES contributed to increased levels of inhibitory receptors in T cell among the tumour tissues and resulted in the poor prognosis of hepatocellular carcinoma (HCC). By analysing the correlation between EOMES in tumour-infiltrating T cells and the clinical features, we demonstrated that the EOMES was related to the advanced stage and poor prognosis of HCC. Further mechanistic studies revealed that the EOMES mainly expressed in the CD8+ T cells and were down-regulated in tumour samples. Moreover, we demonstrated that the EOMES directly bound at the transcriptional regulatory regions of the key inhibitory factors including PD-1, CTAL-4 and CD39, and lower levels of EOMES contributed to overexpression of these factors in T cells. Together, our studies provide new insight into the transcriptional deregulation of the inhibitory receptors on T cells during the tumorigenesis.

Role of Lipids and Apolipoproteins in Predicting the Prognosis of Hepatocellular Carcinoma After Resection.

PURPOSE: To further clarify the association between abnormal levels of serum lipid components as the main features of dyslipidaemia and hepatocellular carcinoma, which remains unclear. PATIENTS AND METHODS: We examined the serum level of lipids and apolipoproteins pattern in 471 patients undergoing curative resection for HCC, 193 patients with chronic liver disease, and 104 patients with benign liver diseases. We performed uni- and multivariate analyses to evaluate the predictive roles of lipids and apolipoproteins for recurrence and survival of HCC in a training cohort of 242 patients and then validated in a cohort of 229 patients. RESULTS: The majority circulating lipid and apolipoprotein levels such as ApoA1, HDL, and LDL in chronic liver disease and HCC were slightly significantly decreased as compared to those in benign lesion. But no significant differential expression patterns of lipids and apolipoproteins were observed between chronic liver hepatitis and HCC. Multivariable analysis identified ApoA1 as a key parameter related to recurrence and survival in both training and validation cohorts. Moreover, we further demonstrated that low ApoA1 was an independent prognostic factor of poor early recurrence in two cohorts. CONCLUSION: Although the alterations of circulating lipids and apolipoproteins were observed in HCC, none of lipids or apolipoproteins could serve as a diagnostic marker. Serum ApoA1 merits consideration as a novel prognostic marker for patients with HCC undergoing surgery since it predicts early recurrence and survival, especially for early stage patients and may improve the prognostic stratification of patients for clinical management and promote HCC clinic outcomes.

Clinical significance of herpes virus entry mediator expression in hepatitis B virus-related hepatocellular carcinoma.

Herpes virus entry mediator (HVEM) is overexpressed in several malignancies, including hepatocellular carcinoma (HCC). However, to the best of our knowledge, the clinical significance of HVEM in hepatitis B virus (HBV)-related HCC remains unclear. Thus, the present study aimed to explore the clinical significance of HVEM in HBV-related HCC. In the present study, HVEM expression was evaluated in HCC cell lines and HCC frozen samples. The prognostic value of HVEM was assessed in a cohort of 221 patients with HBV-related HCC, following radical resection. B- and T-lymphocyte attenuator (BTLA) expression in subsets of CD8+ T cells was determined via flow cytometry analysis. The results demonstrated high HVEM expression in HCC cell lines, and in HCC tissues compared with paired non-cancerous liver tissues. HVEM expression was demonstrated to be significantly associated with tumor encapsulation and vascular invasion. Furthermore, tumor HVEM status was significantly associated with infiltration of regulatory T cells, but not with CD8+ T cells. Notably, high HVEM expression in HCC was determined to be an independent predictor of an unfavorable outcome of patients with HCC following radical resection. Higher BTLA expression (the receptor of HVEM) was observed in both HCC-infiltrating CD8+ effector memory (CCR7- CD45RA-) and CD45RA+ effector memory (CCR7- CD45RA+) T cells in HCC tissues and blood compared with those in paired peritumor tissues or peripheral blood. Taken together, the results of the present study suggest that HVEM may serve a critical role in HBV-related HCC, most likely by promoting tumor progression and tumor immune evasion, thus the HVEM/BLTA signaling pathway may be a potential target in tumor immunotherapy.

Population-based analysis on predictors for lymph node metastasis in T1 colon cancer.

BACKGROUND: In this study, we aimed to identify independent predictive factors for lymph node metastasis (LNM) in T1 colon cancer. METHODS: Data of 8056 eligible patients were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database during 2004-2012. We performed logistic regression analysis to identify predictive factors for LNM. Both unadjusted and adjusted Cox regression analyses were used to determine the association between LNM and patient survival. Finally, we used competing risks analysis and the cumulative incidence function (CIF) to further confirm the prognostic role of LNM in cancer-specific survival (CSS). RESULTS: The overall risk of LNM in patients with T1 colon cancer was 12.0% (N = 967). Adjusted logistic regression models revealed that mucinous carcinoma [odds ratio (OR) = 2.26, P < 0.001], moderately differentiated (OR 1.74, P < 0.001), poorly differentiated (OR 5.16, P < 0.001), and undifferentiated carcinoma (OR 3.01, P = 0.003); older age (OR 0.66, P < 0.001 for age 65-79 years, OR 0.44, P < 0.001 for age over 80 years); and carcinoma located in the ascending colon (OR 0.77, P = 0.018) and sigmoid colon (OR 1.24, P = 0.014) were independent predictive factors for LNM. Adjusted Cox regression analysis showed that positive lymph node involvement was significantly associated with CSS [hazard ratio (HR) = 3.02, P < 0.001], which was further robustly confirmed using a competing risks model and the CIF. CONCLUSIONS: This population-based study showed that mucinous carcinoma, tumor grade, age, and primary tumor location were independent predictive factors for LNM in T1 colon cancer. The risk of LNM should be carefully evaluated in patients with T1 colon cancer, before clinical management.

Combined preoperative albumin-bilirubin (ALBI) and serum γ-glutamyl transpeptidase (GGT) predicts the outcome of hepatocellular carcinoma patients following hepatic resection.

Background: Liver function is an important prognostic factor for patients with hepatocellular carcinoma. The purpose of this study was to develop and validate a nomogram integrating the albumin-bilirubin (ALBI) and serum γ-glutamyl transpeptidase (GGT) level to predict postoperative overall survival (OS) and disease-free survival (DFS) of hepatocellular carcinoma (HCC). Methods: The effect of combined of ALBI and GGT on HCC prognosis was investigated using univariate and multivariate Cox analyses. The nomogram for OS and DFS were developed, respectively, and their predictive ability was compared with other conventional staging systems, including the American Joint Commission on Cancer (AJCC), Barcelona Clinic Liver Cancer (BCLC) and the Cancer of the Liver Italian Program (CLIP). Results: Combined ALBI and GGT was highly associated with OS (P<0.001) and DFS (P<0.001) of HCC patients treated with hepatic resection. In addition, the C-index of the OS (0.706±0.034) or DFS (0.674±0.032) nomogram in the training cohort was larger than AJCC, BCLC and CLIP. The Akaike information criterion (AICs) of the OS (2178.405) or DFS (2961.018) nomogram in the training cohort was smaller than above staging systems. The results suggested that the OS or DFS nomogram was the most powerful model to predict HCC prognosis. The similar trend was observed in the validation cohort. Conclusion: The novel nomogram integrating ALBI and GGT was highly associated with OS and DFS of postoperative HCC patients.

Interspecies analysis of MYC targets identifies tRNA synthetases as mediators of growth and survival in MYC-overexpressing cells.

Aberrant MYC oncogene activation is one of the most prevalent characteristics of cancer. By overlapping datasets of Drosophila genes that are insulin-responsive and also regulate nucleolus size, we enriched for Myc target genes required for cellular biosynthesis. Among these, we identified the aminoacyl tRNA synthetases (aaRSs) as essential mediators of Myc growth control in Drosophila and found that their pharmacologic inhibition is sufficient to kill MYC-overexpressing human cells, indicating that aaRS inhibitors might be used to selectively target MYC-driven cancers. We suggest a general principle in which oncogenic increases in cellular biosynthesis sensitize cells to disruption of protein homeostasis.

Inflammation-nutrition score predicts prognosis of patients with resectable hepatocellular carcinoma.

BACKGROUND: Various inflammation-based prognostic scores have been associated with poor survival in patients with hepatocellular carcinoma (HCC). METHODS: Data were collected retrospectively from 674 HCC patients who underwent curative resection. The correlation between INS (inflammation-nutrition score), BCLC (Barcelona Clinic Liver Cancer) stage and inflammatory indices and overall survival (OS) and disease free survival (DFS) was examined. RESULTS: An elevated INS was associated with both tumor and host clinical characteristics. The combination of INS and BCLC stage stratifies OS and DFS from 80% and 65% (INS = 0, stage A) to 0% (INS = 2, stage C). Univariate and multivariate analyses revealed that the INS was an independent predictor for OS and DFS, and was superior to inflammation-based scores. In addition, INS was demonstrated to be a prognostic factor for patients with early stage and had a higher AUC value in comparison with inflammation scores. CONCLUSION: This study demonstrates that the INS is an independent marker of poor prognosis in patients with resectable HCC, especially for those with early stage, and it provides complimentary prognostic information to BCLC stage, and may aid in treatment strategy.

The Septate Junction Protein Tsp2A Restricts Intestinal Stem Cell Activity via Endocytic Regulation of aPKC and Hippo Signaling.

Hippo signaling and the activity of its transcriptional coactivator, Yorkie (Yki), are conserved and crucial regulators of tissue homeostasis. In the Drosophila midgut, after tissue damage, Yki activity increases to stimulate stem cell proliferation, but how Yki activity is turned off once the tissue is repaired is unknown. From an RNAi screen, we identified the septate junction (SJ) protein tetraspanin 2A (Tsp2A) as a tumor suppressor. Tsp2A undergoes internalization to facilitate the endocytic degradation of atypical protein kinase C (aPKC), a negative regulator of Hippo signaling. In the Drosophila midgut epithelium, adherens junctions (AJs) and SJs are prominent in intestinal stem cells or enteroblasts (ISCs or EBs) and enterocytes (ECs), respectively. We show that when ISCs differentiate toward ECs, Tsp2A is produced, participates in SJ assembly, and turns off aPKC and Yki-JAK-Stat activity. Altogether, our study uncovers a mechanism allowing the midgut to restore Hippo signaling and restrict proliferation once tissue repair is accomplished.

Multiomics of azacitidine-treated AML cells reveals variable and convergent targets that remodel the cell-surface proteome.

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are diseases of abnormal hematopoietic differentiation with aberrant epigenetic alterations. Azacitidine (AZA) is a DNA methyltransferase inhibitor widely used to treat MDS and AML, yet the impact of AZA on the cell-surface proteome has not been defined. To identify potential therapeutic targets for use in combination with AZA in AML patients, we investigated the effects of AZA treatment on four AML cell lines representing different stages of differentiation. The effect of AZA treatment on these cell lines was characterized at three levels: the DNA methylome, the transcriptome, and the cell-surface proteome. Untreated AML cell lines showed substantial overlap at all three omics levels; however, while AZA treatment globally reduced DNA methylation in all cell lines, changes in the transcriptome and surface proteome were subtle and differed among the cell lines. Transcriptome analysis identified five commonly up-regulated coding genes upon AZA treatment in all four cell lines, TRPM4 being the only gene encoding a surface protein, and surface proteome analysis found no commonly regulated proteins. Gene set enrichment analysis of differentially regulated RNA and surface proteins showed a decrease in metabolic pathways and an increase in immune defense response pathways. As such, AZA treatment led to diverse effects at the individual gene and protein levels but converged to common responses at the pathway level. Given the heterogeneous responses in the four cell lines, we discuss potential therapeutic strategies for AML in combination with AZA.

Autophagy Facilitates Metadherin-Induced Chemotherapy Resistance Through the AMPK/ATG5 Pathway in Gastric Cancer.

BACKGROUND/AIMS: Metadherin (MTDH) is overexpressed in some malignancies and enhances drug resistance; however, its role in gastric cancer (GC) and the underlying mechanisms remain largely unexplored. Here, we explore the mechanism by which MTDH induces drug resistance in GC. METHODS: We analysed the level of MTDH in GC and adjacent normal gastric mucosal tissues by real-time quantitative PCR (q-PCR). We also analysed the level of autophagy by western blot analysis, confocal microscopy, and transmission electron microscopy after MTDH knockdown and overexpression, and examined fluorouracil (5-FU) resistance by Cell Counting Kit-8 at the same time. Finally, GC patient-derived xenograft tumours were used to demonstrate 5-FU resistance. An AMPK pathway inhibitor was applied to determine the molecular mechanisms of autophagy. RESULTS: MTDH expression was significantly increased in the GC specimens compared with that in the adjacent normal gastric mucosal tissues. Further study showed a positive correlation between the expression level of MTDH and 5-FU resistance. MTDH overexpression in MKN45 cells increased the levels of P-glycoprotein (P-gp) and promoted 5-FU resistance, while inhibition of MTDH showed the opposite result. The simultaneous inhibition of autophagy and overexpression of MTDH decreased the levels of P-gp and inhibited 5-FU resistance. Moreover, MTDH induced AMPK phosphorylation, regulated ATG5 expression, and finally influenced autophagy, suggesting that MTDH may activate autophagy via the AMPK/ATG5 signalling pathway. Our findings reveal a unique mechanism by which MTDH promotes GC chemoresistance and show that MTDH is a potential target for improved chemotherapeutic sensitivity and GC patient survival. CONCLUSIONS: MTDH-stimulated cancer resistance to 5-FU may be mediated through autophagy activated by the AMPK/ATG5 pathway in GC.

Interaction between CD133 and PI3K-p85 promotes chemoresistance in gastric cancer cells.

Chemoresistance in gastric cancer is the leading cause of tumor recurrence and poses a substantial therapeutic challenge. The stem cell biomarker CD133 has been implicated in drug resistance of tumor-initiating cells in a number of cancers including gastric cancer. Therefore, we investigated the molecular mechanism of CD133-associated multidrug resistance in gastric cancer cells. Using CD133 overexpressing and knockdown gastric cancer cell lines, we demonstrated that loss of CD133 significantly increased the growth inhibition of chemotherapeutic agents; whereas, overexpression significantly reduced growth inhibition. Furthermore, CD133 knockdown significantly reduced the enzymatic activity of phosphatidylinositol-3 kinase (PI3K) and the expression of P-glycoprotein (P-gp), B-cell lymphoma 2 (BCL2), and phosphorylated-protein kinase B (p-AKT), but elevated the expression of BCL2 associated X (BAX). Conversely, overexpression of CD133 significantly increased PI3K enzymatic activity, expression of P-gp, BCL2, and p-AKT, and decreased BAX expression. The PI3K/AKT inhibitor LY294002 mirrored the effects of loss of CD133; whereas, the PI3K/AKT activator epidermal growth factor reproduced the effects of CD133 overexpression. To identify the interaction between CD133 and PI3K, we used site-directed mutagenesis to mutate individual tyrosine residues of CD133. We found that binding between CD133 and p85, the regulatory subunit of PI3K, was significantly reduced when tyrosine 852 was mutated. In summary, we have demonstrated that CD133 activates the PI3K/AKT signal transduction pathway through direct interaction with PI3K-p85, resulting in multidrug resistance of gastric cancer cells. These results suggest that the interaction between CD133 and PI3K-p85 may offer a novel therapeutic target in multidrug resistant gastric cancer.

The Prognostic Impact of the Metastatic Lymph Nodes Ratio in Colorectal Cancer.

Background: This study was designed to validate the prognostic significance of the ratio of positive to examined lymph nodes (LNR) in patients with colorectal cancer. Methods: 218,314 patients from the SEER database and 1,811 patients from the three independent multicenter were included in this study. The patients were divided into 5 groups on a basis of previous published LNR: LNR0, patients with no metastatic lymph nodes; LNR1, patients with the LNR between 0.1 and 0.17; LNR2, patients with the LNR between 0.18 and 0.41; LNR3, patients with the LNR between 0.42 and 0.69; LNR4, patients with the LNR >0.7. The 5-year OS and CSS rate were estimated using Kaplan-Meier method and the survival difference was tested using log-rank test. Multivariate Cox analysis was used to further assess the influence of the LNR on patients' outcome. Results: The 5-year OS rate of patients within LNR0 to LNR4 group was 71.2, 55.8, 39.3, 22.6, and 14.6%, respectively (p < 0.001) in the SEER database. While the 5-year OS rate of those with LNR0 to LNR4 was 75.2, 66.1, 48.0, 34.0, and 17.7%, respectively (p < 0.001) in the international multicenter cohort. In the multivariate analysis, LNR was demonstrated to be a strong prognostic factor in patients with < 12 and ≥12 metastatic lymph nodes. Furthermore, the LNR had a similar impact on the patients' prognosis in colon cancer and rectal cancer. Conclusion: The LNR allowed better prognostic stratification than the positive node (pN) in patients with colorectal cancer and the cut-off values were well validated.

Large Wolffian adnexal tumor of the ovary: A case report and literature review.

Female Wolffian adnexal tumor (WAT) is a rare neoplasm arising from the remnants of the mesonephric duct and <100 cases have been reported globally. The present case report describes a 73-year-old female patient with WAT in the left ovary which, to the best of our knowledge, is the largest benign WAT tumor to be reported. In addition, the present case report reviewed previous studies on the clinical characteristics and therapy for WAT and the surgery methods for female WAT of ovary were summarized. WATs are typically benign; however, a number factors may increase the risk of malignancy.

Activin signaling mediates muscle-to-adipose communication in a mitochondria dysfunction-associated obesity model.

Mitochondrial dysfunction has been associated with obesity and metabolic disorders. However, whether mitochondrial perturbation in a single tissue influences mitochondrial function and metabolic status of another distal tissue remains largely unknown. We analyzed the nonautonomous role of muscular mitochondrial dysfunction in Drosophila Surprisingly, impaired muscle mitochondrial function via complex I perturbation results in simultaneous mitochondrial dysfunction in the fat body (the fly adipose tissue) and subsequent triglyceride accumulation, the major characteristic of obesity. RNA-sequencing (RNA-seq) analysis, in the context of muscle mitochondrial dysfunction, revealed that target genes of the TGF-ß signaling pathway were induced in the fat body. Strikingly, expression of the TGF-ß family ligand, Activin-ß (Actß), was dramatically increased in the muscles by NF-κB/Relish (Rel) signaling in response to mitochondrial perturbation, and decreasing Actß expression in mitochondrial-perturbed muscles rescued both the fat body mitochondrial dysfunction and obesity phenotypes. Thus, perturbation of muscle mitochondrial activity regulates mitochondrial function in the fat body nonautonomously via modulation of Activin signaling.

Metadherin regulates actin cytoskeletal remodeling and enhances human gastric cancer metastasis via epithelial-mesenchymal transition.

Metadherin (MTDH) can be recruited to mature tight junction complexes, and it regulates mesenchymal marker protein expression in many tumors and promote cancer metastasis. This study investigated the influence of MTDH expression on gastric cancer and to elucidate the potential mechanisms by which MTDH regulates actin cytoskeletal remodeling and enhances human gastric cancer metastasis via epithelial-mesenchymal transition (EMT). Relative MTDH mRNA expression levels were assessed by quantitative real-time PCR (Q-PCR), and MTDH protein expression levels and localization were evaluated via immunohistochemical (ICH) staining. We studied the role of MTDH in cancer cell migration and invasion by modulating MTDH expression in the gastric cancer cell lines MKN45 and AGS. We also confirmed the functions of MTDH through in vivo experiments. We found that MTDH expression levels were correlated with lymph node metastasis, TNM stages and decreased OS (P=0.002, <0.001 and 0.010, respectively) in human gastric cancer and that MTDH upregulation promoted EMT in vitro. Consistent with this finding, MTDH downregulation inhibited cell migration and invasion in vitro and suppressed tumor growth and metastasis in vivo. Furthermore, MTDH knockdown regulated actin cytoskeletal remodeling and inhibited EMT. Overall, our results provide a novel role for MTDH in regulating gastric cancer metastasis.

Prognostic Nomograms Stratify Survival of Patients with Hepatocellular Carcinoma Without Portal Vein Tumor Thrombosis After Curative Resection.

BACKGROUND: The prognosis of patients with hepatocellular carcinoma (HCC) without portal vein tumor thrombosis (PVTT) after curative resection is at variance. We identified the risk factors of poor postoperative prognosis and consequently developed prognostic nomograms generating individual risk of death and recurrence for this subgroup of patients with HCC. METHODS: The risk factors were identified and nomograms were developed based on a retrospective study of 734 patients in the primary cohort who underwent curative resection for HCC from 2010 to 2012. The predictive accuracy and discriminative ability of the nomograms were determined by concordance index (C-index) and calibration curve and compared with traditional staging systems of HCC. The results were validated in an independent cohort of 349 patients operated at the same institution in 2007. RESULTS: All of the independent factors for survival in multivariate analysis in the primary cohort were selected into the nomograms. The calibration curve for probability of survival showed good agreement between prediction by nomograms and actual observation. The C-indices of the nomograms for predicting overall survival and recurrence-free survival were 0.755 (95% confidence interval [CI], 0.752-0.758) and 0.665 (95% CI, 0.662-0.668), respectively, which were statistically higher than the C-indices of other HCC prognostic models. The results were further confirmed in the validation cohort. CONCLUSION: The proposed nomograms resulted in more accurate prognostic prediction for patients with HCC without PVTT after curative resection. The Oncologist 2017;22:561-569 IMPLICATIONS FOR PRACTICE: Hepatocellular carcinoma (HCC) poses a great therapeutic challenge due to the poor prognosis in patients underwent surgical resection. The portal vein tumor thrombosis (PVTT) as a robust risk factor for survival has been routinely integrated to staging systems. Nonetheless, the prognosis stratification for patients without PVTT was neglected to some extent. Herein, independent risk factors of OS and RFS in HCC patients without PVTT were reconfirmed. A predictive nomogram was constructed on these risk factors and was demonstrated to be a more accurate predictive model in HCC patients without PVTT, compared with the traditional staging systems.

Serum gamma-glutamyl transferase levels affect the prognosis of patients with intrahepatic cholangiocarcinoma who receive postoperative adjuvant transcatheter arterial chemoembolization: A propensity score matching study.

BACKGROUND: The postoperative prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is far from satisfactory. Whether postoperative adjuvant transcatheter arterial chemoembolization (TACE) is effective for patients with ICC after R0 liver resection remains controversial. MATERIALS AND METHODS: We retrospectively reviewed the data of 272 patients with ICC who received a radical hepatectomy at our center between 2000 and 2011. After the propensity score of postoperative TACE was calculated, 75 patients who received TACE were matched at a 1:2 ratios with 150 patients who did not receive TACE. Univariate and multivariate Cox analyses were performed to identify the independent predictors of overall survival. RESULTS: The postoperative protective effect of adjuvant TACE was significantly influenced by serum gamma-glutamyl transferase (GGT) levels (P for interaction = 0.026). Postoperative TACE was not a significant predictor of overall survival (hazard ratio = 0.89, P = 0.704) in patients with GGT levels ≤ 54 U/L. Postoperative TACE was a significant predictor of overall survival in patients with GGT levels >54 U/L (hazard ratio = 0.44, P = 0.001). Regarding short-term outcomes, a total of 74 patients (32.9%) had varying degrees of complications, and the majority of these complications were grade I (18.7%) or II (10.2%). CONCLUSION: The safety of postoperative TACE was validated, and the results suggest that only patients with elevated serum GGT levels will benefit from this treatment following curative liver resection for ICC.