Prognostic value of aspartate aminotransferase/alanine aminotransferase ratio in hepatocellular carcinoma after hepatectomy.

BACKGROUND: The prognostic significance of the aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio in hepatocellular carcinoma remains uncertain. The aim of the current study was to evaluate the association between the AST/ALT ratio and prognosis in patients with hepatocellular carcinoma after hepatectomy, and to explore the role of underlying liver diseases as mediators. METHODS: This retrospective study included patients with hepatocellular carcinoma who underwent hepatectomy between January 2014 and January 2018 at two Chinese hospitals. The maximally selected rank statistic and g-computation approach were used to quantify and visualize the association between the AST/ALT ratio and overall survival or recurrence-free survival. The role of mediators (chronic hepatitis B, hepatic steatosis and liver cirrhosis) was analysed. RESULTS: Among the 1519 patients (mean(s.d.) age at baseline, 50.5(11.3) years), 1309 (86.2%) were male. During a median follow-up of 46.0 months, 514 (33.8%) patients died and 358 (23.6%) patients experienced recurrence. The optimal cut-off value for the AST/ALT ratio was 1.4, and the AST/ALT ratio greater than or equal to 1.4 was independently associated with a 39.0% increased risk of death and a 30.0% increased risk of recurrence (overall survival: hazard ratio (HR), 1.39; 95% c.i. 1.15 to 1.68; recurrence-free survival: HR, 1.30; 95% c.i. 1.12 to 1.52) after adjusting for confounders. Chronic hepatitis B significantly mediated the association of the ratio of AST/ALT with both overall survival and recurrence-free survival (20.3% for overall survival; 20.1% for recurrence-free survival). CONCLUSION: The AST/ALT ratio greater than or equal to 1.4 was associated with shorter overall survival and recurrence-free survival in patients with hepatocellular carcinoma after hepatectomy, and chronic hepatitis B may play a role in their association.

Interacting and joint effects of triglyceride-glucose index (TyG) and body mass index on stroke risk and the mediating role of TyG in middle-aged and older Chinese adults: a nationwide prospective cohort study.

BACKGROUND: Individuals who are overweight or obese often develop insulin resistance, mediation of the association between body mass index (BMI) and stroke risk through the triglyceride-glucose index (TyG) seems plausible but has not been investigated. This study aims to examine whether TyG mediates associations of BMI with stroke risk and the extent of interaction or joint relations of TyG and BMI with stroke outcome. METHODS: The China Health and Retirement Longitudinal Study, initiated in 2011, is a nationally representative, ongoing prospective cohort study involving 8 231 middle-aged and older Chinese adults without a stroke history at baseline. Exposures examined include BMI and the TyG, the latter being the logarithmized product of fasting triglyceride and glucose concentrations. The primary study outcome is stroke incidence, as determined through self-reports, with a follow-up period extending from June 1, 2011, to June 30, 2018. RESULTS: Of the 8 231 participants, 3 815 (46.3%) were men; mean (SD) age was 59.23 (9.32) years. During a median follow-up of 7.1 years, 585 (7.1%) participants developed stroke. The TyG was found to mediate the association between BMI and incident stroke, proportions mediated were 16.3% for BMI in the 24.0-27.9 kg/m2 group and 53.8% for BMI ≥ 28.0 kg/m2 group. No significant multiplicative and additive interactions were found between BMI and TyG on incident stroke (Additive: RERI = 1.78, 95% CI - 1.29-4.86; Multiplicative, HR = 1.40, 95% CI 0.86-2.27). HRs for individuals with BMI ≥ 28.0 kg/m2 and quartile 4 of TyG compared with those with BMI < 24.0 kg/m2 and quartile 1 of TyG were 2.05 (95% CI 1.37-3.06) for incident stroke. Combining BMI and TyG enhanced predictive performance for stroke when compared to their individual (AUCBMI+TyG vs AUCBMI vs AUCTyG, 0.602 vs 0.581 vs 0.583). CONCLUSIONS: TyG appeared to be associated with stroke risk and mediates more than 50% of the total association between BMI and stroke in middle-aged and older Chinese adults. Public health efforts aiming at the reduction of body weight might decrease the stroke risk due to insulin resistance and the burden of stroke.

Specific gut microbiome signature predicts hepatitis B virus-related hepatocellular carcinoma patients with microvascular invasion.

BACKGROUND: We aimed to assess differences in intestinal microflora between patients with operable hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) with microvascular invasion (MVI) and those without MVI. Additionally, we investigated the potential of the microbiome as a non-invasive biomarker for patients with MVI. METHODS: We analyzed the preoperative gut microbiomes (GMs) of two groups, the MVI (n = 46) and non-MVI (n = 56) groups, using 16S ribosomal RNA gene sequencing data. At the operational taxonomic unit level, we employed random forest models to predict MVI risk and validated the results in independent validation cohorts [MVI group (n = 17) and non-MVI group (n = 15)]. RESULTS: ß diversity analysis, utilizing weighted UniFrac distances, revealed a significant difference between the MVI and non-MVI groups, as indicated by non-metric multidimensional scaling and principal coordinate analysis. We also observed a significant correlation between the characteristic intestinal microbial communities at the genus level and their main functions. Nine optimal microbial markers were identified, with an area under the curve of 79.76% between 46 MVI and 56 non-MVI samples and 79.80% in the independent verification group. CONCLUSION: This pioneering analysis of the GM in patients with operable HBV-HCC with and without MVI opens new avenues for treating HBV-HCC with MVI. We successfully established a diagnostic model and independently verified microbial markers for patients with MVI. As preoperative targeted biomarkers, GM holds potential as a non-invasive tool for patients with HBV-HCC with MVI.

Changes in the triglyceride glucose-body mass index estimate the risk of stroke in middle-aged and older Chinese adults: a nationwide prospective cohort study.

BACKGROUND: Stroke was reported to be highly correlated with the triglyceride glucose-body mass index (TyG-BMI). Nevertheless, literature exploring the association between changes in the TyG-BMI and stroke incidence is scant, with most studies focusing on individual values of the TyG-BMI. We aimed to investigate whether changes in the TyG-BMI were associated with stroke incidence. METHODS: Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS), which is an ongoing nationally representative prospective cohort study. The exposures were changes in the TyG-BMI and cumulative TyG-BMI from 2012 to 2015. Changes in the TyG-BMI were classified using K-means clustering analysis, and the cumulative TyG-BMI was calculated as follows: (TyG-BMI2012 + TyG-BMI2015)/2 × time (2015-2012). Logistic regressions were used to determine the association between different TyG-BMI change classes and stroke incidence. Meanwhile, restricted cubic spline regression was applied to examine the potential nonlinear association of the cumulative TyG-BMI and stroke incidence. Weighted quantile sum regression was used to provide a comprehensive explanation of the TyG-BMI by calculating the weights of FBG, triglyceride-glucose (TG), and BMI. RESULTS: Of the 4583 participants (mean [SD] age at baseline, 58.68 [9.51] years), 2026 (44.9%) were men. During the 3 years of follow-up, 277 (6.0%) incident stroke cases were identified. After adjusting for potential confounders, compared to the participants with a consistently low TyG-BMI, the OR for a moderate TyG-BMI with a slow rising trend was 1.01 (95% CI 0.65-1.57), the OR for a high TyG-BMI with a slow rising trend was 1.62 (95% CI 1.11-2.32), and the OR for the highest TyG-BMI with a slow declining trend was 1.71 (95% CI 1.01-2.89). The association between the cumulative TyG-BMI and stroke risk was nonlinear (Passociation = 0.017; Pnonlinearity = 0.012). TG emerged as the primary contributor when the weights were assigned to the constituent elements of the TyG-BMI (weight2012 = 0.466; weight2015 = 0.530). CONCLUSIONS: Substantial changes in the TyG-BMI are independently associated with the risk of stroke in middle-aged and older adults. Monitoring long-term changes in the TyG-BMI may assist with the early identification of individuals at high risk of stroke.

Case report: Conversion therapy to permit resection of initially unresectable hepatocellular carcinoma.

Most patients with hepatocellular carcinoma (HCC) are diagnosed when the disease is already at an advanced stage, so they are not eligible for resection and their prognosis is poor. The combination of transarterial chemoembolization (TACE) with immune checkpoint inhibitors or tyrosine kinase inhibitors can improve unresectable HCC to the point that patients can be treated with surgery. Here we describe two cases of such "conversion therapy". One patient was a 52-year-old man in Child-Pugh class A with treatment-naive HCC whose 11.3-cm tumor had invaded the middle hepatic vein and right branch of the portal vein. He was treated with TACE plus camrelizumab, and radical resection was performed 3 months later. No evidence of recurrence was observed during 5-month follow-up. The other patient was a 42-year-old man in Child-Pugh class A with HCC involving a 11.4-cm tumor and severe liver cirrhosis. The patient was treated with TACE and lenvatinib, but the embolic effect after one month was unsatisfactory, so the regional treatment was changed to hepatic artery infusion chemotherapy and transcatheter arterial embolization. Radical resection was performed 2 months later, and no recurrence was evident at 1-month follow-up. These cases demonstrate two conversion therapies that may allow patients with initially unresectable HCC to benefit from resection.

Operable hepatitis B virus-related hepatocellular carcinoma: gut microbiota profile of patients at different ages.

Background: Age was important prognostic factors for operable hepatocellular carcinoma patients. The aim of the present study was to assess the difference in gut microbiota in patients with operable hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) at different ages ; to investigate the features of the microbiota and its function associated with different ages; to provide a preliminary look at effects of the gut microbiota dimension on prognostic. Methods: From September 2020 to May 2021, patients with HBV-HCC were able to undergo liver resection and were recruited consecutively and divided into the younger age group (age <45 years) (Y.AG) (n=20), middle age group (age from 45 to 65 years) (M.AG) (n=13) 45-65 years, and older age group (age >65 years) (O.AG) (n=20). The relationships between gut microbiota and different ages were explored using 16S rRNA gene sequencing data. PICRUST2 was used to examine the metagenomic data in PHLF patients. Fisher's exact and Mann-Whitney U-test were used for the data analysis. Results: Pairwise comparison between the three groups showed that the α-diversity of Y.AG was significantly higher than that of O.AG (ACE Index, P=0.017; chao1 Index, P=0.031; observed_species Index, P=0.011; and goods_coverage Index, P=0.041). The ß-diversity in the 3 groups differed significantly (stress =0.100), while the composition (ß-diversity) differed significantly between the Y.AG and the M.AG (stress =0.090), the M.AG and the O.AG (stress =0.095), and the Y.AG and the O.AG (stress =0.099). At the genus level, 7 bacterial genera were significantly enriched in the O.AG compared with the Y.AG, of which Streptococcus, Blautia, Erysipelotrichaceae_UCG-003, and Fusicatenibacter represented the major variances in O.AG microbiomes. Eleven genera were significantly increased in the O.AG, of which Prevotella, Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, Ruminiclostridium, and Phascolarctobacterium represented the major variances in the O.AG. The Y.AG and the O.AG were predicted by PICRUSt2 analysis, which found 72 pathways related to differential gut microbiome at the genus level. Redundancy analysis showed that 7 environmental factors were significantly correlated with intestinal microorganisms, especially in the Y.AG compared with the O.AG. Conclusions: Analysis of gut microbiota characteristics in patients of different ages could ultimately contribute to the development of novel avenues for the treatment of HCC at different ages.

Cross-Sectional Study of the Effects of Job Burnout on Immune Function in 105 Female Oncology Nurses at a Tertiary Oncology Hospital.

BACKGROUND Nurses who work in hospitals experience a high level of burnout and the relationship between immune variables and burnout syndrome has yet to be elucidated. The aim of the present study was to investigate the effects of job burnout on immune function in female oncology nurses in a tertiary oncology hospital in Guangxi, China. The aspects of the human immune system evaluated were humoral and cellular immunity and complement components 3 (C3) and 4 (C4). MATERIAL AND METHODS We administered the Maslach Burnout Inventory-General Survey (MBI-GS), which includes scales for emotional exhaustion, depersonalization (DP), and personal accomplishment (PA), to measure variables related to immune function in 105 female nurses in a tertiary oncology hospital in Guangxi, China. Levels of humoral immunity and C3 and C4 were detected with immune turbidimetry. Cellular immunity was assessed with indirect immunofluorescence. RESULTS A Spearman rank correlation analysis revealed that levels of C3, C4, and CD4- and CD8-positive T cells were significantly associated with burnout symptoms (P<0.05, P<0.01, and P<0.05, respectively). Furthermore, there was a correlation between demographic data and humoral and cellular immunity (both P<0.05). Multivariable linear regression analysis showed that C4 levels were closely related to DP (P<0.05) and that CD4 and CD8 levels were closely related to PA (P<0.01). CONCLUSIONS These results suggest that DP and PA have an impact on immune function, and that timely psychological and behavioral interventions can be used to reduce the degree of job burnout among nurses and regulate their immunity, thus enabling them to better serve patients.

Factors associated with resilience among non-local medical workers sent to Wuhan, China during the COVID-19 outbreak.

BACKGROUND: To investigate the resilience of non-local medical workers sent to support local medical workers in treating the outbreak of 2019 novel coronavirus disease (COVID-19). METHODS: In February 2020, non-local medical workers who had been sent to Wuhan as support staff to respond to the COVID-19 outbreak were asked to complete an online survey composed of the Connor Davidson Resilience Scale (CD-RISC), Hospital Anxiety Depression Scale (HADS) and Simplified Coping Style Questionnaire (SCSQ). RESULTS: Survey responses from 114 non-local medical workers were analyzed. CD-RISC scores were high (67.03 ± 13.22). The resilience level was highest for physicians (73.48 ± 11.49), followed by support staff, including health care assistants, technicians (67.78 ± 12.43) and nurses (64.86 ± 13.46). Respondents differed significantly in the levels of education, training/support provided by the respondent's permanent hospital (where he or she normally works), and in their feelings of being adequately prepared and confident to complete tasks (P < 0.05). Resilience correlated negatively with anxiety (r = -.498, P < 0.01) and depression (r = -.471, P < 0.01) but positively with active coping styles (r = .733, P < 0.01). Multiple regression analysis showed that active coping (ß = 1.314, p < 0.05), depression (ß = -.806, p < 0.05), anxiety (ß = - 1.091, p < 0.05), and training/support provided by the respondent's permanent hospital (ß = 3.510, p < 0.05) were significant associated with resilience. CONCLUSION: Our data show that active coping, depression, anxiety, and training/support provided by the respondent's permanent hospital are associated with resilience. Managers of medical staff should use these data to develop psychosocial interventions aimed at reinforcing the resilience of medical workers during highly stressful and prolonged medical emergencies, as seen during the COVID-19 outbreak.

Development and validation of a nomogram for assessing survival in patients with hepatocellular carcinoma after hepatectomy.

BACKGROUND AND AIM: Assessing the average survival rate of patients with hepatocellular carcinoma (HCC) after hepatectomy is important for making critical decisions in everyday clinical practice. The present study aims to develop and validate a nomogram for assessing the overall survival probability for such patients. METHODS: The putative prognostic indicators for constructing the nomogram were identified using multivariable Cox regression and model selection based on the Akaike information criterion. The nomogram was subjected to internal and external validation. The nomogram endpoints were death within 1, 3, and 5 years. RESULTS: A consecutive sample of 522 HCC patients who underwent potentially curative hepatectomy was retrospectively analyzed. Age, Barcelona clinic liver cancer (BCLC) stage, tumor size, alanine transaminase, alpha fetal protein, and serum prealbumin were included in the final model. The nomogram's discriminative ability was good in the training set (C-index was 0.74 for 1 year, 0.73 for 3 years, 0.70 for 5 years) and was validated using both an internal bootstrap method (C-index was 0.73 for 1 year, 0.72 for 3 years, 0.69 for 5 years) and an external validating set (C-index was 0.72 for 1 year, 0.72 for 3 years, 0.69 for 5 years). The calibration plots for the endpoints showed optimal agreement between the nomogram's assessment and actual observations. CONCLUSIONS: The nomogram (an Excel-based tool) can be useful for assessing the probability of survival at 1, 3, and 5 years in patients with HCC after hepatectomy.

Dose-Response Between Serum Prealbumin and All-Cause Mortality After Hepatectomy in Patients With Hepatocellular Carcinoma.

BACKGROUND: The relationship between serum prealbumin and the risk of all-cause mortality after hepatectomy in patients with hepatocellular carcinoma (HCC) needs to be evaluated. METHODS: We conducted a retrospective study. A Cox proportional hazards regression model was used to adjust for potential confounders. Prealbumin level was transformed by Z-scores and categorized into quartiles (Q1: <147 mg/L, Q2: 147-194 mg/L, Q3: 194-239 mg/L, Q4: >239 mg/L). We assessed the dose-response relationship between serum prealbumin and the risk of all-cause mortality using a restricted cubic spline model. RESULTS: Data were included from 2,022 HCC patients who underwent hepatectomy at Guangxi Medical University Cancer Hospital in China between January 2006 and January 2016. The adjusted hazard ratios (HRs) for increasing quartiles of serum prealbumin were 0.78 [95% confidence interval (CI): 0.64-0.95] for Q2, 0.66 (0.53-0.81) for Q3, and 0.51 (0.41-0.64) for Q4 in the Cox model (all P < 0.001). Serum prealbumin showed an L-shaped, non-linear dose-response relationship with the risk of all-cause mortality (P < 0.001). Among patients whose serum prealbumin was below 250 mg/L, risk of all-cause mortality decreased by 27% (95% CI: 18-36%) per increase of one standard deviation (69.8 mg/L) in serum prealbumin. CONCLUSIONS: Levels of serum prealbumin under 250 mg/L may be considered dangerous with respect to all-cause mortality after hepatectomy in HCC patients. Serum prealbumin may be useful as a prognostic marker in HCC patients undergoing hepatectomy.

The lncRNA SNHG16 affects prognosis in hepatocellular carcinoma by regulating p62 expression.

Long noncoding RNAs (lncRNAs) regulate tumor development and progression by promoting proliferation, invasion, and metastasis. The oncogenic role of lncRNA SNHG16 in hepatocellular carcinoma (HCC) has not been revealed. LncRNA SNHG16 is upregulated in HCC and correlates with poorer prognosis. Patients with high SNHG16 expression showed lower rates of overall and disease-free survival than patients with low SNHG16 expression. Multivariate Cox regression revealed that SNHG16 expression was an independent predictor of poor overall and disease-free survival. In vitro, SNHG16 promoted HCC cell proliferation, migration, and invasion while inhibiting apoptosis; in vivo, it accelerated tumor development. Altering SNHG16 expression altered levels of miR-17-5p, which in turn modified expression of p62, which has been shown to regulate the mTOR and NF-κB pathways. Indeed, altering SNHG16 expression in HCC cells activated mTOR and NF-κB signaling. These results reveal a potential mechanism for the oncogenic role of SNHG16 in HCC. SNHG16 may therefore be a promising diagnostic marker as well as therapeutic target in HCC.

Association between LKB1 expression and prognosis of patients with solid tumours: an updated systematic review and meta-analysis.

OBJECTIVES: Liver kinase B1 (LKB1) is considered a tumour suppressor that can control cell growth and metabolism. Whether LKB1 expression levels are related to clinicopathology and prognosis is controversial. This review aimed to quantitatively examine the latest evidence on this question. DESIGN: An updated systematic review and meta-analysis on the association between LKB1 expression and prognosis of patients with solid tumours were performed. DATA SOURCES: Eligible studies were identified through literature searches from database establishment until 15 June 2018 in the following databases: Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure and Wan Fang databases. ELIGIBILITY CRITERIA: The association between LKB1 expression and clinicopathological characteristics, overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) of patients with solid tumours were reported. Sufficient data were available to calculate the OR or HR and 95% CI. DATA EXTRACTION AND SYNTHESIS: Relevant data were meta-analysed for OS, DFS, RFS and various clinical parameters. RESULTS: The systematic review included 25 studies containing 6012 patients with solid tumours. Compared with patients with high LKB1 expression, patients with low expression showed significantly shorter OS in univariate analysis (HR=1.63, 95% CI 1.35 to 1.97, p<0.01) and multivariate analysis (HR=1.61, 95% CI 1.26 to 2.06, p<0.01). In contrast, the two groups showed similar DFS in univariate analysis (HR=1.49, 95% CI 0.73 to 3.01, p=0.27) as well as similar RFS in univariate analysis (HR=1.44, 95% CI 0.65 to 3.17, p=0.37) and multivariate analysis (HR=1.02, 95% CI 0.42 to 2.47, p=0.97). Patients with low LKB1 expression showed significantly worse tumour differentiation (OR=1.71, 95% CI 1.14 to 2.55, p<0.01), larger tumours (OR=1.68, 95% CI 1.24 to 2.27, p<0.01), earlier lymph node metastasis (OR=1.43, 95% CI 1.26 to 1.62, p<0.01) and more advanced tumour, node, metastases (TNM) stage (OR=1.80, 95% CI 1.56 to 2.07, p<0.01). CONCLUSION: Low LKB1 expression predicts shorter OS, worse tumour differentiation, larger tumours, earlier lymph node metastasis and more advanced TNM stage. Low LKB1 expression may be a useful biomarker of poor clinicopathology and prognosis.

Comparison of the ability of Child-Pugh score, MELD score, and ICG-R15 to assess preoperative hepatic functional reserve in patients with hepatocellular carcinoma.

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.

Hepatic resection for elderly patients with hepatocellular carcinoma: a systematic review of more than 17,000 patients.

BACKGROUND: With the aging population and increasing incidence of hepatic malignancies in elderly patients, establishing the safety and efficacy of hepatic resection for elderly patients with hepatocellular carcinoma (HCC) is crucial. The present systematic review investigates postoperative morbidity, hospital mortality, median survival time, overall and disease-free survival in elderly patients with undergoing hepatic resection. METHODS: Some databases were systematically searched for prospective or retrospective studies to reveal the safety and efficacy of hepatic resection for elderly patients with primary HCC. RESULTS: Fifty studies involving 4,169 elderly patients and 13,158 young patients with HCC were included into analyses. Elderly group patients had similar rate of median postoperative morbidity (28.2% vs. 29.6%) but higher mortality (3.0% vs. 1.2%) with young group patients. Moreover, elderly group patients had slightly lower median survival time (55 vs. 58 months), 5-years overall survival (51% vs. 56%) and 5-years disease-free survival (27% vs. 28%) than young group patients. There was an upward trend in 5-years overall and disease-free survival in either elderly or young group. CONCLUSION: Though old age may increase the risk of hospital mortality for patients with HCC after hepatic resection, elderly patients can obtain acceptable long-term prognoses from hepatic resection.

Expression of HSP90AA1/HSPA8 in hepatocellular carcinoma patients with depression.

BACKGROUND: Depression may influence susceptibility to cancer, and the genes and signaling pathways that may mediate this association are unclear. METHODS: Here, we used isobaric tagging for relative and absolute quantitation, 2-dimensional liquid chromatography, and mass spectrometry to compare proteins expressed in hepatocellular carcinoma in patients with or without depression. RESULTS: A total of 89 proteins were up-regulated and 44 were down-regulated in patients with depression. HSP90AA1 and HSPA8 were up-regulated, which correlated with elevated levels of VEGF, VEGFR2, PI3K, and AKT1 and reduced levels of caspase 9 and BAD. Disease-free survival rate was significantly lower and risk of tumor recurrence was significantly higher in patients with depression, which may reflect high HSP90AA1/HSPA8 expression. CONCLUSION: These results suggest that the VEGF/VEGFR2 pathway may be associated with HCC recurrence in patients expressing high levels of HSP90AA1/HSPA8.

Prognostic value of PD -L1 expression in patients with primary solid tumors.

Programmed death-ligand 1 (PD-L1) is thought to play a critical role in immune escape by cancer, but whether PD-L1 expression can influence prognosis of patients with solid tumors is controversial. Therefore, we meta-analyzed available data on whether PD-L1 expression correlates with overall survival (OS) in such patients. PubMed, EMBASE and other databases were systematically searched for cohort or case-control studies examining the possible correlation between PD-L1 expression and OS of patients with solid tumors. OS was compared between patients positive or negative for PD-L1 expression using scatter plots, and subgroup analyses were performed based on tumor type and patient characteristics. Data from 59 studies involving 20,004 patients with solid tumors were meta-analyzed. The median percentage of tumors positive for PD-L1 was 30.1%. OS was significantly lower in PD-L1-positive patients than in PD-L1-negative patients at 1 year (P = 0.039), 3 years (P < 0.001) and 5 years (P < 0.001). The risk ratios of OS (and associated 95% confidence intervals) were 2.02 (1.56-2.60) at 1 year, 1.57 (1.34-1.83) at 3 years and 1.43 (1.24-1.64) at 5 years. Similar results were obtained in subgroup analyses based on patient ethnicity or tumor type. The available evidence suggests that PD-L1 expression negatively affects the prognosis of patients with solid tumors. PD-L1 might serve as an efficient prognostic indicator in solid tumor and may represent the important new therapeutic target.

Expression of P62 in hepatocellular carcinoma involving hepatitis B virus infection and aflatoxin B1 exposure.

This study aims to clarify the relationship and mechanism between expression of autophagy-related protein P62 and prognosis of patients with hepatocellular carcinoma (HCC) involving chronic hepatitis B virus (HBV) infection and aflatoxin B1 (AFB1) exposure. HCC patients who underwent resection were divided into three groups: HBV(+)/AFB1(+) (n = 26), HBV(+)/AFB1(-) (n = 68), and HBV(-)/AFB1(-) (n = 14). The groups were compared in terms of mRNA and protein levels of P62, disease-free survival (DFS), and overall survival (OS) and the expression of NRF2, Nqo1, and AKR7A3 in P62 high-expression and low-expression group. HBV(+)/AFB1(+) group has lower DFS and OS, and higher P62 expression than in the other two groups. P62 expression generally correlated with elevated NRF2 and Nqo1 expression, and reduced AKR7A3 expression. Patients expressing high levels of P62 showed significantly lower DFS and OS rates than patients expressing low levels. HCC involving HBV infection and AFB1 exposure is associated with relatively high risk of tumor recurrence, and this poor prognosis may relate to high P62 expression. High P62 expression activates the NRF2 pathway, promotes tumor recurrence. The downregulation of AKR7A3 also reduced liver detoxification of aflatoxin B1.

Optimizing stage of single large hepatocellular carcinoma: A study with subgroup analysis by tumor diameter.

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 <10 cm or a single-tumor ≥10 cm showed lower OS than patients with a single-tumor >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.