The effects of different impeller combinations in the Sphingan WL gum fermentation process.

The fermentation of the high-viscosity polysaccharide WL gum has always been associated with poor mass transfer. Appropriate impeller configurations are key factors in maintaining homogeneity and sufficient mass transfer conditions. Therefore, a flat-folded disc turbine impeller (FFDT) taking into account both the reduced cavitation effect and the increased contact area was designed. Besides, a curved cross impeller (CC) and a fishbone-shaped impeller (FS) generating axial flow were also designed. The energy consumption and efficiency of the designed impellers and eight reported impellers were evaluated through fermentation and principal component analysis (PCA). Compared to the commonly-used six-blade flat-blade disc turbine (FBDT), the ungassed power number of FFDT was reduced by 50 %. Combinations of six-blade Brumajin impeller (BM) + FFDT and CC + FFDT produced high WL gum production and viscosity (34.0 g/L, 35.50 g/L, and 62.64 Pa·s, 61.68 Pa·s, respectively) and were suitable impellers for WL biosynthesis. WL gum from BM + FFDT showed higher viscosity, viscoelasticity, and molecular weight than that from FBDT + FBDT. In addition, fewer amino acids and pyruvic acid intermediates were formed using BM + FFDT, indicating a greater metabolic flux towards WL gum synthesis. This work provided an important reference for the design of impellers in high-viscosity fermentation systems.

Enhancing regeneration and repair of long-distance peripheral nerve defect injuries with continuous microcurrent electrical nerve stimulation.

Introduction: Peripheral nerve injuries, especially those involving long-distance deficits, pose significant challenges in clinical repair. This study explores the potential of continuous microcurrent electrical nerve stimulation (cMENS) as an adjunctive strategy to promote regeneration and repair in such cases. Methods: The study initially optimized cMENS parameters and assessed its impact on Schwann cell activity, neurotrophic factor secretion, and the nerve regeneration microenvironment. Subsequently, a rat sciatic nerve defect-bridge repair model was employed to evaluate the reparative effects of cMENS as an adjuvant treatment. Functional recovery was assessed through gait analysis, motor function tests, and nerve conduction assessments. Additionally, nerve regeneration and denervated muscle atrophy were observed through histological examination. Results: The study identified a 10-day regimen of 100uA microcurrent stimulation as optimal. Evaluation focused on Schwann cell activity and the microenvironment, revealing the positive impact of cMENS on maintaining denervated Schwann cell proliferation and enhancing neurotrophic factor secretion. In the rat model of sciatic nerve defect-bridge repair, cMENS demonstrated superior effects compared to control groups, promoting motor function recovery, nerve conduction, and sensory and motor neuron regeneration. Histological examinations revealed enhanced maturation of regenerated nerve fibers and reduced denervated muscle atrophy. Discussion: While cMENS shows promise as an adjuvant treatment for long-distance nerve defects, future research should explore extended stimulation durations and potential synergies with tissue engineering grafts to improve outcomes. This study contributes comprehensive evidence supporting the efficacy of cMENS in enhancing peripheral nerve regeneration.

The causal effect of mTORC1-dependent circulating protein levels on nonalcoholic fatty liver disease: A Mendelian randomization study.

BACKGROUND: The mechanistic target of rapamycin (mTOR) signal pathway plays a crucial role in the development of nonalcoholic fatty liver disease (NAFLD). However, the causal effect of mTOR downstream proteins on NAFLD remains unknown. AIMS: We conducted a two-sample Mendelian randomization (MR) study to investigate whether the mTOR-dependent circulating proteins, including Eukaryotic Initiation Factor 4E Binding Proteins (eIF4EBPs), Ribosomal Protein S6K kinase 1 (RP-S6K), Eukaryotic Initiation Factor 4E (eIF4E), Eukaryotic Initiation Factor 4A (eIF4A) and Eukaryotic Initiation Factor 4 G (eIF4G), have causal effects on the risk of NAFLD. METHODS: The causal estimate was evaluated with the inverse-variance weighted (IVW) method in discovery stage and validation stage. The single-nucleotide polymorphisms (SNPs) were selected to genetically predict exposures from Genome-Wide Association Studies (GWAS). Exposures with statistically significant effects in the discovery dataset would be further validated in the validation dataset. RESULTS: MR study revealed that eIF4E had a causal effect on NAFLD in both discovery stage (OR = 1.339, P = 0.037) and validation stage (OR = 1.0007, P = 0.022). Sensitivity analyses confirmed robustness of the results. CONCLUSION: The genetically predicted higher level of mTOR-dependent eIF4E in plasma might have a causal effect on the occurrence of NAFLD.

Development and validation of web calculators to predict early recurrence and long-term survival in patients with duodenal papilla carcinoma after pancreaticoduodenectomy.

BACKGROUND: Duodenal papilla carcinoma (DPC) is prone to relapse even after radical pancreaticoduodenectomy (PD) (including robotic, laparoscopic and open approach). This study aimed to develop web calculators to predict early recurrence (ER) (within two years after surgery) and long-term survival in patients with DPC after PD. METHODS: Patients with DPC after radical PD were included. Univariate and multivariate logistic regression analyses were used to identify independent risk factors. Two web calculators were developed based on independent risk factors in the training cohort and then tested in the validation cohort. RESULTS: Of the 251 patients who met the inclusion criteria, 180 and 71 patients were enrolled in the training and validation cohorts, respectively. Multivariate logistic regression analysis revealed that tumor size [Odds Ratio (OR) 1.386; 95% confidence interval (CI) 1070-1.797; P = 0.014]; number of lymph node metastasis (OR 2.535; 95% CI 1.114-5.769; P = 0.027), perineural invasion (OR 3.078; 95% CI 1.147-8.257; P = 0.026), and tumor differentiation (OR 3.552; 95% CI 1.132-11.152; P = 0.030) were independent risk factors for ER. Nomogram based on the above four factors achieved good C-statistics of 0.759 and 0.729 in predicting ER in the training and the validation cohorts, respectively. Time-dependent ROC analysis (timeROC) and decision curve analysis (DCA) revealed that the nomogram provided superior diagnostic capacity and net benefit compared with single variable. CONCLUSIONS: This study developed and validated two web calculators that can predict ER and long-term survival in patients with DPC with high degree of stability and accuracy.

Upregulation of WDR6 drives hepatic de novo lipogenesis in insulin resistance in mice.

Under normal conditions, insulin promotes hepatic de novo lipogenesis (DNL). However, during insulin resistance (IR), when insulin signalling is blunted and accompanied by hyperinsulinaemia, the promotion of hepatic DNL continues unabated and hepatic steatosis increases. Here, we show that WD40 repeat-containing protein 6 (WDR6) promotes hepatic DNL during IR. Mechanistically, WDR6 interacts with the beta-type catalytic subunit of serine/threonine-protein phosphatase 1 (PPP1CB) to facilitate PPP1CB dephosphorylation at Thr316, which subsequently enhances fatty acid synthases transcription through DNA-dependent protein kinase and upstream stimulatory factor 1. Using molecular dynamics simulation analysis, we find a small natural compound, XLIX, that inhibits the interaction of WDR6 with PPP1CB, thus reducing DNL in IR states. Together, these results reveal WDR6 as a promising target for the treatment of hepatic steatosis.

Inhibition of PPARγ by BZ26, a GW9662 derivate, attenuated obesity-related breast cancer progression by inhibiting the reprogramming of mature adipocytes into to cancer associate adipocyte-like cells.

Obesity has been associated with the development of 13 different types of cancers, including breast cancer. Evidence has indicated that cancer-associated adipocytes promote the proliferation, invasion, and metastasis of cancer. However, the mechanisms that link CAAs to the progression of obesity-related cancer are still unknown. Here, we found the mature adipocytes in the visceral fat of HFD-fed mice have a CAAs phenotype but the stromal vascular fraction of the visceral fat has not. Importantly, we found the derivate of the potent PPARγ antagonist GW9662, BZ26 inhibited the reprogramming of mature adipocytes in the visceral fat of HFD-fed mice into CAA-like cells and inhibited the proliferation and invasion of obesity-related breast cancer. Further study found that it mediated the browning of visceral, subcutaneous and perirenal fat and attenuated inflammation of adipose tissue and metabolic disorders. For the mechanism, we found that BZ26 bound and inhibited PPARγ by acting as a new modulator. Therefore, BZ26 serves as a novel modulator of PPARγ activity, that is, capable of inhibiting obesity-related breast cancer progression by inhibiting of CAA-like cell formation, suggesting that inhibiting the reprogramming of mature adipocytes into CAAs or CAA-like cells may be a potential therapeutic strategy for obesity-related cancer treatment.

AGDF-Net: Attention-Gated and Direction-Field-Optimized Building Instance Extraction Network.

Building extraction from high-resolution remote sensing images has various applications, such as urban planning and population estimation. However, buildings have intraclass heterogeneity and interclass homogeneity in high-resolution remote sensing images with complex backgrounds, which makes the accurate extraction of building instances challenging and regular building boundaries difficult to maintain. In this paper, an attention-gated and direction-field-optimized building instance extraction network (AGDF-Net) is proposed. Two refinements are presented, including an Attention-Gated Feature Pyramid Network (AG-FPN) and a Direction Field Optimization Module (DFOM), which are used to improve information flow and optimize the mask, respectively. The AG-FPN promotes complementary semantic and detail information by measuring information importance to control the addition of low-level and high-level features. The DFOM predicts the pixel-level direction field of each instance and iteratively corrects the direction field based on the initial segmentation. Experimental results show that the proposed method outperforms the six state-of-the-art instance segmentation methods and three semantic segmentation methods. Specifically, AGDF-Net improves the objective-level metric AP and the pixel-level metric IoU by 1.1%~9.4% and 3.55%~5.06%.

Silencing of RAB42 down-regulated PD-L1 expression to inhibit the immune escape of hepatocellular carcinoma cells through inhibiting the E2F signaling pathway.

OBJECTIVE: To investigate the mechanistic role of RAB42 and corresponding regulatory path in hepatocellular carcinoma (HCC). METHODS: The expression of RAB42 in HCC tissue was checked by RT-qPCR and immunohistochemical staining assay. Cell proliferation was checked by colony formation and CCK-8 assay. Cell apoptosis and cycle distribution were analyzed with flow cytometry. The relevance of RAB42 and PD-L1 was analyzed from TCGA database. The binding of E2F1 to PD-L1 was detected by JASPAR database, luciferase and ChIP assay. The expression of PD-L1, cell apoptosis- and E2F pathway-related proteins were checked by western blotting. RESULTS: RAB42 was highly expressed in HCC tissue. RAB42 silencing could inhibit proliferation and induce G1 phase arrest and apoptosis of HCC cells. TCGA database disclosed that PD-L1 was highly associated with RAB42 expression. Silencing of RAB42 could retard PD-L1 expression in HCC cells. GSEA analysis showed RAB42 could activate E2F signaling pathway. Silencing of RAB42 could observably weaken the expression of E2F1, CDK1 and CDC20 in HCC cells. JASPAR database predicted the binding site between E2F1 and PD-L1, and E2F1 overexpression could promote PD-L1 expression. Overexpression of E2F1 could reverse the biological function of RAB42 silencing in HCC cells. CONCLUSION: Silencing of RAB42 could down-regulate PD-L1 expression to inhibit immune escape through inhibiting E2F signaling pathway in HCC cells. RAB42 may become a novel clinical diagnostic and therapy marker for HCC.

The Impact of a History of Different Other Cancers on the Long-Term Outcomes of Patients with Intrahepatic Cholangiocarcinoma: A Population-Based Analysis.

Background: The characteristics and outcomes of patients with intrahepatic cholangiocarcinoma (ICC) with prior malignancy are poorly clarified. This study is aimed at exploring the impact of prior malignancy on the long-term outcomes of ICC patients. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) program, ICC patients diagnosed between 2004 and 2018 were identified. Kaplan-Meier curves and Cox analysis were used to evaluate the impact of prior malignancy on the prognosis of ICC patients. Results: A total of 9667 ICC patients were identified; among them, 782 (8.09%) had a history of prior cancer. Prostate, breast, colorectal, bladder, and liver/gallbladder/other biliary cancers were the most common types of prior cancer. Patients with prior cancer had better tumor-related profiles than those without prior cancer, namely, the former patients showed a lower proportion of positive AFP levels and vascular invasion, a lower AJCC stage, a smaller tumor size, and a lower stage of tumor grade. The median survival times after the diagnosis of ICC were 10 and 11.5 months for patients with and without prior cancer, respectively. Multivariate regression analysis suggested that prior cancer did not contribute to inferior overall survival (OS, HR 0.870, 95% CI 0.797-0.950, and p = 0.002) or cancer-specific survival (CSS, HR 0.820, 95% CI 0.741-0.906, and p < 0.001). Conclusions: A history of prior cancer does not lead to worse OS or CSS for ICC patients. The exclusion of patients with prior cancer from clinical trials should be reconsidered.

Identification of the Expression Patterns and Potential Prognostic Role of 5-Methylcytosine Regulators in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a poor prognosis. 5-methylcytosine (m5C) modification plays a nonnegligible role in tumor pathogenesis and progression. However, little is known about the role of m5C regulators in HCC. Methods: Based on 9 m5C regulators, the m5C modification patterns of HCC samples extracted from public databases were systematically evaluated and correlated with tumor immune and prognosis characteristics. An integrated model called the "m5Cscore" was constructed using principal component analysis, and its prognostic value was evaluated. Results: Almost all m5C regulators were differentially expressed between HCC and normal tissues. Through unsupervised clustering, three different m5Cclusters were ultimately uncovered; these clusters were characterized by differences in prognosis, immune cell infiltration, and pathway signatures. The m5Cscore was constructed to quantify the m5C modifications of individual patients. Subsequent analysis revealed that the m5Cscore was an independent prognostic factor of HCC and could be a novel indicator to predict the prognosis of HCC. Conclusion: This study comprehensively explored and systematically profiled the features of m5C modification in HCC. m5C modification patterns play a crucial role in the tumor immune microenvironment (TIME) and prognosis of HCC. The m5Cscore provides a more holistic understanding of m5C modification in HCC and provides a practical tool for predicting the prognosis of HCC. This study will help clinicians identify effective indicators of HCC to improve the poor prognosis of this disease.

Analysis of N6-methyladenosine-related lncRNAs in the tumor immune microenvironment and their prognostic role in pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) is a rare solid malignancy with a poor prognosis. N6-methyladenosine (m6A) and long noncoding RNAs (lncRNAs) play essential roles in tumorigenesis and progression. However, little is known about the role of m6A-related lncRNAs in PC. METHODS: m6A-related lncRNAs were extracted by Pearson analysis, and then prognosis-related lncRNAs were filtered from the m6A-related lncRNAs by univariate Cox regression analysis. Based on the expression patterns of the prognosis-related lncRNAs, samples were classified into distinct clusters. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to construct a m6A-lncRNA-related prognostic signature for PC patients. Receiver operating characteristic (ROC) curves and the corresponding area under the curve (AUC) values were used to evaluate the prognostic ability of the model. RESULTS: A total of 178 tumor and 4 normal samples were extracted from The Cancer Genome Atlas (TCGA) database in our study. Based on the expression of 12 filtered prognosis-related lncRNAs, two distinct clusters were eventually identified; these clusters were characterized by differences in the tumor immune microenvironment (TIME) and prognosis. A risk model comprising ten m6A-related lncRNAs was identified as an independent predictor of prognosis. ROC analysis revealed that this model had an acceptable prognostic value for PC patients. The prognostic signature was related to the TIME and the expression of critical immune checkpoint molecules. CONCLUSION: This study comprehensively assessed the expression pattern and prognostic value of m6A-related lncRNAs in PC. The different clusters correlated with distinct TIMEs and prognoses. The study also constructed a ten-gene signature prognostic model based on m6A-related lncRNAs, which showed good accuracy in predicting overall survival.

Identification of a glycolysis-related gene signature for predicting prognosis in patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer in the world. Although great advances in HCC diagnosis and treatment have been achieved, due to the complicated mechanisms in tumor development and progression, the prognosis of HCC is still dismal. Recent studies have revealed that the Warburg effect is related to the development, progression and treatment of various cancers; however, there have been a few explorations of the relationship between glycolysis and HCC prognosis. METHODS: mRNA expression profiling was downloaded from public databases. Gene set enrichment analysis (GSEA) was used to explore glycolysis-related genes (GRGs), and the LASSO method and Cox regression analysis were used to identify GRGs related to HCC prognosis and to construct predictive models associated with overall survival (OS) and disease-free survival (DFS). The relationship between the predictive model and the tumor mutation burden (TMB) and tumor immune microenvironment (TIME) was explored. Finally, real-time PCR was used to validate the expression levels of the GRGs in clinical samples and different cell lines. RESULTS: Five GRGs (ABCB6, ANKZF1, B3GAT3, KIF20A and STC2) were identified and used to construct gene signatures to predict HCC OS and DFS. Using the median value, HCC patients were divided into low- and high-risk groups. Patients in the high-risk group had worse OS/DFS than those in the low-risk group, were related to higher TMB and were associated with a higher rate of CD4+ memory T cells resting and CD4+ memory T cells activated. Finally, real-time PCR suggested that the five GRGs were all dysregulated in HCC samples compared to adjacent normal samples. CONCLUSIONS: We identified five GRGs associated with HCC prognosis and constructed two GRGs-related gene signatures to predict HCC OS and DFS. The findings in this study may contribute to the prediction of prognosis and promote HCC treatment.

Progression of Prothrombin Induced by Vitamin K Absence-II in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer-related death worldwide. Due to the lack of efficient tools for early detection, asymptomatic HCC patients are diagnosed at an advanced stage, leading to a poor prognosis. To improve survival, serum biomarker prothrombin induced by vitamin K absence-II (PIVKA-II) was under investigation. PIVKA-II is an abnormal protein produced in HCC. The coagulation function was insufficient due to the lack of Gla residues. Elevated PIVKA-II was associated with bad tumor behavior in terms of proliferation, metastasis, and invasion. Three major signaling pathways were proposed to clarify the mechanism. With the advantages including affordability, minimal invasiveness, convenience, and efficiency, PIVKA-II could improve HCC management consisting of four aspects. First, PIVKA-II was an effective and dynamic tool for improving HCC surveillance in high-risk population. Changes in the serum levels of PIVKA-II provided valuable molecular alteration information before imaging discovery. Second, PIVKA-II offered a complementary approach for HCC early detection. Compared to traditional diagnostic approaches, the combination of PIVKA-II and other biomarkers had better performance. Third, PIVKA-II was an indicator for the assessment of response to treatment in HCC. Preoperative assessment was for selecting personalized therapy, and postoperative measurement was for assessing treatment efficacy. Fourth, PIVKA-II was considered as a prognostic predictor for HCC. Patients with elevated PIVKA-II were more likely to develop microvascular invasion, metastasis, and recurrence.

Ethyl 2-[2,3,4-Trimethoxy-6-(1-Octanoyl)Phenyl] Acetate (TMPA) Ameliorates Lipid Accumulation by Disturbing the Combination of LKB1 with Nur77 and Activating the AMPK Pathway in HepG2 Cells and Mice Primary Hepatocytes.

BACKGROUND: The AMP-activated protein kinase alpha (AMPKα) pathway has widely been considered a key factor in energy metabolism. Ethyl 2-[2,3,4-trimethoxy-6-(1-octanoyl)phenyl] acetate (TMPA) is a novel AMPK agonist, which influences the stability of Nuclear Receptor Subfamily 4, Group A, Member 1 (Nur77)-serine-threonine kinase 11 (LKB1) in the nucleus. A recent study has determined that TMPA can ameliorate the reduction of insulin resistance in type II db/db mice. However, the role of TMPA in hepatocyte lipid metabolism has not been elucidated. OBJECTIVE: To investigate whether TMPA could ameliorate liver lipid accumulation under the stimulation of free fatty acids (FFAs) in vitro. METHODS: We evaluated differences of Nur77 and AMPK pathway in mice fed a high-fat diet and those fed a normal diet. In vitro, TMPA was added to HepG2 cells and primary hepatocytes before FFAs stimulation. Oil red O staining, Nile red staining were used to evaluate lipid deposition. Western blot and immunofluorescence were used to quantify related proteins. RESULTS: Nur77, AMPKα, LKB1, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), acetyl-CoA carboxylase phosphorylation (p-ACC), and carnitine palmitoyltransferase 1 (CPT1A) showed significant differences in vivo. Under the intervention of TMPA, HepG2 cells and primary hepatocytes showed considerable amelioration of lipid deposition and improved the expression of phosphorylated (p)-AMPKα (p-AMPKα), p-LKB1, p-ACC, and CPT1A. Furthermore, Western blotting and immunofluorescence studies indicated that LKB1 dramatically increased expression in the cytoplasm but decreased in the nucleus. Further, AMPKα phosphorylation (p-AMPKα) also showed a higher expression in cytoplasm instead of the nucleus. CONCLUSION: TMPA ameliorated lipid accumulation by influencing the stability of Nur77-LKB1 in vitro.

Second Primary Malignancies in Patients With Hepatocellular Carcinoma: A Population-Based Analysis.

BACKGROUND: Second primary malignancy (SPM) is becoming a threat for the health of cancer survivors. However, data on the features and results of patients with hepatocellular carcinoma (HCC) with SPMs are scarce. This study aimed to explore the characteristics of HCC patients with SPMs and to screen HCC patients who are at a high risk of developing SPMs. METHOD: HCC patients diagnosed between 2000 and 2014 in the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively analyzed. Eligible patients were divided into the only one primary malignancy and SPM groups. The Fine-Gray proportional subdistribution hazards model was used to explore the risk factors of developing SPMs, and a competing-risk model was established to predict the probability of developing SPMs for HCC patients after initial diagnosis. The calibration curves, concordance index (C-index), and decision curve analysis (DCA) were used to evaluate the performance of the nomogram. RESULTS: A total of 40,314 HCC patients were identified, 1,593 (3.95%) of whom developed SPMs 2 months after the initial diagnosis with a maximum follow-up time of approximately 18 years. The 3-, 5-, and 10-year cumulative incidence of SPMs were 2.35%, 3.12%, and 4.51%, respectively. Age at initial diagnosis, extent of disease, tumor size, and treatment were identified as the independent risk factors of developing SPMs and integrated into the competing-risk nomogram. The C-index of the nomogram was 0.677 (95% confidence interval 0.676-0.678), and the calibration curves showed an excellent agreement between the nomogram prediction and the actual observations. Furthermore, DCA indicated that the nomogram had good net benefits in clinical scenarios. CONCLUSIONS: HCC survivors remain at a high risk of developing SPMs. The development of SPMs was associated with the clinical features and treatment strategies. A competing-risk nomogram was constructed to help surgeons identify the patients who are at a high risk of developing SPMs and contribute to the further management of SPMs.

Impact of Postoperative Complications on Long-Term Survival After Resection of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Controversy exists over the relationship between postoperative complications (POCs) and long-term survival for hepatocellular carcinoma (HCC) after hepatectomy. This study aimed to evaluate the impact of POCs on overall survival (OS) and disease-free survival (DFS) for HCC after liver resection. PATIENTS AND METHODS: The PubMed, EMBASE, and Cochrane Library databases were used to search for eligible studies published through 18 April 2020, and studies comparing the long-term outcomes between HCC patients with and without POCs after hepatectomy were included. A random-effects model was used to calculate the pooled hazard ratio (HR) with a 95% confidence interval (CI). Subgroup analysis and meta-regression were performed to assess the potential influence of study-, patient-, and tumor-related factors on the relationship between POCs and oncologic outcomes and to adjust their effect. This study was registered at the International Prospective Register of Systematic Reviews (CRD42019136109). RESULTS: Thirty-seven studies, including 14,096 patients, were deemed eligible and included in this study. Compared with those without POCs, patients who developed POCs had a significant reduction in OS (HR 1.39, 95% CI 1.28-1.50, P < 0.001; prediction interval 1.04-1.85) and tended to have worse DFS (HR 1.25, 95% CI 1.16-1.35, P < 0.001; prediction interval 0.98-1.60). Contour-enhanced funnel plots suggested a risk of publication bias. Subgroup analysis and meta-regression showed that POCs remained a threat to OS and DFS regardless of the influence of clinicopathological factors. CONCLUSION: This study demonstrated that POCs had an adverse impact on OS and DFS in HCC patients after liver resection.

A new sarcopenia score prognostic for postoperative complications in hepatic alveolar echinococcosis: a multicenter retrospective study.

BACKGROUND: Skeletal muscle depletion and excessive visceral adipose tissue have been shown to be independent risk factors for postoperative complications (PCs) in various diseases. However, their impact on surgical PCs in hepatic alveolar echinococcosis (HAE) is still unknown. METHODS: We retrospectively reviewed the clinical data of HAE patients who underwent liver resection at our hospital between January 2008 and December 2018. We segmented skeletal muscle and adipose tissue and measured the area of skeletal muscle tissue and adipose tissue at the level of the third lumbar vertebra by manual tracing from preoperative plain computed tomography (CT) images. Sarcopenia features were selected to construct a formula based on the least absolute shrinkage and selection operator (LASSO) logistic regression model in the primary set. Then, integrating the results of multiple clinicopathologic characteristics, we built a nomogram for predicting major PCs in HAE. The results were validated using bootstrap resampling and clinical data from other HAE centers in western China. RESULTS: The sarcopenia score is based on the personalized levels of the five features from the primary set (n=233). In the multivariate logistic analysis of the primary set, the independent factors for PCs were γ-glutamyl transferase (GGT), and surface area of hepatectomy, which were integrated into the nomogram combined with sarcopenia score. The model had a good prediction capability with a C-index of 0.84 (95% CI, 0.72-0.96). The calibration plot for the probability of PCs showed an optimal agreement between the nomogram predictions and actual observations in the primary and validation sets. CONCLUSION: Our study showed that sarcopenia score was significantly correlated with PCs in patients with HAE. In addition, we constructed a prognostic nomogram for predicting complications in HAE patients after liver surgery. The nomogram displayed excellent discrimination and calibration. Improving the nutritional status and physical health of patients before surgery might reduce the incidence of postoperative complications for the high-risk patients.

Development and Validation of Nomograms for Predicting Cancer-Specific Survival in Elderly Patients with Intrahepatic Cholangiocarcinoma After Liver Resection: A Competing Risk Analysis.

BACKGROUND: There are few studies on the prognosis of elderly intrahepatic cholangiocarcinoma (iCCA) patients after liver resection. The aims of this study were to assess the cumulative incidences of cancer-specific mortality in elderly iCCA patients and to construct a corresponding competing risk nomogram for elderly iCCA patients. METHODS: We performed a retrospective analysis of elderly patients with iCCA who underwent liver resection between January 2006 and December 2019. Eligible elderly iCCA patients were randomly divided into training and validation sets at a ratio of 7:3. Based on the results of multivariate analysis using the Fine-Gray competing risk model, we developed a competing risk nomogram using data from the training set to predict the cumulative probabilities of iCCA-specific mortality. The performance of the nomogram was measured by the concordance index (C-index) and calibration curves. To evaluate the clinical usefulness of the nomogram, the clinical benefit was measured by using decision curve analysis (DCA). Furthermore, the patients were categorized into two groups according to the dichotomy values of the nomogram-based scores, and their survival differences were assessed using Kaplan-Meier and cumulative incidence function (CIF) curves. RESULTS: The 1-year, 3-year and 5-year cumulative iCCA-specific mortalities were 19.7%, 48.3% and 56.1%, respectively, for elderly iCCA patients. The multivariate Fine-Gray analysis indicated that microvascular invasion, macroscopic vascular invasion and lymph node metastasis were related to a significantly higher likelihood of iCCA specific mortality. The established nomogram was well calibrated and had a good discriminative ability, with a concordance index (C-index) of 0.742 (95% CI, 0.708-0.748). Furthermore, the DCA indicated that the nomogram had positive net benefits compared with the conventional staging systems. In the training set and validation sets, the high-risk group had the higher probabilities of iCCA cancer-specific mortality than the low-risk group; meanwhile, the patients in the high-risk the group had significantly poorer overall survival (OS) than those in the low-risk group. CONCLUSION: Elderly iCCA patients had comparable long-term outcomes with non-elderly iCCA patients. In addition, we constructed a prognostic nomogram for predicting survival in elderly iCCA patients based on the competing risk analysis. The competing risk nomogram displayed excellent discrimination and calibration.

Integrated nomograms to predict overall survival and recurrence-free survival in patients with combined hepatocellular cholangiocarcinoma (cHCC) after liver resection.

The current clinical classification of primary liver cancer is unable to efficiently predict the prognosis of combined hepatocellular cholangiocarcinoma (cHCC). Accurate satellite nodules (SAT) and microvascular invasion (MVI) prediction in cHCC patients is very important for treatment decision making and prognostic evaluation. The aim of this work was to explore important factors affecting the prognosis of cHCC patients after liver resection and to develop preoperative nomograms to predict SAT and MVI in cHCC patients. The nomogram was developed using the data from 148 patients who underwent liver resection for cHCC patients at our hospital between January 2006 and December 2014. Based on the results of the multivariate analysis, a nomogram integrating all significant independent factors affecting overall survival and recurrence-free survival was constructed to predict the prognosis of cHCC. Next, risk factors for SAT and MVI were evaluated with logistic regression. Blood signatures were established using the LASSO regression, and then, we combined the clinical risk factors and blood signatures of the patients to establish predictive models for SAT and MVI. The C-index of the nomogram for predicting survival was 0.685 (95% CI, 0.638 to 0.732), which was significantly higher than the C-index for other liver cancer classification systems.