ABSTRACT
BACKGROUD: We aimed to develop a novel preoperative nomogram to predict lymph node metastasis (LNM) in perihilar cholangiocarcinoma (pCCA) patients. METHODS: 160 pCCA patients were enrolled at Lihuili Hospital from July 2006 to May 2022. A novel nomogram model was established to predict LNM in pCCA patients based on the independent predictive factors selected by the multivariate logistic regression model. The precision of the nomogram model was evaluated through internal and external validation with calibration curve statistics and the concordance index (C-index). Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate and determine the clinical utility of the nomogram. RESULTS: Multivariate logistic regression demonstrated that age (OR = 0.963, 95% CI: 0.930-0.996, P = 0.030), CA19-9 level (> 559.8 U/mL vs. ≤559.8 U/mL: OR = 3.162, 95% CI: 1.519-6.582, P = 0.002) and tumour diameter (OR = 1.388, 95% CI: 1.083-1.778, P = 0.010) were independent predictive factors of LNM in pCCA patients. The C-index was 0.763 (95% CI: 0.667-0.860) and 0.677 (95% CI: 0.580-0.773) in training cohort and validation cohort, respectively. ROC curve analysis indicated the comparative stability and adequate discriminative ability of nomogram. The sensitivity and specificity were 0.820 and 0.652 in training cohort and 0.704 and 0.649 in validation cohort, respectively. DCA revealed that the nomogram model could augment net benefits in the prediction of LNM in pCCA patients. CONCLUSIONS: The novel prediction model is useful for predicting LNM in pCCA patients and showed adequate discriminative ability and high predictive accuracy.
Subject(s)
Bile Duct Neoplasms , Klatskin Tumor , Humans , Klatskin Tumor/surgery , Lymphatic Metastasis , CA-19-9 Antigen , Calibration , Bile Duct Neoplasms/surgeryABSTRACT
BACKGROUND: Inflammation plays a significant role in tumour development, progression, and metastasis. In this study, we focused on comparing the predictive potential of inflammatory markers for overall survival (OS), recurrence-free survival (RFS), and 1- and 2-year RFS in hepatocellular carcinoma (HCC) patients. METHODS: A total of 360 HCC patients were included in this study. A LASSO regression analysis model was used for data dimensionality reduction and element selection. Univariate and multivariate Cox regression analyses were performed to identify the independent risk factors for HCC prognosis. Nomogram prediction models were established and decision curve analysis (DCA) was conducted to determine the clinical utility of the nomogram model. RESULTS: Multivariate Cox regression analysis indicated that the prognostic nutritional index (PNI) and neutrophil-to-lymphocyte ratio (NLR) were independent prognostic factors of OS, and aspartate aminotransferase-to-platelet ratio (APRI) was a common independent prognostic factor among RFS, 1-year RFS, and 2-year RFS. The systemic inflammation response index (SIRI) was an independent prognostic factor for 1-year RFS in HCC patients after curative resection. Nomograms established and achieved a better concordance index of 0.772(95% CI: 0.730-0.814), 0.774(95% CI: 0.734-0.815), 0.809(95% CI: 0.766-0.852), and 0.756(95% CI: 0.696-0.816) in predicting OS, RFS, 1-year RFS, and 2-year RFS respectively. The risk scores calculated by nomogram models divided HCC patients into high-, moderate- and low-risk groups (P < 0.05). DCA analysis revealed that the nomogram models could augment net benefits and exhibited a wider range of threshold probabilities in the prediction of HCC prognosis. CONCLUSIONS: The nomograms showed high predictive accuracy for OS, RFS, 1-year RFS, and 2-year RFS in HCC patients after surgical resection. The nomograms could be useful clinical tools to guide a rational and personalized treatment approach and prognosis judgement.
Subject(s)
Carcinoma, Hepatocellular/mortality , Liver Neoplasms/mortality , Nomograms , Risk Assessment/methods , Aged , Aspartate Aminotransferases/blood , Biomarkers/analysis , Blood Platelets/metabolism , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/surgery , Databases, Factual , Female , Hepatectomy , Humans , Liver Neoplasms/blood , Liver Neoplasms/surgery , Lymphocytes/metabolism , Male , Middle Aged , Neutrophils/metabolism , Postoperative Period , Predictive Value of Tests , Prognosis , Regression Analysis , Retrospective Studies , Risk Factors , Survival RateABSTRACT
Background: Essential hypertension is a multifactorial disease with high morbidity. The researches on the influence of genes on the disease are still in its infancy, and the mechanism of gene regulation is not clear. MiRNAs are key molecules that regulate the expression control of protein-coding or protein-non-coding RNA. It may be an important biological molecule risk factor for essential hypertension.Methods: A case-control study with 98 EH and 98 non-EH was conducted in our experiment. The candidate miRNAs including miR-10a-5p and miR-497-5p were detected and verified by qRT-PCR.Results: The expression level of miRNA in EH cases was significantly lower than the healthy control (P = 0.005). In addition, the relative expression of miR-10a-5p was closely positive correlated with DBP (r = 0.162, P = 0.023) and SBP (r = 0.223, P = 0.002). After adjusting confound factors, the result of the logistic regression indicated that hypo-expression of miR-10a-5p is a risk factor for EH (OR(95%CI) = 1.676(1.302,2.157), adjusted P < 0.0001). And the ROC analysis shows that the combined line with BMI and miR-10a-5p was a values marker for EH (AUC: 0.728, P < 0.0001).Conclusions: Lower expression of miR-10a-5p, as the key role, is significantly related to the risk of EH and maybe as a potential biomolecule for EH.
Subject(s)
Essential Hypertension/genetics , MicroRNAs/genetics , Aged , Area Under Curve , Biomarkers , Case-Control Studies , Female , Gene Expression Regulation , Humans , Male , Middle Aged , ROC Curve , Risk FactorsABSTRACT
BACKGROUND: Essential hypertension (EH) is a high prevalence with multifactorial diseases. Human studies on the impact of genes on this disease are just in the initial stage, the mechanism of gene regulation is still remains unclear. Circular RNAs (circRNAs) as a continuous cycle of covalent closure, RNA molecules added to the 3'-5' end covalently bound by the formation of incidental event. CircRNAs may be an important biomolecule in revealing the molecule regulate mechanisms of EH. METHODS: The circRNAs were selected and validated with qRT-PCR followed. Our experiment was conducted with case-control studies among 200â¯EH participants. The t-test was used to evaluate the different expression of circRNAs and miRNAs, the significance of which was set as pâ¯<â¯0.05. RESULTS: The hsa_circ_0037911 expression level in EH cases were significantly higher than healthy controls (pâ¯=â¯0.005). There was still important significance when adjusted by logistic regression (adjusted pâ¯=â¯0.026). We also found that hsa_circ_0037911 was an effective marker of EH (area under curveâ¯=â¯0.627; pâ¯=â¯0.002). The levels of hsa_circ_0037911 were significantly differences in gender, BMI, smoking and drinking among EH cases. There was a positive correlation between Serum creatinine (Scr) and hsa_circ_0037911. CONCLUSIONS: Our findings suggested that higher expression hsa_circ_0037911 may be key circRNAs for EH development by changing the concentration of Scr and could be a stable biomarker for early diagnosis of EH.
Subject(s)
Essential Hypertension/genetics , RNA/genetics , Adult , Aged , Case-Control Studies , Essential Hypertension/epidemiology , Female , Gene Expression Regulation , Humans , Male , MicroRNAs/genetics , Middle Aged , RNA, Circular , Risk Factors , TranscriptomeABSTRACT
Essential hypertension (EH) is a multifactorial disease. Interferon-γ (IFN-γ) plays an important role in the onset of EH through cytokine-mediated systemic inflammatory responses. We aimed to determine whether the methylation status of the IFN-γ gene (IFNG) promoter is involved in the pathogenesis of EH. Six copies of CpG dinucleotides are distributed between 3,203 bp and 3,121 bp upstream from the transcription initiation site of IFNG, termed CpG1 to CpG6 in the 5'-to-3' direction. We recruited 96 patients with EH and 96 sex- and age-matched healthy subjects as controls. Using bisulfate pyrosequencing datasets, we analyzed the methylation status of the six CpG sites and thus found that CpG5 was consistently methylated in all of the 96 EH patients and 96 control subjects. Among the remaining five CpG sites, there was no significant difference in the methylation levels of CpG4 and CpG6 between the two groups. By contrast, CpG1 (P = 0.003) and CpG3 (P = 5.87 × 10-7) were highly methylated among the EH subjects compared with the controls, whereas CpG2 (P = 1.24 × 10-12) was significantly less methylated in among EH subjects. The methylation levels of CpG2 were still lower after adjustment with logistic regression (adjusted P = 0.032). The CpG2 methylation level was an effective marker of EH (area under curve = 0.384; P = 1.40 × 10-15). The present study shows that hypomethylation of the IFNG promoter is significantly related to the risk of EH, providing new insights into the pathogenesis of EH.
Subject(s)
DNA Methylation , Essential Hypertension/genetics , Genetic Predisposition to Disease , Interferon-gamma/genetics , Adult , Aged , Case-Control Studies , China , CpG Islands , Epigenesis, Genetic , Female , Genetic Association Studies , Humans , Logistic Models , Male , Middle Aged , Promoter Regions, Genetic , Reproducibility of Results , Risk Factors , Sensitivity and SpecificityABSTRACT
UNLABELLED: The purpose of the present study was to investigate whether methylation of the angiotensin II type 1 receptor (AGTR1) promoter contributed to the risk of essential hypertension (EH). A total of 96 EH cases and 96 gender- and age-matched healthy controls were recruited. Methylation of 8 CpG dinucleotides (CpG1-8) in the AGTR1 promoter was examined using the bisulphite pyrosequencing technology. Three CpG dinucleotides (CpG6-8) could not be well sequenced, therefore only the remaining 5 CpG sites were analysed. A significantly lower CpG1 methylation level was identified in EH cases than in controls (cases vs. CONTROLS: 6.74 ± 4.32% vs. 9.66 ± 5.45%, p = 0.007), and no significant association was observed in the remaining analyses. In addition, significantly lower CpG1 (p = 0.028) and higher CpG2 (p = 0.032) methylation levels were observed in males than in females. In the breakdown association test by gender, a higher CpG1 methylation level was also identified in EH in both males (p = 0.034) and females (p = 0.020). Receiver operating characteristic curves showed that CpG1 methylation was a significant predictor of EH. Furthermore, CpG1 methylation was inversely correlated with uric acid levels in controls. The present study suggests that CpG1 hypomethylation in the AGTR1 promoter is likely associated with the risk of EH in the population assessed.
Subject(s)
DNA Methylation , Genetic Predisposition to Disease/genetics , Hypertension/genetics , Promoter Regions, Genetic/genetics , Receptor, Angiotensin, Type 1/genetics , Aged , Blood Pressure , Body Mass Index , Case-Control Studies , Cholesterol/blood , CpG Islands/genetics , Female , Humans , Hypertension/blood , Hypertension/physiopathology , Lipoproteins, HDL/blood , Lipoproteins, LDL/blood , Logistic Models , Male , Middle Aged , Risk Factors , Sequence Analysis, DNA/methods , Triglycerides/bloodABSTRACT
Adverse events (AEs) are a significant concern for healthcare systems. However, it is difficult to evaluate their influence because of the complexity of various medical services. This study aimed to assess the influence of AEs on the outcomes of hospitalized patients using a diagnosis-related group (DRG) database. We conducted a case-control study of hospitalized patients at a multi-district tertiary hospital with 2200 beds in China, using data from a DRG database. An AE refers to an unintended physical injury caused or contributed to by medical care that requires additional hospitalization, monitoring, treatment, or even death. Relative weight (RW), a specific indicator of DRG, was used to measure the difficulty of diagnosis and treatment, disease severity, and medical resources utilized. The primary outcomes were hospital length of stay (LOS) and hospitalization costs. The secondary outcome was discharge to home. This study applied DRG-based matching, Hodges-Lehmann estimate, regression analysis, and subgroup analysis to evaluate the influence of AEs on outcomes. Two sensitivity analyses by excluding short LOS and changing adjustment factors were performed to assess the robustness of the results. We identified 2690 hospitalized patients who had been divided into 329 DRGs, including 1345 patients who experienced AEs (case group) and 1345 DRG-matched normal controls. The Hodges-Lehmann estimate and generalized linear regression analysis showed AEs led to prolonged LOS (unadjusted difference, 7 days, 95% confidence interval [CI] 6-8 days; adjusted difference, 8.31 days, 95% CI 7.16-9.52 days) and excess hospitalization costs (unadjusted difference, $2186.40, 95% CI: $1836.87-$2559.16; adjusted difference, $2822.67, 95% CI: $2351.25-$3334.88). Logistic regression analysis showed AEs were associated with lower odds of discharge to home (unadjusted odds ratio [OR] 0.66, 95% CI 0.54-0.82; adjusted OR 0.75, 95% CI 0.61-0.93). The subgroup analyses showed that the results for each subgroup were largely consistent. LOS and hospitalization costs increased significantly after AEs in complex diseases (RW ≥ 2) and in relation to high degrees of harm subgroups (moderate harm and above groups). Similar results were obtained in sensitivity analyses. The burden of AEs, especially those related to complex diseases and severe harm, is significant in China. The DRG database serves as a valuable source of information that can be utilized for the evaluation and management of AEs.
Subject(s)
Diagnosis-Related Groups , Length of Stay , Tertiary Care Centers , Humans , Female , Male , Middle Aged , Case-Control Studies , Aged , Adult , China , Databases, Factual , Hospitalization/statistics & numerical data , Inpatients/statistics & numerical data , Hospital Costs , Young AdultABSTRACT
Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of a cluster of conditions associated with lipid metabolism disorders. Ideal animal models mimicking the human NASH need to be explored to better understand the pathogenesis. A choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) has recently been used to induce the NASH model, but the advantages are not established. NASH models were induced using the well-known traditional methionine- and choline-deficient (MCD) diet for 5 weeks and the recently used CDAHFD for 3 weeks. Liver phenotypes were analyzed to evaluate the differences in markers related to NASH. Lipidomics and metabolism analyses were used to investigate the effects of dietary regimens on the lipidome of the liver. The CDAHFD induced stronger NASH responses than the MCD, including lipid deposition, liver injury, inflammation, bile acid overload and hepatocyte proliferation. A significant difference in the hepatic lipidome was revealed between the CDAHFD and MCD-induced NASH models. In particular, the CDAHFD reduced the hepatic levels of phosphatidylcholines (PCs) and acylcarnitines (ACs), which was supported by the metabolism analysis and in line with the tendency of human NASH. Pathologically, the CDAHFD could effectively induce a more human-like NASH model over the traditional MCD. The hepatic PCs, ACs and their metabolism in CDAHFD-treated mice were down-regulated, similar to those in human NASH.
Subject(s)
Choline Deficiency , Non-alcoholic Fatty Liver Disease , Humans , Animals , Mice , Non-alcoholic Fatty Liver Disease/metabolism , Choline Deficiency/complications , Choline , Diet, High-Fat/adverse effects , Methionine , Disease Models, AnimalABSTRACT
Sarcomatoid carcinoma of the pancreas (SCP) is a rare and aggressive subtype of undifferentiated pancreatic ductal adenocarcinoma, with a generally poor prognosis and only sporadic cases reported worldwide. Histologically, the most notable feature of SCP is the presence of abundant of mesenchymatoid spindle tumor cells in the tumor, which lack glandular differentiation. Immunohistochemically, SCP is characterized by the expression of both mesenchymal and epithelial markers. With only a few reported cases, there is limited knowledge about its molecular and clinicopathological characteristics. Therefore, the present study performed a literature search to identify all relevant published studies. The present review provides an overview of the histogenesis, diagnosis, genetic features, prognosis and treatment of SCP, specifically focusing on the molecular alterations. Furthermore, a single-center experience is reported, which adds to the limited evidence available in the literature.
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OBJECTIVE: To determine the risk factors for acute rejection in liver transplantation and its impact on the outcomes of the recipients. METHODS: Clinicopathological data of 290 patients who underwent liver transplantation from January 2012 to December 2021 at our center were retrospectively evaluated. Patients were grouped into an acute rejection (AR) group and a normal (NM) group based on the confirmed histopathological diagnosis of acute rejection. Univariate and multivariate logistic regression were used to determine the risk factors for acute rejection. RESULTS: 244 patients were included in the study. Acute rejection occurred in 27 (11.1%) of the patients. Warm ischemia time (P = 0.137), cold ischemia time (P = 0.064) and chronic liver failure (P = 0.001) were potential risk factors for acute rejection. Chronic liver failure (P < 0.001, OR = 8.22, 95% CI = 2.47-27.32) was the independent risk factor. There was no significant difference in overall survival between recipients with acute rejection and those without it (P = 0.985). The 1-, 3- and 5-year overall survival in the NM group was 98.1%, 85.7% and 78.6% respectively vs 88.9%, 82.5% and 82.5% respectively in the AR group. CONCLUSION: Acute rejection does not appear to affect the long-term survival of the recipients. Only chronic liver failure was an independent risk factor for acute rejection. Our findings further illustrate that contradictions still exist on which factors influence acute rejection in liver transplant recipients. SUMMARY: Clinicopathological data of 290 liver transplant recipients at our center between January 2012 and December 2021 were retrospectively evaluated to determine the risk factors for acute rejection and its impact on the outcomes of the recipients. 244 patients were included in the analysis. 27 of the 244 experienced acute rejection. Propensity score matching was performed to reduce the confounding effect. Patients were assigned to an acute rejection group (n = 27) and a normal group (n = 54). Chronic liver failure (P < 0.001, OR = 8.22, 95% CI = 2.47-27.32) was the determined to be independent risk factor for acute rejection. Acute rejection did not appear to affect the long-term survival of the recipients and there was no significant difference in overall survival between the patients with acute rejection and those without it.
Subject(s)
End Stage Liver Disease , Liver Transplantation , Humans , Liver Transplantation/adverse effects , Retrospective Studies , Graft Rejection/etiology , Risk Factors , Graft SurvivalABSTRACT
BACKGROUND: Radical resection is a curative treatment for patients with hepatocellular carcinoma (HCC), but the incidence of recurrence remains high. We aimed to explore the performance of predicting HCC recurrence by longitudinal surveillance of the protein induced by vitamin K absence (PIVKA-II), alpha- fetoprotein (AFP), and lectin-reactive AFP (AFP-L3) during postoperative follow-up. METHODS: Patients who underwent radical resection for HCC at the Ningbo Medical Centre Lihuili Hospital between January 2015 and December 2020 were included. All enrolled patients regularly monitor PIVKA-II, AFP, AFP-L3 every 3 months during postoperative follow-up. The surveillance performance of PIVKA-II, AFP, AFP-L3 during follow-up for the prediction of HCC recurrence was compared in patients. The generalized estimation equation (GEE) was used to analyze the trends of the tumor biomarkers and interactions with time. Area under the receiver operator characteristic (AUROC) curves, the optimal cut-off value, the sensitivity and specificity were calculated to evaluate the performance of the three biomarkers. The recurrence-free survival (RFS) and overall survival (OS) of patients with any of the elevated biomarkers was analyzed by Kaplan-Meier curves and the log-rank test. Multivariate logistic regression models were used to analyze potential risk factors for recurrence. RESULTS: The GEE analysis indicated that PIVKA-II, AFP, AFP-L3 in the recurrence patients were higher than the no recurrence patients during follow-up, PIVKA-II and AFP showed increasing trends from 6 months before recurrence. In predicting recurrence, the AUROCs for PIVKA-II, AFP, AFP-L3 and their combination were 0.885, 0.754, 0.781 and 0.885 respectively, the optimal cut-off value for PIVKA-II, AFP, AFP-L3 was 29.5 mAU/ml, 10.7 ng/L, 1.5% respectively. The sensitivity in predicting recurrence for PIVKA-II, AFP, AFP-L3 and combination were 75.0, 54.7, 57.8 and 79.7% respectively. The RFS and the OS of patients with any of the biomarkers elevated during the follow-up was significantly shorter than that without elevated biomarkers ( P â <â 0.001). Multivariate analysis showed that any of the biomarkers elevated was the independent risk factor of recurrence. CONCLUSION: Longitudinal surveillance of PIVKA-II, AFP and AFP-L3 can effectively predict recurrence of HCC after operation.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/pathology , alpha-Fetoproteins/metabolism , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Protein Precursors , Biomarkers , Biomarkers, Tumor , ProthrombinABSTRACT
OBJECTIVES: To analyze the predictive factors on early postoperative recurrence of hepatocellular carcinoma (HCC) and to establish a new nomogram to predict early postoperative recurrence of HCC. METHODS: A retrospective analysis of 383 patients who had undergone curative resection between February 2012 and September 2020 in our center was performed. The Kaplan-Meier method was used for survival curve analysis. Univariate and multivariate Cox regression were performed to identify independent risk factors associated with early recurrence, and a nomogram for predicting early recurrence of HCC was established. RESULTS: A total of 152/383 patients developed recurrence after surgery, of which 83 had recurrence within 1 year. Multivariate Cox regression analysis showed that preoperative alpha-fetoprotein level ≥400 ng/ml (P = 0.001), tumor diameter ≥5 cm (P = 0.009) and MVI (P = 0.007 and macrotrabecular-massive HCC (P = 0.003) were independent risk factors for early postoperative recurrence of HCC. The macrotrabecular-massive-based nomogram obtained a good C-index (0.74) for predicting early recurrence of HCC, and the area under the curve for predicting early recurrence was 0.767, which was better than the single American Joint Committee on Cancer T stage and Barcelona Clinic Liver Cancer stage. CONCLUSIONS: The nomogram based on macrotrabecular-massive HCC can effectively predict early postoperative recurrence of HCC.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Nomograms , Liver Neoplasms/pathology , Retrospective Studies , Hepatectomy , Neoplasm Recurrence, Local/pathologyABSTRACT
BACKGROUND: We aimed to identify risk factors associated with reoperation for postoperative intraperitoneal hemorrhage (PIH) after orthotopic liver transplantation and investigate if partial liver transplantation (PLT) increases the risk of PIH. METHODS: We retrospectively analyzed the medical records of 304 consecutive recipients who underwent orthotopic liver transplantation at the Affiliated Lihuili Hospital, Ningbo University, from January 2016 to July 2022. Data were compared between recipients who experienced PIH requiring reoperation and those who did not. Subgroup propensity score matching analysis was performed to assess the impact of PLT on PIH risk. Neither prisoners nor participants who were coerced or paid were used in the study. RESULTS: Among the 304 recipients, 22 (7.2%) underwent reoperation for PIH. Multivariate analysis revealed that the recipient Model for End-Stage Liver Disease (MELD) score (odds ratio = 1.066, 95% CI [1.025-1.109], P = .001) and volume of intraoperative packed red blood cell transfusion (odds ratio = 1.089, 95% CI [1.032-1.481], P = .002) were independent risk factors for PIH. No significant differences were observed in the risk of PIH between PLT and whole liver transplantation. CONCLUSION: Preoperative MELD score and intraoperative packed red blood cell transfusion should be carefully considered to manage the risk of PIH in liver transplantation recipients. Partial liver transplantation, a crucial approach for addressing donor shortages, does not increase the risk of reoperation for PIH in recipients.
Subject(s)
End Stage Liver Disease , Liver Transplantation , Humans , Liver Transplantation/adverse effects , End Stage Liver Disease/surgery , Retrospective Studies , Severity of Illness Index , Postoperative Hemorrhage/epidemiology , Postoperative Hemorrhage/etiology , Risk FactorsABSTRACT
BACKGROUD: In this study, we aimed to develop a prognostic model to predict HCC early recurrence (within 1-year) in patients with microvascular invasion who received postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE). METHODS: A total of 148 HCC patients with MVI who received PA-TACE were included in this study. The modes were verified in an internal validation cohort (n = 112) and an external cohort (n = 36). Univariate and multivariate Cox regression analyses were performed to identify the independent prognostic factors relevant to early recurrence. A clinical nomogram prognostic model was established, and nomogram performance was assessed via internal validation and calibration curve statistics. RESULTS: After data dimensionality reduction and element selection, multivariate Cox regression analysis indicated that alpha fetoprotein level, systemic inflammation response index, alanine aminotransferase, tumour diameter and portal vein tumour thrombus were independent prognostic factors of HCC early recurrence in patients with MVI who underwent PA-TACE. Nomogram with independent factors was established and achieved a better concordance index of 0.765 (95% CI: 0.691-0.839) and 0.740 (95% CI: 0.583-0.898) for predicting early recurrence in training cohort and validation cohort, respectively. Time-dependent AUC indicated comparative stability and adequate discriminative ability of the model. The DCA revealed that the nomogram could augment net benefits and exhibited a wider range of threshold probabilities than AJCC T stage. CONCLUSIONS: The nomogram prognostic model showed adequate discriminative ability and high predictive accuracy.
Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/surgery , Prognosis , Liver Neoplasms/surgery , Retrospective Studies , NomogramsABSTRACT
BACKGROUND Liver regeneration after partial liver transplantation, including living donor liver transplantation and split liver transplantation, is important for successful transplantation. MATERIAL AND METHODS We retrospectively analyzed 68 patients who underwent partial liver transplantation and calculated their regeneration index (RI)-based difference in postoperative and preoperative liver volume. We collected clinical data of donors and recipients and analyzed the correlation between clinical characteristics and RI. According to the above results, the generalized estimating equation (GEE) model included white blood cell count (WBC), neutrophils, lymphocytes, platelets, prothrombin time (PT), and activated partial thromboplastin time (APTT) on Days 1, 3, and 7 after LT and was used to predict the RI. RESULTS The mean RI was 40%, which was used as the cutoff value to divide all patients to the high-RI group and the low-RI group. The percentage of Child-Pugh C patients was 44% in the high-RI group, which was significantly more than that (21%) in the low-RI group (P=0.038). Among the postoperative monitoring parameters, neutrophil (P=0.044) and platelet (P=0.036) levels declined in the high-RI group on Day 3, while APTT was higher on Day 1 compared to the low-RI group. The predictive model based on GEE analysis achieved a good effect, with the area under the receiver operating characteristic curve on Day 1 (0.681; 95% CI, 0.556-0.807) and Day 3 (0.705; 95% CI, 0.578-0.832) showing significant differences (P=0.010 and 0.004, respectively). CONCLUSIONS The combination of decreased counts of WBC, neutrophils, lymphocytes, and platelets, as well as elevated PT and APTT on Day 3 after LT showed a good capability to predict a higher rate of liver regeneration after partial liver transplantation.
Subject(s)
Liver Transplantation , Humans , Liver Transplantation/methods , Retrospective Studies , Living Donors , Liver , Blood Platelets , Liver RegenerationABSTRACT
Objectives: This study aimed to develop and externally validate a nomogram for predicting liver metastasis after radical resection in patients with pancreatic ductal adenocarcinoma (PDAC). Methods: A total of 247 PDAC patients who underwent radical resection were retrospectively reviewed from January 2015 to March 2022 at Ningbo Medical Centre Lihuili Hospital Eastern Section, and used as a training cohort to develop the nomogram. 83 PDAC patients from the Ningbo Medical Centre Lihuili Hospital Xingning Section were enrolled as the validation cohort. The postoperative liver metastasis was recorded during the follow-up, and the liver metastasis-free survival was defined as the time from operation to the date of liver metastasis diagnosis or death. The nomogram was established based on independent prognostic factors selected by LASSO and multivariate Cox regression model. The performance was assessed using the concordance index (C-index) and calibration curves. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to determine the clinical utility of the nomogram model. Results: From the training cohort of 247 patients, a total of 132 patients developed liver metastasis during the follow-up, the 1-, 2- and 3- year liver metastasis-free survival were 52.4%, 43.5% and 40% respectively. The LASSO and multivariate Cox regression analysis indicated that postoperative CA125 (hazard ratio [HR] = 1.007, p <0.001), tumor differentiation (HR = 1.640, p = 0.010), tumor size (HR = 1.520, p = 0.029), lymph node ratio (HR = 1.897, p = 0.002) and portal/superior mesenteric/splenic vein invasion degree (PV/SMV/SV) (HR = 2.829, p <0.001) were the independent factors of liver metastasis. A nomogram with independent factors was developed and the C-index was 0.760 (95% confidence interval [CI], 0.720-0.799) and 0.739 (95% CI, 0.669-0.810) in the training and validation cohorts, respectively. The areas under curve (AUC) of the nomogram at 1-, 2- and 3-year were 0.815, 0.803 and 0.773 in the training cohort, and 0.765, 0.879 and 0.908 in the validation cohort, respectively, higher than those in TNM stage. Decision curve analysis (DCA) analysis revealed that the nomogram model provided superior net benefit in clinical utility. Liver metastasis-free survival curves showed a significant discriminatory ability for liver metastasis risk based on the nomogram (p <0.001). Conclusions: The nomogram showed high accuracy in predicting liver metastasis for PDAC after radical resection, and may serve as a clinical support tool to guide personalized and prescient intervention.
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BACKGROUND: The gap between the demand and supply of donor livers is still a considerable challenge. Since static cold storage is not sufficient in marginal livers, machine perfusion is being explored as an alternative. The objective of this study was to assess (dual) hypothermic oxygenated machine perfusion (HOPE/D-HOPE) and normothermic machine perfusion (NMP) in contrast to static cold storage (SCS). METHODS: Three databases were searched to identify studies about machine perfusion. Graft and patient survival and postoperative complications were evaluated using the random effects model. RESULTS: the incidence of biliary complications was lower in HOPE vs. SCS (OR: 0.59, 95% CI: 0.36-0.98, p = 0.04, I2: 0%). There was no significant difference in biliary complications between NMP and SCS (OR: 0.76, 95% CI: 0.41-1.40, p = 0.38, I2: 55%). Graft and patient survival were significantly better in HOPE than in SCS (HR: 0.40, 95% CI: 0.23-0.71, p = 0.002, I2: 0%) and (pooled HR: 0.43, 95% CI: 0.20-0.93, p = 0.03, I2: 0%). Graft and patient survival were not significantly different between NMP and SCS. CONCLUSION: HOPE/D-HOPE and NMP are promising alternatives to SCS for donor liver preservation. They may help address the widening gap between the demand for and availability of donor livers by enabling the rescue and transplantation of marginal livers.
ABSTRACT
Aims: We explored the relationship between the mutation at the p.G245S site in TP53 and the short-term recurrence of hepatocellular carcinoma (HCC). Materials and Methods: 101 HCC patients were included in this study. The TP53 p.G245S mutation frequency spectrum was examined by direct sequencing of genomic DNA from tissue specimens of HCC patients. Univariate and multivariate Cox regression analyses were performed to evaluate the independent prognostic factors of tumor recurrence. ROC curve analysis was applied to determine the cut-off value for the p.G245S mutation frequency and to verify the predictive ability of the Cox model compared with single risk factor indices. Results: A multivariate Cox regression analysis showed that TP53 p.G245S mutation frequency (HR = 1.231, 95% CI: 1.006-1.505, p = 0.043), AFP (HR = 2.432, 95% CI: 1.297-4.561, p = 0.006), MTM (HR = 2.656, 95% CI: 0.930-7.583, p = 0.068), and PVTT (HR = 14.297, 95% CI: 3.085-66.243, p = 0.001) were independent prognostic factors for short-term recurrence. The cut-off value for the TP53 p.G245S mutation frequency (18.5%) was determined by ROC analysis. A predictive model integrating the TP53 p.G245S mutation frequency with PVTT, MTM, and AFP values appears to an excellent predictive indicator of short-term recurrence in HCC patients (AUC = 0.849, 95% CI = 0.748-0.950, p = 0.000001). Survival analysis indicated that the probability of short-term recurrence-free survival was significantly different among different TP53 p.G245S mutation frequency, MTM, PVTT, and AFP risk groups (p < 0.05). Conclusion: The mutation frequency of the p.G245S site is a novel prognostic risk factor for the short-term recurrence of HCC.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , alpha-Fetoproteins/metabolism , Carcinoma, Hepatocellular/pathology , Diphosphates , Liver Neoplasms/pathology , Mutation Rate , Retrospective Studies , Tumor Suppressor Protein p53/genetics , RecurrenceABSTRACT
Background: Liver metastasis arises in many postoperative patients with PDAC, occurring in the early stage appears to lead to a very poor prognosis. Objective: We aimed to analyze the risk factors for early liver metastasis after radical resection for patients with pancreatic ductal adenocarcinoma (PDAC) and to indicate the poor prognosis of early liver metastasis. Methods: Patients who underwent pancreatectomy for PDAC at the Ningbo Medical Centre Lihuili Hospital between January 2015 and June 2021 were included. The exclusion criteria were death within 30 days after the operation, complications with other malignancies, and a positive final resection margin (R1). Liver metastasis and its occurrence time were recorded, and risk factors for early (≤6 months) liver metastasis were analyzed by logistic regression models. The prognosis of patients with early liver metastasis and different recurrence patterns was analyzed by Kaplan-Meier curves and the log-rank test. Results: From the identified cohort of 184 patients, 172 patients were included for further analysis. 55 patients developed early liver metastasis within 6 months after the operation. Univariate analysis showed that CA125 ≥ 30 IU/ml, tumor size ≥ 4 cm, poor tumor differentiation, and portal vein/superior mesenteric vein (PV/SMV) reconstruction were risk factors, and multivariate analysis showed that poor tumor differentiation and PV/SMV reconstruction were independent risk factors for early liver metastasis. The prognosis of liver metastasis was the worst among the different recurrence patterns. Early liver metastasis indicates a poor prognosis in patients with PDAC. Conclusions: Poor differentiation and PV/SMV reconstruction are independent risk factors for early liver metastasis in patients with PDAC, and early liver metastasis indicates a poor prognosis.
ABSTRACT
Background: The macrotrabecular-massive subtype of hepatocellular carcinoma (MTM-HCC) is an aggressive histological type and results in poor prognosis. We developed a nomogram model based on laboratory results to predict the presence of MTM-HCC. Methods: A total of 357 HCC patients who underwent radical surgery between January 2015 and December 2020 at Ningbo Medical Center Lihuili Hospital were grouped according to histological type. After propensity score matching (PSM), 267 patients were divided into MTM-HCC (n = 76) and non-MTM-HCC (n = 191) groups. A LASSO regression analysis model was used to select predictive factors. Finally, a nomogram for predicting the presence of MTM-HCC was established. Decision curve analysis (DCA) was conducted to determine the clinical usefulness of the nomogram model by quantifying the net benefits along with the increase in threshold probabilities. Results: The 1-, 3-, and 5-year disease-free survival (DFS) and overall survival (OS) rates for MTM-HCC were 60.0%, 36.0%, 32.4% and 92.1%, 68.7%, 52.2%, respectively. Survival analysis indicated that the probabilities of achieving DFS and OS were significantly worse in the MTM-HCC group than in the non-MTM-HCC group (P < 0.05). The nomogram model that included AST levels, PT and AFP levels achieved a better C-index of 0.723 (95% CI: 0.659-0.787). DCA revealed that the nomogram model could lead to net benefits and exhibited a wider range of threshold probabilities in the prediction of MTM-HCC. Conclusion: The nomogram model included AST, PT and AFP could achieve an optimal performance in the preoperative prediction of MTM-HCC.