Development and validation of nomograms to evaluate the survival outcome of HCC patients undergoing selective postoperative adjuvant TACE.

PURPOSE: The objective of this study was to develop and validate a novel prognostic nomogram to evaluate the survival benefit of hepatocellular carcinoma (HCC) patients receiving postoperative adjuvant transarterial chemoembolization (PA-TACE). MATERIALS AND METHODS: Clinical data of HCC patients who underwent hepatectomy at four medical centers were retrospectively analyzed, including those who received PA-TACE and those who did not. These two categories of patients were randomly allocated to the development and validation cohorts in a 7:3 ratio. RESULTS: A total of 1505 HCC patients who underwent hepatectomy were included in this study, comprising 723 patients who did not receive PA-TACE and 782 patients who received PA-TACE. Among them, patients who received PA-TACE experienced more adverse events, although these events were mild and manageable (Grade 1-2, all p < 0.05). Nomograms were constructed and validated for patients with and without PA-TACE using independent predictors that influenced disease-free survival (DFS) and overall survival (OS). These two nomograms had C-indices greater than 0.800 in the development cohort and exhibited good calibration and discrimination ability compared to six conventional HCC staging systems. Patients in the intermediate-to-high-risk group in the nomogram who received PA-TACE had higher DFS and OS (all p < 0.05). In addition, tumor recurrence was significantly controlled in the intermediate-to-high-risk group of patients who received PA-TACE, while there was no significant difference in the low-risk group of patients who received PA-TACE. CONCLUSION: The nomograms were developed and validated based on large-scale clinical data and can serve as online decision-making tools to predict survival benefits from PA-TACE in different subgroups of patients.

Survival effects of postoperative adjuvant TACE in early-HCC patients with microvascular invasion: A multicenter propensity score matching.

Background: The presence of microvascular invasion (MVI) significantly worsens the surgical outcome of hepatocellular carcinoma (HCC). The purpose of this research was to investigate the survival benefit of adjuvant transarterial chemoembolization (TACE) in patients with MVI after hepatectomy. Methods: A retrospective analysis was conducted on 1372 HCC patients who underwent curative liver resection in four medical institutions. In order to minimize confounding factors and selection bias between groups, Propensity Score Matching (PSM) (1:1) was performed to ensure balanced clinical characteristics. Results: A total of 1056 patients were enrolled after PSM, including 672 patients with MVI and 384 patients without MVI. Adjuvant TACE improves DFS (Median, 36 months vs 14 months, p < 0.001) and OS (Median, NA vs 32 months, p < 0.001) in patients harboring MVI, but not in those (all p > 0.05) lacking MVI. In different different CNLC stages, adjuvant TACE improved DFS (CNLC stage I, Median, 37 vs 15 months; CNLC stage II, Median, 25 vs 11 months, p < 0.001) and OS (CNLC stage I, Median, NA vs 32 months, p < 0.001; CNLC stage II, Median, NA vs 26 months, p = 0.002) in patients who carried MVI, but not in those (CNLC stage I-II, all p > 0.05) who lacked MVI. Conclusions: Adjuvant TACE may be a potentially effective treatment option for improving survival outcomes in early-HCC patients harboring MVI, but not in those lacking MVI.

Exploring the factors affecting the occurrence of postoperative MVI and the prognosis of hepatocellular carcinoma patients treated with hepatectomy: A multicenter retrospective study.

OBJECTIVE: To investigate the influencing factors affecting the occurrence of microvascular invasion (MVI) and the prognosis of hepatocellular carcinoma (HCC) patients treated with hepatectomy, and to explore how MVI affects prognosis in subgroups with different prognostic factors. METHODS: Clinical data of a total of 1633 patients treated surgically for HCC in four treatment centers were included, including 754 patients with MVI. By using the Cox risk regression model and the Mann-Whitney U-test, the common independent influences on prognosis and MVI were made clear. The incidence of MVI in various subgroups was then examined, as well as the relationship between MVI in various subgroups and prognosis. RESULTS: The Cox risk regression model showed that MVI, Child-Pugh classification, alpha-fetoprotein (AFP), hepatocirrhosis, tumor diameter, lymphocyte-to-monocyte ratio (LMR), and, Barcelona clinic liver cancer (BCLC) grade were independent determinants of overall survival (OS), and MVI, AFP, hepatocirrhosis, tumor diameter, and LMR were influencing determinants for disease-free survival (DFS). The receiver operating characteristic (ROC) curve showed that MVI was most closely associated with patient prognosis compared to other prognostic factors. AFP, hepatocirrhosis, tumor diameter, and LMR were discovered to be common influences on the prognosis of patients with HCC and MVI when combined with the results of the intergroup comparison of MVI. After grouping, it was showed that patients with hepatocirrhosis, positive AFP (AFP ≥ 20 ng/mL), tumor diameter >50 mm, and LMR ≤3.4 had a significantly higher incidence of MVI than patients in other subgroups, and all four subgroups of MVI-positive patients had higher rates of early recurrence and mortality (p < 0.05). CONCLUSIONS: MVI was found to be substantially linked with four subgroups of HCC patients with hepatocirrhosis, positive AFP, tumor diameter >50 mm, and LMR ≤3.4, and the prognosis of MVI-positive patients in all four subgroups tended to be worse.

Development and Validation of a Nomogram for Predicting Postoperative Early Relapse and Survival in Hepatocellular Carcinoma.

BACKGROUND: Early relapse after hepatectomy presents a significant challenge in the treatment of hepatocellular carcinoma (HCC). The aim of this study was to construct and validate a novel nomogram model for predicting early relapse and survival after hepatectomy for HCC. PATIENTS AND METHODS: We conducted a large-scale, multicenter retrospective analysis of 1,505 patients with surgically treated HCC from 4 medical centers. All patients were randomly divided into either the training cohort (n=1,053) or the validation cohort (n=452) in a 7:3 ratio. A machine learning-based nomogram model for prediction of HCC was established by integrating multiple risk factors that influence early relapse and survival, which were identified from preoperative clinical data and postoperative pathologic characteristics of the patients. RESULTS: The median time to early relapse was 7 months, whereas the median time from early relapse to death was only 19 months. The concordance indexes of the postoperative nomogram for predicting disease-free survival and overall survival were 0.741 and 0.739, respectively, with well-calibrated curves demonstrating good consistency between predicted and observed outcomes. Moreover, the accuracy and predictive performance of the postoperative nomograms were significantly superior to those of the preoperative nomogram and the other 7 HCC staging systems. The patients in the intermediate- and high-risk groups of the model had significantly higher probabilities of early and critical recurrence (P<.001), whereas those in the low-risk group had higher probabilities of late and local recurrence (P<.001). CONCLUSIONS: This postoperative nomogram model can better predict early recurrence and survival and can serve as a useful tool to guide clinical treatment decisions for patients with HCC.

CK5/6-positive, P63-positive lymphoepithelioma-like hepatocellular carcinoma: A case report and literature review.

BACKGROUND: Lymphoepithelioma-like carcinoma (LELC), a rare and unique variant of liver cancer, can be divided into lymphoepithelioma-like hepatocellular carcinoma and lymphoepithelioma-like intrahepatic cholangiocarcinoma. Dense lymphocytic infiltration is its characteristic pathological feature. In recent years, the number of reported cases of this type has increased each year. Studies have shown that lymphoepithelioma-like cholangiocarcinoma occurs more frequently in Asian women; LELC is associated with Epstein-Barr virus infection of liver cells of epithelial origin. Existing research shows that the prognosis of this tumour is good. CASE SUMMARY: A 38-year-old female patient was hospitalized after 3 mo of abdominal pain and nausea. She had been infected with hepatitis B virus more than 10 years prior. The patient was hospitalized on January 21, 2022. Magnetic resonance imaging showed a 36 mm × 28 mm mass under the envelope of the left inner lobe of the liver. No metastasis of lymph nodes or other organs was observed. After left hemihepatectomy, biopsy and immunohistochemistry yielded a final diagnosis of lymphoepithelial hepatocellular carcinoma. After 12 mo of outpatient follow-up and chemotherapy, no tumour metastases were found on the latest computed tomography examination. CONCLUSION: Herein, the patient was treated surgically and then followed up as an outpatient for 12 mo. This case will further expand our overall knowledge of the diagnosis and treatment of this rare tumor.

Efficacy of adjuvant TACE on the prognosis of patients with HCC after hepatectomy: a multicenter propensity score matching from China.

BACKGROUND: The survival benefit of adjuvant transarterial chemoembolization (TACE) in patients with hepatectomy for hepatocellular carcinoma (HCC) after hepatectomy remains controversial. We aimed to investigate the survival efficacy of adjuvant TACE after hepatectomy for HCC. METHODS: 1491 patients with HCC who underwent hepatectomy between January 2018 and September 2021 at four medical centers in China were retrospectively analyzed, including 782 patients who received adjuvant TACE and 709 patients who did not receive adjuvant TACE. Propensity score matching (PSM) (1:1) was performed to minimize selection bias, which balanced the clinical characteristics of the two groups. RESULTS: A total of 1254 patients were enrolled after PSM, including 627 patients who received adjuvant TACE and 627 patients who did not receive adjuvant TACE. Patients who received adjuvant TACE had higher disease-free survival (DFS, 1- ,2-, and 3-year: 78%-68%-62% vs. 69%-57%-50%, p < 0.001) and overall survival (OS, 1- ,2-, and 3-year: 96%-88%-80% vs. 90%-77%-66%, p < 0.001) than those who did not receive adjuvant TACE (Median DFS was 39 months). Among the different levels of risk factors affecting prognosis [AFP, Lymphocyte-to-monocyte ratio, Maximum tumor diameter, Number of tumors, Child-Pugh classification, Liver cirrhosis, Vascular invasion (imaging), Microvascular invasion, Satellite nodules, Differentiation, Chinese liver cancer stage II-IIIa], the majority of patients who received adjuvant TACE had higher DFS or OS than those who did not receive adjuvant TACE. More patients who received adjuvant TACE accepted subsequent antitumor therapy such as liver transplantation, re-hepatectomy and local ablation after tumor recurrence, while more patients who did not receive adjuvant TACE accepted subsequent antitumor therapy with TACE after tumor recurrence (All p < 0.05). CONCLUSIONS: Adjuvant TACE may be a potential way to monitor early tumor recurrence and improve postoperative survival in patients with HCC.

Postoperative adjuvant transarterial chemoembolisation improves survival of hepatocellular carcinoma patients with microvascular invasion: A multicenter retrospective cohort.

BACKGROUND: We aimed to investigate the efficacy of postoperative adjuvant transarterial chemoembolisation (PA-TACE) in patients with hepatocellular carcinoma (HCC) complicated by microvascular invasion (MVI). METHODS: A retrospective analysis of 1505 patients with HCC who underwent hepatectomy at four medical centers, including 782 patients who received PA-TACE and 723 patients who did not receive adjuvant PA-TACE, has been conducted. Propensity score matching (PSM) (1:1) was performed on the data to minimise selection bias, which resulted in a balanced clinical profile between groups. RESULTS: After PSM, 620 patients who received PA-TACE and 620 patients who did not receive PA-TACE were included. Disease-free survival (DFS, 1-, 2-, and 3-year: 88%-68%-61% vs. 70%-58%-51%, p < 0.001) and overall survival (OS, 1-, 2-, and 3-year: 96%-89%-82% vs. 89%-77%-67%, p < 0.001) were significantly higher in patients who received PA-TACE than in those who did not. Patients with MVI who received PA-TACE had significantly higher DFS (1-, 2-, and 3-year: 68%-57%-48% vs. 46%-31%-27%, p < 0.001) and OS (1-, 2-, and 3-year: 96%-84%-77% vs. 79%-58%-40%, p < 0.001) than those who did not receive PA-TACE. Among the six different liver cancer stages, MVI-negative patients did not have significant survival outcomes from PA-TACE (p > 0.05), whereas MVI-positive patients achieved higher DFS and OS from it (p < 0.05). Liver dysfunction, fever, and nausea/vomiting were the most common adverse events in patients receiving PA-TACE. There was no significant difference in grade 3 or 4 adverse events between the groups (p > 0.05). CONCLUSIONS: Postoperative adjuvant transarterial chemoembolisation has a good safety profile and may be a potentially beneficial treatment modality for survival outcomes in patients with HCC, especially those with concomitant MVI.

Mutual effects between single-stranded DNA conformation and Na+-Mg2+ ion competition in mixed salt solutions.

The ion-dependence of single-stranded DNA (ssDNA) conformational changes has attracted growing attention because of its biological and technological importance. Although single-species ion effects have been extensively explored, it is challenging to study the ssDNA conformational properties under mixed monovalent/divalent ion conditions due to the complications of ssDNA flexibility and ion-ion competition. In this study, we apply Langevin dynamics simulations to investigate mixed Na+/Mg2+ ion-dependent ssDNA conformations. The ssDNA structure is described using a coarse-grained model, in which the phosphate, base, and sugar of each nucleotide are represented by three different beads. A novel improvement in our simulation model is that mixed-salt-related electrostatic interactions are computed via combining Manning counterion condensation (MCC) theory with the Monte Carlo tightly bound ion (MCTBI) model. Based on this MCC-MCTBI combination, we report new empirical functions to describe the ion-concentration-dependent and ssDNA conformation/structure-dependent electrostatic effects. The calculation results relating to the ion binding properties and the simulation results relating to the ssDNA conformational properties are validated against experimental results. In addition, our simulation results suggest a quantitative relationship between the ssDNA conformation and Na+-Mg2+ competition; this in turn reveals their mutual impact in the ion atmosphere.

Dataset of normalized probability distributions of virtual bond lengths, bond angles, and dihedral angles for the coarse-grained single-stranded DNA structures.

The utility of the coarse-grained (CG) single-stranded DNA (ssDNA) model can drastically reduce the compute time for simulating the ssDNA dynamics. The model-matched CG potentials and the inherent potential constants can be derived by coarse-graining the experimentally measured ssDNA structures. A useful and widespread treatment of the CG model is to use three different pseudo-atoms P, S, and B to represent the atomic groups of phosphate, sugar, and base, respectively, in each nucleotide of the ssDNA structures. The three pseudo-atoms generate nine types of the structural parameters to characterize the unstructured ssDNA conformations, including three (virtual) bond lengths (P-S, S-B, and S-P) between two neighbouring beads, four bond angles (P-S-P, S-P-S, P-S-B, and B-S-P) between three adjacent bonds, and two dihedral angles (P-S-P-S and S-P-S-P) between three successive bonds. This paper mainly presents the data of normalized probability distributions of the bond lengths, bond angles, and dihedral angles for the CG ssDNAs.