Establishing and Externally Validating a Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) Score-Based Nomogram for Predicting Early Recurrence in BCLC Stage 0/A Hepatocellular Carcinoma Patients After Radical Liver Resection: A Multi-Center Study.

Purpose: Early recurrence (ER) is associated with poor prognosis in hepatocellular carcinoma (HCC). In this study, we developed and externally validated a nomogram based on the hemoglobin, albumin, lymphocytes, and platelets (HALP) score to predict ER for patients with BCLC stage 0/A HCC who underwent radical liver resection. Patients and Methods: A total of 808 BCLC stage 0/A HCC patients from six hospitals were included in this study, and they were assigned to a training cohort (n = 500) and an external validation cohort (n = 308). We used univariate and multivariate Cox regression analysis to identify the independent risk factors for disease-free survival (DFS). We also established and externally validated a nomogram based on these risk predictors. The nomogram was evaluated using the area under the receiver operating characteristic curve (AUC), the concordance index (C-index), the calibration curve, decision curve analysis (DCA), and Kaplan‒Meier analysis. Results: Multivariate COX regression showed that HBV DNA ≥10,000 IU/mL (P < 0.001), HALP score ≤38.20 (P < 0.001), tumor size (P = 0.003), clinically significant portal hypertension (P = 0.001), Edmondson-Steiner grade (III-IV) (P = 0.007), satellite nodules (P < 0.001), and MVI (P = 0.001) were independent risk factors for post-operative tumor recurrence. The AUC of our nomogram for predicting the 2-year and 5-year DFS was 0.756 and 0.750, respectively, in the training cohort and 0.764 and 0.705, respectively, in the external validation cohort. We divided the patients into low-, intermediate- and high-risk groups according to the risk score calculated by the nomogram. There were statistically significant differences in the DFS and overall survival (OS) among the three groups of patients (P < 0.001). Conclusion: We developed and externally validated a new nomogram, which is accurate and can predict ER in BCLC stage 0/A HCC patients after curative liver resection.

Safety of nighttime elective hepatectomy for hepatocellular carcinoma patients: a retrospective study.

Purpose: This study aimed to investigate whether nighttime elective surgery influenced the short-term outcomes and prognosis of hepatocellular carcinoma (HCC) patients. Methods: The 1,339 HCC patients who underwent hepatectomy were divided into the daytime surgery group (8 a.m.-6 p.m., n = 1,105) and the nighttime surgery group (after 6 p.m., n = 234) based on the start time of surgery. The 1:2 propensity score matching (PSM) analysis was used to control confounding factors. The short-term outcomes of HCC patients in the 2 groups were compared before and after PSM. Factors associated with major complications (Clavien-Dindo grade, ≥III) and textbook oncologic outcomes (TOO) were separately identified by multivariable logistic regression based on variables screened via least absolute shrinkage and selection operator (LASSO). The Kaplan-Meier method was used to analyze overall survival (OS) and recurrence-free survival (RFS). Results: TOO was achieved after surgery in 897 HCC patients. HCC patients in the nighttime surgery group had a higher body mass index (P = 0.010). After 1:2 PSM, the baseline characteristics of patients between the 2 groups were similar. Short-term outcomes in HCC patients were comparable both before and after PSM (all Ps > 0.05), as were TOO in the 2 groups before (P = 0.673) and after PSM (P = 0.333). In our LASSO-logistic regression, nighttime surgery was not an independent factor associated with major complications or TOO. Both groups also had similar OS (P = 0.950) and RFS (P = 0.740) after PSM. Conclusion: Our study revealed the safety of nighttime elective hepatectomy for HCC patients.

PIVKA-II combined with tumor burden score to predict long-term outcomes of AFP-negative hepatocellular carcinoma patients after liver resection.

BACKGROUND: This study aimed to establish a simple prognostic scoring model based on tumor burden score (TBS) and PIVKA-II to predict long-term outcomes of α-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC) patients. METHODS: 511 patients were divided into the training cohort (n = 305) and the validation cohort (n = 206) at a ratio of 6:4. Receiver operating characteristic curves (ROC) were established to identify cutoff values of TBS and PIVKA-II. Kaplan-Meier curves were used to analyze survival outcomes. The multivariable Cox regression was used to identify variables independently associated with survival outcomes. The predictive performance of the TBS-PIVKA II score (TPS) model was compared with Barcelona clinic liver cancer (BCLC) stage and American Joint Committee on Cancer (AJCC TNM) stage. RESULTS: The present study established the TPS model using a simple scoring system (0, 1 for low/high TBS [cutoff value: 4.1]; 0, 1 for low/high PIVKA-II [cutoff value: 239 mAU/mL]). The TPS scoring model was divided into three levels according to the summation of TBS score and PIVKA-II score: TPS 0, TPS 1, and TPS 2. The TPS scoring model was able to stratify OS (training: p < 0.001, validation: p < 0.001) and early recurrence (training: p < 0.001; validation: p = 0.001) in the training cohort and the validation cohort. The TPS score was independently associated with OS (TPS 1 vs. 0, HR: 2.28, 95% CI: 1.01-5.17; TPS 2 vs. 0, HR: 4.21, 95% CI: 2.01-8.84) and early recurrence (TPS 1 vs. 0, HR: 3.50, 95% CI: 1.71-7.16; TPS 2 vs. 0, HR: 3.79, 95% CI: 1.86-7.75) in the training cohort. The TPS scoring model outperformed BCLC stage and AJCC TNM stage in predicting OS and early recurrence in the training cohort and the validation cohort. But the TPS scoring model was unable to stratify the late recurrence in the training cohort (p = 0.872) and the validation cohort (p = 0.458). CONCLUSIONS: The TPS model outperformed the BCLC stage and AJCC TNM stage in predicting OS and early recurrence of AFP-negative HCC patients after liver resection, which might better assist surgeons in screening AFP-negative HCC patients who may benefit from liver resection.

Nomogram to predict liver surgery-specific complications for hepatocellular carcinoma: A multicenter study.

BACKGROUND: Early identification of patients at risk for surgical complications enables surgeons to make better treatment decisions and optimize resource utilization. We propose to develop a nomogram for predicting the risk of moderate-to-severe liver surgery-specific complications after hepatectomy in hepatocellular carcinoma (HCC) patients. METHODS: We retrospectively enrolled HCC patients who underwent radical hepatectomy at four medical centers from January 2014 to January 2019 in southwestern China, randomly (7:3) divided into training and validation cohorts. We used least absolute shrinkage and selection operator (LASSO) logistic regression to build a nomogram model. RESULTS: The nomogram model contained 6 variables: diabetes mellitus (yes vs. no, OR: 2.32, 95% CI: 1.16-4.64, P = 0.02), major hepatectomy (yes vs. no, OR: 2.65, 95% CI: 1.64-4.27, P < 0.001), platelets (PLT, ≥100 × 103/µl vs. <100 × 103/µl, OR: 0.53, 95% CI: 0.33-0.87, P = 0.01), prothrombin time (PT, >13 s vs. ≤13 s, OR: 1.78, 95% CI: 1.04-3.05, P = 0.04), albumin-indocyanine green evaluation grade (ALICE grade, grade B vs. grade A, OR: 2.06, 95% CI: 1.17-3.61, P = 0.01), and prognostic nutrient index (PNI, >48 vs. ≤48, OR: 0.55, 95% CI: 0.33-0.92, P = 0.02). The concordance index (C-index) and area under the receiver operating characteristic curve (AUC) were 0.751 (95% CI, 0.703-0.799) and 0.743 (95% CI, 0.653-0.833) for the training and validation cohorts, respectively. Decision curve analysis (DCA) showed that the nomogram had good clinical value. CONCLUSION: We provide good preoperative predictors for the risk of moderate-to-high FABIB score complications in patients with HBV-related HCC posthepatectomy.

Insurance status impacts survival of hepatocellular carcinoma patients after liver resection.

BACKGROUND: This study intends to examine the effect of public insurance status on survival outcomes of HCC patients after liver resection in China. METHODS: We divided 2911 HCC patients after liver resection included in our study into the Urban Employed-based Medical Insurance group (UEBMI group, n = 1462) and the non-Urban Employed-based Medical Insurance group (non-UEBMI group, n = 1449). A propensity score matching (PSM) analysis was used to control confounding factors. Overall survival (OS) was estimated by Kaplan-Meier curves and Cox proportional hazard models based on variables screened by Lasso regression. Competing risk analysis was used to analyze cancer-specific survival (CSS). RESULTS: UEBMI group had more male patients (p = 0.031), patients in the UEBMI group were older (p < 0.001) and had lower Charlson Comorbidity Index scores (CCI score, p < 0.001). Meanwhile, patients in the UEBMI group had better liver function (albumin-bilirubin grade I [ALBI I], p < 0.001) and lower tumor burden (α-fetoprotein [AFP], p = 0.009; Barcelona Clinic Liver Cancer stage [BCLC], p = 0.026; Milan criteria, p < 0.001; tumor size, p < 0.001; microvascular invasion [MVI], p = 0.030; portal vein tumor thrombosis [PVTT], p = 0.002). More patients in the UEBMI group received laparoscopic surgery (p = 0.024) and adjuvant transarterial chemoembolization (TACE, p < 0.001). After PSM, patients in the two matched groups had similar characteristics. Patients with recurrent HCC in the UEBMI were more likely to receive curative therapy (p < 0.001) and less likely to receive supportive care (p < 0.001). HCC patients after liver resection in the non-UEBMI group had a worse OS before (p < 0.0001) and after PSM (p = 0.002). [Correction added on August 16, 2023 after first online publication. The p value has been updated in the preceding sentence.] In our Lasso-Cox risk regression model, public health insurance status was an independent factor linked with OS (non-UEBMI vs. UEBMI, hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 1.12-1.46; p < 0.001). In the competing risk analysis, patients in the UEBMI group had a lower cumulative incidence of CSS before (p < 0.001) and after PSM (p = 0.001), and public insurance status of HCC patients after liver resection remained independently associated with CSS (non-UEBMI vs. UEBMI; HR:1.36; 95% CI: 1.18-1.58; p < 0.001). CONCLUSIONS: Underinsured HCC patients after liver resection had worse survival outcomes. Less access to care for underinsured patients may explain the difference in survival, but the corresponding conclusions need to be further explored.

Tumor burden score-AFP-albumin-bilirubin grade score predicts the survival of patients with hepatocellular carcinoma after liver resection.

PURPOSE: There is little information regarding the overall survival (OS) predictive ability of the combination of tumor burden score (TBS), α-fetoprotein (AFP), and albumin-bilirubin (ALBI) grade for patients with hepatocellular carcinoma (HCC). Here, we aimed to develop a model including TBS, AFP, and ALBI grade to predict HCC patient OS following liver resection. METHODS: Patients (N = 1556) from six centers were randomly divided 1:1 into training and validation sets. The X-Tile software was used to determine the optimal cutoff values. The time-dependent area under the receiver operating characteristic curve (AUROC) was calculated to assess the prognostic ability of the different models. RESULTS: In the training set, tumor differentiation, TBS, AFP, ALBI grade, and Barcelona Clinic Liver Cancer (BCLC) stage were independently related to OS. According to the coefficient values of TBS, AFP, and ALBI grade, we developed the TBS-AFP-ALBI (TAA) score using a simplified point system (0, 2 for low/high TBS, 0, 1 for low/high AFP and 0,1 for ALBI grade 1/2). Patients were further divided into low TAA (TAA ≤ 1), medium TAA (TAA = 2-3), and high TAA (TAA= 4) groups. TAA scores (low: referent; medium, HR = 1.994, 95% CI = 1.492-2.666; high, HR = 2.413, 95% CI = 1.630-3.573) were independently associated with patient survival in the validation set. The TAA scores showed higher AUROCs than BCLC stage for the prediction of 1-, 3-, and 5-year OS in both the training and validation sets. CONCLUSION: TAA is a simple score that has better OS prediction performance than the BCLC stage in predicting OS for HCC patients after liver resection.

The application and prospection of augmented reality in hepato-pancreato-biliary surgery.

Augmented Reality (AR) is one of the main forms of Extended Reality (XR) application in surgery. hepato-pancreato-biliary (HPB) surgeons could benefit from AR as an efficient tool for making surgical plans, providing intraoperative navigation, and enhancing surgical skills. The introduction of AR to HPB surgery is less than 30 years but brings profound influence. From the early days of projecting liver models on patients' surfaces for locating a better puncture point to today's assisting surgeons to perform live donor liver transplantation, a series of successful clinical practices have proved that AR can play a constructive role in HPB surgery and has great potential. Thus far, AR has been shown to increase efficiency and safety in surgical resection, and, at the same time, can improve oncological outcomes and reduce surgical risk. Although AR has presented admitted advantages in surgery, AR's application is still immature as an emerging technique and needs more exploration. In this paper, we reviewed the principles of AR and its developing history in HPB surgery, describing its significant practical applications over the past 30 years. Reviewing the past attempts of AR in HPB surgery could make HPB surgeons a better understanding of future surgery and the digital trends in medicine. The routine uses of AR in HPB surgery, as an indication of the operating room entering the new era, is coming soon.

TIDE: adjuvant tislelizumab plus donafenib combined with transarterial chemoembolization for high-risk hepatocellular carcinoma after surgery: protocol for a prospective, single-arm, phase II trial.

Background: The high recurrence rate of hepatocellular carcinoma (HCC) after surgery negatively affects the prognosis of patients. There is currently no widely accepted adjuvant therapy strategy for patients with HCC. A clinical study of effective adjuvant therapy is still needed. Methods: In this prospective, single-arm, phase II clinical trial, an adjuvant regimen of donafenib plus tislelizumab combined with transarterial chemoembolization (TACE) will be used to treat enrolled HCC patients after surgery. Briefly, patients newly diagnosed with HCC by pathological examination who underwent curative resection and had a single tumor more than 5 cm in diameter with microvascular invasion as detected by pathological examination are eligible. The primary endpoint of the study is the recurrence-free survival (RFS) rate at 3 years, and secondary endpoints are the overall survival (OS) rate and the incidence of adverse events (AEs). The planned sample size, 32 patients, was calculated to permit the accumulation of sufficient RFS events in 3 years to achieve 90% power for the RFS primary endpoint. Discussion: Vascular endothelial growth factor (VEGF) and programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathways regulate the relevant immunosuppressive mechanisms of HCC recurrence. Our trial will evaluate the clinical benefit of adding donafenib plus tislelizumab to TACE in patients with early-stage HCC and a high risk of recurrence. Clinical trial registration: www.chictr.org.cn, identifier ChiCTR2200063003.