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Tumor necrosis is a significant risk factor affecting patients' prognosis after liver resection (LR) for hepatocellular carcinoma (HCC). We aimed to develop a model with tumor necrosis as a variable to predict early tumor recurrence in HCC patients undergoing LR. Patients who underwent LR between 2010 and 2018 for newly diagnosed HCC but did not receive neoadjuvant therapy were enrolled in this retrospective study. Six predictive factors based on pathological features-tumor size > 5 cm, multiple tumors, high-grade tumor differentiation, tumor necrosis, microvascular invasion, and cirrhosis-were chosen a priori based on clinical relevance to construct a multivariate logistic regression model. The variables were always retained in the model. The impact of each variable on early tumor recurrence within one year of LR was estimated and visualized using a nomogram. The nomogram's performance was evaluated using calibration plots with bootstrapping. Early tumor recurrence was observed in 161 (21.3%) patients. The concordance index of the proposed nomogram was 0.722. The calibration plots showed good agreement between nomogram predictions and actual observations of early recurrence. We developed a nomogram incorporating tumor necrosis to predict early recurrence of HCC after LR. Its predictive accuracy is satisfactory.

Background The aim of this study is to investigate the real-world efficacy and safety of nivolumab in combination with chemotherapy for patients with advanced human epidermal growth factor receptor 2 (HER2)-negative gastric cancer (GC). Methods We enrolled patients diagnosed with unresectable advanced or metastatic GC who received nivolumab plus chemotherapy as first-line systemic treatment. The combined positive score (CPS), indicating the number of programmed cell death-ligand 1 (PD-L1)-stained cells, was utilized. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier method. Adverse events (AEs) were graded, and treatment was ceased upon disease progression or intolerance. Results A total of 27 patients were included in the study, comprising 15 patients with CPS ≥ 5 and 12 patients with CPS < 5. The objective response rate (ORR) was 55.6%, with a disease control rate (DCR) of 74.1%. Patients in the CPS ≥ 5 group exhibited higher ORR and DCR compared to those in the CPS < 5 group. Median PFS and OS were 6.1 months and 14.6 months, respectively; patients with CPS ≥ 5 showed a trend towards better PFS and OS than those with CPS < 5. Most AEs were grade 1–2, with a few instances of grade 3–4 toxicities reported, including neutropenia, thrombocytopenia, diarrhea, and anemia. There were no grade 5 AEs reported in our cohort. Furthermore, 64.7% of patients received subsequent anticancer treatment following disease progression on nivolumab plus chemotherapy. Conclusions The results of our study demonstrate the efficacy and safety of nivolumab plus chemotherapy in real-world practice support its adoption as a new standard first-line treatment for patients with advanced HER2-negative GC, particularly those with CPS ≥ 5.

Hepatocellular carcinoma (HCC) is a leading cause of cancer death globally, with the majority of cases detected at advanced stages when curative options are limited. Current systemic therapies, including immune checkpoint inhibitors, demonstrate limited efficacy with durable responses in only 15–20% of patients. This poor response is largely attributed to HCC’s immunosuppressive microenvironment, which blunts effective T-cell responses. By illustrating that innate immune cells can acquire memory-like characteristics through a process known as trained immunity, recent evidence has challenged the conventional belief that innate immunity is devoid of memory. This review investigates the potential of trained immunity, which is defined by the long-term functional reprogramming of innate immune cells through epigenetic, transcriptomic, and metabolic changes, to provide new therapeutic opportunities for HCC. We discuss mechanisms by which trained immunity can transform the HCC microenvironment, including enhanced inflammatory cytokine production, repolarization of tumor-associated macrophages toward anti-tumor phenotypes, increased immune cell infiltration, and improved bridging to adaptive immunity. We further evaluate emerging therapeutic strategies leveraging trained immunity principles, including BCG vaccination, β-glucan administration, cytokine-trained NK cell therapy, and innovative combination approaches. Finally, we address potential resistance mechanisms and future directions for clinical application. By integrating trained immunity into conventional immunotherapeutic regimens, we may significantly improve outcomes for HCC patients, potentially transforming advanced disease into a more manageable condition.

To determine the impact of microvascular invasion (MVI) on outcome in patients with solitary hepatocellular carcinoma (HCC) of ≤ 2 cm undergoing liver resection (LR). This retrospective study enrolled consecutive patients between 2007-2019 with newly diagnosed solitary HCC ≤ 2 cm who were undergoing LR at our institution. Overall survival (OS) and recurrent-free survival (RFS) were compared between patients with or without MVI. Of the 229 patients included in this study, 71 had MVI. The median follow-up period was 28.8 months (interquartile range: 13.5-70.1). Although the 90-day mortality rate was 0, 18 deaths occurred during the study, and the 5-year survival rate was 87.1%. Tumor recurrence occurred in 45 cases, and 5-year RFS was 71.9%. The presence or absence of MVI did not significantly affect the OS and RFS rates (log rank test, p = 0.10 and 0.38, respectively). In univariate and multivariate analysis, the presence of MVI was not associated with OS and RFS. The presence of MVI was not associated with OS and RFS in patients with solitary HCC ≤ 2 cm who underwent LR in this cohort.

Background Malnutrition is not uncommon among the elderly undergoing pancreatoduodenectomy (PD) and is related to increased complications. Previous studies have shown that the Geriatric Nutritional Risk Index (GNRI) predicts outcomes in various populations. Nevertheless, the research exploring the correlation between GNRI and postoperative outcomes in PD is scarce. This study aimed to investigate the preoperative malnutrition, as measured by GNRI, on outcomes in elderly patients undergoing PD. Materials and Methods This retrospective analysis enrolled 144 elderly patients underwent PD for periampullary tumors from November 2016 to December 2021. Patients were stratified based on the GNRI value: high/moderate nutrition risk (GNRI ≤ 92, N  = 54), low nutrition risk (92 < GNRI ≤ 98, N  = 35), and no nutrition risk (GNRI > 98, N  = 55). Perioperative outcomes and postoperative surgical complications were compared between these groups. Univariate and multivariate analyses were performed on major postoperative complications and prolonged postoperative length of stay (PLOS). Results Patients in the high/moderate risk group were significantly older, with lower BMI ( P  = 0.012), higher mortality rate (11.1%, P  = 0.024), longer PLOS ( P  < 0.001), and higher incidence of over grade IIIB complications (37.0%, P  = 0.001), Univariate and multivariate analyses showed the high/moderate risk GNRI group (OR 3.61, P  = 0.032), increased age (OR 1.11, P  = 0.014) and operative time over 8 h (OR 3.04, P  = 0.027) were significantly associated with increased major postoperative complications. The high/moderate risk GNRI group was also a significant predictor for prolonged PLOS (OR 3.91, P  = 0.002). Conclusions Preoperative GNRI has the potential to be a predictive tool for identifying high-risk elderly patients and monitoring nutritional status preoperatively to improve postoperative surgical outcomes following PD.

Metformin is proposed to have chemopreventive effect of various cancer currently. However, the anti-cancer effect of metformin for diabetic patients with hepatocellular carcinoma (HCC) undergoing liver resection remains unclear. The aim of our cohort study was to assess whether metformin influence the recurrence of HCC. We retrospectively enrolled 857 HCC patients who received primary resection from April 2001 to June 2016. 222 patients were diagnosed with diabetes mellitus (DM) from medical record. Factors influence the overall survival (OS) and recurrence-free survival (RFS) were analyzed by multivariate analysis. During the follow-up period (mean, 75 months), 471 (54.9%) patients experienced recurrence, and 158 (18.4%) patients died. Multivariate analysis revealed that DM (p = 0.015), elevated AST (p = 0.006), hypoalbuminemia (p = 0.003), tumor number (p = 0.001), tumor size (p < 0.001), vascular invasion (p <0.001), high Ishak fibrosis score (p <0.001), hepatitis B (p = 0.014), hepatitis C (p = 0.001) were independent predictors for RFS. In diabetic patients, only HbA1c>9% (p = 0.033), hypoalbuminemia (p = 0.030) and vascular invasion (p = 0.001) were independent risk factors for HCC recurrence; but the metformin use revealed no significance on recurrence. DM is a risk factor of HCC recurrence after resection. Adequate DM control can reduce the recurrence of HCC. However, the use of metformin does not reduce the risk of HCC recurrence in diabetic patient after initial resection. Hence, metformin may not have protective influences on HCC recurrence in diabetic patients who undergo initial liver resection.

To assess preoperative image tumor characteristics and alpha-fetoprotein (AFP) levels to predict early recurrence after liver resection (LR) for hepatocellular carcinoma (HCC). This retrospective study's enrolled patients underwent LR for newly diagnosed HCC between 2011 and 2018. Multivariate logistic regression analyses using the Akaike information criterion were adopted to construct a nomogram to predict early recurrence (i.e. recurrence within 1 year). The performance of this nomogram was evaluated using calibration plots with bootstrapping. Early recurrence was identified in 99 patients (11.2%). Four predictive factors, namely an AFP level of >400 ng/mL; image-diagnosed tumor characteristics, including a tumor size of > 5 cm; vascular invasion; and multiple tumors were adopted in the final model of the early recurrence nomogram, with a concordance index of 0.67. The calibration plots showed good agreement between the nomogram predictions and the actual observations of early recurrence. We have developed a simple nomogram with preoperative image tumor characteristics and AFP levels to predict the early recurrence of HCC after LR. 1.Early recurrence after liver resection (LR) for patients with hepatocellular carcinoma (HCC) carries a poor prognosis.2.We have developed a simple nomogram with preoperative image tumor characteristics and alpha-fetoprotein (AFP) levels to predict the early recurrence of HCC after LR.

Background Use of statins is associated with a reduced risk of hepatocellular carcinoma (HCC). However, the effect of statin use on HCC recurrence is unclear. This study aimed to evaluate the effect of statin use on recurrence after curative resection among patients with HCC. Methods We retrospectively assessed 820 patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A HCC who underwent primary resection between January 2001 and June 2016 at Kaohsiung Chang Gung Memorial Hospital. Exposure to statins was defined as use of a statin for at least 3 months before HCC recurrence. Factors that influenced overall survival (OS) and recurrence-free survival (RFS) were analyzed using Cox proportional hazards models. Results Of the 820 patients, 46 (5.6%) used statins (statin group) and 774 (94.4%) did not (non-statin group). During the mean follow-up of 76.5 months, 440 (53.7%) patients experienced recurrence and 146 (17.8%) patients died. The cumulative incidence of HCC recurrence was significantly lower in the statin group than the non-statin group ( p  = 0.001); OS was not significantly different between groups. In multivariate analysis, age (hazard ratio [HR]: 1.291; p  = 0.010), liver cirrhosis (HR: 1.743; p  < 0.001), diabetes (HR:1.418; p  = 0.001), number of tumors (HR: 1.750; p  < 0.001), tumor size (HR: 1.406; p  = 0.004) and vascular invasion (HR: 1.659; p  < 0.001) were independent risk factors for HCC recurrence, whereas statin use (HR: 0.354; p  < 0.001) and antiviral therapy (HR: 0.613; p  < 0.001) significantly reduced the risk of HCC recurrence. The statin group still had lower RFS than the non-statin group after one-to-four propensity score matching. Conclusion Statins may exert a chemo-preventive effect on HCC recurrence after curative resection.

We aimed to develop a preoperative model to predict overall survival (OS) in patients with hepatoma undergoing liver resection (LR). Patients who underwent LR for Barcelona Clinic Liver Cancer (BCLC) stage 0, A, or B hepatoma were enrolled. Tumor burden score (TBS) scores were determined using the following equation: TBS (Pinna et al., 2018) 2 = (largest tumor size [in cm])(Pinna et al., 2018) 2 ​+ ​(tumor number) (Pinna et al., 2018) 22. The cutoff values for radiographic TBS were based on our recently published paper: low, <2.6; medium, 2.6–7.9; high, >7.9. Multivariate analysis showed that radiographic TBS (low: referent; medium: HR ​= ​2.89; 95 ​% CI: 1.60–5.21; p ​< ​0.001; high, HR ​= ​7.60; 95 ​% CI: 3.80–15.2; p ​< ​0.001), AFP (<400 ​ng/mL: referent; ≧400 ​ng/mL: HR ​= ​1.67, 95 ​% CI: 1.11−2.52, p ​= ​0.014), and cirrhosis (absence: referent; presence: HR ​= ​1.88, 95 ​% CI: 1.30–2.72, p ​< ​0.001) were associated with OS. A simplified risk score was superior to BCLC system in concordance index (0.688 vs. 0.623). We have developed a preoperative model that performs better in predicting OS than the BCLC system. •Tumor size, number, AFP, and cirrhosis are prognostic factors in patients with hepatoma undergoing resection.•A simple model was developed based on these variables that performs better in predicting survival than BCLC system.

The albumin-bilirubin (ALBI) grade has been validated as a significant predictor for hepatocellular carcinoma (HCC). However, there is little information about the impact of postoperative ALBI grade in patients with HCC who are undergoing liver resection. We enrolled 525 HCC patients who received primary resection from April 2001 to March 2017. The impact of the pre- and post-operative ALBI grades on overall survival (OS) and recurrence-free survival (RFS) were analyzed by multivariate analysis. During the follow-up period (mean, 65 months), 253 (48.1%) patients experienced recurrence, and 85 (16.2%) patients died. Multivariate analysis revealed that diabetes mellitus (DM) ( p  = 0.011), alpha-fetoprotein levels (AFP) ( p  < 0.001), low platelet count ( p  = 0.008), liver cirrhosis ( p  < 0.001), and the first year of ALBI grade after resection ( p  < 0.001) were independent predictors for RFS. Additionally, old age ( p  = 0.006), DM ( p  = 0.002), AFP ( p  = 0.027), and ALBI grade at the first year after resection ( p  < 0.001) were independent risk factors for poor liver-related survival. Patients with post-operative ALBI grades II/III had older age (p = 0.019), hypoalbuminemia (p = 0.038), DM (p = 0.043), and high stages of pTNM (p = 0.021). The post-operative ALBI grade is better for predicting the outcomes in HCC patients after curative hepatectomy than the pre-operative ALBI grade.