Notable-HCC (NCT05185531) is a phase 1b trial, aiming to evaluate the safety and preliminary effectiveness of neoadjuvant PD-1 blockade plus stereotactic body radiotherapy (SBRT) in early-stage resectable hepatocellular carcinoma (HCC). Twenty patients with HCC of BCLC stage 0-A received 3 $$\times $$× Gy SBRT and two cycles of tislelizumab, an anti-PD-1 monoclonal antibody before the curative HCC resection. Primary endpoints were the surgery delay, radiographic and pathological tumor response after the neoadjuvant therapy, safety and tolerability. During the neoadjuvant therapy, treatment-related adverse events (TRAEs) of grade 1-2 occurred in all 20 patients (100%), eight patients (40%) had grade 3 TRAEs, no grade 4 to 5 TRAE occurred, and all resolved without corticosteroids treatment. Per mRECIST, the objective response rate was 63.2% (12/19), with 3 complete response; the disease control rate was 100%. Two (10.5%) patients achieved complete pathological response. No surgery delay occurred. The neoadjuvant therapy did not increase the surgical difficulty or the incidence of complications. Secondary endpoints of disease-free survival and overall survival were not mature at the time of the analysis. Our pilot trial shows that neoadjuvant therapy with anti-PD-1 + SBRT is safe and promotes tumor responses in early-stage resectable HCC.

Both nonalcoholic fatty liver disease (NAFLD) and colorectal cancer (CRC) are prevalent worldwide. The effects of concomitant NAFLD on the risk of colorectal liver metastasis (CRLM) and its mechanisms have not been definitively elucidated. We observed the effect of concomitant NAFLD on CRLM in the mouse model and explored the underlying mechanisms of specific myeloid-derived suppressor cells (MDSCs) recruitment and then tested the therapeutic application based on the mechanisms. Finally we validated our findings in the clinical samples. Here we prove that in different mouse models, NAFLD induces F4/80⁺ Kupffer cells to secret chemokine CXCL5 and then recruits CXCR2⁺ MDSCs to promote the growth of CRLM. CRLM with NAFLD background is refractory to the anti-PD-1 monoclonal antibody treatment, but when combined with Reparixin, an inhibitor of CXCR1/2, dual therapy cures the established CRLM in mice with NAFLD. Our clinical studies also indicate that fatty liver diseases increase the infiltration of CXCR2⁺ MDSCs, as well as the hazard of liver metastases in CRC patients. Collectively, our findings highlight the significance of selective CXCR2⁺/CD11b⁺/Gr-1⁺ subset myeloid cells in favoring the development of CRLM with NAFLD background and identify a pharmaceutical medicine that is already available for the clinical trials and potential treatment.

Helicobacter pylori (HP) infection is one of the most frequent bacterial infections in humans and is associated with the pathogenesis of gastric motility disorders such as delayed gastric emptying (DGE). Although HP infection is considered to delay gastric emptying, there has been little research on the underlying mechanism. Gastric motility involves interactions among gastrointestinal hormones, smooth muscle, enteric and extrinsic autonomic nerves and interstitial cells of Cajal (ICCs), and ICCs play an important role in gastrointestinal motility. Mutation or loss of stem cell factor (SCF) expression is known to reduce the number of ICCs or alter the integrity of the ICC network, contributing to gastrointestinal dysmotility. The aim of the present study was to investigate whether a reduction in ICCs contributes to the DGE caused by HP. A mouse model of HP infection was established and gastric emptying was compared between HP‑infected and uninfected mice using the bead method. In addition, ICC counts and SCF expression levels in gastric tissue were evaluated using immunohistochemistry and western blotting, respectively. The results revealed that gastric emptying was significantly slower, the number of ICCs in gastric tissue was significantly reduced and the protein level of SCF in gastric tissue was significantly decreased in HP‑infected mice compared with uninfected mice. Therefore, it may be concluded that HP reduced the number of ICCs by decreasing the expression of SCF protein in gastric tissue, thereby causing DGE.

The aim of this study was to evaluate the effect of chronic hepatitis B infection on the risk of synchronous colorectal liver metastasis (synCRLM). A total of 4033 consecutive patients with newly diagnosed colorectal cancer (CRC) with hepatitis B testing were enrolled. The prevalence of synCRLM was compared between hepatitis B surface antigen (HBsAg)–positive and –negative patients; significant predictors for synCRLM were analyzed by logistic regression analysis; Fibrosis-4 Index for Liver Fibrosis (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI), and hepatitis B e antigen (HBeAg) status were compared between patients with or without synCRLM. The prevalence of synCRLM was significantly higher in the HBsAg⁺ patients than that in the HBsAg^– patients (15.57% vs 8.60%; P < .001, χ² test). A logistic regression analysis indicated that HBsAg⁺ showed the highest hazard ratio (2.317 [95% confidence interval, 1.406–3.820]) for synCRLM. Both FIB-4 and APRI were significantly higher in those with HBsAg positivity but no synCRLM compared to those with HBsAg positivity and synCRLM (FIB-4: 1.23 [0.92–1.88] vs 1.09 [0.74–1.51], P = .045; APRI: 0.23 [0.227–0.387] vs 0.18 [0.171–0.309], P = .023, Mann-Whitney test; all shown as median [25th–75th percentile]); HBeAg positivity was detected in 26.32% of those with positive HBsAg and synCRLM compared to 18.45% of those with positive HBsAg but no synCRLM; the difference was not statistically significant. Concomitant chronic HBV infection significantly increases the risk of CRLM, and for HBsAg⁺ CRC patients, elevated FIB-4/APRI may be antimetastatic. Further study is needed to determine whether active HBV replication is prometastatic.