AIM: To assess the efficacy of combined transcatheter arterial chemoembolization (TACE) and percutaneous microwave coagulation therapy (PMCT) for small hepatocellular carcinoma (HCC). METHODS: Thirty-five patients with a total of 41 HCC nodules (≤ 3 cm in diameter) were treated with TACE followed by computed tomograghy (CT)-guided percutaneous microwave coagulation therapy (PMCT) within 1-3 wk. RESULTS: By biopsies and enhanced CT scans, complete necrosis of the tumor and 3-5 mm of the surrounding non-cancerous area were observed in 34 foci. In seven foci, incomplete necrosis of the surrounding parenchyma was observed. Serum alpha-fetoprotein (AFP) levels returned to normal 10 d after treatment in 25 patients who originally had high serum AFP levels. The follow-up period was 6-31 mo, and all patients remained alive. One patient had a recurrence in the subsegments of the liver, and another patient had a recurrence near the original lesion. CONCLUSION: Combined therapy with TACE and PMCT is a safe and effective treatment without severe complications for small HCC.

Purpose: In recent years, immune checkpoint inhibitors have been used in combination with tyrosine kinase inhibitors and local therapies, creating a new era in treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, the benefits of this triple therapy remain unclear. Thus, this study evaluated whether the combination of transarterial chemoembolization (TACE), lenvatinib, and programmed death-1 (PD-1) inhibitors (triple therapy) was effective and safe for unresectable HCC with main trunk portal vein tumor thrombus (Vp4). Patients and Methods: This study enrolled patients receiving triple therapy at four institutions between August 2018 and April 2022. Patient characteristics and course of treatment were extracted from patient records. Tumors and tumor thrombus response were evaluated using an HCC-specific modified RECIST. Kaplan–Meier curve analysis demonstrated overall survival (OS) and progression-free survival (PFS). Adverse events (AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Results: Median follow-up duration was 18 (4.0– 26.3) months. Overall, 41 patients with HCC and Vp4 receiving first-line triple therapy were enrolled. The intrahepatic tumor objective response rate was 68.3%. The median OS was 21.7 (range, 2.8– 30.5) months, whereas the median PFS was 14.5 (range, 1.3– 27.6) months. Twelve patients received sequential resections. Resection was independently associated with favorable OS and PFS. Fever (31.7%), hypertension (26.8%), fatigue (24.4%), abnormal liver function (63.4%) and decreased appetite (21.9%) were the AEs frequently associated with treatment. No treatment-related mortality occurred. Conclusion: TACE plus lenvatinib and PD-1 inhibition was effective and tolerable for treating unresectable HCC with Vp4, with a high tumor response rate and favorable prognosis.

Background: The subsequent therapy for hepatocellular carcinoma (HCC) patients with refractory to transarterial chemoembolization (TACE) is still controversial. This study was performed to evaluate the efficacy and safety of combination therapy comprising hepatic artery infusion chemotherapy (HAIC), lenvatinib, and programmed death-1 inhibitors relative to HAIC combined with lenvatinib.Methods: In this single-center retrospective study, we analyzed data from HCC patients with refractory to TACE from June 2017 to July 2022. Primary study outcomes were overall survival (OS) and progression-free survival (PFS), while the secondary outcomes were the objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events.Results: We enrolled 149 patients finally, including 75 patients who received HAIC combined with lenvatinib plus PD-1 inhibitors therapy (HAIC+L+P group) and 74 patients who received HAIC combined with lenvatinib therapy (HAIC+L group). The median OS in the HAIC+L+P group (16.0; 95% CI: 13.6~18.3 months) was significantly higher compared to the HAIC+L group (9.0; 95% CI: 6.5~11.4 months) (p = 0.002), while the median PFS in the HAIC+L+P group (11.0; 95% CI: 8.6~13.3 months) was significantly higher compared to the HAIC+L group (6.0; 95% CI: 5.0~6.9 months) (p < 0.001). Significant between-group differences in DCR (p = 0.027) were found. Additionally, 48 pairs of patients were matched after propensity matching analysis. The survival prognosis between two groups before propensity matching is similar to that after propensity matching. Moreover, the percentage of patients with hypertension in the HAIC+L+P group was significantly higher compared to the HAIC+L group (28.00% vs. 13.51%; p = 0.029).Conclusions: A combination therapy of HAIC, lenvatinib, and programmed death-1 inhibitors significantly improved oncologic response and prolonged survival duration, showing a better survival prognosis for HCC patients with refractory toTACE.

This study aims to explore the mechanism by which KAL inhibits the proliferation and migration of cholangiocarcinoma (CCA) cells through the downregulation of miR-21, thereby modulating the PTEN/AKT signaling pathway. Cholangiocarcinoma cell lines HUCCT1 and RBE were cultured and transfected with KAL overexpression plasmids or miR-21 mimics. Transfection efficiency was validated by Western blot. Cell viability was assessed using the CCK8 assay, apoptosis levels were analyzed via flow cytometry, and cell invasion capability was evaluated through Transwell assays. PIP3 levels were measured using ELISA. Western blot was used to detect the expression levels of PTEN, AKT/mTOR signaling pathway proteins, and apoptosis-related proteins, including BCL-2 and Cleaved-Caspase3. Dual-luciferase reporter assays were performed to confirm the interaction between PTEN and miR-21-5p. Based on in vitro experimental results, HUCCT1 cells were selected for in vivo tumorigenicity experiments to assess the effects of KAL overexpression lentivirus on CCA tumor growth. Tumor size, volume, and weight were measured, and immunohistochemistry was used to detect the positive expression levels of KI67, PTEN, BCL-2, and Cleaved-Caspase3 in tumor tissues. PCR and Western blot analyses confirmed the effective transfection of KAL overexpression into HUCCT1 and RBE cells. Overexpression of KAL significantly inhibited CCA cell proliferation and invasion, reduced PIP3 production, suppressed the AKT/mTOR signaling pathway, and promoted apoptosis. PCR results demonstrated that miR-21 mimic transfection into HUCCT1 and RBE cells was successful. Overexpression of miR-21 reversed the inhibitory effects of KAL on CCA cell proliferation and migration, as well as the pro-apoptotic effects of KAL. Additionally, miR-21 suppressed the KAL-induced upregulation of PTEN and Cleaved-Caspase3 and promoted BCL-2 expression. Dual-luciferase reporter assays confirmed a targeted interaction between PTEN and miR-21-5p. In vivo tumorigenicity experiments showed that KAL overexpression significantly inhibited tumorigenesis in CCA cells. Tumor tissues from the KAL overexpression group exhibited significantly increased expression levels of Cleaved-Caspase3 and PTEN and decreased positive expression levels of KI67 and BCL-2, indicating suppressed proliferation and enhanced apoptosis in CCA cells. Overexpression of KAL inhibits CCA cell proliferation and promotes apoptosis. Overexpression of miR-21 reverses the effects of KAL on CCA cells, suggesting that KAL suppresses CCA growth through miR-21-mediated modulation of the PTEN/AKT signaling pathway.