Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

Efficacy and safety of transarterial chemoembolization combined with lenvatinib, programmed death-1 inhibitor, and iodine-125 seed brachytherapy for hepatocellular carcinoma with portal vein tumor thrombosis.

BACKGROUND: Therapy for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) is still controversial. This study was performed to evaluate the efficacy and safety of the combination therapy comprising transarterial chemoembolization (TACE), lenvatinib (L), programmed death-1 inhibitor (P), and iodine-125 seed (I125) brachytherapy relative to TACE in combination with lenvatinib plus programmed death-1 inhibitor therapy and TACE plus lenvatinib therapy. METHODS: The data of HCC patients with PVTT from July 2017 to August 2022 were assessed in this single-center retrospective study. Primary study outcomes were progression-free survival (PFS) and overall survival (OS), while the secondary outcomes were disease control rate (DCR), objective response rate (ORR), and treatment-related adverse events. RESULTS: We enrolled 150 patients totally, including 50 patients treated with TACE plus lenvatinib therapy (TACE+L group), 45 patients treated with TACE in combination with lenvatinib plus programmed death-1 inhibitor therapy (TACE+L+P group), and 55 patients treated with the combination therapy of TACE along with I125 brachytherapy, lenvatinib, and programmed death-1 inhibitor therapy (TACE+L+P+I125 group). The median OS in the TACE+L+P+I125 group (21.0; 95% confidence interval [CI]: 18.4∼23.5 months) was significantly longer than that in the TACE+L group (10; 95% CI: 7.8∼12.1months) (p = 0.006), while it was insignificantly longer than that in the TACE+L+P group (14.0; 95% CI: 10.7∼17.2months) (p = 0.058). The median PFS in the TACE+L+P+I125 group (13.0; 95% CI: 10.2∼15.7 months) was significantly longer than that in the TACE+L group (5.0; 95% CI: 4.2∼5.7 months) (p = 0.014) and the TACE+L+P group (9.0; 95% CI: 6.7∼11.2 months) (p = 0.048). Statistically significant differences between groups were found in DCR (p = 0.015). There were no significant between-group differences in treatment-related adverse events (p > 0.05). CONCLUSIONS: A combination therapy of TACE, lenvatinib, programmed death-1 inhibitor, and I125 seed brachytherapy significantly improve OS, PFS, and DCR and show better survival prognosis for HCC patients accompanied by PVTT.

Real-world efficacy and safety of TACE plus camrelizumab and apatinib in patients with HCC (CHANCE2211): a propensity score matching study.

OBJECTIVES: This study aimed to investigate the efficacy and safety of transarterial chemoembolization (TACE) plus camrelizumab, a monoclonal antibody targeting programmed death-1, and apatinib for patients with intermediate and advanced hepatocellular carcinoma (HCC) in a real-world setting. METHODS: A total of 586 HCC patients treated with either TACE plus camrelizumab and apatinib (combination group, n = 107) or TACE monotherapy (monotherapy group, n = 479) were included retrospectively. Propensity score matching analysis was used to match patients. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety in the combination group were described in comparison to monotherapy. RESULTS: After propensity score matching (1:2), 84 patients in the combination group were matched to 147 patients in the monotherapy group. The median age was 57 years and 71/84 (84.5%) patients were male in the combination group, while the median age was 57 years with 127/147 (86.4%) male in the monotherapy group. The median OS, PFS, and ORR in the combination group were significantly higher than those in the monotherapy group (median OS, 24.1 vs. 15.7 months, p = 0.008; median PFS, 13.5 vs. 7.7 months, p = 0.003; ORR, 59.5% [50/84] vs. 37.4% [55/147], p = 0.002). On multivariable Cox regression, combination therapy was associated with significantly better OS (adjusted hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.26-0.64; p < 0.001) and PFS (adjusted HR, 0.52; 95% CI, 0.37-0.74; p < 0.001). Grade 3 or 4 adverse events occurred in 14/84 (16.7%) and 12/147 (8.2%) in the combination and monotherapy groups, respectively. CONCLUSIONS: TACE plus camrelizumab and apatinib showed significantly better OS, PFS, and ORR versus TACE monotherapy for predominantly advanced HCC. CLINICAL RELEVANCE STATEMENT: Compared with TACE monotherapy, TACE plus immunotherapy and molecular targeted therapy showed better clinical efficacy for predominantly advanced HCC patients, with a higher incidence of adverse events. KEY POINTS: • This propensity score-matched study demonstrates that TACE plus immunotherapy and molecular targeted therapy have a longer OS, PFS, and ORR compared with TACE monotherapy in HCC. • Grade 3 or 4 adverse events occurred in 14/84 (16.7%) patients treated with TACE plus immunotherapy and molecular targeted therapy compared with 12/147 (8.2%) patients in the monotherapy group, while no grade 5 adverse events were observed in all cohorts.

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001).

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

Effect and mechanism of pirfenidone combined with 2-methoxy-estradiol perfusion through portal vein on hepatic artery hypoxia-induced hepatic fibrosis.

PURPOSE: The aim of this study was to explore the effect and mechanism of pirfenidone (PFD) combined with 2-methoxyestradiol (2-ME2) perfusion through portal vein on hepatic artery hypoxia-induced hepatic fibrosis. MATERIALS AND METHODS: Sprague-Dawley rats were divided into 5 groups (n â€‹= â€‹3/group): control group, hepatic artery ligation (HAL) group, HAL â€‹+ â€‹PFD (portal vein perfusion of PFD) group, HAL+2-ME2 (portal vein perfusion of 2-ME2) group and HAL â€‹+ â€‹PFD+2-ME2 group depending on whether they received HAL and/or portal vein perfusion (PFD and/or 2-ME2). Livers were harvested for pathology, western blotting (WB), and quantitative real-time PCR (qRT-PCR). RESULTS: Sirius red staining showed that portal vein perfusion of drugs resulted in degradation of liver fibrosis. Immunohistochemistry showed decreased hypoxia-inducible factor-1 α (HIF-1α) and α-smooth muscle actin (α-SMA) after portal intravenous drugs infusion compared with HAL group (P â€‹< â€‹0.05). WB analysis showed increased Smad7 in HAL â€‹+ â€‹PFD group compared with HAL group (P â€‹< â€‹0.05). qRT-PCR analysis showed decreased matrix metallo-proteinase 2 (MMP2), transforming growth factor ß1 (TGF-ß1), monocyte chemoattractant protein-1 (MCP-1), and Collagen I mRNA in HAL â€‹+ â€‹PFD group except for tissue inhibitor of metalloproteinase-1 (TIMP-1) compared with HAL group (P â€‹< â€‹0.05). Compared with HAL â€‹+ â€‹PFD group, the addition of 2-ME2 did not lead to better results in qRT-PCR analysis. CONCLUSIONS: The portal vein perfusion of PFD significantly reduced the hepatic artery hypoxia-induced fibrosis degree in treated rats by down-regulating the expression of HIF-1α, α-SMA, MMP2, TGF-ß1, MCP-1, and Collagen I, as well as up-regulating the TIMP-1 expression and Smad7 protein level. Combined 2-ME2 infusion was not better than PFD alone.

Safety and efficacy of biliary stenting combined with iodine-125 seed strand followed by hepatic artery infusion chemotherapy plus lenvatinib with PD-1 inhibitor for the treatment of extrahepatic cholangiocarcinoma with malignant obstructive jaundice.

Objectives: To evaluate the efficacy and safety of biliary stenting implantation with iodine-125 seed strand (SI) followed by hepatic artery infusion chemotherapy (HAIC) plus lenvatinib (Len) with programmed death-1 (PD-1) inhibitor for patients diagnosed with extrahepatic cholangiocarcinoma (ECC) and malignant obstructive jaundice (MOJ). Methods: In this single-center retrospective study, the data of ECC patients with MOJ from March 2015 to January 2023 was assessed. Using probability score matching (PSM), the selection bias of patients was reduced. Primary study outcomes included overall survival (OS) and progression-free survival (PFS). The OS and PFS were performed using the Kaplan-Meier method and evaluated with the log-rank test. Results: A total of 104 patients were enrolled finally, including 52 patients treated with interventional therapy (SI+HAIC) plus Len with PD-1 inhibitor (SI+HAIC+Len+P group) and 52 patients treated with interventional therapy (SI+HAIC) plus lenvatinib (SI+HAIC+Len group). 26 pairs of patients were matched after PSM analysis. After PSM analysis, the median OS and PFS in the SI+HAIC+Len+P group were significantly longer compared to those in the SI+HAIC+Len group (OS:16.6 vs. 12.3 months, P = 0.001; PFS:12.6 vs 8.5 months, P = 0.004). The DCR was significantly different between groups (P = 0.039), while ORR not (P = 0.548). The addition of PD-1 inhibitor was generally well tolerated without treatment-associated mortality. Conclusion: Interventional therapy (SI+HAIC) plus Len with PD-1 inhibitor was effective for ECC patients accompanied by MOJ with a manageable safety profile.

Endovascular Repair of Spontaneous Iliac Vein Rupture.

Spontaneous iliac vein rupture is a relatively rare but fatal disease. Herein, 2 cases are reported. The two middle-aged and elderly females complaining of abdominal pain were admitted without any history of trauma. The computed tomography image both showed one huge hematoma in the lower abdominal cavity and the left external iliac venous thrombus. Venogram showed ruptures of the left external iliac vein and stenosis of the left common iliac vein after percutaneous mechanical thrombectomy. Stent grafts were implanted by endovascular technique. Favorable outcomes were achieved in both cases.

Application of Guglielmi detachable coils in embolization of iatrogenic renal hemorrhage.

BACKGROUND: This study aims to evaluate the application value of Guglielmi detachable coils (GDCs) in the embolization of iatrogenic renal hemorrhage. METHODS: Twelve iatrogenic renal hemorrhage patients who failed conservative treatment were randomly treated by superselective transcatheter arterial embolization (TAE) with GDCs, gelatin sponge, and microcoil embolization, respectively. The efficacy of treatment, damage to renal function, and renal infarct size were observed. RESULTS: Embolizations were successful in all patients on the first attempt. Hematuria disappeared completely after the surgery; no recurrence of hemorrhage and no abnormal renal function were observed during the follow-up period. Postoperative angiography revealed that patients treated with GDC embolization had minimum renal infarcts. CONCLUSIONS: In summary, while superselective TAE provides a safe and effective therapy in patients with iatrogenic renal hemorrhage, the application of GDCs can better prevent the loss of normal renal tissue after embolization.

Combined therapy with transcatheter arterial chemoembolization and percutaneous microwave coagulation for small hepatocellular carcinoma.

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.

Portal vein embolization induces compensatory hypertrophy of remnant liver.

AIM: To evaluate the effectiveness and safety of different portal vein branch embolization agents in inducing compensatory hypertrophy of the remnant liver and to offer a theoretic basis for clinical portal vein branch embolization. METHODS: Forty-one adult dogs were included in the experiment and divided into four groups. Five dogs served as a control group, 12 as a gelfoam group, 12 as a coil-gelfoam group and 12 as an absolute ethanol group. Left portal vein embolization was performed in each group. The results from the embolization in each group using different embolic agents were compared. The safety of portal vein embolization (PVE) was evaluated by liver function test, computed tomography (CT) and digital subtraction angiography (DSA) of liver and portal veins. Statistical test of variance was performed to analyze the results. RESULTS: Gelfoam used for PVE was inefficient in recanalization of portal vein branch 4 wk after the procedure. The liver volume in groups of coil-gelfoam and absolute ethanol increased 25.1% and 33.18%, respectively. There was no evidence of recanalization of embolized portal vein, hepatic dysfunction, and portal hypertension in coil-gelfoam group and absolute ethanol group. CONCLUSION: Portal vein branch embolization using absolute ethanol and coil-gelfoam could induce atrophy of the embolized lobes and compensatory hypertrophy of the remnant liver. Gelfoam is an inefficient agent.