Does the presence of systemic artery-pulmonary circulation shunt during bronchial arterial embolization increase the recurrence of noncancer-related hemoptysis? A retrospective cohort study.

BACKGROUND: The presence of systemic artery-pulmonary circulation shunt (SPS) during the bronchial arterial embolization (BAE) procedure, has been inferred to be a potential risk factor for recurrence. The aim of this study is to reveal the impact of SPS on the recurrence of noncancer-related hemoptysis after BAE. METHODS: In this study, 134 patients with SPS (SPS-present group) and 192 patients without SPS (SPS-absent group) who underwent BAE for noncancer-related hemoptysis from January 2015 to December 2020 were compared. Four different Cox proportional hazards regression models were used to clarify the impact of SPSs on hemoptysis recurrence after BAE. RESULTS: During the median follow-up time of 39.8 months, recurrence occurred in 75 (23.0%) patients, including 51 (38.1%) in the SPS-present group and 24 (12.5%) in the SPS-absent group. The 1-month, 1-year, 2-year, 3-year and 5-year hemoptysis-free survival rates in the SPS-present and SPS-absent groups were 91.8%, 79.7%, 70.6%, 62.3%, and 52.6% and 97.9%, 94.7%, 89.0%, 87.1%, and 82.3%, respectively (P < 0.001). The adjusted hazard ratios of SPSs in the four models were 3.37 [95% confidence intervals (CI), 2.07-5.47, P < 0.001 in model 1], 1.96 (95% CI, 1.11-3.49, P = 0.021 in model 2), 2.29 (95% CI, 1.34-3.92, P = 0.002 in model 3), and 2.39 (95% CI, 1.44-3.97, P = 0.001 in model 4). CONCLUSIONS: The presence of SPS during BAE increases the recurrence probability of noncancer-related hemoptysis after BAE.

Transarterial chemoembolization combined with lenvatinib versus transarterial chemoembolization combined with sorafenib for unresectable hepatocellular carcinoma: A comparative retrospective study.

AIM: Tyrosine kinase inhibitors target transarterial chemoembolization (TACE)-mediated vascular endothelial growth factor to inhibit tumor revascularization and to slow tumor progression. The present study aimed to compare the clinical outcomes of TACE combined with lenvatinib (TACE-lenvatinib) and TACE combined with sorafenib (TACE-sorafenib) in patients with unresectable hepatocellular carcinoma (HCC). METHODS: The clinical data of patients diagnosed with unresectable HCC who received TACE-lenvatinib or TACE-sorafenib between January 2018 and April 2021 were retrospectively reviewed. The tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated and compared between the two groups. RESULTS: A total of 112 patients were enrolled and classified into the TACE-lenvatinib group (n = 53) and the TACE-sorafenib group (n = 59). The objective response rates of patients in the TACE-lenvatinib and TACE-sorafenib groups were 54.7% and 44.1%, respectively (p = 0.260), and the disease control rates (DCRs) were 81.1% and 61.0% (p = 0.020). The median PFS time was significantly longer in the TACE-lenvatinib group than in the TACE-sorafenib group (10.7 vs. 6.0 months; p = 0.002). The median OS time between the TACE-lenvatinib and TACE-sorafenib groups also showed a significant difference (30.5 vs. 20.5 months, p = 0.018). All treatment-related AEs and grade 3/4 AEs were comparable between the two groups (p > 0.05). CONCLUSION: Compared to TACE-sorafenib, TACE-lenvatinib was associated with better DCR, PFS and OS outcomes in patients with unresectable HCC. In subgroups of Barcelona Clinic Liver Cancer B stage or TACE-refractory patients, TACE-lenvatinib also showed a trend of superiority.

Bronchial artery embolization for the management of frequent hemoptysis caused by bronchiectasis.

BACKGROUND: To retrospectively evaluate the effectiveness of bronchial artery embolization (BAE) compared with conservative therapy for the treatment of frequent hemoptysis caused by bronchiectasis. METHODS: From January 2015 to December 2019, consecutive patients who were admitted due to frequent (more than three times per year) bronchiectasis-related hemoptysis were retrospectively reviewed. Those who were treated with either BAE (n = 69) or conservative therapy (n = 47) were enrolled for analysis. The technical success, clinical success, and complications of the BAE procedure were evaluated. Long-term hemoptysis-free survival rates and clinical success were compared between patients in the BAE group and patients in the conservative group. A Cox proportional hazard regression model was used to identify the predictors of recurrent hemoptysis. RESULTS: The technical success rate was 100% for the BAE procedure, and clinical success was achieved in 92.8% (64 of 69) of cases. No major procedure-related complications occurred, and minor complications were observed in 16 cases (23.2%). The 1-, 2-, and 3-year hemoptysis-free survival rates were 88.3, 71.3, and 66.2%, respectively, for the BAE group and 31.9, 17.6, and 2.5%, respectively, for the conservative treatment group (P <  0.001). Multivariate analysis showed that BAE was a protective factor against recurrent hemoptysis in treated patients. In addition, the presence of cystic bronchiectasis was the only independent risk factor for rebleeding in the whole population and in the BAE group. CONCLUSIONS: BAE may provide an effective option for patients with frequent bronchiectasis-related hemoptysis, especially for those without cystic bronchiectasis.

Ischemic Stroke Increased Gadolinium Deposition in the Brain and Aggravated Astrocyte Injury After Gadolinium-Based Contrast Agent Administration: Linear Versus Macrocyclic Agents.

BACKGROUND: Gadolinium (Gd)-based contrast agents (GBCAs) have been widely used in MRI. However, several studies have reported Gd deposition in the brain, which has raised concerns about safety. PURPOSE: To investigate the effects of ischemic stroke on Gd deposition in the brain after repeated administration of linear or macrocyclic GBCAs and to determine whether GBCAs aggravate astrocyte injury after stroke. STUDY TYPE: Animal study. ANIMAL MODEL: Twenty-seven male Sprague-Dawley rats were randomized to an exposure group (n = 24) and a healthy control group (n = 3). Half of the exposure group (n = 12) underwent transient middle cerebral artery occlusion (tMCAO) and half (n = 12) had a sham procedure. In each subgroup (tMCAO or sham), the rats had repeated gadopentetate (n = 6) or gadobutrol (n = 6) injections. Oxygen-glucose deprivation and reoxygenation (OGD/R) was used as an in vitro model of stroke. ASSESSMENT: On day 3 and day 28 after the last injection (p.i.), the Gd concentration in the cerebrum was quantified by inductively coupled plasma mass spectrometry. Cell viability, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were analyzed in vitro. STATISTICAL TESTS: One-way analysis of variance and two-sample t-tests were performed. RESULTS: The Gd concentration in the ipsilateral hemisphere homogenates of tMCAO group was significantly higher than that in the brain homogenates of the sham group on day 3 p.i. of either gadobutrol (0.065 ± 0.006 vs. 0.042 ± 0.007 µg/g, P < 0.05) or gadopentetate (0.093 ± 0.010 vs. 0.069 ± 0.008 µg/g, P < 0.05). Increased Gd deposition was also found in the ipsilateral hemisphere homogenates of the tMCAO group compared with the brain homogenates of the sham group on day 28 p.i. of gadopentetate (0.075 ± 0.012 vs. 0.044 ± 0.003 µg/g, P < 0.05), but not gadobutrol (0.012 ± 0.007 vs. 0.010 ± 0.001 µg/g, P = 0.80). The Gd concentration in the ipsilateral hemisphere in the tMCAO group was significantly higher for gadopentetate than gadobutrol on both day 3 p.i. (0.085 ± 0.006 vs. 0.049 ± 0.005 µg/g, P < 0.05) and day 28 p.i (0.075 ± 0.012 vs. 0.012 ± 0.007 µg/g, P < 0.05). Additionally, compared with gadobutrol, gadopentetate decreased viability, increased ROS accumulation, and decreased MMP in OGD/R-induced astrocytes (all P < 0.05). DATA CONCLUSION: Administration of GBCAs after an animal model of ischemic stroke increased Gd deposition in the brain and aggravated astrocyte injury. The effect of gadopentetate appeared to be more pronounced than that of gadobutrol.

Skeletal-muscle index predicts survival after percutaneous transhepatic biliary drainage for obstructive jaundice due to perihilar cholangiocarcinoma.

BACKGROUND: Sarcopenia is emerging as a prognostic factor in patients with malignant diseases. The prognostication of perihilar cholangiocarcinoma (PHC) with obstructive jaundice was complex, because these patients suffered compete mortality events beyond cancer itself. Our study was to investigate the association between low skeletal-muscle index and overall survival (OS) after percutaneous transhepatic biliary drainage (PTBD) for obstructive jaundice due to PHC. METHODS: We performed a retrospective survival analysis of patients undergoing PTBD for PHC-related obstructive jaundice between January 2016 and March 2019. Using computed tomography, we measured skeletal-muscle mass at the third lumbar vertebra (L3) to obtain a skeletal-muscle index (SMI). Then, we compared OS between low- and high-SMI groups. Furthermore, factors that could potentially affect OS were assessed. RESULTS: One hundred and four patients (56 males; mean age 66 ± 12 years) were analyzed. Median OS after PTBD was 150 days. OS was shorter in patients with low SMI than in those with high SMI (median OS, 120 vs. 270 days; P < 0.001). Multivariate analysis indicated that low SMI (hazard ratio [HR] 3.46; 95% confidence interval [CI] 1.14-5.60; P < 0.001), intrahepatic metastasis (HR 2.98; 95% CI 1.89-4.69; P < 0.001) and elevated carbohydrate antigen (CA) 19-9 level (HR 1.00; 95% CI 1.00-1.00; P = 0.04) were significantly associated with OS. CONCLUSION: Low SMI was a predictor of dismal OS after PTBD for patients with PHC-related obstructive jaundice.

Development of a model to predict recurrence after bronchial artery embolization for non-cancer related hemoptysis.

BACKGROUND: Relapse after effective bronchial arterial embolization (BAE) for controlling hemoptysis is not uncommon. Studies reported diverse predictors of recurrence. However, a model to assess the probability of recurrence in non-cancer related hemoptysis patients after BAE has not been reported. This study was to develop a model to predict recurrence after BAE for non-cancer related hemoptysis. METHODS: The study cohort included 487 patients who underwent BAE for non-cancer-related hemoptysis between January 2015 and December 2019. We derived the model's variables from univariate and multivariate Cox regression analyses. The model presented as a nomogram scaled by the proportional regression coefficient of each predictor. Model performance was assessed with respect to discrimination and calibration. RESULTS: One-month and 1-, 2-, 3- and 5-year recurrence-free rates were 94.5%, 88.0%, 81.4%, 76.2% and 73.8%, respectively. Risk factors for recurrence were underlying lung diseases and the presence of systemic arterial-pulmonary circulation shunts. This risk prediction model with two risk factors provided good discrimination (area under curve, 0.69; 95% confidence interval, 0.62-0.76), and lower prediction error (integrated Brier score, 0.143). CONCLUSION: The proposed model based on routinely available clinical and imaging features demonstrates good performance for predicting recurrence of non-cancer-related hemoptysis after BAE. The model may assist clinicians in identifying higher-risk patients to improve the long-term efficacy of BAE.

Hypoxic conditioned medium derived from bone marrow mesenchymal stromal cells protects against ischemic stroke in rats.

In recent years, studies have shown that the secretome of bone marrow mesenchymal stromal cells (BMSCs) contains many growth factors, cytokines, and antioxidants, which may provide novel approaches to treat ischemic diseases. Furthermore, the secretome may be modulated by hypoxic preconditioning. We hypothesized that conditioned medium (CM) derived from BMSCs plays a crucial role in reducing tissue damage and improving neurological recovery after ischemic stroke and that hypoxic preconditioning of BMSCs robustly improves these activities. Rats were subjected to ischemic stroke by middle cerebral artery occlusion and then intravenously administered hypoxic CM, normoxic CM, or Dulbecco modified Eagle medium (DMEM, control). Cytokine antibody arrays and label-free quantitative proteomics analysis were used to compare the differences between hypoxic CM and normoxic CM. Injection of normoxic CM significantly reduced the infarct area and improved neurological recovery after stroke compared with administering DMEM. These outcomes may be associated with the attenuation of apoptosis and promotion of angiogenesis. Hypoxic preconditioning significantly enhanced these therapeutic effects. Fourteen proteins were significantly increased in hypoxic CM compared with normoxic CM as measured by cytokine arrays. The label-free quantitative proteomics analysis revealed 163 proteins that were differentially expressed between the two groups, including 107 upregulated proteins and 56 downregulated proteins. Collectively, our results demonstrate that hypoxic CM protected brain tissue from ischemic injury and promoted functional recovery after stroke in rats and that hypoxic CM may be the basis of a potential therapy for stroke patients.

Retrospective comparison of different percutaneous approaches to manage occluded primary uncovered self-expandable metal stents in patients with unresectable malignant hilar biliary obstruction.

Purpose: To compare different percutaneous approaches to manage occluded primary uncovered self-expandable metal stents (SEMS) in patients with unresectable malignant hilar biliary obstruction (MHBO).Materials and Methods: A retrospective study was performed in patients with MHBO who underwent percutaneous management of occluded primary uncovered SEMS between January 2014 and January 2018. Patients were assigned into three groups based on the types of secondary stents, which included SEMS, internal-external drainage (IED), and external drainage (ED). Clinical success, requirement for reintervention, survival times, complications, and cost were evaluated.Results: A total of 58 patients were identified, with 21, 9, and 28 patients received SEMS, IED, and ED treatments, respectively. The overall clinical success rate was 67.2% (39/58), with no significant difference among three groups (p = .489). The median time to reintervention was 82, 57, and 61 days for the SEMS, IED, and ED groups, respectively (p = .045 for SEMS vs. IED; p = .011 for SEMS vs. ED). There was no significant difference in the median survival times among three groups (p = .308). Seven patients (12.7%) experienced minor complications including self-limiting haemobilia (n = 3) and catheter-related pain (n = 4). Fourteen patients (24.1%) had major complications, including early cholangitis (n = 8), pancreatitis (n = 3), stent dislodgement (n = 2), and bile leakage (n = 1). There was no statistical difference in the mean cost of the management of occluded primary SEMS between the three groups (p = .162).Conclusion: Uncovered SEMS could provide a longer duration to reintervention compared to the catheter drainages to manage occluded primary SEMS in patients with unresectable MHBO.

Effects of Diabetes Mellitus and Admission Glucose in Patients Receiving Mechanical Thrombectomy: A Systematic Review and Meta-analysis.

BACKGROUND: We performed a meta-analysis to evaluate the outcomes of acute ischemic stroke (AIS) in patients treated with mechanical thrombectomy (MT), according to diabetes mellitus and admission glucose level (AGL). METHODS: We systematically reviewed previous studies in PubMed that reported outcomes of MT in AIS patients and their relationships with diabetes mellitus or AGL. We used functional independence (modified Rankin score ≤ 2 at 3 months) as the primary end point. RESULTS: Data from 12,653 patients in 47 articles that evaluated the effect of diabetes mellitus or AGL on outcomes after MT were included. Compared with patients without a history of diabetes mellitus, patients with a diabetes mellitus history had significantly lower odds of functional independence in both the unadjusted meta-analysis (odds ratio [OR] 0.64; 95% confidence interval [CI] 0.54-0.75) and the multivariable analysis (OR 0.48; 95% CI 0.33-0.71). Similarly, higher AGL was associated with an unfavorable functional outcome in the unadjusted meta-analysis (pooled effect size - 0.38; 95% CI - 0.45 to - 0.31), and the adjusted OR (95% CI) per 1 mmol/L increase in AGL was 0.87 (0.83-0.92) for functional independence according to the combined multivariable results. Recanalization rate and symptomatic intracranial hemorrhage were neither related to AGL nor different in patients with or without diabetes mellitus. CONCLUSIONS: The present study confirms that a history of diabetes mellitus and high AGL are associated with unfavorable functional outcomes at 3 months after MT in AIS patients. However, the causal relationship between hyperglycemia and poor prognosis remains undetermined, and further investigations are required to ascertain whether AIS patients receiving MT could benefit from intensive glucose control.

Recovery of oculomotor nerve palsy after endovascular treatment of ruptured posterior communicating artery aneurysm.

PURPOSE: Oculomotor nerve palsy (ONP) may result from Posterior communicating artery (Pcom) aneurysms. Endovascular treatment of ruptured Pcom aneurysms generally is a safe procedure, but the effect of this therapy on ONP is incompletely elucidated. This retrospective study evaluates outcomes of ONP after endovascular treatment for ruptured Pcom aneurysm and with the intention to clarify predictors of recovery. METHODS: From May 2010 to October 2015, 210 patients with Pcom aneurysms underwent endovascular treatment at our institution. Among them, 34 patients with ruptured aneurysms and either complete or incomplete ONP were identified. The outcomes and predictors of ONP recovery were analyzed. RESULTS: At the last available clinical follow-up, ONP resolution was complete in 21 (61.8%) patients and incomplete in 8 (23.5%) patients. The mean resolution time after embolization was 24.5 days. Five patients showed no signs of ONP recovery. In no case was an initial incomplete ONP observed to worsen. There was a statistically insignificant trend toward complete recovery among patients with initial incomplete ONP (OR = 4.17; 95% CI, 0.75-23.18; P = 0.103). CONCLUSION: Endovascular treatment appears to be an effective treatment modality for ruptured Pcom aneurysm and related ONP. The initial incomplete ONP might encourage complete ONP recovery after endovascular treatment.

Chemoembolization of recurrent hepatoma after curative resection: prognostic factors.

OBJECTIVE: The long-term prognosis after hepatic resection for the treatment of hepatocellular carcinoma (HCC) has been disappointing because of the high recurrence rates in the remnant liver, which constitutes the major cause of death. The purpose of this study was to identify the prognostic factors for overall survival after transarterial chemoembolization (TACE) in recurrent HCC after the initial curative surgical resection. MATERIALS AND METHODS: From January 2003 through October 2012, 362 patients who developed recurrent HCC after initial surgical resection and underwent TACE as the first-line therapy were retrospectively studied at a single institution in our hospital. Patients who met our inclusion criteria were followed until December 2012. Prognostic factors for overall survival were analyzed. RESULTS: In total, 287 patients were enrolled. The median overall survival period was 747 days. The 1-, 2-, and 3-year overall survival rates after TACE were 72.9%, 51.8%, and 31.8%, respectively. Multivariate analysis indicated that the number of resected HCCs (≥ 2, p < 0.001), the number (≥ 2, p < 0.001) and size (> 5 cm, p = 0.022) of the recurrent HCCs, and the number of TACE sessions (≤ 3, p < 0.001) are independent risk factors for poor survival after TACE for recurrent HCC after HCC resection. CONCLUSION: TACE appears to be an effective treatment of patients who experienced a recurrence after curative HCC resection. An initial solitary HCC, a solitary recurrence, and recurrent tumor mass 5 cm or smaller are statistically significant independent prognostic factors for survival.

Minimally invasive salvage therapy for transplanted renal allografts.

PURPOSE: To evaluate the effectiveness of interventional therapy for complications of transplanted renal allografts. MATERIALS AND METHODS: Between January 2009 and March 2014, 14 patients underwent interventional therapy for complications of renal allografts. Complications included transplant renal artery stenosis (TRAS), TRAS combined with pseudoaneurysms, transplant renal venous kinking and ureteral obstruction (UO). Serum creatinine (S.Cr) levels were evaluated before and after procedure. The characteristics and procedure outcomes of these patients with vascular and nonvascular complications were also analyzed. RESULTS: All primary procedures were successfully performed, which included percutaneous transluminal angioplasty (PTA) for TRAS (n = 4), stenting and coil embolization for TRAS combined with pseudoaneurysms (n = 1), stenting for renal vein kinking (n = 2), and percutaneous nephrostomy (PCN) for UO (n = 7) and secondary antegrade stent placement in six UO patients after 1 week of PCN. No major procedure related complications occurred. S.Cr level subsequently improved from 6.0 ± 3.6 to 2.6 ± 2.1 mg/dL (p < 0.001), as well as patients' clinical features within 1 week after procedure. In our study, the onset time of vascular complications was earlier (<6 months) than nonvascular complications with significant difference (p < 0.001). During follow-up, the patient with TRAS and pseudoaneurysms suffered acute rejection 1 month after treatment and received transplant renal artery embolization. One patient with TRAS showed restenosis 4 months after procedure, and was retreated successfully with stenting. Thirteen cases reserved their transplanted renal allografts. CONCLUSION: Interventional therapy could be prior considered for transplanted renal allograft complications as its effectiveness and minimal invasiveness in saving the transplanted renal grafts.

Comparative study of the relative signal intensity on DWI, FLAIR, and T2 images in identifying the onset time of stroke in an embolic canine model.

In acute stroke magnetic resonance imaging, many attempts have been made to identify the onset time of ischemic events using the simply quantitative judgment of relative signal intensity (rSI) from various MR images. However, no uniform opinion has been achieved broadly till now. The controversy might derive from the potential patients' selection bias of clinical retrospective study, the discrepant MR parameters, and the various sample sizes among different studies. Thus, we evaluated the temporal change of the relative DWI signal intensity (rDWI), relative ADC value (rADC), relative FLAIR signal intensity (rFLAIR), and relative T2 signal intensity (rT2), and further compare their diagnostic value in identifying the hyperacute lesions based on our embolic canine model with clear onset time. Twenty ischemic models were successfully established. All rSI values were linearly correlated to time with significance until 24 h after model establishment (P < 0.05). Paired comparison of ROC curves showed that significant difference was found between rADC and other three rSIs (P < 0.0001). However, no significant difference was found among rDWI, rT2 and rFLAIR. Our results indicated that rDWI, rFLAIR and rT2 may be helpful to predict the onset time of ischemic events with the similar diagnostic value. However, the rADC does not have comparable predictive value in our embolic canine model.

Role of Transarterial Chemoembolization in the Era of Tyrosine Kinase Inhibitor and Immune Checkpoint Inhibitor Combination Therapy for Unresectable Hepatocellular Carcinoma: A Retrospective Propensity Score Matched Analysis.

RATIONALE AND OBJECTIVES: As an effective locoregional therapy, transarterial chemoembolization (TACE) can induce vascular endothelial growth factor and PD-1/PDL-1 upregulation, accompanied by a reduction in tumor burden. The present study aimed to compare the efficacy of TACE combined with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs) (TACE-TKI-ICIs) versus TKIs plus ICIs (TKI-ICIs) in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The clinical data of 198 patients diagnosed with unresectable HCC who received a TKI (lenvatinib or sorafenib) plus an ICI (sintilimab or camrelizumab) with or without TACE were retrospectively reviewed between October 2019 and April 2022. Baseline characteristics of the TACE-TKI-ICI group and the TKI-ICI group were matched by propensity score matching in a 1:1 ratio. The tumor response, progression-free survival (PFS), and overall survival (OS) were evaluated and compared between the two groups. RESULTS: After matching, 54 patients were enrolled in each group. The objective response rate (ORR) and disease control rate (DCR) were higher in the TACE-TKI-ICI group (ORR: 63.0% vs. 29.6%, P < 0.001; DCR: 85.2% vs. 53.7%, P < 0.001). The median PFS was significantly longer in the TACE-TKI-ICI group (9.9 vs. 5.8 months; P = 0.026). The median OS between the two groups also reached a significant difference (not reached vs. 18.5 months; P = 0.003). CONCLUSION: In this retrospective study, the results indicated that the addition of TACE to TKI-ICI therapy could contribute to better tumor control, PFS, and OS benefits in patients with unresectable HCC.

Efficacy of Atezolizumab Plus Bevacizumab Combined with Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Real-World Study.

Purpose: Transarterial chemoembolization (TACE), when used in combination with immunotherapy and antiangiogenic therapy, has been shown to have synergistic anticancer effects. The aim of this study was to further assess the efficacy and safety of TACE combined with atezolizumab and bevacizumab in the treatment of unresectable hepatocellular carcinoma (HCC) in the real world. Methods: Between August 2021 and September 2023, clinical information was collected from consecutive HCC patients who received treatment via TACE-Atezo/Bev at four tertiary institutions. This study evaluated the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) as outcomes. Predictors for OS and PFS were also analyzed. Treatment-related adverse events (TRAEs) were recorded and assessed. Results: Ninety-two patients were enrolled in this study, with a median follow-up duration of 14.1 months. The ORRs based on the modified Response Evaluation Criteria in Solid Tumors (RECIST) and RECIST 1.1 criteria were 54.3% and 41.3%, respectively. The median OS and PFS of the patients were 15.9 months [95% confidence interval (CI), 14.5-17.2 months] and 9.1 months (95% CI, 7.4-10.8 months), respectively. Multivariate analyses revealed that the Eastern Cooperative Oncology Group score and neutrophil‒lymphocyte ratio were independent risk factors for OS, whereas tumor size and extrahepatic metastasis were independent risk factors for PFS. Grade 3/4 TRAEs occurred in 16.3% (15/92) of the patients and were controlled conservatively. Conclusion: The combination of Atezo/Bev with TACE demonstrated acceptable synergistic therapeutic effects and manageable safety profiles in patients with unresectable HCC.

Transarterial chemoembolization combined with molecular targeted agents plus immune checkpoint inhibitors for unresectable hepatocellular carcinoma beyond the up-to-seven criteria: a propensity score-matching analysis.

PURPOSE: Not all patients benefit from transarterial chemoembolization (TACE) due to the heterogeneity of the tumour burden in intermediate-stage hepatocellular carcinoma (HCC). To compare the outcomes of transarterial chemoembolization (TACE) combined with molecular-targeted agents plus immune checkpoint inhibitors (TACE-MTAs-ICIs) with those of TACE for patients with unresectable hepatocellular carcinoma (uHCC) that were beyond the up-to-seven criteria. PATIENTS AND METHODS: Between January 2019 and July 2022, 130 patients diagnosed with uHCC beyond the up-to-seven criteria were retrospectively identified, including 47 patients who received TACE-MTAs-ICIs and 83 patients who received TACE alone. The primary endpoints were overall survival (OS) and progression-free survival (PFS); the secondary endpoints included tumour response and adverse events (AEs). RESULTS: There were 43 matched patients. The median OS and PFS times in the TACE-MTAs-ICIs group were significantly longer than those in the TACE group (OS: 27.2 vs. 15.9 months, p = 0.007; PFS: 15.4 months vs. 4.8 months, p < 0.001). The objective response rate (ORR) in the TACE-MTAs-ICIs group was higher than that in the TACE group (65.1% vs. 37.2%, p = 0.010). Reversible AEs (grade 3 or 4) occurred differently in TACE-MTAs-ICIs and TACE groups (83.7% vs. 51.2%, p = 0.001). Univariate and multivariate analyses revealed that TACE-MTAs-ICIs treatment was an independent favourable prognostic factor for both PFS and OS (p < 0.001). CONCLUSION: For uHCC patients beyond the up-to-seven criteria, TACE-MTAs-ICIs provided superior ORR and OS. Early combined TACE and systemic treatment should shift for patients who are beyond these criteria.

The ORR and median OS reached 65.1% and 27.2 months, respectively, in the treatment model of TACE-MTAs-ICIs for patients with unresectable HCC that were beyond the up-to-seven criteria.TACE-TKI-ICI yielded a synergistic effect on these patients and was an independent favourable prognostic factor for PFS and OS.

Efficacy and Safety of TACE Combined with a Tyrosine Kinase Inhibitor for the Treatment of TACE-Refractory Hepatocellular Carcinoma: A Retrospective Comparative Study.

PURPOSE: Combining angiogenesis inhibitors may enhance therapeutic efficacy synergistically after TACE refractoriness. The purpose of this study was to compare the outcomes of transarterial chemoembolization (TACE) plus a tyrosine kinase inhibitor (TACE-TKI) with TKI only for patients with TACE-refractory hepatocellular carcinoma (HCC). METHODS: From January 2019 to March 2022, 101 HCC patients confirmed with TACE-refractory were retrospectively reviewed in the study. Progression-free survival (PFS), overall survival (OS), tumor response, and adverse events (AEs) were evaluated between groups. RESULTS: Fifty-two patients undergoing TACE-TKI, while 32 patients receiving TKI alone were included. The objective response rate (ORR) was higher in the TACE-TKI group compared with the TKI group (55.8% vs. 25.0%, P = 0.006). The median PFS in the TACE-TKI group was significantly longer than that in the TKI group (7.6 months vs. 4.9 months, P = 0.018). The median OS was non reach to statistical longer than that in the TKI alone group (19.5 months vs. 17.7 months, P = 0.055). Subgroup analysis showed that TACE-TKI treatment resulted in a significantly longer median PFS and OS for Barcelona Clinic Liver Cancer (BCLC) stage B patients (PFS 11.8 months vs. 5.1 months, P = 0.017; OS 30.3 months vs. 19.4 months, P = 0.022). CONCLUSION: For patients with TACE-refractory HCC, TACE-TKI appeared to be superior to TKI monotherapy with regard to tumor control and PFS. Furthermore, for the BCLC stage B subgroup, TACE-TKI therapy was superior to TKI monotherapy in both OS and PFS.

Transarterial Chemoembolization Combined with Tyrosine Kinase Inhibitors Plus Immune Checkpoint Inhibitors Versus Tyrosine Kinase Inhibitors Plus Immune Checkpoint Inhibitors in Unresectable Hepatocellular Carcinoma with First- or Lower-Order Portal Vein Tumor Thrombosis.

PURPOSE: To compare the efficacy of transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs) (TACE-TKI-ICI) versus TKIs plus ICIs (TKI-ICI) for unresectable hepatocellular carcinoma (HCC) with first- or lower-order portal vein tumor thrombosis (PVTT). MATERIALS AND METHODS: A retrospective study was performed in HCC patients with first- or lower-order PVTT receiving TKIs (Lenvatinib or sorafenib) plus ICIs (camrelizumab, sintilimab, or atezolizumab) with or without TACE from four institutions between January 2019 and January 2022. Propensity score-based method was performed to minimize bias by confounding factors. Tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated and compared between the two groups. RESULTS: After inverse probability of treatment weighting, two balanced pseudopopulations were created: 106 patients in the TACE-TKI-ICI group and 109 patients in the TKI-ICI group. The objective response rate was higher in the TACE-TKI-ICI group (50.9% vs. 28.4%, P < 0.001). The median PFS and OS were significantly longer in the TACE-TKI-ICI group than in the TKI-ICI group (PFS: 9.1 vs. 5.0 months, P = 0.005; OS: 19.1 vs. 12.7 months, P = 0.002). In Cox regression, TACE-TKI-ICI treatment was an independent predictor of favorable OS. Treatment-related grade 3/4 AEs were comparable between the two groups (22.6% vs. 17.9%, P = 0.437). CONCLUSION: TACE-TKI-ICI therapy contributed to better tumor control, PFS and OS than TKI-ICI therapy in unresectable HCC patients with first- or lower-order PVTT.

An endovascular canine stroke model: middle cerebral artery occlusion with autologous clots followed by ipsilateral internal carotid artery blockade.

Stroke is one of the leading causes of death worldwide and the main reason for long-term disability. An appropriate animal model of stroke is urgently required for understanding the exact pathophysiological mechanism of stroke and testing any new therapeutic regimen. Our work aimed to establish a canine stroke model occluding the middle cerebral artery (MCA) and blocking the ipsilateral internal carotid artery (ICA), and to assess the infarct lesions by magnetic resonance imaging. The stroke model was generated by injecting two autologous clots into each MCA, followed by 2-h ipsilateral ICA blockade (ilICAB) using a catheter in 15 healthy adult beagles. Outcome measurements included 24-h and 7-day postocclusion T2-weighted imaging (T2WI)-based infarct volume calculation. In addition, pial collateral score, canine neurobehavioral score and histopathologic results were documented. Out of 15 dogs, 12 with successful MCA occlusion (MCAO) and ilICAB survived 7 days without complications or casualties and MCA were reperfused at 7 days after occlusion. High signal intensity in the basal ganglia and cerebral cortex on T2WI was initially observed in each dog at 6 h after the procedure. The mean percentage hemispherical infarct volume corrected for edema in all dogs on T2WI at 24 h after occlusion was 12.99±1.57%, and the degree of variability was 12.08%. The infarct volumes at 24 h after occlusion correlated with pial collateral scores and canine neurobehavioral scores well. This canine stroke model with combined MCAO and ilICAB reported here were proven to be highly feasible and reproducible.