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Background Futile recanalization affects more than half of acute ischemic stroke (AIS) patients. Neutrophil extracellular traps (NETs) are a major factor of microvascular hypoperfusion after stroke. Deoxyribonuclease I (DNase) targeting NETs exhibited a neuroprotective effect in young mice with AIS. This study explored a novel direct intra‐arterial administration of DNase therapy and its effect in aged mice with AIS. Method AIS was induced in aged C57BL/6 mice followed by reperfusion and immediate, intra‐arterial DNase administration via the internal carotid artery. Cerebral blood flow (CBF), neurological function, cerebral infarct volume, and NET markers were examined. Results Direct intra‐arterial DNase therapy significantly increased CBF, reduced neurological deficit scores, increased the latency to fall in the wire hang test, reduced cerebral infarct volume, and decreased neutrophil and NET count in both the parenchyma and micro vessels in aged mice with AIS compared with age‐matched vehicle controls. Conclusion Our data is the first to demonstrate that successful, direct intra‐arterial DNase therapy provides more efficient cerebral reperfusion and better outcomes after recanalization during the treatment of large vessel occlusion in aged mice. This study provides evidence for the potential clinical application of catheter‐delivered intra‐arterial DNase therapy post‐recanalization. We explored a novel direct intra‐arterial DNase therapy and its effect in aged mice with AIS. IA DNase therapy decreased neutrophil and NET burden in the penumbra in aged mice with AIS, provided more efficient cerebral reperfusion, and better functional outcomes after recanalization during the treatment of stroke.

To evaluate advantages of micellar nanoparticles encapsulating SN-38, a biologically active metabolite of irinotecan, in intraarterial therapy for pancreatic cancer. Rat pancreatic cancer cells (DSL-6A/C1) were implanted in Lewis rats under laparotomy. This study consists of two parts. Firstly, after confirming tumor formation by ultrasonography, celiac arteriography was performed, and tumor blood supply was visually evaluated by dye injection and CT during arteriography. Secondly, 18 rats were divided into two groups; the Micellar Nanoparticles group and the Irinotecan Infusion group. Micellar nanoparticles or irinotecan was injected via the celiac artery, and SN-38 and irinotecan concentrations in the tumor, duodenum and pancreatic parenchyma, were measured at 5 min, 6 h and 24 h. The maximum concentration (Cmax) of SN-38 were shown at 6 h in the Micellar Nanoparticles group, while Cmax of irinotecan was shown at 5 min in the Irinotecan Infusion group. Tumor concentration in the Micellar Nanoparticles group maintained elevated for 24 h without significant decrease (P = 0.068). Conversely, a significant decrease was observed in the regular pancreas parenchyma (P = 0.006) and duodenum (P = 0.028). In the Irinotecan Infusion group, tumor irinotecan concentration significantly decreased at 24 h (P = 0.016). Micellar nanoparticles may improve arterial infusion chemotherapy for pancreatic cancer. These nanoparticles have the potential to reduce SN-38 accumulation in duodenum, while increasing it in the tumor. Further research is warranted to validate and expand upon these findings.

PurposeIntrahepatic cholangiocarcinoma (ICC) has a poor prognosis, when unresectable; therefore, intra-arterial therapies (IAT) such as trans-arterial chemoembolization (TACE) and trans-arterial radioembolization (TARE) have been employed. With the present systematic review and meta-analysis, we aimed to analyse published studies to understand if one IAT can be superior to the alternative.Materials and methodsA systematic search of PubMed and Web of Science databases was performed for articles published until 1 March 2020 relevant to IAT for ICC. Overall survival was the primary end point. Occurrence of clinical adverse events and tumour overall response were secondary outcome measures.ResultsA total of 31 articles (of 793, n.1695 patients) were selected for data extraction, 13 were on TACE (906 patients) and 18 were on TARE (789 patients). Clinical and tumour characteristics showed moderate heterogeneity between the two groups. The median survival after TACE was 14.2 months while after TARE was 13.5 months (95%C.I.: 11.4–16.1). The survival difference was small (d = 0.112) at 1 year and negligible at 2 years (d = 0.028) and at 3 years (d = 0.049). The radiological objective response after TACE was 20.6% and after TARE was 19.3% (d = 0.032). Clinical adverse events occurred in 58.5% after TACE, more frequently than after TARE (43.0%, d = 0.314).ConclusionIn conclusion, IATs are promising treatments for improving outcomes for patients with unresectable ICC. To date, TACE and TARE provide similar good outcomes, except for adverse events. Therefore, the decision about techniques is determined by ability to utilize these resources and patient specific factors (liver function or lesion dimension).

Background Assessment of patient performance status is often subjective. Sarcopenia—measurement of muscle wasting—may be a more objective means to assess performance status and therefore mortality risk following intra-arterial therapy (IAT). Methods Total psoas area (TPA) was measured on cross-sectional imaging in 216 patients undergoing IAT of hepatic malignancies between 2002 and 2012. Sarcopenia was defined as TPA in the lowest sex-specific quartile. Impact of sarcopenia was assessed relative to other clinicopathological factors. Results Indications for IAT included hepatocellular carcinoma (51 %), intrahepatic cholangiocarcinoma (13 %), colorectal liver metastasis (7 %), or other metastatic disease (30 %). Median TPA among men (568 mm 2 /m 2 ) was greater than women (413 mm 2 /m 2 ). IAT involved conventional chemoembolization (54 %), drug-eluting beads (40 %), or yttrium-90 (6 %). Median tumor size was 5.8 cm; most patients had multiple lesions (74 %). Ninety-day mortality was 9.3 %; 3-year survival was 39 %. Factors associated with risk of death were tumor size (HR = 1.84) and Child's score (HR = 2.15) (all P  < 0.05). On multivariate analysis, sarcopenia remained independently associated with increased risk of death (lowest vs. highest TPA quartile, HR = 1.84; P  = 0.04). Sarcopenic patients had a 3-year survival of 28 vs. 44 % for non-sarcopenic patients. Conclusions Sarcopenia was an independent predictor of mortality following IAT with sarcopenic patients having a twofold increased risk of death. Sarcopenia is an objective measure of frailty that can help clinical decision-making regarding IAT for hepatic malignancies.

The liver is frequently the most common site of metastasis in patients with colorectal cancer, occurring in more than 50% of patients. While surgical resection remains the only potential curative option, it is only eligible in 15–20% of patients at presentation. In the past two decades, major advances in modern chemotherapy and personalized biological agents have improved overall survival in patients with unresectable liver metastasis. For patients with dominant liver metastatic disease or limited extrahepatic disease, liver-directed intra-arterial therapies such as hepatic arterial chemotherapy infusion, chemoembolization and radioembolization are treatment strategies which are increasingly being considered to improve local tumor response and to reduce systemic side effects. Currently, these therapies are mostly used in the salvage setting in patients with chemo-refractory disease. However, their use in the first-line setting in conjunction with systemic chemotherapy as well as to a lesser degree, in a neoadjuvant setting, for downstaging to resection have also been investigated. Furthermore, some clinicians have considered these therapies as a temporizing tool for local disease control in patients undergoing a chemotherapy ‘holiday’ or acting as a bridge in patients between different lines of systemic treatment. This review aims to provide an update on the current evidence regarding liver-directed intra-arterial treatment strategies and to discuss potential trends for the future.

Objective To develop and validate a risk scoring scale model (RSSM) for stratifying prognostic risk after intra-arterial therapies (IATs) for hepatocellular carcinoma (HCC). Methods Between February 2014 and October 2022, 2338 patients with HCC who underwent initial IATs were consecutively enrolled. These patients were divided into training datasets (TD, n  = 1700), internal validation datasets (ITD, n  = 428), and external validation datasets (ETD, n  = 200). Five-years death was used to predict outcome. Thirty-four clinical information were input and five supervised machine learning (ML) algorithms, including eXtreme Gradient Boosting (XGBoost), Categorical Gradient Boosting (CatBoost), Gradient Boosting Decision Tree (GBDT), Light Gradient Boosting Machine (LGBT), and Random Forest (RF), were compared using the areas under the receiver operating characteristic (AUC) with DeLong test. The variables with top important ML scores were used to build the RSSM by stepwise Cox regression. Results The CatBoost model achieved the best discrimination when 12 top variables were input, with the AUC of 0.851 (95% confidence intervals (CI), 0.833–0.868) for TD, 0.817 (95%CI, 0.759–0.857) for ITD, and 0.791 (95%CI, 0.748–0.834) for ETD. The RSSM was developed based on the immune checkpoint inhibitors (ICI) (hazard ratios (HR), 0.678; 95%CI 0.549, 0.837), tyrosine kinase inhibitors (TKI) (HR, 0.702; 95%CI 0.605, 0.814), local therapy (HR, 0.104; 95%CI 0.014, 0.747), response to the first IAT (HR, 4.221; 95%CI 2.229, 7.994), tumor size (HR, 1.054; 95%CI 1.038, 1.070), and BCLC grade (HR, 2.375; 95%CI 1.950, 2.894). Kaplan–Meier analysis confirmed the role of RSSM in risk stratification ( p  < 0.001). Conclusions The RSSM can stratify accurately prognostic risk for HCC patients received IAT. On the basis, an online calculator permits easy implementation of this model. Clinical relevance statement The risk scoring scale model could be easily implemented for physicians to stratify risk and predict prognosis quickly and accurately, thereby serving as a more favorable tool to strengthen individualized intra-arterial therapies and management in patients with unresectable hepatocellular carcinoma. Key Points • The Categorical Gradient Boosting (CatBoost) algorithm achieved the optimal and robust predictive ability (AUC, 0.851 (95%CI, 0.833–0.868) in training datasets, 0.817 (95%CI, 0.759–0.857) in internal validation datasets, and 0.791 (95%CI, 0.748–0.834) in external validation datasets) for prediction of 5-years death of hepatocellular carcinoma (HCC) after intra-arterial therapies (IATs) among five machine learning models. • We used the SHapley Additive exPlanations algorithms to explain the CatBoost model so as to resolve the black boxes of machine learning principles. • A simpler restricted variable, risk scoring scale model (RSSM), derived by stepwise Cox regression for risk stratification after intra-arterial therapies for hepatocellular carcinoma , provides the potential forewarning to adopt combination strategies for high-risk patients.

Background: Transcatheter arterial chemoembolisation (TACE) is the treatment of choice for intermediate stage hepatocellular carcinoma (HCC). Doxorubicin-loaded drug-eluting beads (DEB)-TACE is expected to improve the performance of conventional TACE (cTACE). The aim of this study was to compare DEB-TACE with cTACE in terms of time-to-tumour progression (TTP), adverse events (AEs), and 2-year survival. Methods: Patients were randomised one-to-one to undergo cTACE or DEB-TACE and followed-up for at least 2 years or until death. Transcatheter arterial chemoembolisation was repeated ‘on-demand’. Results: We enrolled 177 patients: 89 underwent DEB-TACE and 88 cTACE. The median number of procedures was 2 in each arm, and the in-hospital stay was 3 and 4 days, respectively ( P =0.323). No differences were found in local and overall tumour response. The median TTP was 9 months in both arms. The AE incidence and severity did not differ between the arms, except for post-procedural pain, more frequent and severe after cTACE ( P <0.001). The 1- and 2-year survival rates were 86.2% and 56.8% after DEB-TACE and 83.5% and 55.4% after cTACE ( P =0.949). Eastern Cooperative Oncology Group (ECOG), serum albumin, and tumour number independently predicted survival ( P <0.05). Conclusions: The DEB-TACE and the cTACE are equally effective and safe, with the only advantage of DEB-TACE being less post-procedural abdominal pain.

Advanced biliary cancer (ABC) is still regarded as an incurable condition. However, the improved depth and duration of response enabled by chemo-immunotherapy may foster intensified strategies, including surgical procedures, radiotherapy and intra-arterial techniques. The prevalence, clinical features and treatment outcomes of ABC receiving multimodality treatment in the immunotherapy era are unknown. Newly diagnosed ABC treated with chemo-immunotherapy and loco-regional procedures from February 2022 to December 2024 were retrospectively identified at 10 tertiary referral cancer centres in Italy. Categorical variables were compared using the chi-squared test, and the inverse probability of treatment weighting analysis was performed to reduce selection biases. Of 241 ABC receiving first-line treatment, 12 (4.9%) fulfilled the inclusion criteria. The median age was 69 (range 36-80), and 9 patients (75%) had intrahepatic cholangiocarcinoma (iCCA). Ten (83.3%) presented with de novo unresectable ABC: 3 (25%) had locally advanced, and 7 (50.3%) had metastatic disease. The median number of metastatic sites was one, with lymph nodes being the most commonly involved location (41.6%,  = 5). Patients treated with intensified therapy were more likely to have low tumour burden (  = 0.03) and iCCA (  = 0.06). Overall, four patients underwent surgery, three transarterial radioembolization, three stereotactic body radiotherapy and two liver transplants. As of data cut-off, 11 patients were alive (91.6%), and five patients were disease-free (41.6%). After adjusting for age, gender, Eastern Cooperative Group Performance Status (ECOG PS), primary site, disease status and number of metastases, the overall survival for the multimodality strategy versus systemic treatment alone was not reached versus 14.1 months (  < 0.001). This study, the first on multimodality treatment of ABC in the immunotherapy era, suggests that a highly selected subset of patients may achieve long-term disease control with an intensified approach. Oligometastatic patients and those affected by iCCA appear as the best candidates. Future studies are needed to confirm these preliminary findings.

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related deaths worldwide with rapidly growing incidence rates in the USA and Europe. Despite improving surveillance programs, most patients are diagnosed at intermediate to advanced stages and are no longer amenable to curative therapies, such as ablation, surgical resection and liver transplantation. For such patients, catheter-based image-guided embolotherapies such as transarterial chemoembolization (TACE) represent the standard of care and mainstay therapy, as recommended and endorsed by a variety of national guidelines and staging systems. The main benefit of these therapies is explained by the preferentially arterial blood supply of liver tumors, which allows to deliver the anticancer therapy directly to the tumor-feeding artery while sparing the healthy hepatic tissue mainly supplied by the portal vein. The tool box of an interventional oncologist contains several different variants of transarterial treatment modalities. Ever since the first TACE more than 30 years ago, these techniques have been progressively refined, both with respect to drug delivery materials and with respect to angiographic micro-catheter and image-guidance technology, thus substantially improving therapeutic outcomes of HCC. This review will summarize the fundamental principles, technical and clinical data on the application of different embolotherapies, such as bland transarterial embolization, Lipiodol-based conventional transarterial chemoembolization as well as TACE with drug-eluting beads (DEB-TACE). Clinical data on 90 Yttrium radioembolization as an emerging alternative, mostly applied for niche indications such as HCC with portal vein invasion, will be discussed. Furthermore, we will summarize the principle of HCC staging, patient allocation and response assessment in the setting of HCC embolotherapy. In addition, we will evaluate the role of cone-beam computed tomography as a novel intra-procedural image-guidance technology. Finally, this review will touch on new technical developments such as radiopaque, imageable DEBs and the rationale and role of combined systemic and locoregional therapies, mostly in combination with Sorafenib.

PurposeTo assess the value of quantitative analysis of tumor burden on baseline MRI for prediction of survival in patients with neuroendocrine tumor liver metastases (NELM) undergoing intra-arterial therapies. Materials and MethodsThis retrospective single-center analysis included 122 patients with NELM who received conventional (n = 74) or drug-eluting beads, (n = 20) chemoembolization and radioembolization (n = 28) from 2000 to 2014. Overall tumor diameter (1D) and area (2D) of up to 3 largest liver lesions were measured on baseline arterially contrast enhanced MR images. Three-dimensional quantitative analysis was performed using the qEASL tool (IntelliSpace Portal Version 8, Philips) to calculate enhancing tumor burden (the ratio between enhancing tumor volume and total liver volume). Based on Q-statistics, patients were stratified into low tumor burden (TB) or high TB.ResultsThe survival curves were significantly separated between low TB and high TB groups for 1D (p < 0.001), 2D (p < 0.001) and enhancing TB (p = 0.008) measurements, with, respectively, 2.7, 2.6 and 2.2 times longer median overall survival (MOS) in the low TB group (p < 0.001, p < 0.001 and p = 0.008). Multivariate analysis showed that 1D, 2D, and enhancing TB were independent prognostic factors for MOS, with respective hazard ratios of 0.4 (95%CI: 0.2–0.6, p < 0.001), 0.4 (95%CI: 0.3–0.7, p < 0.001) and 0.5 (95%CI: 0.3–0.8, p = 0.003).ConclusionThe overall tumor diameter, overall tumor area, and enhancing tumor burden are strong prognostic factors of overall survival in patients with neuroendocrine tumor liver metastases undergoing intra-arterial therapies.