Current trends in the acute treatment of ischemic stroke: analysis from the Paul Coverdell National Acute Stroke Program.

BACKGROUND: The intra-arterial treatment (IAT) of acute ischemic stroke (AIS) is now evidence-based and given the highest level of recommendation among eligible patients. Using a multi-state stroke registry, we studied the trend in IAT among patients with AIS over 11 years and its impact on the utilization of intravenous thrombolysis (IVT) within the same 11 years. METHODS: Using data from the Paul Coverdell National Acute Stroke Program (PCNASP), we studied trends in IVT and IAT for patients with AIS between 2008 and 2018. Trends over time were examined for rates of IVT only, IAT only, or a combination of IVT and IAT (IVT+IAT). Favorable outcome was defined as discharge to home. RESULTS: During the study period there were 595 677 patients (mean age 70.4 years, 50.4% women) from 646 participating hospitals with a clinical diagnosis of AIS in the PCNASP. Trends for IVT only, IAT only, and IVT+IAT all significantly increased over time (P<0.001). Total use of IVT and IAT increased from 7% in 2008 to 19.1% in 2018. The rate of patients discharged to home increased significantly over time among all treatment groups (P<0.001). CONCLUSION: In our large registry-based analysis, we observed a significant increase in the use of IAT for the treatment of AIS, with continued increases in the use of IVT. Concurrently, the percent of patients with favorable outcomes continued to increase.

Intra-arterial vasodilators for vasospasm following aneurysmal subarachnoid hemorrhage: a meta-analysis.

OBJECTIVE: The efficacy of intra-arterial vasodilators (IADs) for the treatment of vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) remains debatable. The objective of this meta-analysis was to pool estimates of angiographic and neurological response, clinical outcome, and mortality following treatment of vasospasm with IADs. METHODS: We searched PubMed, Embase, Scopus, Clinicaltrials.gov, Cochrane database, and CINAHL in December 2015 and August 2016. Studies reporting angiographic and neurological response, clinical outcome, and mortality following IAD treatment of vasospasm in 10 or more adults with aSAH were included. All established IADs were allowed. Two authors independently selected studies and abstracted the data. Mean weighted probabilities (MWP) were calculated using random effects model. RESULTS: Inclusion criteria were met by 55 studies (n=1571). MWP for immediate angiographic response to IAD treatment was 89% (95% CI 83% to 94%), post-IAD neurological improvement 57% (95% CI 49% to 65%), good outcome 66% (95% CI 60% to 71%), and mortality was 9% (95% CI 7% to 12%). After adjusting for publication bias, MWP for mortality was 5% (95% CI 4% to 7%). When transcranial Doppler (TCD) was used along with clinical deterioration for patient selection, rates of neurological response (64%) and good outcome (72%) were better. IADs were not superior to controls (balloon angioplasty or medical management). CONCLUSION: IAD treatment leads to a robust angiographic response and fair (but lower) rates of neurological response and good clinical outcome. Mortality was lower than the average reported in the literature. Rates of neurological response and good outcome were better when TCD was used for patient selection. Carefully designed studies are needed to compare IADs against medical management and balloon angioplasty.

Intra-Arterial Therapy and Post-Treatment Infarct Volumes: Insights From the ESCAPE Randomized Controlled Trial.

BACKGROUND AND PURPOSE: The goal of reperfusion therapy in acute ischemic stroke is to limit brain infarction. The objective of this study was to investigate whether the beneficial effect of endovascular treatment on functional outcome could be explained by a reduction in post-treatment infarct volume. METHODS: The Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial was a multicenter randomized open-label trial with blinded outcome evaluation. Among 315 enrolled subjects (endovascular treatment n=165; control n=150), 314 subject's infarct volumes at 24 to 48 hours on magnetic resonance imaging (n=254) or computed tomography (n=60) were measured. Post-treatment infarct volumes were compared by treatment assignment and recanalization/reperfusion status. Appropriate statistical models were used to assess relationship between baseline clinical and imaging variables, post-treatment infarct volume, and functional status at 90 days (modified Rankin Scale). RESULTS: Median post-treatment infarct volume in all subjects was 21 mL (interquartile range =65 mL), in the intervention arm, 15.5 mL (interquartile range =41.5 mL), and in the control arm, 33.5 mL (interquartile range =84 mL; P<0.01). Baseline National Institute of Health Stroke Scale (P<0.01), site of occlusion (P<0.01), baseline noncontrast computed tomographic scan Alberta Stroke Program Early CT score (ASPECTS) (P<0.01), and recanalization (P<0.01) were independently associated with post-treatment infarct volume, whereas age, sex, treatment type, intravenous alteplase, and time from onset to randomization were not (P>0.05). Post-treatment infarct volume (P<0.01) and delta National Institute of Health Stroke Scale (P<0.01) were independently associated with 90-day modified Rankin Scale, whereas laterality (left versus right) was not. CONCLUSIONS: These results support the primary results of the ESCAPE trial and show that the biological underpinning of the success of endovascular therapy is a reduction in infarct volume. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01778335.

Endovascular superselective treatment of brain tumors: a new endovascular era? A quick review.

BACKGROUND: Intra-arterial therapy for malignant brain tumors, especially high-grade gliomas, has been administered since the 1950s and 1960s when the structure of the blood-brain barrier was first described. However, only with the advent of modern techniques used by endovascular neurosurgeons has it been possible to proceed with the release of chemotherapeutic agents in an ultraselective mode by superselective intra-arterial cerebral infusion (SIACI). METHODS: A brief review was performed of all the published works from January 2000 to December 2013 in which the main issue was the superselective endovascular treatment of brain tumors with chemotherapy drugs. RESULTS: Intra-arterial non-selective therapy has been reported to be effective in chemosensitive tumors whereas the results in glioblastoma, at least in the pre-bevacizumab era, have been disappointing. CONCLUSIONS: If the SIACI method for delivering bevacizumab after disruption of the blood-brain barrier is proved to be safe and effective in larger phase II and III trials, this paradigm may significantly alter the way chemotherapies are delivered to patients with both diffusely infiltrating low-grade and those with high-grade malignant brainstem gliomas and open a new endovascular era.

Clinical significance of and future perspectives for hepatic arterial infusion chemotherapy in patients with liver metastases from colorectal cancer.

The most common site of metastases in patients with colorectal cancer is the liver. Hepatic resection is considered to be the treatment of choice for liver metastasis from colorectal cancer; however, hepatic resection can be performed in only 20 or 25% of all patients. Recurrence develops in the remnant liver or other organs after hepatic resection in over half of all patients with liver-only metastasis. Hepatic arterial infusion (HAI) chemotherapy can provide relatively high concentrations of drugs to microscopic or macroscopic metastases in the liver, with less toxicity than systemic administration. Meta-analyses have shown HAI chemotherapy to have a significantly higher response rate than systemic chemotherapy and its effect on extrahepatic metastases is negligible. HAI chemotherapy provides much better local control of liver metastases from colorectal cancer than systemic chemotherapy. However, well-controlled studies are needed to elucidate the optimal treatment strategies for neoadjuvant and postoperative adjuvant chemotherapy that optimally combine HAI chemotherapy, molecular targeted agents, and systemic chemotherapy such as FOLFOX or FOLFIRI.

Aumento asimétrico de la captación en las extremidades superiores de una gammagrafía ósea con 99mTc-MDP producida por inyección intra-arterial: diferentes patrones de captación en tres casos / Asymmetrically increased uptake in upper extremities on 99mTc-MDP bone scintigraphy caused by intra-arterial injection: Different uptake patterns in three cases

Hallazgos inesperados en la gammagrafía ósea, tales como la captación asimétrica en las extremidades, pueden causar confusión en el diagnóstico. Los autores describen tres casos de inyección intraarterial accidental de 99mTc-metilenedifosfonato (99mTc-MDP) en la región antecubital, discutiendo el origen de los hallazgos y su diagnóstico diferencial(AU)

Unexpected findings on bone scintigraphy such as asymmetrical uptake in extremities may cause confusion for the diagnosis. The authors describe three cases of accidental intraarterial injection of Tc-99m methylene diphosphonate (99mTc-MDP) on the antecubital region and discuss the findings and differential diagnosis(AU)

Intracarotid delivery of drugs: the potential and the pitfalls.

The major efforts to selectively deliver drugs to the brain in the past decade have relied on smart molecular techniques to penetrate the blood-brain barrier, whereas intraarterial drug delivery has drawn relatively little attention. Meanwhile, rapid progress has been made in the field of endovascular surgery. Modern endovascular procedures can permit highly targeted drug delivery by the intracarotid route. Intracarotid drug delivery can be the primary route of drug delivery or it could be used to facilitate the delivery of smart neuropharmaceuticals. There have been few attempts to systematically understand the kinetics of intracarotid drugs. Anecdotal data suggest that intracarotid drug delivery is effective in the treatment of cerebral vasospasm, thromboembolic strokes, and neoplasms. Neuroanesthesiologists are frequently involved in the care of such high-risk patients. Therefore, it is necessary to understand the applications of intracarotid drug delivery and the unusual kinetics of intracarotid drugs.

Intracarotid transplantation of bone marrow stromal cells increases axon-myelin remodeling after stroke.

The present study investigates the induction of axon and myelin remodeling as a possible mechanism by which treatment of stroke with bone marrow stromal cells improves neurological functional recovery. Adult male Wistar rats were subjected to 2 h of middle cerebral artery occlusion, followed by an injection of 2 x 10(6) rat bone marrow stromal cells or phosphate-buffered saline into the internal carotid artery 24 h later. Animals were killed at 28 days after stroke. Functional tests, histo- and immunohistochemical staining were performed. Significant functional recovery was found after bone marrow stromal cell administration in all the three tests performed (modified neurological severity score, adhesive-removal and corner tests). Bone marrow stromal cell treatment markedly increased vessel sprouting, synaptophysin expression and NG2 positive cell numbers and density in the cortical peri-infarct area. In bone marrow stromal cell-treated rats, the number of Ki-67 positive proliferating cells and oligodendrocyte precursor cells in the corpus callosum increased significantly in concert with the enhancement of the areas of the corpus callosum in both hemispheres. These results suggest that bone marrow stromal cells facilitate axonal sprouting and remyelination in the cortical ischemic boundary zone and corpus callosum, which may underlie neurological functional improvement caused by bone marrow stromal cell treatment.

[Intra-arterial chemotherapy in urological cancer].

We herein describe the present status of intra-arterial chemotherapy for patients with renal cell carcinoma and bladder cancer, and discuss the prospect of intra-arterial chemotherapy in these urological diseases. The combination of immunotherapy and intra-arterial chemoembolization with microcapsules may prolong the survival of patents with unresectable tumors. However, the role of intra-arterial chemotherapy in renal cell carcinoma is limited. For bladder cancer, several modifications to increase the effect of intra-arterial chemotherapy have been documented. The combination of intra-arterial chemotherapy and radiotherapy resulted in a complete response rate of 84-91%, supporting the possibility of bladder preservation for patients with invasive bladder cancer. To establish the effectiveness of intra-arterial chemotherapy, large scaled prospective randomized studies are necessary.

[Hepatic metastases of colorectal cancers: intra-arterial chemotherapy. Value and indications]. / Métastases hépatiques des cancers colorectaux: chimiothérapies intra-artérielles. Intérêt et indications.

Intraarterial hepatic chemotherapy (IAHC) increases the tumoral exposure of the liver metastases to cytotoxic agents. IAHC may be used in case of non resectable and isolated liver metastases from colorectal origin. It gives a tumor response rate of about 50%. Seven phase III trials and a recent metaanalysis testing IAHC using FUDR demonstrated its superiority over systemic chemotherapy using FUDR or bolus 5FU in terms of response rate and an increase in survival compared to symptomatic treatment. IAHC drawbacks are the biliary toxicity observed with some protocols, the development of extrahepatic metastasis and its cost. The ongoing protocols aim to improve the IAHC efficacy and tolerance and are frequently associated to systemic chemotherapy. The discovery of new active products in colorectal cancer and the optimisations of combinations of 5FU and leucovorin in terms of efficacy stimulate research aimed at developing more active combinations of IAHC and active systemic chemotherapy. The best IAHC indications are presently unresectable hepatic metastases from colorectal cancer without extra-hépatic metastases, with less than 50% liver involvement, with a CEA level under 100 ng/ml.

The surgeon and chemotherapy: twenty five years personal experience.

The realm of cancer chemotherapy is complex and often conflicting. The massive use of cytotoxic agents during the past 25 years has now reached a point where major decisions have to be made. The respective roles of regional techniques, systemic therapy for metastatic disease and adjuvant cytotoxic chemotherapy, all need the most careful re-appraisal. It is important that surgical opinion continues to be expressed and that surgeons continue to participate in the study and practice of cancer chemotherapy.