Search

Background: Health-related quality of life measured with the EuroQol Group 5-Dimension Self-Report Questionnaire was one of the secondary outcomes in the Multicenter Randomized Clinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN).We reported no statistically significant difference in EuroQol Group 5-Dimension Self-Report Questionnaire score between the intervention and control groups, but deaths were not included. Aims: Reanalyze the effect of intra-arterial treatment for large vessel occlusion in acute ischemic stroke patients on health-related quality of life in more detail. We now include patients who died during follow-up. Methods: The EuroQol Group 5-Dimension Self-Report Questionnaire questionnaires were obtained 90 days after treatment. We used the Dutch tariff to derive a utility index from the EuroQol Group 5-Dimension Self-Report Questionnaire score. Treatment effect was estimated with the Mann-Whitney U test and linear regression. The effect of treatment on the distribution of EuroQol Group 5-Dimension Self-Report Questionnaire dimension scores was assessed with ordinal logistic regression. Results: We obtained EuroQol Group 5-Dimension Self-Report Questionnaire scores from 457 (91.7%) of the 500 patients, including 108 who died before follow-up. Median EuroQol Group 5-Dimension Self-Report Questionnaire score in the intervention group was 0.57, and 0.39 in the control group (p=0.03). Treatment effect estimated with linear regression was 0.07 (95%CI: -0.001 to 0.143). Treatment specifically affected EuroQol Group 5-Dimension Self- Report Questionnaire dimensions "mobility" (OR: 0.43, 95%CI: 0.29-0.66), "self-care" (OR: 0.60, 95%CI: 0.41-0.89), and "usual activities" (OR: 0.53, 95%CI: 0.36-0.79). Conclusion: Treatment had a limited effect on quality of life, as measured with the EuroQol Group 5-Dimension Self-Report Questionnaire. Nevertheless, patients with acute ischemic stroke caused by an intracranial occlusion in the anterior circulation, who had intra-arterial treatment, experience better health-related quality of life than patients without intra-arterial treatment. Trial Registration: URL: http://www.isrctn.com/ISRCTN10888758 Unique identifier: ISRCTN10888758 [ABSTRACT FROM AUTHOR]

Background: The most frequent pattern of recurrence is remnant liver after hepatectomy for gastric cancer liver metastases (GLM). The evidence of adjuvant hepatic artery infusion chemotherapy (HAIC) after hepatectomy for GLM is lacking. The aim of this study was to evaluate the efficacy of adjuvant HAIC after hemihepatectomy for GLM.Methods: Between 2001 and 2012, 14 patients who underwent hemihepatectomy for GLM were included in this study. Adjuvant HAIC to the remnant hemiliver was the FEM regimen (333 mg/m2 5-fluorouracil each week, 30 mg/m2 epirubicin once every 4 weeks, and 2.7 mg/m2 mitomycin-C once every 2 weeks) and was administered for 6 months after hemihepatectomy. Clinicopathological prognostic factors for survival were analyzed using a prospectively collected database.Results: Nine patients had solitary GLM, and 5 patients had multiple GLM before surgery. The median period from hemihepatectomy to HAIC was 30 days. The 6-month HAIC completion rate was 79% (n = 11/14). Reasons of HAIC failure included liver dysfunction (n = 1), catheter infection (n = 1), and development of multiple recurrence (n = 1). The median follow-up was 29 (range 8-166) months. Recurrences were detected in 8 patients (57%). The site of recurrences included lung (n = 1), lymph nodes (n = 1), peritoneal dissemination (n = 1), brain (n = 1), pleural (n = 1), and multiple sites (n = 3). The overall 5-year survival rate was 43%. The pathological T4 classification and the preoperative CEA ≥5 ng/mL were significant prognostic factors for overall survival.Conclusions: Adjuvant HAIC after hemihepatectomy for GLM prevents remnant liver recurrence and may contribute to long-term survival. [ABSTRACT FROM AUTHOR]

Background: The hepatic artery infusion (HAI) of irinotecan, oxaliplatin and 5-fluorouracil with intravenous cetuximab achieved outstanding efficacy in previously treated patients with initially unresectable liver metastases from colorectal cancer. This planned study aimed at the identification of pharmacogenetic predictors of outcomes.Methods: Circulating mononuclear cells were analysed for 207 single-nucleotide polymorphisms (SNPs) from 34 pharmacology genes. Single-nucleotide polymorphisms passing stringent Hardy-Weinberg equilibrium test were tested for their association with outcomes in 52 patients (male/female, 36/16; WHO PS, 0-1).Results: VKORC1 SNPs (rs9923231 and rs9934438) were associated with early and objective responses, and survival. For rs9923231, T/T achieved more early responses than C/T (50% vs 5%, P=0.029) and greatest 4-year survival (46% vs 0%, P=0.006). N-acetyltransferase-2 (rs1041983 and rs1801280) were associated with up to seven-fold more macroscopically complete hepatectomies. Progression-free survival was largest in ABCB1 rs1045642 T/T (P=0.026) and rs2032582 T/T (P=0.035). Associations were found between toxicities and gene variants (P<0.05), including neutropenia with ABCB1 (rs1045642) and SLC0B3 (rs4149117 and rs7311358); and diarrhoea with CYP2C9 (rs1057910), CYP2C19 (rs3758581), UGT1A6 (rs4124874) and SLC22A1 (rs72552763).Conclusion: VKORC1, NAT2 and ABCB1 variants predicted for HAI efficacy. Pharmacogenetics could guide the personalisation of liver-targeted medico-surgical therapies. [ABSTRACT FROM AUTHOR]

Purpose Intra-arterial chemotherapy ( IAC) has become an essential technique for the treatment of advanced and relapsed intra-ocular retinoblastoma. The outcome of IAC for retinoblastoma is influenced by a variety of medical and non-medical factors. In this study, we aimed to examine the outcome of IAC and determine the factors influencing clinical outcome. Methods A total of 107 eyes of 73 patients with retinoblastoma undergoing IAC between January 2011 and April 2013 were retrospectively reviewed for clinical outcomes. The factors influencing clinical outcomes were determined using univariate and multivariate analyses. Results After IAC, an overall globe salvage rate of 78.5% was observed during follow-up periods. Specifically, globe salvage was achieved in Group B (100%), Group C (100%), Group D (78.6%), and Group E (62%). Short-term ocular adverse events included eyelid oedema (14%), bulbar conjunctiva congestion (29.9%) and excessive tearing (9.3%). Long-term complications included vitreous haemorrhage (8.4%), subretinal haemorrhage (9.3%), retinal vasculopathy (7.5%) and ophthalmic artery spasm with reperfusion (4.7%). Univariate and multivariate analyses showed that the globe salvage of IAC was significantly associated with tumour staging and previous treatment (p < 0.05, respectively). Conclusion Intra-arterial chemotherapy (IAC) is safe and effective for the management of retinoblastoma. Patients with advanced retinoblastoma and previous failed treatment may have a poor outcome after IAC. [ABSTRACT FROM AUTHOR]

Background: The choice of anaesthetic techniques is important for the outcome of traumatic brain injury (TBI) emergency surgery. The objective of this study was to compare patient outcomes for target-controlled infusion (TCI) of propofol and sevoflurane anaesthesia. Methods: A total of 110 severe TBI patients, aged 18-60, who underwent emergency brain surgery were randomised into Group T (TCI) (n = 55) and Group S (sevoflurane) (n = 55). Anaesthesia was maintained in Group T with propofol target plasma concentration of 3-6 µg/mL and in Group S with minimum alveolar concentration (MAC) of sevoflurane 1.0-1.5. Both groups received TCI remifentanil 2-8 ng/mL for analgesia. After the surgery, patients were managed in the intensive care unit and were followed up until discharge for the outcome parameters. Results: Demographic characteristics were comparable in both groups. Differences in Glasgow Outcome Scale (GOS) score at discharge were not significant between Group T and Group S (P = 0.25): the percentages of mortality (GOS 1) [27.3% versus 16.4%], vegetative and severe disability (GOS 2-3) [29.1% versus 41.8%] and good outcome (GOS 4-5) [43.6% versus 41.8%] were comparable in both groups. There were no significant differences in other outcome parameters. Conclusion: TCI propofol and sevoflurane anaesthesia were comparable in the outcomes of TBI patients after emergency surgery. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to describe a novel system for treating advanced head and neck cancer consisting of an external carotid arterial sheath (ECAS) and a microcatheter to inject drugs retrogradely into multiple feeding arteries through the superficial temporal artery (STA).Materials and Methods: Four consecutive patients with head and neck cancer that had more than one feeding artery were enrolled in this study. The ECAS was made of polyurethane and surface-coated with heparin resin to prevent thrombus formation, allowing it to remain in place for a prolonged period of time. The ECAS was inserted through the STA, and its tip was placed between the maxillary artery and facial artery. The tumor-feeding arteries were selected using a hooked-shaped microcatheter through the ECAS.Results: A total of 13 target arteries were selected in the four patients. The microcatheter inserted via the ECAS was used to catheterize ten arteries (five lingual arteries and five facial arteries). The remaining three lingual arteries were directly selected by the catheter without ECAS. All of the target arteries were able to be catheterized superselectively. The technical success rate was 100%. Vascular occlusion, which might have been caused by the ECAS, was observed in one patient. No neurologic toxicities occurred.Conclusion: This ECAS system is a new approach for retrograde superselective intra-arterial chemotherapy that covers the entire tumor with anticancer drugs. It has the potential to increase the effectiveness of therapy for advanced head and neck cancer.Level Of Evidence: Level 4, Case Series. [ABSTRACT FROM AUTHOR]

Objective The safety and efficacy of intra-arterial treatment (IAT) in patients with acute ischemic stroke (AIS) due to cervical artery dissection (CeAD) has not been formally studied. The purpose of this study was twofold: first, describe a large series with CeAD treated with IAT; second, analyze outcomes with CeAD receiving IAT versus (a) CeAD not treated with IAT, (b) CeAD receiving intravenous thrombolysis (IVT) alone, and (c) non-CeAD mechanism of AIS receiving IAT. Design Demographics, clinical characteristics, treatment, and outcomes were summarized for all CeAD patients treated with IAT from January 2010 to May 2015. Outcomes included favorable 90 day modified Rankin Scale (mRS) score of 0-2, symptomatic intracerebral hemorrhage (sICH), recanalization (Thrombolysis in Cerebral Infarction 2b-3), procedural complications, and mortality. Outcomes were analyzed with X2 tests and multivariate logistic regression. Results There were 161 patients with CeAD: 24 were treated with IAT and comprised our target population. Dissections were more common in the internal carotid (n=18) than in the vertebral arteries (n=6). All but one patient had intracranial embolus. IAT techniques included thrombectomy (n=19), IA thrombolysis (n=17), stent (n=14), and angioplasty (n=7). Outcomes included favorable 90 day mRS score of 0-2 in 63%, 4 deaths, 1 sICH, and 3 procedural complications. After adjustment, favorable mRS in our target population was similar to comparison populations: (a) in CeAD, IAT versus no IAT (OR 0.62, p=0.56); (b) In CeAD, IAT versus IVT alone (OR 1.32, p=0.79); and (c) IAT in CeAD versus non-CeAD mechanism of AIS (OR 0.58, p=0.34). Conclusions IAT is a valid alternative therapeutic option for AIS caused by CeAD due to the low complication rate and excellent outcomes observed in this study. [ABSTRACT FROM AUTHOR]

Background: Intra-arterial chemotherapy (IAC) for oral cancer can deliver a higher concentration of anticancer agent into a tumor-feeding artery than intravenous systemic chemotherapy. However, distribution of anticancer agent into several branches of the external carotid artery (ECA) in IAC has not demonstrated sufficient treatment efficacy. To improve the effectiveness of IAC, the flow distribution of anticancer agent into the branches of the ECA in several IAC methods was investigated using computational fluid dynamics (CFD).Methods: Patient-specific three-dimensional vessel models were created from CT images of 2 patients with tongue cancer. Catheter models were combined with the vessel models. Thirty-two models were generated with varying vertical and horizontal positions of the catheter tip. With the use of a zero-dimensional resistance model of the peripheral vessel network, conventional IAC and superselective IAC were simulated in 30 and 2 models, respectively. The flow distribution of anticancer agent into the branches of the ECA was investigated in 32 models. Additionally, the blood streamline was traced from the inlet of the common carotid artery toward each outlet to examine the flow of anticancer agent in all models, and the wall shear stress of the vessel was calculated for some models.Results: The CFD simulations could be conducted within a reasonable computational time. In several models, the anticancer agent flowed into the target artery only when the catheter tip was located below the bifurcation of the ECA and each target artery. Furthermore, the anticancer agent tended to flow into the target artery when the catheter tip was shifted toward the target artery. In all ECA branches that had flow of anticancer agent, the blood streamlines to the target arteries contacted the catheter tip. Anticancer agent flowed into only the target artery in patients' models for superselective IAC. However, high wall shear stress was observed at the target artery in one patient's model.Conclusions: This CFD study showed that location of the catheter tip was important in controlling the anticancer agent in conventional IAC. The distribution rate of anticancer agent into the tumor-feeding artery tended to increase when the catheter tip was placed below and toward the target artery. Although superselective IAC can reliably supply anticancer agent to the target artery, high wall shear stress at the target artery can occur, depending on vessel geometry of the patient, which may cause serious complications during the treatment. [ABSTRACT FROM AUTHOR]

Background: Based on promising results from a Phase I study of hepatic arterial infusion chemotherapy using a combination of miriplatin and cisplatin powder (DDP-H) for unresectable hepatocellular carcinoma (UMIN-CTR000003541), a multicenter, open-label, randomized phase II study was conducted to evaluate the efficacy and safety of the combination therapy versus miriplatin monotherapy.Methods: Nineteen patients, five and fourteen Barcelona-Clinic Liver Cancer staging classification A and B cases, respectively, were randomly assigned to receive either miriplatin monotherapy (n = 9) or miriplatin/DDP-H combination therapy (n = 10). DDP-H and/or miriplatin were administered through the hepatic arteries supplying the lobes of the liver containing tumors, and progression free survival was analyzed as a primary end point in addition to other secondary endpoints. The corresponding therapy was repeated unless disease progression or severe adverse events were recorded.Results: The monotherapy or combination therapy was performed for 15 or 36 sessions in total, respectively. Although there were no significant differences between the two groups for treatment intervals (p = 0.96) or the dose of miriplatin used in each session (p = 0.99), the progression free survival and overall disease control rate were significantly better in the combination therapy group (91 vs 423 days, p = 0.025; 40.0 vs 77.8%, p = 0.0025, respectively). Consistent with these observations, a trend of a significantly slower increase in des-γ-carboxyprothrombin was observed, and the number of treatment sessions was nearly significantly larger in the combination therapy group (p < 0.0001, p = 0.057, respectively). Conversely, the median survival time did not show a significant difference (706 days, monotherapy vs 733 days, combination therapy; p = 0.40). A significant decrease in cholinesterase was observed during the course of treatment only in patients receiving combination therapy (r = -0.86, p < 0.0001). A few cases in both arms showed hematological and/or non-hematological toxicities that were categorized as grade 1 (NCI-CTCAE).Conclusions: The higher disease control effects with the combination of miriplatin and DDP-H indicate that it is a promising alternative treatment for cases with multiple HCCs, especially for those that can tolerate the treatment without experiencing a reduction in hepatic reserve.Trial Registration: This study was registered on 1 January 2012 with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index.htm , UMIN000004691). [ABSTRACT FROM AUTHOR]

Purpose: Superselective intra-arterial cerebral infusion (SIACI) of bevacizumab (BV) has emerged as a novel therapy in the treatment of recurrent glioblastoma (GB). This study assessed the use of apparent diffusion coefficient (ADC) in predicting length of survival after SIACI BV and overall survival in patients with recurrent GB. Methods: Sixty-five patients from a cohort enrolled in a phase I/II trial of SIACI BV for treatment of recurrent GB were retrospectively included in this analysis. MR imaging with a diffusion-weighted (DWI) sequence was performed before and after treatment. ROIs were manually delineated on ADC maps corresponding to the enhancing and non-enhancing portions of the tumor. Cox and logistic regression analyses were performed to determine which ADC values best predicted survival. Results: The change in minimum ADC in the enhancing portion of the tumor after SIACI BV therapy was associated with an increased risk of death (hazard ratio = 2.0, 95% confidence interval(CI) [1.04-3.79], p = 0.038), adjusting for age, tumor size, BV dose, and prior IV BV treatments. Similarly, the change in ADC after SIACI BV therapy was associated with greater likelihood of surviving less than 1 year after therapy (odds ratio = 7.0, 95% CI [1.08-45.7], p = 0.04). Having previously received IV BV was associated with increased risk of death (OR 18, 95% CI [1.8-180.0], p = 0.014). Conclusion: In patients with recurrent GB treated with SIACI BV, the change in ADC value after treatment is predictive of overall survival. [ABSTRACT FROM AUTHOR]

Objective. Intrathecal drug delivery (ITDD) is commonly used for intractable pain management. A paucity of good-quality studies in chronic non cancer patients and concerns over increased dosages have focused interest on different modes of administration. The aim of this international multicenter randomized double-blind crossover trial was to compare the efficacy of the same daily dose of drugs administered by intermittent boluses vs simple continuous infusion. Methods. Eligible patients implanted with a programmable ITDD device were randomized to receive two weeks of either intermittent boluses or a simple continuous flow in period 1, followed by a crossover to the alternative mode of administration. The primary outcome measure was the Patients' Global Impression of Change (PGIC) scale. Results. The mean proportion of positive responders (at least "minimally improved") was 38.4% in the continuous condition vs 37.3% in the bolus (difference in proportions = 1.1%, 95% confidence interval [CI] = -21.8-24.0%, P = 0.93). The mean PGIC in the continuous condition was 3.8 vs 3.9 in the bolus (mean difference = -0.1, -0.6-0.4, P = 0.72). Exploratory analyses revealed a tendency for the mean proportion of positive responders to be higher at low vs high flow rates for both bolus and continuous administrations. Two patients were withdrawn from the study due to adverse events during the bolus phase, both with symptoms of increased pain, and one patient with additional symptoms of numbness and urinary retention. Conclusion. The mean PGIC and proportion of positive responders was not substantially different after intermittent bolus vs continuous administration. [ABSTRACT FROM AUTHOR]

Background Since proof emerged that IA treatment (IAT) is beneficial for patients with acute ischemic stroke, it has become the standard method of care. Despite these positive results, recovery to functional independence is established in only about one-third of treated patients. The effect of IAT is commonly assessed by functional outcome, whereas its effect on brain tissue salvage is considered a secondary outcome measure (at most). Because patient and treatment selection needs to be improved, understanding the treatment effect on brain tissue salvage is of utmost importance. Objective To introduce infarct probability maps to estimate the location and extent of tissue damage based on patient baseline characteristics and treatment type. Methods Cerebral infarct probability maps were created by combining automatically segmented infarct distributions using follow-up CT images of 281 patients from the MR CLEAN trial. Comparison of infarct probability maps allows visualization and quantification of probable treatment effects. Treatment impact was calculated for 10 Alberta Stroke Program Early CT Score (ASPECTS) and 27 anatomical regions. Results The insular cortex had the highest infarct probability in both control and IAT populations (47.2% and 42.6%, respectively). Comparison showed significant lower infarct probability in 4 ASPECTS and 17 anatomical regions in favor of IAT. Most salvaged tissue was found within the ASPECTS M2 region, which was 8.5% less likely to infarct. Conclusions Probability maps intuitively visualize the topographic distribution of infarct probability due to treatment, which makes it a promising tool for estimating the effect of treatment. [ABSTRACT FROM AUTHOR]

The key element that has determined us to initiate a study concerning the benefits of intra-arterial chemotherapy is the fact that, despite progress regarding therapy, the ENT cancer prognosis is poor, especially in stages that have regional invasion, with a higher risk of therapeutic failure. ENT cancer treatment has raised many questions, the present therapeutic standard being simultaneous radio-chemotherapy with cisplatin, a quality regional control being obtained by hyper-fractionated radiotherapy, targeted on the tumour volume. The technical inconveniences that, in some cases, make impossible the accomplishment of a correct treatment, have determined us to make a retrospective analysis of the studies published in medical journals, with the aim of discerning a therapeutic method that has a role in increasing the loco-regional control of the disease. The studies speak about intra-arterial chemoinfusion with cisplatin, alongside radiotherapy, demonstrating with certainty the superiority of this method versus administrating the drug intravenously, in terms of local tumour control and tolerability. Because the benefits regarding the survival rate and the disease-free period have not reached the statistically significant level, intra-arterial chemoinfusion of cisplatin, alongside radiotherapy, remains a subject that is open to further studies. The efficacy of intra-arterial chemoinfusion of cisplatin hasn't been studied in the case of a relapse, remaining still a subject that is worthy of being approached, seeing as this method was shown to be efficient regarding the safety profile, having a good tolerability and also having a good activity profile, leading to increase in the quality of life and an increase in survival through a local tumour control that is superior than in the case of intravenous administration of the drug. [ABSTRACT FROM AUTHOR]

Introduction: To investigate the effects of hepatic arterial infusion chemotherapy (HAIC) with or without systemic chemotherapy compared to systemic chemotherapy alone in patients with locally advanced hepatocellular carcinoma (HCC)., Methods: Following a registered protocol (PROSPERO 2023 CRD42023386780 Available from: https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42023386780), a comprehensive search was performed using reputable databases and registries up to December 26, 2022, with no language, publication date, or status restrictions. Only randomized controlled trials (RCTs) investigating the effects of HAIC with or without systemic chemotherapy versus systemic therapy alone were included. The primary outcomes were overall survival (OS), progression-free survival (PFS), and adverse events. The secondary outcomes included the objective response rate (ORR) and disease control rate (DCR). A random-effects model was used, and the certainty of the evidence was rated using GRADE., Results: Seven RCTs involving 1,010 patients were included. All trials utilized sorafenib as the comparator. Five trials (690 patients) compared HAIC plus sorafenib to sorafenib alone, while two trials (320 patients) compared HAIC to sorafenib. The results indicate that HAIC, with or without sorafenib, may increase OS, PFS, and ORR compared with sorafenib alone. HAIC may enhance DCR, but the evidence is very uncertain. Adverse events were comparable between HAIC plus sorafenib and sorafenib alone. However, adverse events might be decreased in HAIC alone., Discussion: HAIC with or without systemic chemotherapy may improve survival outcomes and response rates of patients with HCC. Since the current body of evidence is moderate to very low, more robust randomized trials are needed to confirm the efficacy of HAIC., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=386780, identifier CRD42023386780., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kim, Lee, Shim, Bang, Cho, Chung, Hwang, Hwang and Bae.)

The role of serum uric acid (SUA), an inflammatory agent and potential mediator of cardiovascular diseases, in endothelial function (EF) has been tested only in middle-aged subjects affected by specific diseases. Our aim was to assess the relationship between SUA and measures of EF in a cohort of elderly community-dwellers. This study involved 424 males and 426 females aged 70 years from the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS), having complete data on SUA and EF assessed by flow-mediated vasodilation (FMD) and by intra-arterial infusion of acetylcholine (endothelium-dependent vasodilation, EDV) and sodium nitroprusside (endothelium-independent vasodilation, EIDV). Univariate and multivariate regression models obtained by backward selection from initial fully-adjusted models were built to assess the relationship between SUA and measures of EF in both genders. Cardiovascular risk factors, serum hormonal and metabolic mediators, and body composition were considered as potential confounders. In the univariate model, SUA was inversely associated in both genders with log(EDV) (β ± SE males − 0.39 ± 0.17, p = 0.03; females − 0.57 ± 0.19, p = 0.003) and log(EIDV) (males − 0.23 ± 0.12, p = 0.05; females − 0.49 ± 0.15, p = 0.002), but not with log(FMD). After adjustment for BMI, only the association between SUA and log(EIDV) in females persisted, though attenuated (− 0.32 ± 0.16, p = 0.049), and was no longer significant in the fully-adjusted multivariate model including waist/hip ratio. In conclusion, in older subjects, especially women, SUA is associated with EF not independently of a list of confounders including BMI and trunk fat mass, suggesting a role as surrogate metabolic marker rather than an active player in EF. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to evaluate the pharmacokinetics and histopathological findings of transarterial chemoembolization (TACE) using cisplatin powder mixed with degradable starch microspheres (DSM) (Cis/DSM-TACE) compared with cisplatin arterial infusion (Cis-AI).Materials and Methods: Eighteen rabbits with VX2 liver tumors were divided into two groups: Cis/DSM-TACE (n = 9) and Cis-AI (n = 9) groups. In the Cis/DSM-TACE group, a mixture of cisplatin powder and DSM was injected until stasis of hepatic arterial flow was achieved. In the Cis-AI group, cisplatin solution was infused.Results: The platinum concentrations in VX2 tumors in the Cis/DSM-TACE group at 24 and 72 h were significantly elevated compared with those in the Cis-AI group (P = .016 and .019, respectively). There were no significant differences in the platinum concentrations in plasma. Histopathological examination revealed the presence of several microspheres inside the tumors at 1 h, which completely disappeared at 24 h. Tumor cell apoptosis at 1 h in the Cis/DSM-TACE group was more frequently observed compared with that in the Cis-AI group (P = .006).Conclusions: TACE using cisplatin powder mixed with DSM provides a higher drug concentration in tumors, thereby achieving stronger antitumor effects compared with arterial infusion of cisplatin solution. [ABSTRACT FROM AUTHOR]

Background. Lipiodol has been applied for decades in transarterial chemoembolization to treat liver malignancies, but its intrahepatic pathway through arterioportal shunt (APS) in the liver has not been histologically revealed. This rodent experiment was conducted to provide evidence for the pathway of Lipiodol delivered through the hepatic artery (HA) but found in the portal vein (PV) and to elucidate the observed unidirectional APS. Methods. Thirty rats were divided into 5 groups receiving systemic or local arterial infusion of red-stained iodized oil (RIO) or its hydrosoluble substitute barium sulfate suspension (BSS), or infusion of BSS via the PV, monitored by real-time digital radiography. Histomorphology of serial frozen and paraffin sections was performed and quantified. Results. After HA infusion, RIO and BSS appeared extensively in PV lumens with peribiliary vascular plexus (PVP) identified as the responsible anastomotic channel. After PV infusion, BSS appeared predominantly in the PV and surrounding sinusoids and to a much lesser extent in the PVP and HA (P<0.001). Fluid mechanics well explains the one-way-valve phenomenon of APS. Conclusions. Intravascularly injected rat livers provide histomorphologic evidences: (1) the PVP exists in between the HA and PV, which is responsible to the APS of Lipiodol; and (2) the intrahepatic vascular inflow appears HA-PVP-PV unidirectional without a physical one-way valve, which can be postulated by the fluid mechanics. [ABSTRACT FROM AUTHOR]

Background: This study aimed to retrospectively assess the safety and usefulness of hepatic arterial infusion chemotherapy (HAIC) with cisplatin in patients with hepatocellular carcinoma (HCC) and Child-Pugh (C-P) score ≥ 8, who were refractory to or ineligible for transcatheter arterial chemoembolization (TACE). Methods: In this study, 28 cisplatin-naïve patients with HCC, C-P score ≥ 8, and no evidence of extrahepatic lesions were treated using HAIC with cisplatin between July 2004 and July 2 013. Results: Of 28 patients, 10 were refractory to TACE and 18 ineligible for TACE. In terms of C-P score, 17 patients had a score of 8, 6 a score of 9, and 5 a score of 10. The injected dose of cisplatin was reduced in 64.3% of cases. The overall response rate was 10.7%, with a disease control rate of 35.7%. Overall, median survival time (MST) and progression-free survival were 186 and 80 days, respectively. In patients with macroscopic vascular invasion (MVI-positive; n = 9), these values decreased to 161 and 72 days, respectively; while they increased to 341 and 87 days, respectively, in MVI-negative patients (n = 19). Patients achieving partial response (PR) and stable disease (SD) status as well as those achieving SD status showed significantly better survival than patients with progressive disease (PD status): PR+ SD vs. PD: MST = 447 vs. 123 days, P < 0.001; SD vs. PD: MST = 447 vs. 123 days, P = 0.001). No serious adverse event or treatment-related death occurred. Conclusions: HAIC with cisplatin can be safely administered in patients with HCC and C-P score ≥ 8, who are TACE-refractory or -ineligible. An extended survival time is expected when the treatment outcome is either SD or more favorable. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to determine the prevalence of hepatic artery stenosis ( HAS) and the prognostic implications of hepatic arterial collaterals in liver transplant ( LT) recipients with biliary strictures. Methods The 105 LT recipients transplanted between 2004 and 2015 at our center had documented biliary strictures. HAS and collaterals were assessed in high-quality imaging of the hepatic artery available from 66 recipients. Clinical, demographic, and biochemical recipient and donor data were retrospectively analyzed and tested for their association with biliary or arterial complications after LT. Results The prevalence of HAS was 68% (45 of 66) in LT recipients with biliary strictures. Seventy-six percent (37 of 49) of patients with nonanastomotic biliary strictures had HAS. This was significantly higher than in patients with anastomotic stricture, where 47% (8 of 17) of patients had a pathological hepatic arteriogram ( P=.039). The location of bile duct strictures was not predictive for outcome. In contrast, arterial collaterals were associated with significantly better patient and graft survival. Conclusion Impaired hepatic arterial perfusion is frequently associated with nonanastomotic strictures, but less closely correlated with anastomotic strictures. On survival analysis, hepatic arterial collaterals have a protective effect. [ABSTRACT FROM AUTHOR]

Intrahepatic cholangiocarcinoma (ICC) is the second most common malignancy arising from the liver. ICC makes up about 10% of all cholangiocarcinomas. It arises from the peripheral bile ducts within the liver parenchyma, proximal to the secondary biliary radicals. Histologically, the majority of ICCs are adenocarcinomas. Only a minority of patients (15%) present with resectable disease, with a median survival of less than 3 years. Multidisciplinary management of ICC is complicated by large differences in disease course for individual patients both across and within tumor stages. Risk models and nomograms have been developed to more accurately predict survival of individual patients based on clinical parameters. Predictive risk factors are necessary to improve patient selection for systemic treatments. Molecular differences between tumors, such as in the epidermal growth factor receptor status, are promising, but their clinical applicability should be validated. For patients with locally advanced disease, several treatment strategies are being evaluated. Both hepatic arterial infusion chemotherapy with floxuridine and yttrium-90 embolization aim to downstage locally advanced ICC. Selected patients have resectable disease after downstaging, and other patients might benefit because of postponing widespread dissemination and biliary obstruction. [ABSTRACT FROM AUTHOR]

Background: The feasibility and efficacy of adjuvant hepatic arterial infusion (HAI) in preventing the development of liver metastases in patients with advanced colon carcinoma have not been validated. The aim of this randomized controlled study was to compare the feasibility of HAI and the protective effect against liver metastasis after curative resection to those of systemic chemotherapy.Methods: Between July 2000 and June 2003, 91 patients were enrolled. Patients were randomly assigned to receive 5-fluorouracil (5-FU) via continuous venous infusion (CVI) or intra-hepatic arterial weekly high-dose 5-FU (WHF). The primary endpoint was overall survival (OS).Results: In the WHF group, the cumulative failure rate of hepatic arterial catheterization was 16.7% at 6 months. The occurrence of grade 3 adverse events was comparable between the groups. The 5-year OS rates were 59.0% in the CVI group and 34.9% in the WHF group (P = 0.164). CVI tended to show a protective effect against liver metastasis regarding the 5-year liver-specific cumulative recurrence rate: CVI, 45.0% vs. WHF, 68.3%; P = 0.037).Conclusion: HAI therapy has a certain protective effect against liver metastasis after curative resection in patients with colorectal cancer. However, this therapy did not contribute to any marked improvement in their overall survival. [ABSTRACT FROM AUTHOR]

The cerebral vasospasm is still considered the most devastating complication for the patients with aneurysmal subarachnoid haemorrhage. The aim of this study was to evaluate the efficiency of intra-arterial nimodipine administration in cerebral vasospasm diminutions and outcome of the patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Intra-arterial administration of radiographic contrast media (CM) is discussed to impair renal perfusion. The pathogenesis of contrast-induced Nephropathy (CIN) is still not clarified. OBJECTIVE: This trial was performed to prove the effects of two CM with different molecular structure on renal perfusion. METHODS: A prospective, randomized study on 16 pigs was designed to compare the outcome after application of a low-osmolar iodinated CM (770mOsm/kg H2O-Group 1) and an iso-osmolar iodinated CM (290mOsm/kg H2o-Group2). Color Coded Doppler Sonography (LOGIQ E9, GE, Milwaukee, USA) was applied for measuring the Renal Resistive Index (RRI) before and after the first, fifth, and tenth bolus of CM. Statistics was performed using analysis of variance for repeated measurements with the Factor "CM". RESULTS: All flow spectra were documented free of artifacts and Peak Systolic Velocity (PSV), Enddiastolic Velocity (EDV) and RRI respectively could be calculated. Mean PSV in Group 1 led to a decrease while in Group 2 PSV showed a significant increase after CM (p = 0,042). The course of the mean EDV in both groups deferred accordingly (p = 0,033). Mean RRI over time significantly deferred in both groups (p = 0,001). It showed a biphasic course in Group 2 and a decrease over time in Group 2. CONCLUSION: While iso-osmolar CM induced an increase of PSV and EDV together with a decrease of RRI, low-osmolar CM could not show this effect or rather led to the opposite. [ABSTRACT FROM AUTHOR]

Introduction: Vasospasm still is a major cause of morbidity after aneurysmal subarachnoid hemorrhage. The purpose of this report is to describe the successful management of severe refractory vasospasm with continuous intra-arterial nimodipine (IAN) treatment. Case description: A 72-year old right handed woman was admitted with non-traumatic SAH WFNS grade 1. Cerebral computed tomography demonstrated thick blood filling of the basal cisterns, and intraventricular hemorrhage. Cerebral angiogram failed to detect a vascular abnormality. After an uneventful initial course the patient developed symptomatic left middle cerebral artery vasospasm with aphasia and corresponding restriction in diffusion weighted images in the left frontal lobe. Bolus IAN only transiently improved cerebral circulation and clinical signs and symptoms. Continuous-IAN was started and led to full clinical recovery and normalisation of MRI diffusion restrictions. Discussion and conclusions: Continuous selective intra-arterial infusion of nimodipine may be an option in selected patients with symptomatic vasospasm refractory to conventional treatment after careful consideration of benefits and procedure-related risks. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT), which is based on the activation of photosensitizers with light, can be used to reduce plaque burden. We hypothesized that intra-arterial photosensitizer administration and photo-activation will lead to high and rapid accumulation within the plaque with reduced systemic adverse effects. Thus, this "intra-arterial" PDT would be expected to have less side effects and due to the short time involved would be compatible with percutaneous coronary interventions. Aim: We characterized the dose-dependent uptake and efficacy of intra-arterial PDT using Liposomal Verteporfin (Visudyne®), efficient for cancer-PDT but not tested before for PDT of atherosclerosis. Methods and Results: Visudyne® (100, 200, and 500 ng/ml) was perfused for 5-30 min in atherosclerotic aorta isolated from ApoE-/- mice. The fluorescence Intensity (FI) after 15 min of Visudyne® perfusion increased with doses of 100 (FI-5.5 ± 1.8), 200 (FI-31.9 ± 1.9) or 500 ng/ml (FI-42.9 ± 1.2). Visudyne® (500 ng/ml) uptake also increased with the administration time from 5 min (FI-9.8 ± 2.5) to 10 min (FI-23.3 ± 3.0) and 15 min (FI-42.9 ± 3.4) before reaching saturation at 30 min (FI-39.3 ± 2.4) contact. Intra-arterial PDT (Fluence: 100 and 200 J/cm2, irradiance-334mW/cm2) was applied immediately after Visudyne® perfusion (500 ng/ml for 15 min) using a cylindrical light diffuser coupled to a diode laser (690 nm). PDT led to an increase of ROS (Dihydroethidium; FI-6.9 ± 1.8, 25.3 ± 5.5, 43.4 ± 13.9) and apoptotic cells (TUNEL; 2.5 ± 1.6, 41.3 ± 15.3, 58.9 ± 6%), mainly plaque macrophages (immunostaining; 0.3 ± 0.2, 37.6 ± 6.4, 45.3 ± 5.4%) respectively without laser irradiation, or at 100 and 200 J/cm2. Limited apoptosis was observed in the medial wall (0.5 ± 0.2, 8.5 ± 4.7, 15.3 ± 12.7%). Finally, Visudyne®-PDT was found to be associated with reduced vessel functionality (Myogram). Conclusion: We demonstrated that sufficient accumulation of Visudyne® within plaque could be achieved in short-time and therefore validated the feasibility of local intravascular administration of photosensitizer. Intra-arterial Visudyne®-PDT preferentially affected plaque macrophages and may therefore alter the dynamic progression of plaque development. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) patients with hepatic vein tumor thrombosis (HVTT) extending to the inferior vena cava (IVC) have an extremely poor prognosis. Here we report a case of HCC with HVTT and renal dysfunction after hepatic arterial infusion chemotherapy (HAIC) successfully treated by liver resection and active veno-venous bypass.Case Presentation: A 77-year-old man was diagnosed to have a large HCC with intrahepatic metastases and HVTT extending to the IVC. Due to the advanced stage, HAIC with cisplatin was performed 13 times in a period of 17 months. As a consequence of this treatment, the size of the main HCC markedly decreased, and the advanced part of the HVTT went down to the root of the right hepatic vein (RHV). However, because of renal dysfunction, HAIC with cisplatin was discontinued and right hepatectomy with patch graft venoplasty of the root of the RHV was performed. Because progression of renal dysfunction had to be avoided, veno-venous bypass was activated during IVC clamping to prevent renal venous congestion and hypotension. Histological examination showed foci of a moderately differentiated HCC with extensive fibrosis and necrosis in the main HCC. Histologically, the HVTT in the RHV showed massive necrosis and tightly adhered to the vascular wall of the RHV. The postoperative function of the remnant liver was good, and no further deterioration of renal function was detected. The patient did not show signs of recurrence 15 month after surgery.Conclusion: In the present case, HAIC using cisplatin in combination with hepatic resection and patch graft venoplasty of the IVC provided a good long-term outcome with no HCC recurrence. Renal function was preserved by using active veno-venous bypass during IVC clamping to prevent renal venous congestion and hypotension. [ABSTRACT FROM AUTHOR]

Background: The prognosis of unresectable locally advanced gastric cancer is poor. We applied preoperative chemotherapy via intra-arterial and intravenous administration to convert an initially unresectable gastric cancer to a resectable cancer.Methods: From January 2005 to December 2010, 105 patients with unresectable locally advanced gastric cancer (T3-4N1-3M0) were selected for preoperative chemotherapy with 5-FU + leucovorin + etoposide + oxaliplatin + epirubicin (FLEEOX) regimen. 5-Fu (370 mg/m(2)) and leucovorin (200 mg/m(2)) were administered by intravenous infusion on days 1-5. Intra-arterial administration of etoposide (80 mg/m(2)), oxaliplatin (80 mg/m(2)), and epirubicin (30 mg/m(2)) was performed by Seldinger method on days 6 and 20, repeated two cycles. Patients who achieved partial response (PR) or complete response (CR) underwent D2 dissection, followed by four to six cycles of XELOX chemotherapy. The response rate, 1- and 3-year survival rate, and R0 resection rate were evaluated.Results: The response rate of preoperative chemotherapy was 78.1 % (82 of 105 patients), with 7 cases of CR and 75 cases of PR, respectively. After chemotherapy, a total of 78 patients (74.3 %) underwent surgery, and 67 cases achieved R0 resection (85.9 %). The 1- and 3-year overall survival (OS) rate of all 105 patients was 71.9 and 31.7 % (median survival time, 18 months). The 1- and 3-year OS rate among the 78 patients treated with chemotherapy plus surgery was 84.5 and 40 % (median survival time, 30 months). Patients treated with chemotherapy plus surgery had significantly longer OS times than patients who underwent chemotherapy alone (P < 0.01).Conclusions: Patients with unresectable gastric cancer may obtain a survival benefit from preoperative chemotherapy via intra-arterial and intravenous administration and subsequent surgery. [ABSTRACT FROM AUTHOR]

Although the effectiveness of subarachnoid continuous drug infusion has been established in cancer pain management, its clinical use in children is rare. A 14-year-old girl with neurofibromatosis type I complained of right leg pain stemming from a growing tumor on her right buttock. Continuous and breakthrough right leg pain were unbearable, even at high doses of systemic opioids that caused severe constipation and deep sedation. Subsequent continuous infusion of bupivacaine and morphine through a subarachnoid catheter effectively relieved the girl's pain. The corresponding decrease in systemic opioid also improved her activities of daily living. The patient eventually died of cachexia due to the rapidly growing buttock lesion that was pathologically confirmed post-mortem as a malignant peripheral nerve sheath tumor. Subarachnoid continuous drug infusion may be very useful in controlling severe pain with few side-effects, even in the field of pediatric palliative care. [ABSTRACT FROM AUTHOR]

Background and purpose: Patients with acute ischemic stroke due to intracranial large vessel occlusion benefit from intra-arterial therapy. Uncertainty exists about the effect of intra-arterial therapy in patients with contraindications for treatment with intravenous alteplase treatment. Our aim was to describe the clinical characteristics of this subgroup of patients and whether intra-arterial therapy is as safe and effective as it is after intravenous alteplase treatment. Methods: All 500 MR CLEAN patients were included and we distinguished between patients who were and were not treated with intravenous alteplase treatment. We estimated the effect of intra-arterial therapy on the shift on the modified Rankin Scale score with ordinal logistic regression analysis and tested for interaction of intravenous alteplase treatment with intra-arterial therapy on outcome. Furthermore, safety parameters and serious adverse events were analyzed. Results: Fifty-five patients (11%) were not treated with intravenous alteplase treatment, mostly because of prolonged coagulation time tests or recent surgery. These patients were older and more often had atrial fibrillation or other vascular comorbidity. There was no interaction between intravenous alteplase treatment and intervention effect (p=0.927). Intra-arterial therapy effect size in patients without intravenous alteplase treatment was 2.06 [95% CI: 0.69–6.13] and in patients with intravenous alteplase treatment 1.71 [95% CI: 1.22–2.40]. There were no safety issues. Conclusions: For patients with acute ischemic anterior circulation stroke caused by intracranial large vessel occlusion, who have contraindications for intravenous alteplase, intra-arterial treatment is not less effective or less safe than in patients who receive the treatment after intravenous alteplase. Clinical trial registration: Clinical trial registration-URL: http://www.trialregister.nl. Unique identifier: (NTR)1804. Clinical trial registration-URL: http://www.controlled-trials.com. Unique identifier: ISRCTN10888758. [ABSTRACT FROM AUTHOR]

Background: For patients with liver metastases from gastric cancer (LMGC), combination chemotherapy with fluoropyrimidines and platinum agents has been recognized as standard treatment. However, the prognosis of hepatic progression after first-line treatment failure remains poor. When hepatic progression occurs, hepatic arterial infusion (HAI) chemotherapy may be helpful for preventing disease progression.Purpose: To retrospectively assess the feasibility and efficacy of HAI chemotherapy using 5-fluorouracil, epirubicin, and mitomycin C (FEM) for patients with LMGC after failure of systemic S-1 plus cisplatin.Material and Methods: We reviewed the records of patients who received HAI chemotherapy using FEM for LMGC that progressed during systemic S-1 plus cisplatin treatment while extrahepatic disease was decreased or did not appear. HAI chemotherapy was given as second-line therapy using 5-fluorouracil (330 mg/m(2) weekly), epirubicin (30 or 40 mg/m(2) every 4 weeks), and mitomycin C (2.7 mg/m(2) biweekly).Results: Fourteen patients were analyzed. Toxicity of HAI chemotherapy was generally mild. The objective response rate was 42.9%, including a complete response rate of 14.3%. Median times to hepatic and extrahepatic progression were 9.2 and 7.4 months, respectively. Of 12 patients with documented progression after HAI chemotherapy, 10 patients (83.3%) received additional treatment, including irinotecan or taxanes. Overall, median survival was 12.7 months.Conclusion: Our findings suggest that HAI chemotherapy using FEM is a feasible and effective treatment for patients with LMGC after failure of systemic S-1 plus cisplatin. HAI chemotherapy employed in the second-line setting is useful for achieving long-term disease control of LMGC. [ABSTRACT FROM AUTHOR]

ObjectiveTo evaluate the effect of short-term hormone replacement therapy with tibolone 2.5 mg daily on endothelial function of healthy postmenopausal women, using flow-mediated dilation (FMD) of the brachial artery. MethodsWe performed a randomized, double-blinded, placebo-controlled study. A total of 100 healthy postmenopausal women were randomly allocated to receive tibolone (n = 50) or placebo (n = 50) for 28 days. Measurement of the FMD of the brachial artery was performed before and after the use of tibolone and placebo. ResultsA total of 31 women completed the study in the tibolone group, and 32 women completed the study in the control group. The results of the FMD measurements obtained from the women in the two groups before treatment were similar (0.018 and 0.091, for tibolone and placebo,p = 0.57). The values of the FMD in women who used tibolone and placebo, before and after the treatment, were similar in both groups. The numbers of women who presented an increase in the values of the FMD in both groups were also similar. ConclusionOur results demonstrate that the administration of 2.5 mg tibolone to healthy postmenopausal women for 28 days does not promote endothelial-dependent vasodilation, measured by FMD of the brachial artery. [ABSTRACT FROM PUBLISHER]

A promising strategy for liver cancer treatment is to deliver chemotherapeutic agents with multifunctional carriers into the tumor tissue via intra-arterial (IA) transcatheter infusion. These carriers should release drugs within the target tissue for prolonged periods and permit intra-procedural multi-modal imaging of selective tumor delivery. This targeted transcatheter delivery approach is enabled via the arterial blood supply to liver tumors and utilized in current clinical practice which is called chemoembolization or radioembolization. During our study, we developed Doxorubicin (Dox) loaded porous magnetic nano-clusters (Dox-pMNCs). The porous structure and carboxylic groups on the MNCs achieved high-drug loading efficiency and sustained drug release, along with magnetic properties resulting in high MRI T2-weighted image contrast. Dox-pMNC within iodinated oil, Dox-pMNCs, and Dox within iodinated oil were infused via hepatic arteries to target liver tumors in a rabbit model. MRI and histological evaluations revealed that the long-term drug release and retention of Dox-pMNCs within iodinated oil induced significantly enhanced liver cancer cell death. [ABSTRACT FROM AUTHOR]

Stroke is still a major health problem in the world. Ischemic stroke accounts for 87% of all acute stroke occurrences. In 2013, the American Heart Association (AHA)/American Stroke Association (ASA), published a Guideline for the Early Management of Patients with Acute Ischemic Stroke. The managements consist of the use of recombinant tissue plasminogen activator (rtPA), endovascular treatment, etc. Unlike acute ischemic stroke, until now, no guidelines have been provided about the management of chronic ischemic stroke that approved universally. The result of the study with the title of "Intra Arterial Heparin Flushing Increases Manual Muscle Test - Medical Research Councils (MMT-MRC) Score in Chronic Ischemic Stroke Patient" is very interesting, because it is a new attempt to treat patients with chronic ischemic stroke. The purpose of this article is to review the study mentioned above, in accordance with the applied scientific principles and is based on the standard literatures and guidelines. Our review is limited only to the discussion of the study results. From this discussion can be proved the existing references that support and/or refuse the study results. Based on the discussions and conclusions of this study, there were no references to support that IAHF can improve motor functions (muscles) in patients with chronic ischemic stroke. [ABSTRACT FROM AUTHOR]

Background Secondary vasospasm and disturbances in cerebrovascular autoregulation are associated with the development of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. An intra-arterial application of nimodipine has been shown to increase the vessel diameter, although this effect is transient. The feasibility of long-term, continuous, intra-arterial nimodipine treatment and its effects on macrovasospasm, autoregulation parameters, and outcome were evaluated in patients with refractory severe macrovasospasm. Methods Ten patients were included with refractory macrovasospasm despite bolus nimodipine application ( n = 4) or with primary severe vasospasm ( n = 6). The patients were assessed with continuous multimodal neuromonitoring (mean arterial pressure, intraceranial pressure, cerebral perfusion pressure, brain tissue oxygen tension probe), daily transcranial Doppler examinations, and computed tomography angiography/perfusion. Autoregulation indices, the pressure reactivity index, and oxygen reactivity index were calculated. Indwelling microcatheters were placed in the extracranial internal carotid arteries and 0.4 mg nimodipine was continuously infused at 50 mL/hour. Results The duration of continuous, intra-arterial nimodipine ranged from 9 to 15 days. During treatment intracranial pressure remained stable, transcranial Doppler flow velocity decreased, and brain tissue oxygen tension improved by 37%. Macrovasospasm, as assessed via computed tomography angiography, had improved ( n = 5) or disappeared ( n = 5) at the end of treatment. Cerebrovascular autoregulation according to the pressure reactivity index and oxygen reactivity index significantly worsened during treatment. All patients showed a favorable outcome (median Glasgow Outcome Scale 5) at 3 months. Conclusions In well-selected patients with prolonged severe macrovasospasm, continuous intra-arterial nimodipine treatment can be applied as a rescue therapy with relative safety for more than 2 weeks to prevent secondary cerebral ischemia. The induced impairment of cerebrovascular autoregulation during treatment seems to have no negative effects. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cell therapy in renal failure is rarely used because of low rates of cell engraftment after systemic delivery. Repeated intra-arterial cell administration may improve results; however, no current delivery method permits repeated intra-arterial infusions in a rat model. In this study, we developed an intra-arterial delivery system for repeated stem cell infusion via the aorta, catheterizing the left femoral artery to the suprarenal aorta under fluoroscopic guidance in rats with adenosine-induced renal failure. Methods: First, we compared our intra-arterial catheter system (C group, n = 3) with tail vein injection (V group, n = 3) for engraftment efficacy, using mesenchymal stem cells from luciferase transgenic rats. Rats were infused with the cells and euthanized the following day; we performed cell-tracking experiments using a bioluminescence imaging system to assess the distribution of the infused cells. Second, we assessed the safety of the system over a 30-day period in a second group of six rats receiving infusions every 7 days. Results: Cells infused through our delivery system efficiently engrafted into the kidney, compared with peripheral venous infusion. In five of the six rats in the safety study, the delivery system remained patent for at least 9 days (range, 9-24 days). Complications became evident only after 10 days. Conclusion: Our intra-arterial catheter system was effective in delivering cells to the kidney and permitted repeated injection of cells. [ABSTRACT FROM AUTHOR]

The article presents the case of an 80-year-old female who was presented to a center due to sudden onset of three subcutaneous nodules on her right limb. She has a clinical history of melanoma on the right leg that was excised surgically 40 years before. Based on positron emission tomography-computed tomography (PET-CT), she was positive in all lesions of the limb. She was confirmed to have V600E-mutated melanoma based on BRAF gene mutation test and was treated with dabrafenib.

Carotid artery stenting is a method used in the treatment of extracranial carotid artery stenosis that is becoming increasingly more common. Acute carotid thrombosis following CAS is a very rare and devastating complication that can be lethal for the patient unless treated immediately. We report a case of acute carotid stent thrombosis occurring immediately after emergent revascularization, and that was treated with intraarterial tissue plasminogen activator and intravenous tirofiban infusion. [ABSTRACT FROM AUTHOR]

Background: Intrahepatic cholangiocarcinoma (ICC) is associated with poor survival. This study compared the outcomes of patients with unresectable ICC treated with hepatic arterial infusion (HAI) plus systemic chemotherapy (SYS) with the outcomes of patients treated with SYS alone.Methods: Consecutive patients with ICC were retrospectively reviewed. Clinicopathologic data were reviewed. Survival rates were compared by Kaplan-Meier analysis and log-rank testing.Results: Between January 2000 and August 2012, 525 patients with ICC were evaluated at Memorial Sloan Kettering Cancer Center, and 236 patients with unresectable tumors (locally advanced or metastatic) were analyzed. Disease was confined to the liver in 104 patients, who underwent treatment with combined HAI and SYS (n = 78 or 75%) or SYS alone (n = 26 or 25%). The response rate in the combined group was better than the rate in the group receiving SYS alone, although this did not reach statistical significance (59% vs 39%, P = .11). Overall survival for the combined group was longer than overall survival for the patients who received SYS alone (30.8 vs 18.4 months, P < .001), and this difference was maintained when patients with portal lymph node disease were included in the survival analysis (29.6 months with HAI and SYS [n = 93] vs 15.9 months with SYS [n = 74], P < .001). Eight patients who initially presented with unresectable tumors responded enough to undergo complete resection and had a median overall survival of 37 months (range, 10.4-92.3 months).Conclusions: In patients with unresectable ICC confined to the liver or with limited regional nodal disease, a combination of SYS and HAI chemotherapy is associated with greater survival than SYS alone. Cancer 2016;122:758-765. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Purpose: Proton beam therapy (PBT), compared with conventional radiotherapy, can deliver high-dose radiation to a tumor, while minimizing doses delivered to surrounding normal tissues. The better dose distribution of PBT may contribute to the improvement in local control rate and reduction in late adverse events. We evaluated therapeutic results and toxicities of PBT combined with selective intra-arterial infusion chemotherapy (PBT-IACT) in patients with stage III-IVB squamous cell carcinoma of the tongue. Materials and methods: After 2 systemic chemotherapy courses and whole-neck irradiation (36 Gy in 20 fractions), we administered concurrent chemoradiotherapy comprising PBT for the primary tumor [28.6-33 Gy(RBE) in 13-15 fractions] and for the metastatic neck lymph node [33-39.6 Gy(RBE) in 15-18 fractions] with weekly retrograde intra-arterial chemotherapy by continuous infusion of cisplatin with sodium thiosulfate. Results: Between February 2009 and September 2012, 33 patients were enrolled. The median follow-up duration was 43 months. The 3-year overall survival, progression-free survival, local control rate, and regional control rate for the neck were 87.0, 74.1, 86.6, and 83.9 %, respectively. Major acute toxicities >grade 3 included mucositis in 26 cases (79 %), neutropenia in 17 cases (51 %), and dermatitis in 11 cases (33 %). Late grade 2 osteoradionecrosis was observed in 1 case (3 %). Conclusions: PBT-IACT for stage III-IVB tongue cancer has an acceptable toxicity profile and showed good treatment results. This protocol should be considered as a treatment option for locally advanced tongue cancer. [ABSTRACT FROM AUTHOR]

Purpose: Cancer patients with predominantly hepatic metastases have poor outcomes and limited options. Hepatic arterial infusion (HAI) of a therapeutic agent may be an appropriate option for producing increased drug concentrations at the tumor sites while reducing systemic adverse effects in normal tissues.Methods: Patients with predominantly hepatic metastases (n = 48) were placed in 6 groups according to nanoparticle albumin-bound paclitaxel (nab-paclitaxel) dose level using a 3 + 3 design plus dose expansion for responsive tumor types. We evaluated the toxicity, antitumor activity, and pharmacokinetics of nab-paclitaxel delivered via HAI.Results: Thirty-eight and ten patients underwent HAI over 1 and 4 h, respectively, at doses of up to 300 mg/m(2). The treatment was safe and exhibited antitumor activity. Pharmacokinetic analyses revealed that HAI of nab-paclitaxel over 4 h resulted in markedly lower peak drug concentrations (C max) and longer times to peak concentration (T max) than that over 1 h. The self-control pharmacokinetic studies showed that HAI of nab-paclitaxel led to much lower C max and areas under the curve (AUC), compared with intravenous infusion.Conclusions: HAI of nab-paclitaxel at up to 300 mg/m(2) over 4 h was well tolerated. Pharmacokinetic evaluation of C max, T max, and AUC implied that 4-h HAI enhanced hepatic extraction of nab-paclitaxel. Further preclinical and clinical studies are required to develop reliable methods of evaluation of hepatic extraction (clinicaltrials.gov registration number NCT00732836, first registered on August 8, 2008, and last updated on October 27, 2014). [ABSTRACT FROM AUTHOR]

Purpose: Portal vein tumor thrombosis is a critical complication in patients with hepatocellular carcinoma (HCC). This prospective multicenter trial assessed the efficacy of hepatic arterial infusion chemoembolization therapy with cisplatin suspended in lipiodol combined with 5-fluorouracil for HCC patients with portal vein tumor thrombosis.Methods: We enrolled 52 HCC patients with portal vein tumor thrombosis. They received hepatic arterial infusion chemoembolization therapy with cisplatin suspension in lipiodol and 5-fluorouracil. The primary efficacy endpoint was progression-free survival (PFS), while the secondary endpoints were overall survival (OS), tumor response rate, safety, and tolerability. Independent factors for survival were also evaluated.Results: The median PFS and OS were 8.6 and 27.0 months, respectively. Ten patients showed complete response, while 29 had partial response (response rate, 75.0 %). The median survival time of 10 patients with complete response and 29 with partial response was 32 months, while that of 15 patients with partial response who later showed disappearance of HCC following additional therapies was 50 months. Multivariate analysis identified response to treatment and disappearance of viable HCC as independent predictors of survival. The treatment was well tolerated, and the only encountered Grade 3 toxicities were thrombocytopenia and hyperbilirubinemia.Conclusions: Hepatic arterial infusion chemoembolization therapy with cisplatin suspension in lipiodol combined with 5-fluorouracil is effective treatment for unresectable HCC with portal vein tumor thrombosis. [ABSTRACT FROM AUTHOR]

Purpose: To assess the technical feasibility of transfemoral intra-arterial chemotherapy for head and neck cancer using a 3-French catheter system (3-Fr).Materials and Methods: Sixty-two patients with head and neck cancer who underwent transfemoral intra-arterial chemotherapy were included in this study. Thirty-three patients underwent treatment using a 3-Fr (group 3-Fr). Twenty-nine patients underwent treatment using a 4-French catheter system (group 4-Fr). The technical success rate, duration of the procedure with fluoroscopy, and rate of procedure-related complications were compared between group 3-Fr and group 4-Fr. In addition, in group 3-Fr, bleeding at the puncture site after 1.5 h of bed rest was evaluated.Results: The technical success rate was 100% in both groups. The duration of the procedure with fluoroscopy didn't differ between group 3-Fr (mean 28.0 min) and group 4-Fr (mean 30.2 min) (p = 0.524). There was no procedure-related complication in either group. In group 3-Fr, no hemorrhagic complication was observed.Conclusion: A 3-French catheter system can be used to perform transfemoral intra-arterial chemotherapy for head and neck cancer and is technically feasible with approximately the same duration of the procedure with fluoroscopy. Furthermore, this method may shorten the bed rest time without hemorrhagic complication, and may reduce the risk of pulmonary embolism. [ABSTRACT FROM AUTHOR]

Background: The incidence of the para-aortic lymph node metastasis (PALM) in patients with advanced gastric cancer is 6 to 33 %. The prognosis is poor and the 5-year survival rate is only 12 to 23 % after gastrectomy with super-extended lymph node dissection. We applied an individualized comprehensive treatment for affected patients including neoadjuvant chemotherapy via intra-arterial and intravenous administration, surgery and radiotherapy, to investigate the safety and prognostic value.Methods: Between January 2005 and December 2010, 47 advanced gastric cancer patients with PALM received 5-Fu (370 mg/m(2)) and leucovorin (200 mg/m(2)) intravenously on days 1-5, and intra-arterial infusion of etoposide (80 mg/m(2)) and oxaliplatin (80 mg/m(2)) on days 6 and 20, repeated 2 cycles. Patients achieved PR or CR of the para-aortic lymph node (PAL) were performed D2 dissection, followed by 6 cycles chemotherapy with XELOX regimen, oxaliplatin (130 mg/m(2)) on day 1 and xeloda (1000 mg/m(2)) on days 1 to 14 of a 28-day cycle, and radiotherapy to the region of PALM.Results: Forty-six patients completed 2 cycles of neoadjuvant chemotherapy. The overall response rate of the primary tumor was 80.4 % (37/46). The response rate of PAL was 76.1 % (35/46). Thirty-two patients underwent D2 dissection and six cases achieved pathological complete response (pCR). The toxicity profile was well tolerable and there was no treatment-related death. The median survival time for all patients was 23 months, and for nonsurgical and surgical patients were 12 and 29 months (p < 0.001), respectively. The 1-year, 2-year and 3-year survival rate was 70.96, 43.27 and 35.48 % for all patients, and for surgical patients was 96.875, 68.75, and 40.63 %.Conclusion: Advanced gastric cancer patients with PALM can obtain a survival benefit from neoadjuvant chemotherapy, subsequent surgery and radiotherapy.Trial Registration: Current Controlled Trials ChiCTR-TRC-12002046 . [ABSTRACT FROM AUTHOR]

Background: The anatomical complexity of the horse's head limits the abilities of radiography. Computed tomography (CT) in combination with contrast enhanced CT is used more often for diagnosing various head pathology in horses. The objective of this study was to compare intravenous and intra-arterial contrast-enhancement techniques and describe normal and abnormal contrast enhancement in the horse's head. Results: All 24 horses included in the study recovered without complication from the procedures. Compared to the pre-contrast studies, post-contrast studies showed significant contrast enhancement in the pituitary gland (IA: p < 0.0001; IV: p < 0.0001), IA nose septum (p = 0.002), nose mucosa (IA: p < 0.0001; IV: p = 0.02), parotid salivary gland (IA: p < 0.0001; IV p < 0.0001), cerebrum (IA: p < 0.0001; IV: p < 0.0001), rectus capitis muscle (IA: p < 0.0001; IV p = 0.001), IA temporal muscle (p < 0.0001), IA masseter muscle (p <0.0001) and IV brainstem (p = 0.01). No significant contrast enhancement was seen in the eye (IA: p = 0.23; IV p = 0.33), tongue (IA p = 0.2; IV p = 0.57), IA brainstem (p = 0.88), IV nose septum (p = 0.26), IV temporal muscle (p = 0.09) and IV masseter muscle (p = 0.46). Three different categories of abnormal enhancement were detected: a strong vascularised mass, an enhanced rim surrounding an unenhanced structure and an inflamed anatomical structure with abnormal contrast enhancement. Conclusion: Using the intra-arterial technique, similar contrast enhancement is achieved using less contrast medium compared to the intravenous technique. And a potential major advantage of the IA technique is the ability to evaluate lesions that are characterized by increased blood flow. Using the intravenous technique, a symmetrical and homogenous enhancement is achieved, however timing is more crucial and the contrast dosage is more of influence in the IV protocol. And a potential major advantage of the IV technique is the ability to evaluate lesions that are characterized by increased vascular permeability. Knowing the different normal contrast enhancement patterns will facilitate the recognition of abnormal contrast enhancements. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop a population pharmacokinetic model of sufentanil and to assess the influence of covariates in critically ill children admitted to a pediatric intensive care unit. After institutional approval, 41 children were enrolled in the study. Blood samples for pharmacokinetic (PK) assessment were collected from routinely placed arterial catheters during and after discontinuation of infusion. Population nonlinear mixed-effects modeling was performed using NONMEM. A 2-compartment model described sufentanil PK sufficiently. Typical values of the central and peripheral volume of distribution and the metabolic and intercompartmental clearance for a theoretical patient weighing 70 kg were VC = 7.90 l, VT = 481 L, Cl =45.3 L/h, and Q = 38.3 L/h, respectively. High interindividual variability of all PK parameters was noted. Allometric/isometric principles to scale sufentanil PK revealed that to achieve the same steady-state sufentanil concentrations in plasma for pediatric patients of different body weights, the infusion rate should follow the formula (infusion rate for a 70-kg adult patient, µg/h) x (body weight/70 kg)0.75. Severity of illness described by PRISM score, the monitored physiological and laboratory parameters, and coadministered drugs such as vasopressors were not found to be significant covariates. [ABSTRACT FROM AUTHOR]