Balloon-Targeted Extra-Anatomic Sharp Recanalization Technique to Re-establish Supraclavicular Vascular Access.

A balloon-targeted extra-anatomic sharp recanalization (BEST) technique was investigated to re-establish supraclavicular vascular access in patients with central venous occlusion. Query of the authors' institution's database yielded 130 patients who underwent central venous recanalization. Of these, a retrospective review of 5 patients with concurrent thoracic central venous and bilateral internal jugular vein occlusions who underwent sharp recanalization using the BEST technique from May 2018 to August 2022 was performed. Technical success was achieved in all cases without major adverse events. Four (80%) of the 5 patients underwent hemodialysis reliable outflow (HeRO) graft placement using the newly established supraclavicular vascular access.

Effect of intra-arterial vasodilator administration during radial artery access on systemic blood pressure in patients receiving moderate sedation.

PURPOSE: The hemodynamic effects of intra-arterial vasodilator administration for the prevention of radial artery spasm during transradial access have not been well characterized. This study evaluates the effect of intra-arterial Verapamil and Nitroglycerine administration on systemic blood pressure and its correlation with timing of moderate sedation administration. MATERIALS AND METHODS: Institutional review board approval was granted. Patients who underwent transradial access from 4/2018 to 4/2019 and received both intra-arterial vasodilators and moderate sedation were identified and their electronic medical records reviewed. Patients were divided into three cohorts based on the timing of sedation and intra-arterial vasodilator administration. Decrease in systolic blood pressure (SBP) was expressed as means with standard deviation which were then compared using Student's t-test. RESULTS: A total of 84 patients who met inclusion criteria demonstrated an overall mean decrease in SBP of 16.45 mmHg ± 15.45 mmHg. Patients receiving sedation and intra-arterial vasodilators within their expected peak SBP effect times had similar SBP change following the intra-arterial vasodilators as those in whom the interval was greater than 10 min (4.2 mmHg; 95% CI (-4.11 to 12.52), p = 0.3171). Two patients experienced asymptomatic hypotension. CONCLUSIONS: Patients undergoing transradial access for procedures utilizing moderate sedation can safely receive intra-arterial Verapamil and Nitroglycerine for prevention of radial artery spasm.

Prospective Study of Radial Artery Occlusion Following Transradial Arterial Access during IR Procedures.

PURPOSE: To prospectively determine the rate of radial artery occlusion (RAO) in patients undergoing transradial access for intra-arterial interventions. MATERIALS AND METHODS: Seventy-seven patients undergoing transradial access from August 2019 to March 2021 for 120 intra-arterial procedures (yttrium-90 mapping [n = 39] and radioembolization [n = 38], uterine artery embolization [n = 19], transarterial chemoembolization [n = 10], active bleed embolization [n = 8], angiomyolipoma embolization [n = 4], and other [n = 2]) were enrolled. The average patient age was 59 years ± 13.1 (range, 30-90 years), and 43 (55.8%) of the 77 patients were men. The patients underwent radial artery (RA) palpation, ultrasound evaluation, the Barbeau test, and the reverse Barbeau test prior to and following the intervention. Verapamil, nitroglycerin, and heparin were administered in a total of 114 (95%) of the 120 procedures prior to starting the procedure. The incidence of RAO and radial artery spasm (RAS) was calculated, and univariate logistic regression was performed to analyze the predictors of RAS. RESULTS: The preprocedural RA diameter (3.0 mm ± 0.67) was not significantly different from the postprocedural RA diameter (3.0 mm ± 0.65, P = .904). The RAO rate was determined to be 0.8% (1/120), and this artery recanalized within 1 week. Due to the small number of occlusions, statistical analysis of predictors of RAO was not performed. The rate of RAS was 22.7% (27/119). None of the variables tested-including age, sex, RA diameter, initial versus repeat access, operator experience, and artery puncture technique-showed significant prediction for RAS. Patients were seen for follow-up after 111 (92.5%) of the 120 procedures. CONCLUSIONS: Transradial access resulted in a <1% rate of RAO.

Principles of Radioembolization.

Radioembolization has become a mainstay therapy in the treatment of primary and secondary liver cancers. This article will specifically discuss a brief history of yttrium treatment as well as an overview of the physical properties of the currently available devices. A discussion of the mechanism of action will be followed by a discussion on patient selection for this treatment.

Treatment Options for Early-Stage Hepatocellular Carcinoma.

Patients with early stage hepatocellular carcinoma have good prognosis and are treated with curative intent. Although this cohort of patients is generally defined by limited tumor burden, good liver function, and preserved functional status, there remains utility in further stratification to optimize overall survival and limit post-operative morbidity and mortality. Transplant, resection, ablation, transarterial radioembolization, and transarterial chemoembolization, either as monotherapy or in combination, may play a crucial role in treating this cohort of patients depending on a multitude of factors. In this section, we review each treatment modality and provide general guidelines for patient selection.

Outcomes of radioembolization for unresectable hepatocellular carcinoma in patients with marginal functional hepatic reserve.

PURPOSE: To evaluate the outcomes of radioembolization (RE) as a therapy for unresectable hepatocellular carcinoma (HCC) in patients with marginal functional hepatic reserve. METHODS: A retrospective review of 471 patients (1/2010-7/2015) treated with RE (Therasphere, BTG, UK) was performed. A total of 36 patients (mean age: 66.1±9.3, male: 86.1%) underwent therapy for HCC with a MELD≥15 (median: 16, range: 15-22). Baseline demographics of the study cohort were as follows: etiology (HCV: 26, 72.2%), cirrhosis (n=32, 88.9%), ECOG 0 (n=16, 44.4%), Child-Pugh class (A=15, B=19, C=2), unilobar distribution (n=27, 75%), AFP>200 (n=11, 30.6%), portal vein thrombosis (PVT, n=7, 19.4%), metastasis (n=3, 8.3%). Outcomes analyzed included CTCAEv4.03 laboratory toxicities (120-day), imaging response (mRECIST), progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 42 treatments were performed with mean dose of 2.02±1.23GBq. The cumulative grade 3/4 toxicity was 28% overall and 21% for bilirubin at 120-days. The objective response and disease control rates were 48.3% (14/29) and 69% (20/29) respectively. The median (95% CI) PFS was 5.9 (4.4-7.7) months. Ten (27.8%) patients received additional locoregional therapy at a median (IQR) of 138 (102-243) days post RE. The mean (95% CI) OS was 21.9 (14.8-29.0) months. The absence of PVT was associated with improved OS (p=0.005) Disease control at 90-days was also associated with an OS benefit (p=0.037). CONCLUSIONS: Patients with unresectable HCC and marginal functional hepatic reserve treated with RE had favorable objective response and disease control rates, both predictive of overall survival.

Radioembolization for Unresectable Intrahepatic Cholangiocarcinoma: Review of Safety, Response Evaluation Criteria in Solid Tumors 1.1 Imaging Response and Survival.

The optimal palliative treatment for unresectable intrahepatic cholangiocarcinoma (ICC) remains controversial. While selective internal radiation therapy (SIRT) using yttrium-90 microspheres is a well-accepted treatment for hepatocellular carcinoma, data related to its use for locally advanced ICC remain relatively scarce. Twenty-nine patients (mean age 66 ± 11 years; 15 female) with unresectable biopsy-proven ICC treated with SIRT between June 2008 and April 2015 were retrospectively evaluated for post-treatment toxicity, overall survival, and imaging response using response evaluation criteria in solid tumors (RECIST) 1.1 criteria. RECIST 1.1 response was evaluable following 26 treatments [complete response (CR):0, partial response (PR):3; stable disease (SD):16, progression of disease (PD):7]. Objective response rate (CR+PR) was 12%. Disease control rate (CR+PR+SD) was 73%. Median time to progression was 5.6 [95% confidence interval (CI): 0-12.0] months. Median survival following SIRT was 9.1 (95% CI: 1.7-16.4) months. Post-treatment survival was prolonged in patients with absence of extrahepatic disease (p = 0.03) and correlated with RECIST 1.1 response (p = 0.02). Toxicities were limited to grade I severity and occurred following 27% of treatments. These findings support the safe, effective use of SIRT for unresectable ICC. Post-treatment survival is prolonged in patients with absence of extrahepatic disease at baseline. RECIST 1.1 response following SIRT for ICC is predictive of survival.

Outcomes of Radioembolization in the Treatment of Hepatocellular Carcinoma with Portal Vein Invasion: Resin versus Glass Microspheres.

PURPOSE: To compare outcomes of yttrium-90 radioembolization performed with resin-based ((90)Y-resin) and glass-based ((90)Y-glass) microspheres in the treatment of hepatocellular carcinoma (HCC) with associated portal vein invasion. MATERIALS AND METHODS: A single-center retrospective review (January 2005-September 2014) identified 90 patients ((90)Y-resin, 21; (90)Y-glass, 69) with HCC and ipsilateral portal vein thrombosis (PVT). Patients were stratified according to age, sex, ethnicity, Child-Pugh class, Eastern Cooperative Oncology Group status, α-fetoprotein > 400 ng/mL, extent of PVT, tumor burden, and sorafenib therapy. Outcome variables included clinical and laboratory toxicities (Common Terminology Criteria Adverse Events, Version 4.03), imaging response (modified Response Evaluation Criteria in Solid Tumors), time to progression (TTP), and overall survival (OS). RESULTS: Grade 3/4 bilirubin and aspartate aminotransferase toxicities developed at a 2.8-fold (95% confidence interval [CI], 1.3-6.1) and 2.6-fold (95% CI, 1.1-6.1) greater rate in the (90)Y-resin group. The disease control rate was 37.5% in the (90)Y-resin group and 54.5% in the (90)Y-glass group (P = .39). The median (95% CI) TTP was 2.8 (1.9-4.3) months in the (90)Y-resin group and 5.9 (4.2-9.1) months in the (90)Y-glass group (P = .48). Median (95% CI) survival was 3.7 (2.3-6.0) months in the (90)Y-resin group and 9.4 (7.6-15.0) months in the (90)Y-glass group (hazard ratio, 2.6; 95% CI, 1.5-4.3, P < .001). Additional multivariate predictors of improved OS included age < 65 years, Eastern Cooperative Oncology Group status < 1, α-fetoprotein ≤ 400 ng/mL, and unilobar tumor distribution. CONCLUSIONS: Imaging response of (90)Y treatment in patients with HCC and PVT was not significantly different between (90)Y-glass and (90)Y-resin groups. Lower toxicity and improved OS were observed in the (90)Y-glass group.

Transradial access for visceral endovascular interventions in morbidly obese patients: safety and feasibility.

PURPOSE: Transradial access (TRA) has been shown to lower morbidity and bleeding complications compared to transfemoral access in percutaneous coronary interventions. Morbid obesity, commonly defined as a body mass index (BMI) ≥40 kg/m2, has been shown to be a risk factor for access site complications irrespective of access site. This study evaluates the safety and feasibility of performing visceral endovascular interventions in morbidly obese patients via TRA. METHODS: Procedural details, technical success, and 30-day major and minor access site, bleeding, and neurological adverse events were prospectively recorded in a database of 1057 procedures performed via the radial artery. From this database we identified 22 visceral interventions performed with TRA in 17 morbidly obese patients (age: 53 ± 11 years, female: 71%) with a median BMI of 42.7 kg/m2. RESULTS: Interventions included radio-embolization (n = 7, 31.8%), chemo-embolization (n = 6, 27.3%), uterine fibroid embolization (n = 4, 18.2%), renal embolization (n = 2, 9.1%), hepatic embolization (n = 1, 4.5%), lumbar artery embolization (n = 1, 4.5%), and renal angioplasty (n = 1, 4.5%). The technical success was 100%. There were no major or minor adverse access site, bleeding, or neurological complications at 30 days. CONCLUSIONS: This study suggests visceral endovascular interventions performed in morbidly obese patients are safe and feasible.

Transradial Approach for Noncoronary Interventions: A Single-Center Review of Safety and Feasibility in the First 1,500 Cases.

PURPOSE: To review safety and feasibility in a single center using transradial access (TRA) for noncoronary interventions. MATERIALS AND METHODS: Retrospective analysis was performed of 946 patients evaluated for 1,531 consecutive TRA procedures from April 2012 to July 2015. Exclusion criteria included sheath > 6 F, Barbeau D waveform, radial artery (RA) diameter < 2 mm on ultrasound, history of severe aortic tortuosity or RA occlusion, and dialysis. TRA was attempted in 936 patients (62% men; median age, 62.4 y) who underwent 1,512 consecutive procedures (chemoembolization [n = 485], yttrium-90 mapping [n = 391] and infusion [n = 293], renal/visceral intervention [n = 172], uterine artery embolization [n = 116], peripheral intervention [n = 43], endoleak repair [n = 10], and other [n = 2]). Patients were evaluated for complications during follow-up at ~30 days. RESULTS: Technical success was 98.2% (1,485/1,512). Major complications (0.13%) included pseudoaneurysm (n = 1) and seizure (n = 1). Minor complications (2.38%) included hematoma/bleeding (n = 13), RA occlusion (n = 11), arm pain (n = 6), and RA spasm (n = 6). Univariate analysis demonstrated a lower rate of adverse events in African American patients (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.07-0.86; P = .027). Twenty-seven cases (1.8%) required crossover to transfemoral access (TFA). Crossover rates were higher in female patients (P = .0055), height < 1.7 m (P = .024), renal/visceral interventions (P = .0003), and endoleak interventions (P = .0357). Multivariate analysis demonstrated intervention type to be the only significant predictor of TFA crossover (renal/visceral [HR, 4.48; 95% CI, 1.84-10.9; P = .001]; endoleak repair [HR, 9.54; 95% CI, 1.09-83.8; P = .042]). CONCLUSIONS: TRA was safe and well tolerated in a heterogeneous patient population across a range of peripheral vascular interventions.

Yttrium-90 Glass-Based Microsphere Radioembolization in the Treatment of Hepatocellular Carcinoma Secondary to the Hepatitis B Virus: Safety, Efficacy, and Survival.

PURPOSE: To evaluate outcomes of yttrium-90 radioembolization performed with glass-based microspheres in the treatment of hepatocellular carcinoma (HCC) secondary to the hepatitis B virus (HBV). MATERIALS AND METHODS: A total of 675 patients treated between January 2006 and July 2014 were reviewed, of which 45 (age 62 y ± 10; 91% male) received glass-based radioembolization for HCC secondary to HBV. All patients were stratified according to previous therapy (naive, n = 14; 31.1%), Child-Pugh class (class A, n = 41; 91%), Eastern Cooperative Oncology Group (ECOG) performance status (PS; < 1, n = 21; 47%), solitary (n = 26; 58%) and unilobar (n = 37; 82%) tumor distribution, tumor size < 5 cm (n = 29; 64%), portal vein thrombosis (n = 14; 31%), α-fetoprotein level > 400 ng/mL (n = 17; 38%), and Barcelona Clinic Liver Cancer stage (A, n = 8; B, n = 9; C, n = 28). RESULTS: A total of 50 radioembolization treatments were performed, with a 100% technical success rate (median target dose, 120 Gy). Clinical toxicities included pain (16%), fatigue (12%), and nausea (4%). Grade 3/4 laboratory toxicities included bilirubin (8%) and aspartate aminotransferase (4%) toxicities. Observed toxicities were independent of treatment dose. The objective response rates were 55% per modified Response Evaluation Criteria In Solid Tumors and 21% per World Health Organization criteria, and the disease control rate was 63%. Disease progression was secondary to new, nontarget HCC in 45% of cases. Median time to progression and overall survival were 6.0 mo (95% confidence interval [CI], 4.4-8.0 mo) and 19.3 mo (95% CI, 11.2-22.7 mo), respectively. Multivariate analysis demonstrated ECOG PS ≥ 1 and AFP level > 400 ng/mL to be independent predictors of inferior overall survival. CONCLUSIONS: Glass-based radioembolization for HCC secondary to HBV can be safely performed, with favorable target lesion response and overall survival.

GI hemorrhage arising from splenic artery: intraprocedure cone-beam CT as problem-solving tool to aide in safe catheterization of offending vessel.

We present the case of a 67-year-old female with melena and hypotension who was found to have a bleeding splenic artery pseudoaneurysm subjacent to a large gastric ulcer on computed tomographic angiography. The lesion was angiographically occult on standard anteroposterior and oblique projections. The offending vessel was identified on intraprocedure cone-beam computed tomography (CT). This case illustrates the value of intraprocedure cone-beam CT as a problem-solving tool for the interventional radiologist.

Early postnatal exposure to methylphenidate alters stress reactivity and increases hippocampal ectopic granule cells in adult rats.

To mimic clinical treatment with methylphenidate (MPH; Ritalin) for attention deficit/hyperactivity disorder (ADHD), rat pups were injected with MPH (5 mg/kg, i.p.) or placebo twice daily during their nocturnal active phase from postnatal day (PND) 7-35. Thirty-nine days after the last MPH administration (PND 76), four litters of rats experienced stressful conditions during the 2003 New York City blackout. MPH-treated rats that endured the blackout lost more weight and regained it at a slower pace than controls (p<0.05; N=7-11 per group). Furthermore, MPH-treated rats had elevated systolic arterial blood pressure (from 115.6+/-1.2 to 126+/-1.8 mmHg; p<0.05), assessed on PND 130 by tail cuff plethysmography. Immunocytochemical studies of transmitter systems in the brain demonstrated rearrangements of catecholamine and neuropeptide Y fibers in select brain regions at PND 135, which did not differ between blackout and control groups. However, MPH-treated rats that endured the blackout had more ectopic granule cells in the hilus of the dorsal hippocampal dentate gyrus compared to controls at PND 135 (p<0.05; N=6 per group). These findings indicate that early postnatal exposure to high therapeutic doses of MPH can have long lasting effects on the plasticity of select brain regions and can induce changes in the reactivity to stress that persist into adulthood.

Transcatheter occlusion of pulmonary arteriovenous malformations using the Amplatzer Vascular Plug II.

Pulmonary arteriovenous malformations (PAVMs) are a relatively uncommon but potentially life-threatening condition manifested by cyanosis, paradoxical embolization, brain abscess, and rupture. A variety of transcatheter closure devices have been used to occlude PAVMs however risks of device embolization, incomplete closure, or large delivery systems have made each of these methods sub-optimal. The Amplatzer Vascular Plug II (AVP II) is a new multisegmented, woven nitinol cylinder that can be deployed through a small delivery catheter. The AVP II differs from the original AVP in having a finer, more tightly woven nitinol frame and three, rather than one occlusive segment. The authors report the first use of the AVP II for occlusion of bilateral large arteriovenous malformations in a patient with hereditary hemorrhagic telangiectasia.

Methylphenidate administration to juvenile rats alters brain areas involved in cognition, motivated behaviors, appetite, and stress.

Thousands of children receive methylphenidate (MPH; Ritalin) for attention deficit/hyperactivity disorder (ADHD), yet the long-term neurochemical consequences of MPH treatment are unknown. To mimic clinical Ritalin treatment in children, male rats were injected with MPH (5 mg/kg) or vehicle twice daily from postnatal day 7 (PND7)-PND35. At the end of administration (PND35) or in adulthood (PND135), brain sections from littermate pairs were immunocytochemically labeled for neurotransmitters and cytological markers in 16 regions implicated in MPH effects and/or ADHD etiology. At PND35, the medial prefrontal cortex (mPFC) of rats given MPH showed 55% greater immunoreactivity (-ir) for the catecholamine marker tyrosine hydroxylase (TH), 60% more Nissl-stained cells, and 40% less norepinephrine transporter (NET)-ir density. In hippocampal dentate gyrus, MPH-receiving rats showed a 51% decrease in NET-ir density and a 61% expanded distribution of the new-cell marker PSA-NCAM (polysialylated form of neural cell adhesion molecule). In medial striatum, TH-ir decreased by 21%, and in hypothalamus neuropeptide Y-ir increased by 10% in MPH-exposed rats. At PND135, MPH-exposed rats exhibited decreased anxiety in the elevated plus-maze and a trend for decreased TH-ir in the mPFC. Neither PND35 nor PND135 rats showed major structural differences with MPH exposure. These findings suggest that developmental exposure to high therapeutic doses of MPH has short-term effects on select neurotransmitters in brain regions involved in motivated behaviors, cognition, appetite, and stress. Although the observed neuroanatomical changes largely resolve with time, chronic modulation of young brains with MPH may exert effects on brain neurochemistry that modify some behaviors even in adulthood.

Ultrastructural localization of estrogen receptor beta immunoreactivity in the rat hippocampal formation.

Several lines of evidence indicate that estrogen affects hippocampal synaptic plasticity through rapid nongenomic mechanisms, possibly by binding to plasma membrane estrogen receptors (ERs). We have previously shown that ERalpha immunoreactivity (ir) is in select interneuron nuclei and in several extranuclear locations, including dendritic spines and axon terminals, within the rat hippocampal formation (Milner et al., [2001] J Comp Neurol 429:355). The present study sought to determine the cellular and subcellular locations of ERbeta-ir. Coronal hippocampal sections from diestrus rats were immunolabeled with antibodies to ERbeta and examined by light and electron microscopy. By light microscopy, ERbeta-ir was primarily in the perikarya and proximal dendrites of pyramidal and granule cells. ERbeta-ir was also in a few nonprincipal cells and scattered nuclei in the ventral subiculum and CA3 region. Ultrastructural analysis revealed ERbeta-ir at several extranuclear sites in all hippocampal subregions. ERbeta-ir was affiliated with cytoplasmic organelles, especially endomembranes and mitochondria, and with plasma membranes primarily of principal cell perikarya and proximal dendrites. ERbeta-ir was in dendritic spines, many arising from pyramidal and granule cell dendrites. In both dendritic shafts and spines, ERbeta-ir was near the perisynaptic zone adjacent to synapses formed by unlabeled terminals. ERbeta-ir was in preterminal axons and axon terminals, associated with clusters of small, synaptic vesicles. ERbeta-labeled terminals formed both asymmetric and symmetric synapses with dendrites. ERbeta-ir also was detected in glial profiles. The cellular and subcellular localization of ERbeta-ir was generally similar to that of ERalpha, except that ERbeta was more extensively found at extranuclear sites. These results suggest that ERbeta may serve primarily as a nongenomic transducer of estrogen actions in the hippocampal formation.

Ultrastructural evidence for mu-opioid modulation of cholinergic pathways in rat dentate gyrus.

Within the rat hippocampal formation, cholinergic afferents and mu-opioid receptors (MORs) are involved in many crucial learning processes, including those associated with drug reward. Pharmacological data, and the overlapping distributions of cholinergic and mu-opioid systems, particularly in the dentate gyrus, suggest that MOR activation is a potential mechanism for endogenous opioid modulation of cholinergic activity. To date, anatomical evidence supporting this has not been reported. To delineate the relationship between cholinergic afferents and MOR-containing processes in the dentate gyrus, hippocampal sections were dually immunolabeled for vesicular acetylcholine transporter (VAChT) and MOR-1 and examined by electron microscopy. VAChT immunoreactivity was in unmyelinated axons and axon terminals, and was most often associated with small synaptic vesicles. MOR immunoreactivity was found in axons, axon terminals and, to a lesser extent, perikarya, which resembled GABAergic basket cells. Semi-quantitative ultrastructural analysis revealed that from 5% to 13% (depending on laminar location) of VAChT-immunoreactive (ir) presynaptic profiles contained MOR immunoreactivity. Additionally, 7% of VAChT-ir presynaptic profiles directly apposed MOR-ir axons and terminals, and there were almost no appositions to MOR-ir dendrites. These data suggest that opioids may directly and indirectly modulate acetylcholine release and/or reuptake. In the hilus and molecular layer, 4% of VAChT-ir terminals contacted dendritic shafts that were also contacted by MOR-ir terminals. This suggests that cholinergic afferents and MOR-containing afferents can converge on granule cell dendrites (which are restricted to the molecular layer) and on interneuron dendrites in the hilus. The results of this study provide ultrastructural evidence for direct and indirect modulation of cholinergic systems by mu-opioids in the hippocampal formation.