Selective Internal Radiation Therapy for Hepatocellular Carcinoma Across the Barcelona Clinic Liver Cancer Stages.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common lethal cancer, and there is a need for effective therapies. Selective internal radiation therapy (SIRT) has been increasingly used, but is not supported by guidelines due to a lack of solid evidence. AIMS: Determine the efficacy and safety of SIRT in HCC across the Barcelona Clinic Liver Cancer (BCLC) stages A, B, and C. METHODS: Consecutive patients that received SIRT between 2006 and 2016 at two centers in Canada were evaluated. RESULTS: We analyzed 132 patients, 12 (9%), 62 (47%), and 58 (44%) belonged to BCLC stages A, B, and C; mean age was 61.2 (SD ± 9.2), and 89% were male. Median survival was 12.4 months (95% CI 9.6-16.6), and it was different across the stages: 59.7 (95% CI NA), 12.8 (95% CI 10.2-17.5), and 9.3 months (95% CI 5.9-11.8) in BCLC A, B, and C, respectively (p = 0.009). Independent factors associated with survival were previous HCC treatment (HR 2.01, 95% CI 1.23-3.27, p = 0.005), bi-lobar disease (HR 2.25, 95% CI 1.30-3.89, p = 0.003), ascites (HR 1.77, 95% CI 0.99-3.13, p = 0.05), neutrophil-to-lymphocyte ratio (HR 1.11, 95% CI 1.02-1.20, p = 0.01), Albumin-Bilirubin (ALBI) grade-3 (HR 2.69, 95% CI 1.22-5.92, p = 0.01), tumor thrombus (HR 2.95, 95% CI 1.65-5.24, p < 0.001), and disease control rate (HR 0.62, 95% CI 0.39-0.96, p = 0.03). Forty-four (33%) patients developed severe adverse events, and ALBI-3 was associated with higher risk of these events. CONCLUSIONS: SIRT has the potential to be used across the BCLC stages in cases with preserved liver function. When using it as a rescue treatment, one should consider variables reflecting liver function, HCC extension, and systemic inflammation, which are associated with mortality.

Prostate perfusion mapped by technetium-99m macroaggregated albumin after selective arterial injection.

PURPOSE: To determine if perfusion of the prostate can be mapped using technetium-99m ((99m)Tc) macroaggregated albumin (MAA) after selective prostate artery catheterization. MATERIALS AND METHODS: Selective prostate artery injections of MAA were performed and analyzed in 14 patients; 9 patients received unilateral injection, and 5 patients received bilateral injections (37 MBq/1 mCi per injection). Fused single-photon emission computed tomography/computed tomography (SPECT/CT) images were subsequently acquired using a fiducial marker technique. Perfusion distribution was assessed, and relative intraprostatic versus extraprostatic activity was quantified and compared between groups. RESULTS: The percentage of the prostate gland containing activity was significantly greater for the bilateral injection group compared with the unilateral injection group (76.6% vs 44.3%, P < .05). The percentage of relative intraprostatic versus extraprostatic activity was significantly lower for the bilateral injection group compared with the unilateral injection group (40.3% vs 75.9%, P < .05). Sites of visualized extraprostatic activity included the seminal vesicles (8 of 14 patients), internal iliac vessels (7 of 14 patients), bladder wall (5 of 14 patients), space of Retzius (3 of 14 patients), rectal wall (3 of 14 patients), and penis (1 of 14 patients). CONCLUSIONS: Perfusion mapping with (99m)Tc-MAA can be effectively performed with SPECT/CT after selective prostate artery catheterization. The relative percentage of intraprostatic versus extraprostatic activity can be quantified, and the distribution of activity within and outside the prostate gland can be determined.

Percutaneous vertebroplasty for osteoporotic vertebral compression fracture.

BACKGROUND: Percutaneous vertebroplasty is widely used to treat acute and subacute painful osteoporotic vertebral fractures although recent placebo-controlled trials have questioned its value. OBJECTIVES: To synthesise the available evidence regarding the benefits and harms of vertebroplasty for treatment of osteoporotic vertebral fractures. SEARCH METHODS: We searched CENTRAL, MEDLINE and EMBASE up to November 2014. We also reviewed reference lists of review articles, trials and trial registries to identify any other potentially relevant trials. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials (RCTs) including adults with painful osteoporotic vertebral fractures of any duration and comparing vertebroplasty with placebo (sham), usual care, or any other intervention. As it is least prone to bias, vertebroplasty compared with placebo was the primary comparison. Major outcomes were mean overall pain, disability, disease-specific and overall health-related quality of life, patient-reported treatment success, new symptomatic vertebral fractures and number of other serious adverse events. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected trials for inclusion, extracted data, performed 'Risk of bias' assessment and assessed the quality of the body of evidence for the main outcomes using GRADE. MAIN RESULTS: Eleven RCTs and one quasi-RCT conducted in various countries were included. Two trials compared vertebroplasty with placebo (209 randomised participants), six compared vertebroplasty with usual care (566 randomised participants) and four compared vertebroplasty with kyphoplasty (545 randomised participants). Trial size varied from 34 to 404 participants, most participants were female, mean age ranged between 63.3 and 80 years, and mean symptom duration varied from a week to more than six months.Both placebo-controlled trials were judged to be at low overall risk of bias while other included trials were generally considered to be at high risk of bias across a range of criteria, most seriously due to lack of participant and study personnel blinding.Compared with placebo, there was moderate quality evidence based upon two trials that vertebroplasty provides no demonstrable benefits with respect to pain, disability, disease-specific or overall quality of life or treatment success. At one month, mean pain (on a scale 0 to 10, higher scores indicate more pain) was 5 points with placebo and 0.7 points better (1.5 better to 0.15 worse) with vertebroplasty, an absolute pain reduction of 7% (15% better to 1.5% worse) and relative reduction of 10% (21% better to 2% worse) (two trials, 201 participants). At one month, mean disability measured by the Roland Morris Disability Questionnaire (scale range 0 to 23, higher scores indicate worse disability) was 13.6 points in the placebo group and 1.1 points better (2.9 better to 0.8 worse) in the vertebroplasty group, absolute improvement in disability 4.8% (12.8% better to 3.3% worse), relative change 6.3% better (17.0% better to 4.4% worse) (two trials, 201 participants).At one month, disease-specific quality of life measured by the QUALEFFO (scale 0 to 100, higher scores indicating worse quality of life) was 2.4 points in the placebo group and 0.40 points worse (4.58 better to 5.38 worse) in the vertebroplasty group, absolute change: 0.4% worse (5% worse to 5% better), relative change 0.7% worse (9% worse to 8% better (based upon one trial, 73 participants). At one month overall quality of life measured by the EQ5D (0 = death to 1 = perfect health, higher scores indicate greater quality of life at one month was 0.27 points in the placebo group and 0.05 points better (0.01 worse to 0.11 better) in the vertebroplasty group, absolute improvement in quality of life 5% (1% worse to 11% better), relative change 18% better (4% worse to 39% better) (two trials, 201 participants). Based upon one trial (78 participants) at one month, 9/40 (or 225 per 1000) people perceived that treatment was successful in the placebo group compared with 12/38 (or 315 per 1000; range 150 to 664) in the vertebroplasty group, RR 1.40 (95% CI 0.67 to 2.95), absolute risk difference 9% more reported success (11% fewer to 29% more); relative change 40% more reported success (33% fewer to 195% more).Based upon moderate quality evidence from three trials (one placebo, two usual care, 281 participants) with up to 12 months follow-up, we are uncertain whether or not vertebroplasty increases the risk of new symptomatic vertebral fractures (28/143 observed in the vertebroplasty group compared with 19/138 in the control group; RR 1.47 (95% CI 0.39 to 5.50).Similary, based upon moderate quality evidence from two placebo-controlled trials (209 participants), we are uncertain about the exact risk of other adverse events (3/106 were observed in the vertebroplasty group compared with 3/103 in the placebo group; RR 1.01 (95% CI 0.21 to 4.85)). Notably, serious adverse events reported with vertebroplasty included osteomyelitis, cord compression, thecal sac injury and respiratory failure.Our subgroup analyses provided limited evidence that the effects did not differ according to duration of pain ≤ 6 weeks versus > 6 weeks. Including data from the six trials that compared vertebroplasty with usual care in a sensitivity analyses inconsistently altered the primary results, with all combined analyses displaying substantial to considerable heterogeneity. AUTHORS' CONCLUSIONS: Based upon moderate quality evidence, our review does not support a role for vertebroplasty for treating osteoporotic vertebral fractures in routine practice. We found no demonstrable clinically important benefits compared with a sham procedure and subgroup analyses indicated that results did not differ according to duration of pain ≤ 6 weeks versus > 6 weeks. Sensitivity analyses confirmed that open trials comparing vertebroplasty with usual care are likely to have overestimated any benefit of vertebroplasty. Correcting for these biases would likely drive any benefits observed with vertebroplasty towards the null, in keeping with findings from the placebo-controlled trials.Numerous serious adverse events have been observed following vertebroplasty. However due to the small number of events, we cannot be certain about whether or not vertebroplasty results in a clinically important increased risk of new symptomatic vertebral fractures and/or other serious adverse events. Patients should be informed about both the lack of high quality evidence supporting benefit of vertebroplasty and its potential for harm.

Canadian Association of Radiologists consensus guidelines for the prevention of contrast-induced nephropathy: update 2012.

PURPOSE: Contrast-induced acute kidney injury or contrast-induced nephropathy (CIN) is a significant complication of intravascular contrast medium (CM). These guidelines are intended as a practical approach to risk stratification and prevention. The major risk factor that predicts CIN is pre-existing chronic kidney disease. METHODS: Members of the committee represent radiologists and nephrologists across Canada. The previous guidelines were reviewed, and an in-depth up-to-date literature review was carried out. RESULTS: A serum creatinine level (SCr) should be obtained, and an estimated glomerular filtration rate (eGFR) should be calculated within 6 months in the outpatient who is stable and within 1 week for inpatients and patients who are not stable. Patients with an eGFR of ≥ 60 mL/min have an extremely low risk of CIN. The risk of CIN after intra-arterial CM administration appears be at least twice that after intravenous administration. Fluid volume loading remains the single most important measure, and hydration regimens that use sodium bicarbonate or normal saline solution should be considered for all patients with GFR < 60 mL/min who receive intra-arterial contrast and when GFR < 45 mL/min in patients who receive intravenous contrast. Patients are most at risk for CIN when eGFR < 30 mL/min. Additional preventative measures include the following: avoid dehydration, avoid CM when appropriate, minimize CM volume and frequency, avoid high osmolar CM, and discontinue nephrotoxic medications 48 hours before administration of CM.

Surveillance of a coiled renal artery aneurysm by contrast-enhanced ultrasound with Definity.

Imaging surveillance is necessary to assess for long-term procedural outcomes after endovascular treatment. This is generally performed by computed tomography (CT) or magnetic resonance imaging (MRI). Contrast-enhanced ultrasound (CEUS) has recognized utility for cardiovascular and abdominal applications and is an alternative option in patients with renal impairment or CT/MR contrast-related reactions. We believe that we present the first reported case of CEUS in the surveillance of a treated renal artery aneurysm. The 57-year-old patient had a severe CT contrast allergy. CEUS performed with Definity microbubble ultrasound contrast (Lantheus Medical Imaging, Billerica, Mass) was well tolerated and showed no residual filling of the aneurysm.

Role of imaging in clinical islet transplantation.

Islet transplantation is an innovative and effective clinical strategy for patients with type 1 diabetes whose clinical condition is inadequately managed even with the most aggressive medical treatment regimens. In islet transplantation, purified islets extracted from the pancreas of deceased donors are infused into the portal vein of the recipient liver. Engrafted islets produce insulin and thus restore euglycemia in many patients. After islet transplantation performed with the original Edmonton protocol, 80% of patients were insulin independent at 1 year and approximately 20% were insulin independent at 5 years. With more recent technical advances, 50% of patients or more maintain insulin independence 5 years after islet transplantation. The success rate with single-donor islet infusions has markedly improved over time. Even in patients who lose insulin independence, islet transplantation is considered successful because it provides improved glycemic control and a higher quality of life. Imaging plays an important role in islet transplantation and is routinely used to evaluate potential recipients, guide the transplantation process, and monitor patients for posttransplantation complications. Because of the success of islet transplantation and its increasing availability worldwide, familiarity with the role of imaging is important.

Embolization of musculoskeletal bone tumors.

Bone tumors may present as incidental findings, with pain or loss of function, or as fractures. There is a broad range of indications for transarterial embolization (TAE) in primary or metastatic bone tumors: to reduce operative hemorrhagic risks, to simplify or allow more definitive surgery, or in the context of pain palliation, fever, bleeding, or hypercalcemic and other rheological factors. Embolization may also increase tumor sensitivity to chemotherapy or radiation therapy. The procedure itself is often complex with significant risk to adjacent structures and is usually part of a wider treatment strategy. There are many options of embolic agent, techniques, and end points but all aim to devascularize the tumor. Catheter angiography at the time of TAE is used to determine the correct embolic agent and technique with care taken to isolate at risk structures. Many factors determine the best choice of embolic material, probably the most important of which is operator experience. In life-threatening situations or in preoperative embolizations of metastatic tumors, many operators opt for a combination of particulate emboli and stainless steel or platinum coils. Agents discussed include polyvinyl alcohol particles, trisacryl microspheres, gelatin sponge, liquid embolic agents, and embolization coils. Tumor types treated include vascular metastatic lesions, commonly renal cell or thyroid, particularly in locations prone to fracture; giant cell tumors; aneurysmal bone cysts; vertebral hemangiomas, osteosarcomas; arteriovenous malformations; and osteoblastomas. TAE should be considered in the treatment algorithm of primary or secondary bone tumors. Specific benefit is present where there is a high risk of bleeding at surgery, where there is spinal involvement and neural encroachment, where active bleeding is present or in awkward surgical locations where prolonged surgery is anticipated.

Visceral Adipose Tissue Radiodensity Is Linked to Prognosis in Hepatocellular Carcinoma Patients Treated with Selective Internal Radiation Therapy.

Hepatocellular carcinoma (HCC) constitutes the fourth leading cause of cancer-related mortality. Various factors, such as tumor size, tumor multiplicity, and liver function, have been linked to the prognosis of HCC. The aim of this study was to explore the prognostic significance of muscle, subcutaneous and visceral adipose tissue (VAT) mass, and radiodensity, in a cohort of 101 HCC patients treated with selective internal radiation therapy (SIRT). Muscle and adipose tissue cross sectional area (cm2/m2) and radiodensity, reported as the Hounsfield Unit (HU), were determined using pre-SIRT computed tomography images. Cox proportional hazard models and exact logistic regression were conducted to assess associations between body composition and adverse outcomes. Majority of the patients were male (88%) with a mean VAT radiodensity of -85 ± 9 HU. VAT radiodensity was independently associated with mortality (HR 1.05; 95% CI: 1.01-1.08; p = 0.01), after adjusting for cirrhosis etiology, Barcelona Clinic Liver Cancer stage, previous HCC treatment, and portal hypertension markers. Patients with a high VAT radiodensity of ≥-85 HU had a two times higher risk of mortality (HR 2.01, 95% CI 1.14-3.54, p = 0.02), compared to their counterpart. Clinical features of portal hypertension were more prevalent in patients with high VAT radiodensity. High VAT radiodensity was associated with severe adverse events after adjusting for confounding factors. High VAT radiodensity is independently associated with both increased mortality and severe adverse events in patients treated with SIRT. VAT radiodensity measurement might serve as an objective approach to identify patients who will experience the most benefit from SIRT.

Effects of probiotic therapy on portal pressure in patients with cirrhosis: a pilot study.

BACKGROUND: Recent literature has supported the role of bacterial translocation as a mediator of splanchnic vasodilatation and portal hypertension. The objective of this study was to determine whether the probiotic VSL#3 would reduce portal pressure in patients with cirrhosis. METHODS: Eight patients with compensated or very early decompensated cirrhosis and hepatic venous pressure gradient (HVPG) >10 mmHg, received 2 months of VSL#3 (3600 billion bacteria daily). The HVPG, intestinal permeability, endotoxin, tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, renin and aldosterone were measured at baseline and study end. RESULTS: There was no change in the HVPG or intestinal permeability from baseline to study end but there was a trend to reduction in plasma endotoxin (P=0.09), a mild but significant increase in serum TNF-alpha (P=0.02) and a significant reduction in plasma aldosterone (P=0.03). CONCLUSIONS: Within the limitations of small sample size, there does not appear to be a benefit of probiotic therapy for portal pressure reduction in patients with compensated or early decompensated cirrhosis. The reductions in endotoxin and aldosterone suggest possible beneficial effects of probiotics for this patient population. The clinical significance of the small but unexpected increase in TNF-alpha is unclear. Future studies are planned in patients with decompensated cirrhosis.

Embolization of musculoskeletal tumors.

Transarterial embolization should be considered in the treatment algorithm of primary or secondary bone tumors. Specific benefit is present where there is a high risk of bleeding at surgery, where there is spinal involvement and neural encroachment, where active bleeding is present, or in awkward surgical locations where prolonged surgery is anticipated.

Using inferior vena cava filters to prevent pulmonary embolism.

OBJECTIVE: To review the evidence for using inferior vena cava (IVC) filters to prevent pulmonary embolism (PE) in high-risk patients. QUALITY OF EVIDENCE: Ovid MEDLINE was searched from 1966 to 2006 for all English-language papers on IVC filters. Evidence was graded according to the 3-level classification system. Most evidence found was level II. MAIN MESSAGE: Inferior vena cava filters are used to prevent PE in patients with contraindications to, complications of, or failure of anticoagulation therapy and patients with extensive free-floating thrombi or residual thrombi following massive PE. Current evidence indicates that IVC filters are largely effective; breakthrough PE occurs in only 0% to 6.2% of cases. Contraindications to implantation of IVC filters include lack of venous access, caval occlusion, uncorrectable coagulopathy, and sepsis. Complications include misplacement or embolization of the filter, vascular injury or thrombosis, pneumothorax, and air emboli. Recurrent PE, IVC thrombosis, filter migration, filter fracture, or penetration of the caval wall sometimes occur with long-term use. CONCLUSION: When used appropriately, IVC filters are a safe and effective method of preventing PE. Using retrievable filters might reduce long-term complications.

Advancing the Understanding of Environmental Transformations, Bioavailability and Effects of Nanomaterials, an International US Environmental Protection Agency-UK Environmental Nanoscience Initiative Joint Program.

Nanotechnology has significant economic, health, and environmental benefits, including renewable energy and innovative environmental solutions. Manufactured nanoparticles have been incorporated into new materials and products because of their novel or enhanced properties. These very same properties also have prompted concerns about the potential environmental and human health hazard and risk posed by the manufactured nanomaterials. Appropriate risk management responses require the development of models capable of predicting the environmental and human health effects of the nanomaterials. Development of predictive models has been hampered by a lack of information concerning the environmental fate, behavior and effects of manufactured nanoparticles. The United Kingdom (UK) Environmental Nanoscience Initiative and the United States (US) Environmental Protection Agency have developed an international research program to enhance the knowledgebase and develop risk-predicting models for manufactured nanoparticles. Here we report selected highlights of the program as it sought to maximize the complementary strengths of the transatlantic scientific communities by funding three integrated US-UK consortia to investigate the transformation of these nanoparticles in terrestrial, aquatic, and atmospheric environment. Research results demonstrate there is a functional relationship between the physicochemical properties of environmentally transformed nanomaterials and their effects and that this relationship is amenable to modeling. In addition, the joint transatlantic program has allowed the leveraging of additional funding, promoting transboundary scientific collaboration.

Episodic Mood Changes Preceding an Exacerbation of Multiple Sclerosis.

Multiple sclerosis is a neurologic inflammatory disease that can manifest with psychiatric symptoms. Although depression is the most common psychiatric diagnosis in patients with multiple sclerosis, how depression develops is not fully understood. We present the case of an individual who displayed episodic mood changes preceding an exacerbation of multiple sclerosis symptoms. The clinical and research implications of this association are discussed.

Diagnosis of a bleeding Dieulafoy lesion on computed tomography and its subsequent embolization.

Dieulafoy lesions are a potentially serious cause of gastrointestinal bleeding. Because they may bleed intermittently, and only be endoscopically evident during hemorrhage, their diagnosis can be challenging. This is the first case to be reported in the English literature of a patient with a Dieulafoy lesion diagnosed during computed tomography (CT) examination. Reduced acquisition times required for multislice helical CT allow the application of CT angiography in the diagnosis of gastrointestinal bleeding. CT scans are now widely used in the diagnostic algorithm for acute gastrointestinal hemorrhage, and the present case illustrates that with fortuitous timing, they can provide critical information and an opportunity for selected angiography and coil embolization.

A preclinical study of the safety and efficacy of Occlusin™ 500 Artificial Embolization Device in sheep.

INTRODUCTION: This study evaluated the safety, effectiveness, and biodegradation of a new embolic agent, Occlusin™ 503 Artificial Embolization Device (OCL 503). The agent consists of biodegradable poly-lactic-co-glycolic acid microspheres (150-212 µm) coated with type I bovine collagen and was compared with Embosphere® Microspheres (300-500 µm) in this controlled study of uterine artery embolization (UAE) in sheep. METHODS: Unilateral UAE was performed in 32 adult ewes randomly assigned. Vessels were embolized to effective stasis. The cohort was divided into four groups, which were sacrificed at 1, 3, 6, and 12 months. RESULTS: Both agents were 100% effective in achieving stasis. At 6 months, all OCL 503-treated arteries were occluded, the microspheres degraded with time, and at 12 months all four animals examined demonstrated recanalization. OCL 503 was found in the untreated uterine artery in one animal with no other evidence of non target embolization. In the Embosphere-treated group, all vessels remained occluded and microspheres were detected in the contralateral uterine artery in 6 of 15 examined vessels and in 10 vaginal, 2 ovarian, and 1 vesical artery. No procedural-related complications were seen in either group. CONCLUSIONS: OCL 503 is as effective an embolic agent as Embosphere® Microspheres when embolizing ovine uterine arteries and resorbs with time, allowing recanalization of the treated arteries. No device-related issues or adverse events were observed.

Lipophilic photosensitizer administration via the prostate arteries for photodynamic therapy of the canine prostate.

BACKGROUND: Current limitations of interstitial photodynamic therapy (PDT) for treatment of prostate cancer include low drug selectivity after intravenous (i.v.) administration and incomplete ablation of glandular tissue. To overcome these limitations, intra-arterial (i.a.) injection of a photosensitizer was tested in a canine model. METHODS: A lipophilic photosensitizer, SL052 formulated in liposomes or dissolved in dimethyl sulphoxide (DMSO), was injected into male dogs as an intravenous injection or intra-arterially via the prostate arteries. Optical fibers were inserted into the prostate 3h after i.v. or immediately following i.a. drug delivery. Laser light was delivered through the fibers in cycles controlled by a computer-driven switch. Drug concentration (fluorescence) and light transmission in prostate tissue were monitored during the course of PDT. Side effect profile and completeness of prostate gland ablation were the primary parameters compared among treatment groups. Control animals received drug-only or light-only treatment. RESULTS AND CONCLUSION: Thirteen dogs were treated by PDT mediated by i.a. injection of SL052 dissolved in DMSO and attained either complete ablation of prostatic glandular tissue or significant reduction of prostate volume compared with that of pre-PDT (p<0.0001). When compared to i.v. administration the i.a. route resulted in more complete photo-ablation. Associated side effect included acute urinary retention which resolved overtime. No incontinence was observed. With careful tailoring of PDT drug and light doses, interstitial PDT with i.a. injection of SL052-DMSO has the potential to provide effective treatment for prostate disease.

Ablative technologies in the management of patients with primary and secondary liver cancer: an overview.

Interventional ablative technologies have played an increasingly important role in the management of patients with primary or secondary liver malignancies. Ethanol and acetic acid ablation were the primary modalities available 2 decades ago. Today, several new technologies are available, including radiofrequency ablation, cryoablation, and microwave ablation. Radiofrequency ablation is the most widely practiced, however, cryoablation and microwave ablation are reasonable choices in certain situations. Irreversible electroporation is a newer technique, which has yet to enter clinical practice, but shows promising preliminary results. Herein, we provide a brief overview of the above-mentioned technologies with a focus on principles of ablation and technique. We also describe the use of these techniques in the context of cytoreduction, a noncurative approach aimed at reducing the overall tumour burden and providing concomitant survival benefit.

Portal vein embolization with radiolabeled polyvinyl alcohol particles in a swine model: hepatic distribution and implications for pancreatic islet cell transplantation.

The distribution of radiolabeled polyvinyl alcohol microspheres (PVAMs) when infused into the portal vein of domestic swine was investigated, with the purpose of assessing implications for pancreatic islet cell transplantation. PVAMs measuring 100-300 microm (Contour SE) and labeled with (99m)Tc were infused into the main portal vein of 12 swine, with intermittent portal venous pressure measurements. The infusion catheter was introduced antegradely via direct or indirect cannulation of the portal vein. The liver was subsequently divided into anatomical segments. Radioactivity (decay corrected) was measured for (99m)Tc microsphere synthesis, dose preparation, gross organ activities, tissue samples, and blood. Particulate labeling, catheter positioning, and infusion were successful in all cases. The number of particles used was (185,000 +/- 24,000) with a volume of 1 ml. Mean portal pressure at 5 min was significantly higher than baseline, but without a significant difference at 15 min. Extrahepatic tissue and serum radioactivity was negligible. A significant difference in number of radioactive particles per gram was detected between segments 6/7 and segments 5/8. Intrasegmental activity was analyzed, and for segments 2/3 a significant difference in the percentage dose per gram across samples was demonstrated (P = 0.001). Effective and stable radiolabeling of PVAMs with (99m)Tc-sulfur colloid was demonstrated. Portal venous infusion of 100- to 300-microm particles showed entrapment in the sinusoidal hepatic system with transient portal pressure elevation. Preferential embolization into the right lateral and posterior segments occurs, suggesting that flow dynamics/catheter tip position plays a role in particle distribution.

Photodynamic therapy of the canine prostate: intra-arterial drug delivery.

PURPOSE: Interstitial photodynamic therapy (PDT) selectively destroys tissue targeted with a photosensitizer and then exposed to light of a specific wavelength. We report a novel delivery method--intra-arterial drug delivery for PDT of the prostate--in a canine model. METHODS: To evaluate drug distribution, the prostatovesical artery was selectively cannulated and photosensitizers alone or in conjunction with 99m-technetium-labeled macro-aggregated albumin ((99m)Tc-MAA) were injected via a 3 Fr microcatheter in 8 animals. One dog was followed for 3 months to determine tolerance and toxicity. The remaining animals were euthanized and imaged with whole-body single photon emission CT and gamma counting for radioactivity distribution. Photosensitizer distribution was further analyzed by fluorescence confocal microscopy and tissue chemical extraction. To evaluate PDT, the photosensitizer QLT0074 was infused in 3 animals followed by interstitial illumination with 690 nm laser light. RESULTS: Intra-arterial infusion selectively delivered drugs to the prostate, with both radioactivity and photosensitizer levels significantly higher (up to 18 times) than in the surrounding organs (i.e., rectum). With unilateral injection of (99m)Tc-MAA, only the injected half of the prostate showed activity whereas bilateral administration resulted in drug delivery to the entire prostate. PDT resulted in comprehensive damage to the prostate without severe complications or systemic toxicity. CONCLUSION: Injection of radiolabeled MAA into the prostatovesical artery results in distribution within the prostate with negligible amounts reaching the adjacent organs. PDT also demonstrates selective damage to the prostate, which warrants clinical application in targeted prostate therapies.