Three-Dimensional Quantitative Color-Coding Analysis of Hepatic Arterial Flow Change during Chemoembolization of Hepatocellular Carcinoma

Purpose

To evaluate feasibility of using three-dimensional (3D) quantitative color-coding analysis (QCA) to quantify substasis endpoints after transcatheter arterial chemoembolization of hepatocellular carcinoma (HCC).

Animal tumor models for PET in drug development

Positron emission tomography (PET) is being increasingly applied to animal tumor models due to the need for proof-of-concept testing and preclinical efficacy studies of anticancer agents. Regardless of the nature of an experiment, investigators should carefully select a suitable animal tumor model as part of the experimental design. This review introduces sources of information and the guiding principles regarding applicability of various animal tumor models for PET in anticancer agent development especially for small animals.     

A Water-Based Liquid Embolic: Evaluation of its Safety and Efficacy in a Rabbit Kidney Model

PurposeTo evaluate a novel aqueous-based liquid embolic (Embrace Hydrogel Embolic System, [HES]) that has been developed to embolize hypervascular tumors by filling the tumor vascular bed and solidifying into a hydrogel. HES was evaluated for embolization safety and efficacy relative to microspheres in a preclinical rabbit kidney model.Materials and MethodsA renal embolization model in New Zealand white rabbits was utilized. Twenty-four rabbits underwent unilateral kidney embolization via the main renal artery with either HES or 40-μm microspheres. Twenty-two rabbits survived the procedure and were monitored for 2, 12, 17.5, or 26 weeks before sacrifice. All rabbits underwent a repeat renal angiogram before necropsy. HES was evaluated for nontarget embolization, safety, and embolization effectiveness as measured by recanalization and viability of embolized tissue.ResultsBoth embolization materials were found to be safe, with targeted tissue necrosis and absence of nontarget embolization. Prenecropsy angiograms found vascular recanalization in 0/14 (0%) HES-embolized kidneys and in 3/8 (38%) microsphere-embolized kidneys (P = .036). Viable kidney tissue was observed in 2/14 (14%) kidneys embolized with HES and 5/8 (63%) kidneys embolized with microspheres (P = .052). All kidneys embolized with microspheres that showed vascular recanalization had viable tissue on histological sections. HES was observed in vessels as small as 10 μm in diameter in histological analysis.ConclusionsHES provided deep, durable vascular bed embolization that resulted in less recanalization and, on an average, less viable target tissue compared with 40-μm microspheres. No systemic effects or nontarget tissue embolization was identified.     

明胶海绵栓塞建立实验动物急性脑梗死模型

目的 探讨明胶海绵栓塞猴颈内动脉复制急性脑梗死模型的可行性。方法选用成年猴6只，经股动脉穿刺插管，明胶海绵栓塞颈内动脉，然后行数字减影血管造影（DSA）显示血管闭塞情况，栓塞后3h，4h，6h，8h，12h，24hCT平扫，观察脑梗死CT表现。结果6只猴栓塞后DSA显示颈内动脉闭塞，大脑前、中动脉未显影。栓塞后6hCT平扫可见栓塞侧大脑半球片状低密度坏死区。结论用明胶海绵栓塞颈内动脉复制急性脑梗死模型可行。     

Three-Dimensional Augmented Reality Visualization Informs Locoregional Therapy in a Translational Model of Hepatocellular Carcinoma

PurposeTo evaluate the utility of visualizing preprocedural MR images in 3-dimensional (3D) space using augmented reality (AR) before transarterial embolization of hepatocellular carcinoma (HCC) in a preclinical model.Materials and MethodsA total of 28 rats with diethylnitrosamine-induced HCCs > 5 mm treated with embolization were included in a prospective study. In 12 rats, 3D AR visualization of preprocedural MR images was performed before embolization. Procedural metrics including catheterization time and radiation exposure were compared vs a prospective cohort of 16 rats in which embolization was performed without AR. An additional cohort of 15 retrospective cases was identified and combined with the prospective control cohort (n = 31) to improve statistical power.ResultsA 37% reduction in fluoroscopy time, from 11.7 min to 7.4 minutes, was observed with AR when compared prospectively, which did not reach statistical significance (P = .12); however, when compared with combined prospective and retrospective controls, the reduction in fluoroscopy time from 14.1 min to 7.4 minutes (48%) was significant (P = .01). A 27% reduction in total catheterization time, from 42.7 minutes to 31.0 minutes, was also observed with AR when compared prospectively, which did not reach statistical significance (P = .11). No significant differences were seen in dose–area product or air kerma prospectively.ConclusionsThree-dimensional AR visualization of preprocedural imaging may aid in the reduction of procedural metrics in a preclinical model of transarterial embolization. These data support the need for further studies to evaluate the potential of AR in endovascular oncologic interventions.     

Liquid Embolic Agents for Endovascular Embolization: Evaluation of an Established (Onyx) and a Novel (PHIL) Embolic Agent in an In Vitro AVM Model

BACKGROUND AND PURPOSE:Embolization plays a key role in the treatment of arteriovenous malformations. The aim of this study was to evaluate an established (Onyx) and a novel (precipitating hydrophobic injectable liquid [PHIL]) liquid embolic agent in an in vitro AVM model.MATERIALS AND METHODS:An AVM model was integrated into a circuit system. The artificial nidus (subdivided into 28 honeycomb-like sections) was embolized with Onyx 18 (group Onyx; n = 8) or PHIL 25 (group PHIL; n = 8) with different pause times between the injections (30 and 60 seconds, n = 4 per study group) by using a 1.3F microcatheter. Procedure times, number of injections, embolization success (defined as the number of filled sections of the artificial nidus), volume of embolic agent, and frequency and extent of reflux and draining vein embolization were assessed.RESULTS:Embolization success was comparable between Onyx and PHIL. Shorter pause times resulted in a significantly higher embolization success for PHIL (median embolization score, 28 versus 18; P = .011). Compared with Onyx, lower volumes of PHIL were required for the same extent of embolization (median volume per section of the artificial nidus, 15.5 versus 3.6 μL; P < .001).CONCLUSIONS:While the embolization success was comparable for Onyx and PHIL, pause time had a considerable effect on the embolization success in an in vitro AVM model. Compared with Onyx, lower volumes of PHIL were required for the same extent of embolization.

Arteriovenous malformations are complex vascular structures composed of feeding arteries, an intervening network of small pathologic blood vessels (the so-called nidus), and draining veins. The lack of an intervening capillary bed allows high-flow arteriovenous shunting of blood. While AVMs can occur throughout the entire body, cerebral AVMs are of particular relevance due to their ability to cause impairing neurologic symptoms and their considerable risk of hemorrhage.¹Alone or in combination with microneurosurgery and stereotactic radiation therapy, embolization plays an important role in the management of cerebral AVMs.² The aim of AVM embolization is complete filling of the nidus, while unwanted reflux into the feeding arteries should be minimized and premature embolization of the draining veins should be avoided.³A wide variety of embolic agents has been and is currently used for embolization of AVMs. At present, the liquid embolic agents (LEAs) ethylene-vinyl alcohol copolymer (EVOH) and n-butyl cyanoacrylate are used most frequently.⁴ Although the embolization results have improved since the introduction of EVOH-based LEAs with rates of complete obliteration ranging from 16% to 100%, the success rate of AVM embolization, especially for complex AVMs, is not yet satisfying.^2,3 Currently, new LEAs are being introduced to improve embolization features, such as embolization efficacy, intraprocedural handling, and control. Furthermore, their use should improve fluoroscopic visibility and reduce artifacts in postinterventional imaging.The aim of this study was to evaluate an established EVOH-based embolic agent and a novel copolymer-based embolic agent in an in vitro AVM model.     

Transcatheter liver lobar ablation: an experimental trial in an animal model

Complete embolization of tumor tissue together with surrounding liver sufficiently prevents collateral blood supply to the tumor, offering curative treatment for hepatic malignancies. The present experiment was designed to test the feasibility of hepatic lobar ablation by means of the transcatheter chemoembolization technique. Five groups of rats (n = 6) were treated with a mixture of iodized oil/ethanol in ratios of 5:1, 4:1, 3:1, 1:1, and 1:0, which was injected selectively into the right-lobe artery until saturation during open surgery. Another group (n = 6) was studied using in vivo microscopy to observe the distribution of the mixture in the liver and changes in hepatic microcirculation. Ethiodol/ethanol mixture entered the portal vein after injection into the hepatic artery creating dual, complete arterial and portal venous embolization. Lobar ablation effects were achieved in 2 weeks in the 5:1, 4:1, and 3:1 ratio groups, indicated by the lobe/liver weight measurements (p < 0.001 vs normal liver). Hepatic arterial administration of the Ethiodol/ethanol mixture creates dual hepatic arterial and portal venous embolization, achieving a lobar ablation effect. Received 12 June 1996; Revision received 23 September 1996; Accepted 14 October 1996     

Hepatic Toxicity After Radioembolization of the Liver Using 90Y-Microspheres: Sequential Lobar Versus Whole Liver Approach

Purpose

⁹⁰Y-radioembolization (RE) is a promising technique for delivering high doses of radiation to liver tumors but may result in compromise of liver function. To gain further perspective, we evaluated the toxicity rates of sequential lobar versus “whole liver” ⁹⁰Y-radioembolization.

Methods

Thirty-four patients with liver malignancy in noncirrhotic livers were included; ⁹⁰Y-radioembolization was performed as either whole liver or sequential lobar treatment in 17 patients each. Standard clinical and liver specific laboratory parameters as well as MR imaging before treatment and at follow-up (6 and 12?weeks) after radioembolization were evaluated for toxicity using the Common Terminology Criteria for Adverse Events (CTCAE). Volumetry of the liver, tumor, and spleen and measurement of portal vein diameter also were performed.

Results

Three months after whole liver RE, 14 liver-related grade 3/4 events were recorded versus 2 events after sequential lobar treatment (P?P?=?0.012). Total liver volume did not change significantly in either group, but shrinkage of the initially treated hepatic lobe with compensatory hypertrophy of the subsequently treated lobe was observed in the sequential lobar group (P?P?=?0.043).

Conclusions

Noncirrhotic patients undergoing sequential lobar radioembolization had less hepatic toxicity compared to whole liver embolization. The sequential approach should be the preferred strategy.     

Transarterial Chemoembolization in a Woodchuck Model of Hepatocellular Carcinoma

PurposeTo assess the feasibility of transarterial chemoembolization with drug-eluting embolic (DEE) microspheres in a woodchuck model of hepatocellular carcinoma (HCC).Materials and MethodsNine woodchucks were studied: 4 normal animals and 5 animals infected with woodchuck hepatitis virus in which HCC had developed. Three animals with HCC underwent multidetector CT. A 3-F sheath was introduced into the femoral artery, and the hepatic arteries were selectively catheterized with 2.0–2.4-F microcatheters. Normal animals underwent diagnostic angiography and bland embolization. Animals with HCC underwent DEE transarterial chemoembolization with 70–150-μm radiopaque microspheres loaded with 37.5 mg doxorubicin per milliliter. Cone-beam CT and multidetector CT were performed. Following euthanasia, explanted livers underwent micro-CT, histopathologic examination, and fluorescence imaging of doxorubicin.ResultsThe tumors were hypervascular and supplied by large-caliber tortuous vessels, with arteriovenous shunts present in 2 animals. There was heterogeneous enhancement on multidetector CT with areas of necrosis. Six tumors were identified. The most common location was the right medial lobe (n = 3). Mean tumor volume was 30.7 cm³ ± 12.3. DEE chemoembolization of tumors was achieved. Excluding the 2 animals with arteriovenous shunts, the mean volume of DEE microspheres injected was 0.49 mL ± 0.17. Fluorescence imaging showed diffusion of doxorubicin from the DEE microspheres into the tumor.ConclusionsWoodchuck HCC shares imaging appearances and biologic characteristics with human HCC. Selective catheterization and DEE chemoembolization may similarly be performed. Woodchucks may be used to model interventional therapies and possibly characterize radiologic–pathologic correlations.     

Development of an animal model for radiofrequency ablation of primary, virally induced hepatocellular carcinoma in the woodchuck

Purpose

To develop a consistent and reproducible method in an animal model for studies of radiofrequency (RF) ablation of primary hepatocellular carcinoma (HCC).

Materials and Methods

Fifteen woodchucks were inoculated with woodchuck hepatitis virus (WHV) to establish chronic infections. When serum γ-glutamyl transpeptidase levels became elevated, the animals were evaluated with ultrasound, and, in most cases, preoperative magnetic resonance (MR) imaging to confirm tumor development. Ultimately, RF ablation of tumors was performed by using a 1-cm probe with the animal submerged in a water bath for grounding. Ablation effectiveness was evaluated with contrast-enhanced MR imaging and gross and histopathologic analysis.

Results

RF ablation was performed in 15 woodchucks. Modifications were made to the initial study design to adapt methodology for the woodchuck. The last 10 of these animals were treated with a standardized protocol using a 1-cm probe that produced a consistent area of tumor necrosis (mean size of ablation, 10.2 mm × 13.1 mm) and led to no complications.

Conclusions

A safe, reliable and consistent method was developed to study RF ablation of spontaneous primary HCC using chronically WHV-infected woodchucks, an animal model of hepatitis B virus–induced HCC.     

Quantitative 4D-Digital Subtraction Angiography to Assess Changes in Hepatic Arterial Flow during Transarterial Embolization: A Feasibility Study in a Swine Model

PurposeTo determine the feasibility of using time-resolved 3D-digital subtraction angiography (4D-DSA) for quantifying changes in hepatic arterial blood flow and velocity during transarterial embolization.Materials and MethodsHepatic arteriography and selective transarterial embolization were performed in 4 female domestic swine (mean weight, 54 kg) using 100–300-μm microspheres. Conventional 2D and 4D-DSA were performed before, during, and after each embolization. From the 4D-DSA reconstructions, blood flow and velocity values were calculated for hepatic arterial branches using a pulsatility-based algorithm. 4D-DSA velocity values were compared to those measured using an intravascular Doppler wire with a linear regression analysis. Paired t-tests were used to compare data before and after embolization.ResultsThere was a weak-to-moderate but statistically significant correlation of flow velocities measured with 4D-DSA and the Doppler wire (r = 0.35, n = 39, P = .012). For vessels with high pulsatility, the correlation was higher (r = 0.64, n = 11, P = .034), and the relationship between 4D-DSA and the Doppler wire fit a linear model with a positive bias toward the Doppler wire (failed to reject at 95% confidence level, P = .208). 4D-DSA performed after partial embolization showed a reduction in velocity in the embolized hepatic arteries compared to pre-embolization (mean, 3.96 ± 0.74 vs 11.8 2± 2.15 cm/s, P = .006).ConclusionQuantitative 4D-DSA can depict changes in hepatic arterial blood velocity during transarterial embolization in a swine model. Further work is needed to optimize 4D-DSA acquisitions and to investigate its applicability in humans.     

The utility of the microcrystalline cellulose sphere as a particulate embolic agent: an experimental study

BACKGROUND AND PURPOSE: Although various particulate materials have been developed as embolization agents, their biocompatibility remains unclear. We used an animal model to examine the possibility of using FDA-approved microcrystalline cellulose spheres (CELPHERE) as solid embolic material for the permanent occlusion of blood vessels. METHODS: Angiographic and histologic studies in 12 canine renal arterial systems were conducted to evaluate the performance of CELPHERE beads at 1 hour, and at 4 and 12 weeks after embolization. RESULTS: The CELPHERE beads traveled to vessels with diameters approximating their own. Larger vessels were occluded by aggregations of beads. There was no disruption of vessel walls and no evidence of perivascular hemorrhage or inflammatory changes. CONCLUSION: Because CELPHERE beads are easy to handle, highly biocompatible, and have few adverse effects, they are suitable for intravascular applications.     

Middle Meningeal Artery Embolization Using Combined Particle Embolization and n-BCA with the Dextrose 5% in Water Push Technique for Chronic Subdural Hematomas: A Prospective Safety and Feasibility Study

BACKGROUND AND PURPOSE:Embolization of the middle meningeal artery for treatment of refractory or recurrent chronic subdural hematomas has gained momentum during the past few years. Little has been reported on the use of the n-BCA liquid embolic system for middle meningeal artery embolization. We present the technical feasibility of using diluted n-BCA for middle meningeal artery embolization.MATERIALS AND METHODS:We sought to examine the safety and technical feasibility of the diluted n-BCA liquid embolic system for middle meningeal artery embolization. Patients with chronic refractory or recurrent subdural hematomas were prospectively enrolled from September 2019 to June 2020. The primary outcome was the safety and technical feasibility of the use of diluted n-BCA for embolization of the middle meningeal artery. The secondary end point was the efficacy in reducing hematoma volume.RESULTS:A total of 16 patients were prospectively enrolled. Concomitant burr-hole craniotomies were performed in 12 of the 16 patients. Two patients required an operation following middle meningeal artery embolization for persistent symptoms. The primary end point was met in 100% of cases in which there were no intra- or postprocedural complications. Distal penetration of the middle meningeal artery branches was achieved in all the enrolled cases. A 7-day post–middle meningeal artery embolization follow-up head CT demonstrated improvement (>50% reduction in subdural hematoma volume) in 9/15 (60%) patients, with 6/15 (40%) showing an unchanged or stable subdural hematoma. At day 21, available CT scans demonstrated substantial further improvement (>75% reduction in subdural hematoma volume).CONCLUSIONS:Embolization of the middle meningeal artery using diluted n-BCA and ethiodized oil (1:6) is safe and feasible from a technical standpoint. The use of a dextrose 5% bolus improves distal penetration of the glue.

Despite traditional treatment with surgical evacuation, chronic subdural hematomas (cSDHs) tend to have an indolent course with frequent recurrences.¹ In recent years, embolization of the middle meningeal artery (MMA) for treatment of refractory or recurrent cSDH has gained momentum, with recent literature showing a significant reduction in the size of the cSDH as well as lower rates of recurrence.² The primary endovascular techniques used to date have involved the use of polyvinyl alcohol particles (PVA) and Onyx liquid embolic (ethylene-vinyl alcohol dissolved in dimethyl-sulfoxide; Medtronic). Another commonly used liquid embolic agent in the neurointerventional area is n-BCA, which is a liquid adhesive that polymerizes rapidly on contact with ionic substances and can be injected to achieve permanent vessel occlusion. The rates of polymerization and flow and the penetration depth can be modified using varying amounts of ethiodized oil as well as concurrent infusion of dextrose 5% in water (D5W) during n-BCA (Trufill, Cordis Neurovascular) injection (D5W-push technique).³ Data on the use of n-BCA as an embolic agent in cases of cSDH are extremely limited. Herein, we sought to study the safety and technical feasibility of using diluted n-BCA for embolization of the MMA for cSDHs.     

Gelatin Microspheres: Correlation between Embolic Effect/Degradability and Cross-linkage/Particle Size

Purpose

To evaluate the embolic effect and degradability of gelatin microspheres (GMS) using various degrees of cross-linkage and particle sizes in rabbit renal artery embolization.

Methods

Four types of GMS were used, as follows: 2 types of cross-linkage and 2 types of particle size. Twenty-four rabbits (6 in each group) were used for the renal artery embolization. Renal angiography was performed before and after embolization of right renal artery. Follow-up renal angiography was performed 2 days (n = 2), 5 days (n = 2), and 15 days (n = 2) after embolization in each group, and then kidneys were removed for histopathological evaluation. Vascular areas of the angiography were measured by Image J software, and the reperfusion rate was calculated. In renal specimens, residual GMS were checked and the degree of degradation was classified according to a 4-point scale.

Results

The mean amounts of large- and small-particle-size GMS injected were 15.0 and 34.3 mg, respectively. Tissue necrosis was confirmed in each group; however, no difference was observed among groups. Renal reperfusion was observed more with small GMS than with large GMS. Renal reperfusion was also observed more with low cross-linked GMS than with high cross-linked GMS. In histopathological specimens, large GMS were confirmed in lobar artery, and small GMS were confirmed in lobular artery. Low cross-linked GMS completely degraded 15 days after embolization. In contrast, high cross-linked GMS were persistent 15 days after embolization.

Conclusion

Degree of cross-linkage and particle size affected degradability and reperfusion.     

Middle Meningeal Artery Embolization with Liquid Embolic Agents for Chronic Subdural Hematoma: A Systematic Review and Meta-analysis

PurposeTo assess the efficacy and safety of middle meningeal artery (MMA) embolization with liquid embolic agents and the outcomes of patients following this procedure.Materials and MethodsA review of the literature was conducted to identify studies investigating the efficacy and safety of MMA embolization with liquid embolic agents in patients with chronic subdural hematoma (cSDH) in PubMed, Scopus, Embase, and Web of Science. The keywords “liquid embolic agent,” “middle meningeal artery,” “cSDH,” and “embolization” as well as their synonyms were used to build up the search strategy. The R statistical software and random-effects model were used for analysis. Heterogeneity was reported as I², and publication bias was calculated using the Egger test.ResultsOf 628 articles retrieved, 14 studies were eligible to be included in this study. Data of 276 patients were analyzed. n-Butyl cyanoacrylate and ethylene vinyl alcohol copolymer were the most commonly used embolic agents. This study revealed a pooled mortality rate of 0% (95% confidence interval [CI], 0.00%–100%), recurrence and failure rate of 3% (95% CI, 1%–10%), reoperation/reintervention rate of 4% (95% CI, 2%–12%), rate of size decrease of 94% (95% CI, 79%–98%), technical success rate of 100% (95% CI, 76%–100%), and adverse event rate of 1% (95% CI, 0.00%–4%).ConclusionsWith low mortality, recurrence, reoperation, and adverse event rates and a remarkable decrease in the size of hematomas, MMA embolization with liquid embolic agents may be considered a safe and effective treatment option in patients in whom surgical intervention has previously failed and as an alternative to conventional treatments.     

Platelet Testing is Associated with Worse Clinical Outcomes for Patients Treated with the Pipeline Embolization Device

BACKGROUND AND PURPOSE:The necessity for platelet-inhibition testing before aneurysm treatment in patients premedicated with antiplatelet agents is controversial. Using the International Retrospective Study of Pipeline Embolization Device registry, we studied complication rates in groups of patients who underwent platelet testing and those who did not undergo platelet testing to determine if these test results were associated with improved outcomes.MATERIALS AND METHODS:Patients in the International Retrospective Study of Pipeline Embolization Device registry with an unruptured aneurysm were categorized as those who underwent platelet testing before Pipeline embolization device treatment or those who did not. Complication rates were compared by using the Fisher exact or Pearson χ² test. Multivariate analysis was performed to determine if platelet function testing was independently associated with poor outcomes after adjusting for age, number of devices and aneurysms, aneurysm location and size, and practitioner and center volume.RESULTS:Compared with the patients who received a Pipeline embolization device without platelet testing, those who underwent platelet testing and Pipeline embolization device placement experienced higher rates of intracranial hemorrhage (0 of 187 [0.0%] vs 12 of 511 [2.3%], respectively; P = .04), neurologic morbidity (4 of 187 [2.1%] vs 42 of 511 [8.2%], respectively; P < .01), and combined neurologic morbidity and mortality (6 of 187 [3.2%] vs 45 of 511 [8.8%], respectively; P = .01). More patients in the platelet testing and Pipeline embolization device group were treated with multiple devices (227 [38.0%] vs 56 [27.8] patients, respectively; P = .01). On multivariate analysis, the group of patients who underwent platelet testing and Pipeline embolization device placement had higher odds of neurologic morbidity (OR, 3.25 [95% CI, 1.10–9.61]; P = .03).CONCLUSIONS:Platelet testing in patients who undergo Pipeline embolization device placement is associated with higher rates of morbidity. Additional prospective studies are needed to determine if and when platelet testing in these patients is appropriate.

The Pipeline embolization device (PED; Covidien, Irvine, California) is increasingly used in the treatment of intracranial aneurysms.^1–4 The PED flow diverter is a bare-metal construct that serves as a scaffold for neointimal proliferation.^5,6 Because of the thrombogenic nature of the bare-metal component of the device, dual-antiplatelet therapy is required in both the preoperative and postoperative settings, and patients are required to take dual-antiplatelet therapy for several months after the procedure.In addition to aspirin, clopidogrel is currently the most commonly prescribed antiplatelet drug for dual-antiplatelet therapy among patients who undergo PED placement. However, there exists wide variability in the activation of clopidogrel among individual patients.⁷ As a result, platelet function testing is widely used among neurointerventionists to ensure proper function of the drug.^8,9 However, controversy exists as to whether platelet testing is necessary in patients who undergo PED placement, because the benefits have yet to be proved.¹⁰ By using the International Retrospective Study of Pipeline Embolization Device (IntrePED) registry,¹¹ we compared the clinical outcomes of patients who underwent platelet testing and those who did not to determine whether this testing was associated with better outcomes among patients who undergo PED placement.     

Photodynamic therapy in colorectal cancer treatment—The state of the art in preclinical research

BackgroundPhotodynamic therapy (PDT) is used in many different oncologic fields. Also in gastroenterology, where have been a few attempts to treat both the premalignant lesion and advanced colorectal cancer (CRC). This review aims to give a general overview of preclinical photodynamic studies related to CRC cells and animal studies of photodynamic effects related to CRC treatment to emphasize their potential in study of PDT mechanism, safety and efficiency to translate these results into clinical benefit in CRC treatment.Materials and methodLiterature on in vitro preclinical photodynamic studies related to CRC cells and animal studies of photodynamic effects related to CRC treatment with the fallowing medical subject headings search terms: colorectal cancer, photodynamic therapy, photosensitizer(s), in vitro, cell culture(s), in vivo, animal experiment(s). The articles were selected by their relevance to the topic.ResultsThe majority of preclinical studies concerning possibility of PDT application in colon and rectal cancer is focused on phototoxic action of photosensitizers toward cultured colorectal tumor cells in vitro. The purposes of animal experiments are usually elucidation of mechanisms of observed photodynamic effects in scale of organism, estimation of PDT safety and efficiency and translation of these results into clinical benefit.Concluding remarksIn vitro photodynamic studies and animal experiments can be useful for studies of mechanisms and efficiency of photodynamic method as a start point on PDT clinical research. The primary disadvantage of in vitro experiments is a risk of over-interpretation of their results during extrapolation to the entire CRC.     

Comparative Outcome Analysis of N-Butyl Cyanoacrylate Embolization of the False Lumen Versus Thoracic Endovascular Aortic Repair in Aortic Dissection

PurposeTo evaluate the feasibility, safety, and effectiveness of N-butyl cyanoacrylate (NBCA) embolization for the treatment of aortic dissection.Materials and MethodsIn this single-center retrospective study conducted from February 2003 to June 2019, NBCA embolization of an aortic false lumen was attempted in 12 patients (median age, 59 y; range, 41–68 y) and thoracic endovascular aortic repair (TEVAR) was performed in 53 patients (median age, 59 y; range, 37–70 y) for aortic dissection with one or more indications of persisting pain, malperfusion, rupture or impending rupture, maximal aortic diameter ≥ 55 mm, and/or rapid aortic enlargement. The main exclusion criterion for embolization was the presence of fast blood flow in the aortic false lumen on aortography. The efficacy of NBCA embolization and TEVAR was compared by evaluating technical and clinical outcomes, repeat intervention–free survival (RFS), and overall survival (OS).ResultsTechnical success was achieved in 11 of the 12 patients treated with NBCA embolization (91.7%), and clinical success was achieved in 9 of these 11 (81.8%). No significant difference was found between embolization and TEVAR in clinical success rates (embolization, 81.8%; TEVAR, 84.9%; P = .409) or procedure-related complications (embolization, 1 patient [8.3%]; TEVAR, 4 patients [7.5%]; P = .701). In addition, embolization showed comparable 5-y RFS (embolization, 82.5% ± 9.3; TEVAR, 85.5% ± 4.8; P = .641) and 5-y OS (embolization, 100%; TEVAR, 95.4% ± 3.2; P = .744) rates to TEVAR.ConclusionsNBCA embolization of the false lumen in aortic dissection seems to be a safe and effective treatment modality for the closure of false lumen in selected patients.     

Neurophysiologic monitoring and pharmacologic provocative testing for embolization of spinal cord arteriovenous malformations

BACKGROUND AND PURPOSE: Embolization of a spinal cord arteriovenous malformation (SCAVM) is still considered risky. We evaluated the efficacy and reliability of pharmacologic provocative testing with neurophysiologic monitoring in the embolization of SCAVMs. METHODS: We retrospectively analyzed results of 60 provocative tests during 84 angiographic procedures (in 52 patients) with intended endovascular embolization. Tests included 47 sodium amytal and 56 lidocaine injections. All procedures were performed with general anesthesia and monitoring of cortical somatosensory evoked potentials (SEPs) and transcranial motor evoked potentials (MEPs). For provocative testing, 50 mg of amytal and 40 mg of lidocaine were consecutively injected through a microcatheter placed at the position of intended embolization. If SEPs and MEPs did not change, embolization was performed with N-butyl-cyanoacrylate (NBCA). If SEPs or MEPs changed, NBCA embolization was not performed from that catheter position. RESULTS: One false-negative result occurred, with an increase in spasticity after embolization. Nineteen positive results occurred: four after amytal injection and 15 after lidocaine injections. Seven injections in a posterior spinal artery feeder resulted in loss of SEPs or MEPs. Eleven injections in the anterior spinal artery feeder and one in the posterior inferior cerebellar artery feeder resulted in loss of MEPs. CONCLUSION: Provocative testing with amytal and lidocaine combined with neurophysiologic monitoring had a high negative predictive value and was a useful adjunct for SCAVM embolization. Both amytal and lidocaine should be used as provocative agents, and both SEPs and MEPs should be monitored.     

The safety and efficiency of photodynamic therapy for the treatment of osteosarcoma: A systematic review of in vitro experiment and animal model reports

BackgroundOsteosarcoma (OS) is an aggressive malignant bone tumour with high mortality. A poor prognosis is noted in patients with distal metastases or multidrug resistance. As an emerging antitumor strategy, photodynamic therapy (PDT) mediated by visible and near infrared light has attracted intensive attention given its target selectivity, remote controllability, minimal or non-invasive features. However, PDT also has obvious limitations. Specifically, due to the limited penetration of light, it is mainly used in the clinical treatment of superficial malignant tumours, such as musculoskeletal sarcomas and melanoma, but it has not been applied to the clinical treatment of deep malignant bone tumours except for a very small number of experiments on deep canine OS models.Materials and methodsWe searched for studies that focused on the effectiveness and safety of PDT for OS based on in vitro experiments and animal models in the last decade. A systematic search was conducted using electronic databases, including PubMed, ClinicalTrials.gov, and the Cochrane Library. Inclusion criteria: (1) original research articles about PDT for OS; (2) articles in English; (3) in vitro or animal model research; and (4) detailed information, including cell name, fluence, irradiation wavelength, time of incubation with PS, duration between PS treatment and irradiation, and duration between irradiation and viability assays. Exclusion criteria: (1) study was a review/systemic review article, patent, letter, or conference abstract/paper; (2) articles were not published in English; (3) studies containing overlapping or insufficient data.ResultsWe identified 201 publications, and 44 articles met the inclusion criteria and were included in the synthesis. Unfortunately, there are no relevant clinical reports of the use of PDT in the treatment of human OS. In these studies, 8 studies only employed in vivo experiments to evaluate the efficiency of PDT in an OS animal model, 19 studies exclusively performed in vitro viability assays of cells treated with PDT under different conditions, and 17 studies included in vitro cell experiments and in vivo animal OS models to evaluate the effect of PDT on OS in vivo and in vitro. All studies have shown that PDT is cytotoxic to OS cells or can inhibit the growth of OS in heterologous or homologous animal OS models but exhibits minimal cytotoxicity at a certain range of dosages.ConclusionBased on this systematic review, PDT can eradicate OS cells in cell culture and there is some evidence for efficacy in animal models. However, the ability for PDT to control human OS is unclear, the animal and human reports do not show evidence of human OS control, they just do show feasibility. The major issues concerning the potential for treatment of osteosarcoma with PDT are that adequate light should be transmitted to tumor loci and if the disease is caught before metastasis and irradiation of tumor sites is feasible, curative potential is there. Otherwise, PDT may be mainly palliative. To determine whether PDT can safely and efficiently be used in the clinical treatment of OS, many preclinical orthotopic animal OS models and OS models of multiple systemic metastases must be performed and interstitial PDT or intraoperative PDT may be a good and potential candidate for human OS treatment. If these problems can be well solved, PDT may be a potentially effective strategy for the treatment of OS patients.