Long-term efficacy of selective arterial embolisation of renal angiomyolipoma.

OBJECTIVE: To evaluate the long-term efficacy of selective arterial embolisation in renal angiomyolipoma (AML), with emphasis on tumour shrinkage, potential regrowth and the necessity of supplementary procedures.  Material and methods: A retrospective review of all 58 consecutive embolisations at two institutions, between 1999 and 2018, was performed. Clinical notes, laboratory data and imaging were reviewed. RESULTS: The overall complication rate was 6.8%, with no Clavien-Dindo grades III-V complications. Kidney function was unaffected by embolisation as measured by creatinine. Median radiological follow-up was 4.8 years (interquartile range [IQR]: 2.8-7.8), and median clinical follow-up was 7.5 years (IQR: 4.7-14.0). Decreasing AML size was observed in 96% of procedures. Maximal shrinkage (30% median diameter decrease; IQR: 15-44) was reached after median 2.2 years (IQR: 0.6-4.8). During follow-up, regrowth occurred in 38% of patients, and four bleeding episodes occurred in three patients with tuberous sclerosis. Growing size and/or rebleeding prompted a redo embolisation in 9% of spontaneous AML and 50% of tuberous sclerosis-associated AML. CONCLUSIONS: Being a well-tolerated treatment with few complications, selective arterial embolisation renders a pronounced size-reduction in most patients with AML, and kidney function is preserved. Regrowth is common, and a radiological follow-up is necessary. Tuberous sclerosis is a risk factor for the need of reintervention.

Endovascular plugs to occlude proximal entries in chronic aortic dissection.

OBJECTIVES: Patients with expanding chronic aortic dissection and patent proximal entries are sometimes poor candidates for open surgery or TEVAR. Occlusion of proximal entries with endovascular plugs has previously been suggested in selected patients, but clinical results over time are unknown. This study analyses aortic remodelling and clinical outcome after proximal entry occlusion. METHODS: Between 2007 and 2016, 14 patients, with expanding chronic aortic dissection, considered poor candidates for standard treatment, were treated with endovascular plugs in proximal entries located in the arch (n = 6) or descending aorta (n = 8). The Amplatzer™ Vascular Plug II was used for entries ≤4 mm and the Amplatzer™ Septal Occluder or Amplatzer™ Muscular VSD Occluder for entries 5-16 mm. Patients were followed for 0.5-13 years (median 7.3) with clinical visits and computed tomography. Diameters and cross-sectional areas along the aorta were measured. RESULTS: Occlusion of proximal entries was achieved in 10/14 patients (71%), including 4 patients with an adjunctive reintervention needed for complete seal in the segment. Unchanged or reduced maximum thoracic aortic diameter was observed in all 10 patients with successful occlusion. In 4 patients, proximal occlusion was not achieved and early conversion to FET (n = 1), FET/TEVAR (n = 2) or TEVAR (n = 1) was performed. Two aorta-related deaths occurred during follow-up, both after early conversion. CONCLUSIONS: Endovascular occlusion of proximal dissection entries of expanding chronic aortic dissections can induce favourable aortic remodelling and may be considered in selected patients with expanding chronic aortic dissection who are poor candidates for open surgery or stent graft repair.

Renal angiomyolipoma-patient characteristics and treatment with focus on active surveillance.

Objectives: To present a patient material of renal angiomyolipoma (AML) with focus on the risk of bleeding during active surveillance (AS).Methods: Medical records, 1999-2014, were studied and 98 patients (80 female, 18 men) with renal AML were identified. Eleven patients had tuberous sclerosis complex (TSC). Mean age was 54 (13-89) years.Results: Sixty patients (61%) were asymptomatic at presentation, 33 (34%) presented with flank pain and five (5%) with hematuria. Retroperitoneal bleeding or hematuria was diagnosed in 20 patients with a mean AML size of 74 mm (25-200 mm). Twenty-one patients were treated with angioembolization at time of diagnosis and 25 had surgery. Forty-five patients with sporadic AML (mean size 34 mm) and six with TSC (mean size 120 mm) were selected for AS. Only one patient with sporadic AML (46 mm) had a bleeding, whereas two of the six TSC patients had bleedings from three kidneys (AML 70-300 mm). In 25 patients (49%), the AML-size increased with 2.7 mm/year in sporadic and 5.4 mm/year in TSC-associated AML. Thirteen patients were treated with AE (including all six TSC-patients) and five with surgery in 22 kidneys due to AML-size in 16, bleeding in four and suspicion of cancer in two.Conclusion: Bleeding occurred in 20% of AML at presentation. In patients selected for AS, we found a very low risk of bleeding in sporadic AML justifying our cut off size of 50 mm to trigger intervention. In TSC-associated AML individually tailored follow-up is needed due to a higher intervention rate.

Autoradiography and biopsy measurements of a resected hepatocellular carcinoma treated with 90 yttrium radioembolization demonstrate large absorbed dose heterogeneities.

PURPOSE: Radioembolization is an alternative palliative treatment for hepatocellular carcinoma. Here, we examine the uptake differences between tumor tissue phenotypes and present a cross-section of the absorbed dose throughout a liver tissue specimen. METHODS AND MATERIALS: A patient with hepatocellular carcinoma was treated with 90Y radioembolization followed by liver tissue resection. Gamma camera images and autoradiographs were collected and biopsy tissue samples were analyzed using a gamma well counter and light microscopy. RESULTS: An analysis of 25 punched biopsy tissue samples identified 4 tissue regions: Normal tissue, viable tumor tissue with and without infarcted areas, and tumor areas with postnecrotic scar tissue. Autoradiography and biopsy tissue sample measurements showed large dose differences between viable and postnecrotic tumor tissue (159 Gy vs 23 Gy). CONCLUSIONS: Radioembolization of 90 yttrium with resin microspheres produces heterogeneous-absorbed dose distributions in the treatment of unifocal hepatic malignancies that could not be accurately determined with current gamma camera imaging techniques.

Radioembolization Versus Bland Embolization for Hepatic Metastases from Small Intestinal Neuroendocrine Tumors: Short-Term Results of a Randomized Clinical Trial.

BACKGROUND: Radioembolization (RE) with intra-arterial administration of 90Y microspheres is a promising technique for the treatment of liver metastases from small intestinal neuroendocrine tumors (SI-NET) not amenable to surgery or local ablation. However, studies comparing RE to other loco-regional therapies are lacking. The aim of this randomized study was to compare the therapeutic response and safety after RE and bland hepatic arterial embolization (HAE), and to investigate early therapy-induced changes with diffusion-weighted MRI (DWI-MRI). METHODS: Eleven patients were included in a prospective randomized controlled pilot study, six assigned to RE and five to HAE. Response according to RECIST 1.1 using MRI or CT at 3 and 6 months post-treatment was recorded as well as changes in DWI-MRI parameters after 1 month. Data on biochemical tumor response, toxicity, and side effects were also collected. RESULTS: Three months after treatment, all patients in the HAE group showed partial response according to RECIST while none in the RE group did (p = 0.0022). After 6 months, the response rates were 4/5 (80%) and 2/6 (33%) in the HAE and RE groups, respectively (NS). DWI-MRI metrics could not predict RECIST response, but lower pretreatment ADC(120-800) and larger ADC(0-800) increase at 1 month were related to larger decrease in tumor diameter when all tumors were counted. CONCLUSION: HAE resulted in significantly higher RECIST response after 3 months, but no difference compared to RE remained after 6 months. These preliminary findings indicate that HAE remains a safe option for the treatment of liver metastases from SI-NET, and further studies are needed to establish the role of RE and the predictive value of MR-DWI.

Simulation Model of Microsphere Distribution for Selective Internal Radiation Therapy Agrees With Observations.

PURPOSE: To perform a detailed analysis of microsphere distribution in biopsy material from a patient treated with (90)Y-labeled resin spheres and characterize microsphere distribution in the hepatic artery tree, and to construct a novel dichotomous bifurcation model for microsphere deposits and evaluate its accuracy in simulating the observed microsphere deposits. METHODS AND MATERIALS: Our virtual model consisted of arteries that successively branched into 2 new generations of arteries at 20 nodes. The artery diameter exponentially decreased from the lowest generation to the highest generation. Three variable parameters were optimized to obtain concordance between simulations and measure microsphere distributions: an artery coefficient of variation (ACV) for the diameter of all artery generations and the microsphere flow distribution at the nodes; a hepatic tree distribution volume (HDV) for the artery tree; and an artery diameter reduction (ADR) parameter. The model was tested against previously measured activity concentrations in 84 biopsies from the liver of 1 patient. In 16 of 84 biopsies, the microsphere distribution regarding cluster size and localization in the artery tree was determined via light microscopy of 30-µm sections (mean concentration, 14 microspheres/mg; distributions divided into 3 groups with mean microsphere concentrations of 4.6, 14, and 28 microspheres/mg). RESULTS: Single spheres and small clusters were observed in terminal arterioles, whereas large clusters, up to 450 microspheres, were observed in larger arterioles. For 14 microspheres/mg, the optimized parameter values were ACV=0.35, HDV = 50 cm(3), and ADR=6 µm. For 4.6 microspheres/mg, ACV and ADR decreased to 0.26 and 0 µm, respectively, whereas HDV increased to 130 cm(3). The opposite trend was observed for 28 microspheres/mg: ACV = 0.49, HDV = 20 cm(3), and ADR = 8 µm. CONCLUSION: Simulations and measurements reveal that microsphere clusters are larger and more common in volumes with high microsphere concentrations and indicate that the spatial distribution of the artery tree must be considered in estimates of microsphere distributions.

Endovascular Closure of Chronic Dissection Entries in the Aortic Arch Using the Amplatzer Vascular Plug II as a Sealing Button.

PURPOSE: To present a new endovascular technique to avoid open surgical arch reconstruction in selected patients with aneurysmal dilatation due to small chronic dissection entries in the aortic arch. TECHNIQUE: The true and the false lumen of the aortic arch are catheterized from the femoral arteries. An Amplatzer Vascular Plug II (AVP II) is advanced through the proximal entry from the false lumen side and deployed as a sealing button in the entry hole, with 1 disc in the true lumen and the remaining 2 discs in the false lumen. This technique was used in 4 patients with chronic dissection involving the aortic arch, three of whom had had previous surgery for acute type A aortic dissection. In 3 patients, the false lumen of the thoracic aorta was successfully obliterated, with thrombosis and aortic diameter reduction during follow-up. In 1 patient, false lumen flow persisted, and he was subsequently treated with a total arch reconstruction and frozen elephant trunk. CONCLUSION: Endovascular closure of small proximal dissection entries in the aortic arch with an AVP II used as a sealing button is feasible and may be an alternative to open surgical arch reconstruction in selected patients with chronic aortic dissection and secondary aneurysm expansion.

Increased absorbed liver dose in Selective Internal Radiation Therapy (SIRT) correlates with increased sphere-cluster frequency and absorbed dose inhomogeneity.

BACKGROUND: The higher tolerated mean absorbed dose for selective internal radiation therapy (SIRT) with intra-arterially infused (90)Y microspheres compared to external beam therapy is speculated to be caused by absorbed dose inhomogeneity, which allows for liver regeneration. However, the complex liver microanatomy and rheology makes modelling less valuable if the tolerance doses are not based on the actual microsphere distribution. The present study demonstrates the sphere distribution and small-scale absorbed dose inhomogeneity and its correlation with the mean absorbed dose in liver tissue resected after SIRT. METHODS: A patient with marginally resectable cholangiocarcinoma underwent SIRT 9 days prior to resection including adjacent normal liver tissue. The resected specimen was formalin-fixed and sliced into 1 to 2-mm sections. Forty-one normal liver biopsies 6-8 mm in diameter were punched from these sections and the radioactivity measured. Sixteen biopsies were further processed for detailed analyses by consecutive serial sectioning of 15 30-µm sections per biopsy, mounted and stained with haematoxylin-eosin. All sections were scrutinised for isolated or conglomerate spheres. Small-scale dose distributions were obtained by applying a (90)Y-dose point kernel to the microsphere distributions. RESULTS: A total of 3888 spheres were found in the 240 sections. Clusters were frequently found as strings in the arterioles and as conglomerates in small arteries, with the largest cluster comprising 453 spheres. An increased mean absorbed dose in the punch biopsies correlated with large clusters and a greater coefficient of variation. In simulations the absorbed dose was 5-1240 Gy; 90% were 10-97 Gy and 45% were <30 Gy, the assumed tolerance in external beam therapy. CONCLUSIONS: Sphere clusters were located in both arterioles and small arteries and increased in size with increasing sphere concentration, resulting in increased absorbed dose inhomogeneity, which contradicts earlier modelling studies.

EVAR Guided by 3D Image Fusion and CO2 DSA: A New Imaging Combination for Patients With Renal Insufficiency.

PURPOSE: To present a new combination of imaging techniques that helps reduce the use of iodinated contrast during endovascular aneurysm repair (EVAR) procedures in patients with renal insufficiency. TECHNIQUE: Relevant anatomical structures are marked in the preprocedure computed tomography (CT) angiogram. A 3D-3D image fusion between the preprocedure CT and an intraprocedure cone-beam CT is performed in order to overlay anatomical information on live fluoroscopy. Verification of the correct overlay matching (or adjustment if necessary) is based on carbon dioxide (CO2) digital subtraction angiograms (DSA) instead of iodine DSA. The stent-graft is placed and deployed based on the overlaid information. Correct device placement is finally verified with conventional contrast angiography. CONCLUSION: The combination of 3D image fusion of a preoperative CT with live fluoroscopy and CO2 DSA verification is feasible and sufficient for guidance of abdominal EVAR. This method minimizes the use of iodinated contrast media, protecting residual function in the setting of preexisting renal insufficiency.

Heterogeneity of microsphere distribution in resected liver and tumour tissue following selective intrahepatic radiotherapy.

BACKGROUND: Selective arterial radioembolisation of liver tumours has increased, because of encouraging efficacy reports; however, therapeutic parameters used in external beam therapy are not applicable for understanding and predicting potential toxicity and efficacy, necessitating further studies of the physical and biological characteristics of radioembolisation. The aim was to characterise heterogeneity in the distribution of microspheres on a therapeutically relevant geometric scale considering the range of yttrium-90 ((90)Y) ß-particles. METHODS: Two patients with intrahepatic cholangiocarcinoma, marginally resectable, were treated by selective arterial embolisation with (90)Y resin microspheres (SIRTEX®), followed 9 days post-infusion by resection, including macroscopic tumour tissue and surrounding normal liver parenchyma. Formalin-fixed, sectioned resected tissues were exposed to autoradiographic films, or tissue biopsies of various dimensions were punched out for activity measurements and microscopy. RESULTS: Autoradiography and activity measurements revealed a higher activity in tumour tissue compared to normal liver parenchyma. Heterogeneity in activity distribution was evident in both normal liver and tumour tissue. Activity measurements were analysed in relation to the sample mass (5 to 422 mg), and heterogeneities were detected by statistical means; the larger the tissue biopsies, the smaller was the coefficient of variation. The skewness of the activity distributions increased with decreasing biopsy mass. CONCLUSIONS: The tissue activity distributions in normal tissue were heterogeneous on a relevant geometric scale considering the range of the ionising electrons. Given the similar and repetitive structure of the liver parenchyma, this finding could partly explain the tolerance of a relatively high mean absorbed dose to the liver parenchyma from ß-particles.

Radiation exposure during liver surgery after treatment with (90)Y microspheres, evaluated with computer simulations and dosimeter measurements.

PURPOSE: Two patients with liver tumours were planned for a combined treatment, including surgery with preceding injections of ß(-) radiation emitting (90)Y microspheres (SIRTEX(®)). The aim of this paper is to present a method of pre-surgical computer simulations of the absorbed dose rate on the surface of tumour tissue, combined with measurements of the actual absorbed dose rate on resected tissue, in order to estimate the absorbed dose to a surgeon's fingers during such surgery procedures. METHODS AND MATERIALS: The dose rates from ß(-) radiation on the surface of tumour tissue were simulated with the software VARSKIN(®) Mod 2. The activity concentrations in tumours were estimated, based on SPECT/CT distribution studies of (99m)Tc-MAA and confirmed by SPECT/CT bremsstrahlung studies of (90)Y microspheres. The activity distributions were considered as homogeneous within the tumour regions. The absorbed dose rates at different tumour tissue spots were calculated based on measurements with thermo-luminescent dosimeters (TLD) fastened on resected tissue. RESULTS: The simulations showed a good agreement with the averaged absorbed dose rates based on TLD measurements performed on resected tissue, differing by 13% and 4% respectively. The absorbed dose rates at the measured maximum hotspots were twice as high as the average dose rates for both patients. CONCLUSION: The data is not sufficient in order to draw any general conclusions about dose rates on tumour tissue during similar surgeries, neither about the influence of dose rate heterogeneities nor about average dose rates. However, the agreement between simulations and measurements on these limited data indicate that this approach is a promising method for estimations of the radiation exposure to the surgeons' fingers during this kind of surgery procedure. More data from similar surgeries are necessary in order to validate the method.

Ethylene vinyl alcohol copolymer (Onyx) to seal type 1 endoleak. A new technique.

The aim of this study was to investigate whether the liquid embolic agent Onyx, an ethylene vinyl alcohol copolymer, can be used to seal type 1 endoleaks during endovascular aortic repair (EVAR). Six patients with large aortic aneurysms and remaining type 1 endoleaks during or after EVAR were treated with Onyx embolization through a microcatheter placed in the proximal neck in five cases and in the distal neck in one case. Four of the patients were treated using the chimney technique. The type 1 endoleak was primarily sealed by Onyx in all six patients. There was no distal embolization. Two patients had complications during follow-up. One patient had occlusions of chimney grafts to the renal arteries and to one leg extension. These occlusions were not anatomically related to Onyx embolization. One patient had late stentgraft migration of the Onyx-treated distal neck with aneurysm rupture 18 months after treatment. Early experience of Onyx embolization as a bailout solution of type 1 endoleaks after complicated EVAR is promising. However, effective seal with Onyx does not prevent late stentgraft migration. More reported patients and longer follow-up are necessary to evaluate this new technique.