Gordon McLennan

Comparative Analysis of the Safety and Efficacy of Transcatheter Arterial Chemoembolization and Yttrium-90 Radioembolization in Patients with Unresectable Hepatocellular Carcinoma

PURPOSE To compare retrospectively the safety and efficacy of yttrium-90 ((90)Y) radioembolization with the safety and efficacy of chemoembolization in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS Survival and complication rates were evaluated for patients with HCC who underwent chemoembolization or radioembolization at a single institution between August 2007 and April 2010. Complications were graded according to a standardized grading system for embolization procedures. Survival was determined via the Kaplan-Meier method, and multivariable analysis for factors affecting survival was performed. RESULTS This study included 73 patients with HCC who underwent index embolization with radioembolization (n = 38; 52.1%) or chemoembolization (n = 35; 47.9%). The two patient populations were similar in terms of demographics, etiology of cirrhosis, functional status, tumor characteristics, Child-Pugh class, previous liver-directed therapy, and number of patients with bilirubin > 2.0 mg/dL. There was no significant difference in survival between the radioembolization (median 8.0 months) and chemoembolization (median 10.3 months) cohorts (P = .33). Postembolization syndrome was significantly more severe in patients who underwent chemoembolization, which led to increased total hospitalization rates in these patients. The rates of other complications and rehospitalization were similar between groups. Increased age, Child-Pugh class B, hepatitis seropositivity, bilobar tumor distribution, tumor vascular invasion, and presence of extrahepatic metastases were associated with reduced patient survival. CONCLUSIONS Patients treated with radioembolization did not show a survival advantage over patients treated with chemoembolization. However, patients who underwent chemoembolization had significantly higher rates of hospitalization as a result of postembolization syndrome.

Retrospective Review of 120 Celect Inferior Vena Cava Filter Retrievals: Experience at a Single Institution

PURPOSE To evaluate retrospectively the safety and retrievability of the Celect IVC filter. MATERIALS AND METHODS All patients undergoing Celect filter placement and retrieval during the period 2007-2012 were assessed for complications and retrievability. RESULTS Of 620 patients who underwent Celect filter placement, 120 presented for removal. The indwelling time in these patients was 158.1 days±103.0 (range, 2-518 d). There were 106 filters (88.3%) removed; 14 filters were left in situ for the following reasons: filter embedment (n=6), caval occlusion (n=3), retained thrombus (n=2), large floating thrombus in IVC (n=2), or tilt >15° (n=1). With filters in place, five patients developed new pulmonary embolism (PE), and two others presented with severe abdominal pain. The available 115 pairs of placement and removal cavagrams suggested limb penetration in 99 cases (86.1%), intracaval migration >2 cm in 5, secondary tilt >15° in 8, filter deformity in 10, retained thrombus within filters in 12, and IVC occlusion in 3. Among 38 available computed tomography (CT) scans, 9 scans (24%) showed asymptomatic limb penetration to the duodenum (n=6), aortic wall (n=2), or kidney (n=1). No filter fracture was found. CONCLUSIONS This study showed a high penetration rate for Celect IVC filters, including penetrations that were symptomatic or involved adjacent structures. Penetration appears to correlate with indwelling time, suggesting that the filter should be removed as soon as PE protection is no longer indicated. Although most of the filters were removed, 5.8% of retrievals were unsuccessful because of technical failure.

Preclinical in vivo testing of the Arrow-Trerotola percutaneous thrombolytic device for venous thrombosis

PURPOSE To test the safety and efficacy of using the Arrow-Trerotola percutaneous thrombolytic device (PTD) for treating deep vein thrombosis (DVT) in an animal model. MATERIALS AND METHODS An established canine model of iliocaval subacute thrombosis was used. Thrombosis was caused by balloon occlusion of the infrarenal inferior vena cava (IVC) for 7 (n = 12), 10 (n = 1), or 17 (n = 1) days. Treatment was performed with use of an 8-F, over-the-wire (0.035-inch) PTD with a 15-mm-diameter basket. The procedure was performed without IVC filtration. Two acute procedures were performed and 12 procedures were intended as survival procedures with 30-day follow-up. Pulmonary arteriography, blood gases, and pulmonary artery pressure measurement were performed before and after the procedure, and at follow-up. The animals were killed after the follow-up procedure and their IVC, iliac veins, and lungs were removed and examined histologically. Heparin was used intraprocedurally but thrombolytic agents were not used. Low-molecular-weight heparin was given daily after the procedure. RESULTS Thrombolysis was completely (12 of 13) or partially (one of 13) successful in all animals in the 7- and 10-day groups, but was unsuccessful in the animal in the 17-day group (n = 1). Variable amounts of segmental and subsegmental pulmonary emboli were found in all animals with small increases in pulmonary artery pressure. Two animals died within 6 days of the procedure, possibly due to pulmonary emboli. At 30-day follow-up, IVC patency was preserved in 80% (eight of 10) of animals, but significant caval narrowing due to intimal hyperplasia was noted at follow-up. All pulmonary emboli had resolved angiographically at follow-up, but evidence of recanalized or resolving pulmonary thromboemboli was found in seven of the 12 surviving animals. No acute vascular injury (eg, perforation) occurred. CONCLUSION The modified PTD used in this study is effective in treating subacute (<7 days old) venous thrombosis, but temporary filtration will probably be necessary to keep pulmonary emboli to a minimum during the procedure. The 30-day patency is encouraging. The results in this animal model indicate that the Arrow-Trerotola PTD may be useful in the percutaneous treatment of DVT in humans.

Active surveillance for renal angiomyolipoma: outcomes and factors predictive of delayed intervention.

To present the outcomes of active surveillance (AS) for renal angiomyolipomas (AMLs) and to assess the clinical features predicting delayed intervention of this treatment option.

Lung Dose Calculation With SPECT/CT for 90Yittrium Radioembolization of Liver Cancer

PURPOSE To propose a new method to estimate lung mean dose (LMD) using technetium-99m labeled macroaggregated albumin ((99m)Tc-MAA) single photon emission CT (SPECT)/CT for (90)Yttrium radioembolization of liver tumors and to compare the LMD estimated using SPECT/CT with clinical estimates of LMD using planar gamma scintigraphy (PS). METHODS AND MATERIALS Images of 71 patients who had SPECT/CT and PS images of (99m)Tc-MAA acquired before TheraSphere radioembolization of liver cancer were analyzed retrospectively. LMD was calculated from the PS-based lung shunt assuming a lung mass of 1 kg and 50 Gy per GBq of injected activity shunted to the lung. For the SPECT/CT-based estimate, the LMD was calculated with the activity concentration and lung volume derived from SPECT/CT. The effect of attenuation correction and the patients breathing on the calculated LMD was studied with the SPECT/CT. With these effects correctly taken into account in a more rigorous fashion, we compared the LMD calculated with SPECT/CT with the LMD calculated with PS. RESULTS The mean dose to the central region of the lung leads to a more accurate estimate of LMD. Inclusion of the lung region around the diaphragm in the calculation leads to an overestimate of LMD due to the misregistration of the liver activity to the lung from the patients breathing. LMD calculated based on PS is a poor predictor of the actual LMD. For the subpopulation with large lung shunt, the mean overestimation from the PS method for the lung shunt was 170%. CONCLUSIONS A new method of calculating the LMD for TheraSphere and SIR-Spheres radioembolization of liver cancer based on (99m)Tc-MAA SPECT/CT is presented. The new method provides a more accurate estimate of radiation risk to the lungs. For patients with a large lung shunt calculated from PS, a recalculation of LMD based on SPECT/CT is recommended.

The Effects of a Mechanical Thrombolytic Device on Normal Canine Vein Valves

PURPOSE To determine if the Arrow-Trerotola Percutaneous Thrombolytic Device (PTD) causes damage to normal vein valves. MATERIALS AND METHODS Ten lateral saphenous veins in five dogs were studied with descending venography with use of a wedge balloon catheter positioned above 48 valves (demonstrating 51 valves) before and after five antegrade passes each with an over-the-wire (0.025-inch), 6.5-F, 9-mm-diameter PTD. Vein diameters were 3.2-11.4 mm (mean, 5.9 mm). Contrast matter was injected at incremental rates from 3 to 15 mL/min during continuous pressure monitoring. Imaging was performed with digital subtraction angiography at a rate of 1 frame/sec. The time to valve reflux was determined by noting the frame at which reflux was first seen through the valve. The time to reflux and pressure required to reflux were compared before and after the PTD passes. All vessels were explanted and evaluated histologically for presence or absence of endothelial loss, thrombus formation, inflammation, or valve degeneration. Four veins in two animals were studied with venography to determine the variability of the venographic method. These veins thrombosed during venography and therefore served as positive pathologic controls. In two animals, one vein was studied with venography and one was not studied to provide pathologic controls. RESULTS With use of two physiologic tests of valve function, 77% of valves had minimal or no damage as assessed by valve competency and 80% had minimal or no damage as demonstrated by the change in the pressures the valve can withstand before reflux. Twenty-six of 51 valves (51%) had no difference or later reflux after PTD use. Thirteen (26%) refluxed 1 second earlier after PTD use and 12 (23%) refluxed > or =2 seconds earlier (six at 2, four at 3, and two at 4). Four of the six valves with more than a 2-second difference in reflux times were in valves with diameters less than 4.2 mm. All these vessels were smaller than 7 mm in diameter. Twenty-one of 48 valve levels (44%) had no difference or sustained higher pressures before reflux after PTD use. Seventeen (36%) had a pressure drop of <10 mm Hg; five (10%) had drops of 12-24 mm Hg; and five (10%) had drops of more than 40 mm Hg. There was a significant difference in endothelial loss, thrombus formation, and inflammation between experimental veins, the veins with thrombus, the venography controls, and the normal vein controls. There was significant difference only in terms of inflammation when the experimental group was compared to the thrombosis group. CONCLUSION The antegrade use of the PTD across normal canine vein valves does not cause physiologically significant damage in valves 7 mm or larger in diameter in this animal model.

Multimodality treatment of neuroendocrine liver metastases.

BACKGROUND Neuroendocrine liver metastases have a distinct tumor biology and symptomatology that render their management challenging. This difficulty is reflected in the literature, which lacks consensus on a treatment algorithm. The aim of this study is to propose a treatment algorithm based on patient morbidity and the efficacy of different treatment options. METHODS The medical records of 127 patients with neuroendocrine liver metastases were reviewed. As first-line treatment, 69 of these patients underwent radiofrequency ablation (RFA), 29 patients were treated by liver resection, and 29 underwent embolization. Clinical characteristics and surgical parameters were analyzed with the chi-square test, and cumulative survival was analyzed with the Kaplan-Meier method. All data are expressed as mean ± standard error of the mean. RESULTS Of the 3 treatment modalities, RFA was the most commonly used initial treatment for patients with up to approximately 16 discrete lesions. Resection was used to debulk large tumors of limited number. Embolization was the first-line treatment for more extensive disease not amenable to RFA or resection. RFA provided effective cytoreduction while affording patients a shorter duration of stay and lower complication rates. On univariate analysis, the size of dominant metastases, extrahepatic disease, resection of primary tumor, and treatment modality affected survival. On multivariate analysis, sex, the size of dominant metastases, and extrahepatic disease were independent predictors of survival. CONCLUSION To our knowledge, this study is the largest report on a multimodality approach to the treatment of neuroendocrine liver metastases yet published in the literature. Because of the patient selection criteria used in our study, a direct comparison of the treatment arms is not strictly possible. We used an initial treatment algorithm based on the presentation of the patient. Because this disease has a multifocal nature and accompanying elevated recurrence rate, careful follow-up of patients and subsequent treatments are often needed to minimize disease burden.

Determination of Radiation Absorbed Dose to Primary Liver Tumors and Normal Liver Tissue Using Post-Radioembolization 90Y PET

Background: Radioembolization with Yttrium-90 (90 Y) microspheres is becoming a more widely used transcatheter treatment for unresectable hepatocellular carcinoma (HCC). Using post-treatment 90 Y positron emission tomography/computerized tomography (PET/CT) scans, the distribution of microspheres within the liver can be determined and quantitatively assessed. We studied the radiation dose of 90 Y delivered to liver and treated tumors. Methods: This retrospective study of 56 patients with HCC, including analysis of 98 liver tumors, measured and correlated the dose of radiation delivered to liver tumors and normal liver tissue using glass microspheres (TheraSpheres®) to the frequency of complications with modified response evaluation criteria in solid tumors (mRECIST). 90 Y PET/CT and triphasic liver CT scans were used to contour treated tumor and normal liver regions and determine their respective activity concentrations. An absorbed dose factor was used to convert the measured activity concentration (Bq/mL) to an absorbed dose (Gy). Results: The 98 studied tumors received a mean dose of 169 Gy (mode 90–120 Gy; range 0–570 Gy). Tumor response by mRECIST criteria was performed for 48 tumors that had follow-up scans. There were 21 responders (mean dose 215 Gy) and 27 non-responders (mean dose 167 Gy). The association between mean tumor absorbed dose and response suggests a trend but did not reach statistical significance (p = 0.099). Normal liver tissue received a mean dose of 67 Gy (mode 60–70 Gy; range 10–120 Gy). There was a statistically significant association between absorbed dose to normal liver and the presence of two or more severe complications (p = 0.036). Conclusion: Our cohort of patients showed a possible dose–response trend for the tumors. Collateral dose to normal liver is non-trivial and can have clinical implications. These methods help us understand whether patient adverse events, treatment success, or treatment failure can be attributed to the dose that the tumor or normal liver received.

Mechanical Thrombolysis of Venous Thrombosis in an Animal Model with Use of Temporary Caval Filtration

PURPOSE To test the effect of temporary caval filtration on pulmonary emboli when a mechanical thrombolytic device is used to treat venous thrombosis and to test the effects of a modified device on caval patency at 30-day follow-up. MATERIALS AND METHODS In a canine model of iliocaval subacute thrombosis, mechanical thrombolysis was performed with use of an 8-F over-the-wire Arrow-Trerotola Percutaneous Thrombolytic Device (PTD) with a 9-mm (iliac) or 15-mm (inferior vena cava [IVC]) basket. In six procedures, the device was made of nitinol monofilament, and in another six, it was made of braided stainless steel. All procedures were performed with a nitinol expandable sheath (temporary filter) in the suprarenal IVC. Low-molecular-weight heparin was given daily after the procedure. Venography, pulmonary arteriography, measurement of blood gases, and pulmonary artery (PA) pressure measurement were performed before and after the procedure and at 30-day follow-up. Pulmonary arteriograms from the group treated with stainless-steel devices were compared to those from an earlier group of animals in which the identical procedure was performed without caval filtration. The IVC was examined histologically. RESULTS Thrombolysis was successful in all animals. Rare segmental and subsegmental pulmonary emboli (PE) were seen arteriographically; compared to procedures without filters, there was a significant reduction in PE (P <.002). However, a mild increase in pulmonary artery pressure, decrease in pH, and increase in pCO(2) were observed postprocedurally. At 30-day follow-up (n = 11), IVC patency was preserved in 45% (n = 5) of animals overall. Caval patency was significantly better in animals in which the combination of stainless-steel devices was used (five of six = 83% vs zero with nitinol device; P =.015). Histologically, the stainless-steel device caused little intimal injury and fibrosis-less than that seen with the nitinol device. CONCLUSIONS Temporary filtration reduces, but does not completely eliminate, PE during mechanical thrombolysis. The stainless-steel device results in less intimal injury and better caval patency than the nitinol device.

Accuracy of CO2 Angiography in Vessel Diameter Assessment: A Comparative Study of CO2 versus Iodinated Contrast Material in an Aortoiliac Flow Model

PURPOSE Precise vessel sizing prior to endovascular intervention is critical to achievement of technical success. Diameter measurements obtained with CO2 and iodinated contrast material in an aortoiliac flow model were compared. MATERIALS AND METHODS Aortoiliac flow was simulated in a compliant, silicone elastomer phantom of the aortoiliac system using an autoperfusion pump (flow volume, approximately 1100 mL/min; mean arterial pressure, 70-80 mm Hg at 80-90 cycles/minute) and a glycerol solution (40% by weight; viscosity 3.7 centipoise at 20 degrees C). Digital subtraction angiography was performed with the phantom in the anteroposterior (AP) plane and in three oblique planes with both CO2 and iodinated contrast material. Five sets of images for both CO2 and iodinated contrast material were obtained for each projection. Two readers independently performed vessel diameter measurements at seven sites (distal abdominal aorta, bilateral proximal and distal common iliac, and mid-external iliac arteries). The model was then evaluated with intravascular ultrasound (IVUS) using a 20-MHz imaging catheter. Actual diameter measurements were taken from the inner wall to inner wall in orthogonal planes at the same locations within the model, as described previously. Analysis was performed to determine local difference in measurements (t tests), difference when compared to the standard AP projection with iodinated contrast material (Dunnetts test) and inter-reader variability (Pitmans test). RESULTS The contralateral iliac vessel segment did not opacify when imaging with CO2 in the 45 degrees obliquities; thus, 22 of 28 sites were available for comparison. At 18 of 22 (81.8%) sites, there was significant difference in vessel measurements (P < .01), with CO2 yielding a significantly larger diameter at 17 of 22 (77.3%) of the sites. The difference in mean diameter ranged from -1.28 to 4.47 mm. With use of the AP iodinated contrast material run as the standard, there were significant differences (P < .05) in vessel diameter at 17 of 22 (77.3%) and four of 21 (19%) sites for CO2 and iodinated contrast material respectively, with CO2 tending toward greater diameter measurements. Significant differences (P < .05) in variance between the two readers were present but occurred primarily with CO2 in the AP projection and iodinated contrast material in the 45 degrees left obliquity. With use of IVUS as the standard, there were significant differences (P < .05) in the measured vessel diameters with CO2 at nine of 22 (40.9%) of the sites and with iodinated contrast material at 17 of 28 (60.7%) of the sites. Of the measurements made with CO2, seven of nine (77.8%) of the measurements were of larger diameter than those obtained with IVUS. By contrast, of the measurements made with iodinated contrast material angiography, IVUS measured larger diameters in 16 of 17 (94.1%). CONCLUSION CO2 angiography consistently yielded significantly larger vessel measurements when compared to both iodinated contrast angiography and WVUS. These results have important implications in regards to planning intervention based solely on CO2 angiography. Further evaluation is needed before recommending CO2 for vessel sizing in clinical practice.