Scott A. Resnick

Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma

BACKGROUND & AIMS Chemoembolization is one of several standards of care treatment for hepatocellular carcinoma (HCC). Radioembolization with Yttrium-90 microspheres is a novel, transarterial approach to radiation therapy. We performed a comparative effectiveness analysis of these therapies in patients with HCC. METHODS We collected data from 463 patients who were treated with transarterial locoregional therapies (chemoembolization or radioembolization) over a 9-year period. We excluded patients who were not appropriate for comparison and analyzed data from 245 (122 who received chemoembolization and 123 who received radioembolization). Patients were followed for signs of toxicity; all underwent imaging analysis at baseline and follow-up time points. Overall survival was the primary outcome measure. Secondary outcomes included safety, response rate, and time-to-progression. Uni- and multivariate analyses were performed. RESULTS Abdominal pain and increased transaminase activity were more frequent following chemoembolization (P < .05). There was a trend that patients treated with radioembolization had a higher response rate than with chemoembolization (49% vs 36%, respectively, P = .104). Although time-to-progression was longer following radioembolization than chemoembolization (13.3 months vs 8.4 months, respectively, P = .046), median survival times were not statistically different (20.5 months vs 17.4 months, respectively, P = .232). Among patients with intermediate-stage disease, survival was similar between groups that received chemoembolization (17.5 months) and radioembolization (17.2 months, P = .42). CONCLUSIONS Patients with HCC treated by chemoembolization or radioembolization with Yttrium-90 microspheres had similar survival times. Radioembolization resulted in longer time-to-progression and less toxicity than chemoembolization. Post hoc analyses of sample size indicated that a randomized study with > 1000 patients would be required to establish equivalence of survival times between patients treated with these two therapies.

Treatment of Unresectable Primary and Metastatic Liver Cancer with Yttrium-90 Microspheres (TheraSphere®): Assessment of Hepatic Arterial Embolization

In Canada and Europe, yttrium-90 microspheres (TheraSphere®; MDS Nordion, Ottawa, Canada) are a primary treatment option for primary and secondary hepatic malignancies. We present data from 30 patients with hepatocellular carcinoma (HCC) and metastatic liver disease treated with TheraSphere from a single academic institution to evaluate the angiographically evident embolization that follows treatment. Seven interventional radiologists from one treatment center compared pretreatment and posttreatment angiograms. The reviewers were blinded to the timing of the studies. The incidence of postembolization syndrome (PES) was determined as well as objective tumor response rates by the World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), and European Association for the Study of the Liver (EASL) criteria. There were 420 independent angiographic observations that were assessed using the chi-squared statistic. The pretreatment and posttreatment angiograms could not be correctly identified on average more than 43% of the time (p = 0.0004). The postprocedure arterial patency rate was 100%. The objective tumor response rates for all patients were 24%, 31%, and 72% for WHO, RECIST, and EASL criteria, respectively. All of the patients tolerated the procedure without complications and were treated on an outpatient basis, and four patients had evidence of PES. This treatment method does not result in macroscopic embolization of the hepatic arteries, thereby maintaining hepatic tissue perfusion. These data support the principle that the favorable response rates reported with TheraSphere are likely due to radiation and microscopic embolization rather than flow-related macroscopic embolization and ischemia.

Chemoembolization for Hepatocellular Carcinoma: Comprehensive Imaging and Survival Analysis in a 172-Patient Cohort

PURPOSE To determine comprehensive imaging and long-term survival outcome following chemoembolization for hepatocellular carcinoma (HCC). MATERIALS AND METHODS One hundred seventy-two patients with HCC treated with chemoembolization were studied retrospectively in an institutional review board approved protocol; this study was HIPAA compliant. Baseline laboratory and imaging characteristics were obtained. Clinical and laboratory toxicities following treatment were assessed. Imaging characteristics following chemoembolization were evaluated to determine response rates (size and necrosis) and time to progression (TTP). Survival from the time of first chemoembolization treatment was calculated. Subanalyses were performed by stratifying the population according to Child-Pugh, United Network for Organ Sharing, and Barcelona Clinic for Liver Cancer (BCLC) staging systems. RESULTS Cirrhosis was present in 157 patients (91%); portal hypertension was present in 139 patients (81%). Eleven patients (6%) had metastases at baseline. Portal vein thrombosis was present in 11 patients (6%). Fifty-five percent of patients experienced some form of toxicity following treatment; 21% developed grade 3 or 4 bilirubin toxicity. Post-chemoembolization response was seen in 31% and 64% of patients according to size and necrosis criteria, respectively. Median TTP was 7.9 months (95% confidence interval: 7.1, 9.4) but varied widely by stage. Median survival was significantly different between patients with BCLC stages A, B, and C disease (stage A, 40.0 months; B, 17.4 months; C, 6.3 months; P < .0001). CONCLUSION The determination of TTP and survival in patients with HCC is confounded by tumor biology and background cirrhosis; chemoembolization was shown to be a safe and effective therapy in patients with HCC.

The Effect of Pelvic MR Imaging on the Diagnosis and Treatment of Women with Presumed Symptomatic Uterine Fibroids

PURPOSE To determine if magnetic resonance (MR) imaging significantly alters the diagnostic thinking and treatment plans of interventional radiologists during the evaluation of women for uterine fibroid embolization (UFE) for presumed uterine fibroids. MATERIALS AND METHODS At a single institution, interventional radiologists prospectively completed questionnaires (n = 60) before and after MR imaging was performed in their evaluation of women presenting for potential UFE. The questionnaires asked these physicians the probability (0%-100%) of their most likely diagnosis before MR imaging and after receiving the MR imaging information. They were also asked their anticipated and final treatment plans. Diagnostic confidence gains and the proportion of patients with changed initial diagnoses or anticipated management were calculated. The Wilcoxon signed-rank test was used to assess gains in diagnostic confidence. RESULTS MR imaging caused a mean gain in diagnostic confidence of 22% (P <.0001). MR imaging changed initial diagnoses in 11 patients (18%). Immediate clinical management changed in 13 patients (22%). UFE was not performed in 11 of 57 women (19%) who were anticipated before MR imaging to receive UFE. CONCLUSIONS MR imaging significantly alters the diagnoses and treatment plans of interventional radiologists evaluating women with presumed symptomatic fibroids. MR imaging should be considered in all patients before UFE.

The Vascular Impact of Uterine Artery Embolization: Prospective Sonographic Assessment of Ovarian Arterial Circulation

PURPOSE The etiology of premature ovarian failure after uterine artery embolization (UAE) is unknown. The authors prospectively assessed ovarian arterial circulation before and after UAE with use of ultrasonography (US). The authors hypothesize that nontarget embolization of the ovary occurs during routine UAE. MATERIALS AND METHODS Twenty-three women (mean age of 42.6 years; range, 35-51 y) participated in the study. Grayscale, color, and pulsed-wave Doppler US studies were performed immediately before and after UAE. Resistive index (RI) and pulsatility index (PI) were calculated. The proportion of women who developed increased vascular impedance after UAE was statistically assessed with use of the Yates-corrected chi(2) test. RESULTS Seventeen of 23 patients (74%) completed the study. Nine of 17 (54%) showed complete loss of ovarian arterial perfusion after UAE. Six of 17 (35%) had increases in RI and PI, whereas two of 17 (11%) had decreases in RI and PI. The increase in vascular impedance after UAE in 15 of 17 patients was significant (P <.0001). CONCLUSION Loss of detectable ovarian arterial perfusion occurs in the majority of patients undergoing UAE. Ovarian vascular impedance increases in nearly all patients as a result of UAE. The authors conclude that inadvertent nontarget embolization of the ovarian arterial bed occurs during routine UAE.

Secondary infections of thoracic and abdominal aortic endografts.

PURPOSE To review several cases of stent-graft infection with respective outcomes to identify clinical presentations and responses to treatment options. MATERIALS AND METHODS The authors performed a single-center retrospective review of all secondary endograft infections from January 2000 to June 2007. Infections were identified from an institutional database containing all abdominal and thoracic endovascular aneurysm repairs (EVAR and TEVAR) performed at the treating hospital. RESULTS From January 2000 to June 2007, 389 EVAR and 105 TEVAR were performed at the treating hospital. Ten endograft infections were identified (five EVAR and five TEVAR). Four infections occurred in grafts placed at outside institutions and six in grafts placed in-house. The in-house prevalence of EVAR and TEVAR infection is 0.26% and 4.77%, respectively. None were placed for a presumed pre-existing mycotic aneurysm. The mean time from the index procedure to the diagnosis of infection was 243.6 days +/- 74.5. Two patients who underwent EVAR presented with a contained rupture, and the remaining eight patients presented with constitutional symptoms and/or abscess formation on imaging studies. Microbiology cultures revealed Propionibacterium species (n = 3), Staphylcoccus species (n = 3), Streptococcus species (n = 2), and Enterobacter cloacae (n = 1). All EVAR patients underwent removal of the infected endograft and reconstruction with extraanatomic bypass (n = 3) or in situ homograft placement (n = 2). During a mean follow-up of more than 1 year, there were no recognized complications or recurrence of infection. Only one of the five TEVAR patients underwent removal and interposition grafting with an antibiotic-impregnated Dacron graft. The remaining four patients were medically managed--one patient survived and was placed in hospice care, two died of mycotic aneurysm rupture, and one died from multiorgan system failure secondary to sepsis. CONCLUSIONS Graft-related septic complications following EVAR or TEVAR are rare but associated with significant mortality. Several surgical treatment options are available, each potentially equally successful. The effect of prophylactic antibiotic use during subsequent invasive procedures must be solidified.

Pretransplant Portal Vein Recanalization-Transjugular Intrahepatic Portosystemic Shunt in Patients With Complete Obliterative Portal Vein Thrombosis.

Background Chronic, obliterative portal vein (PV) thrombosis (PVT) represents a relative contraindication to liver transplantation (LT) in some centers. When PV thromboembolectomy is not feasible, alternative techniques (portacaval hemitransposition, portal arterialization, multivisceral transplantation) are associated with suboptimal outcomes. In cases where a chronically thrombosed PV has become obliterated, we developed PV recanalization (PVR)-transjugular intrahepatic portosystemic shunt (TIPS) to potentiate LT. We evaluated the impact of PVR-TIPS on liver function, transplant eligibility, and long-term outcomes after LT. Methods Forty-four patients with chronic obliterative main PVT were identified during our institutional LT selection committee. After joint imaging review by transplant surgery/radiology, these patients underwent PVR-TIPS to potentiate transplant eligibility. Patients were followed by hepatology/transplant until LT, and ultimately in posttransplant clinic. The TIPS venography and serial ultrasound/MRI were used subsequently to document PV patency. Results The main PV (MPV) was completely thrombosed in 17 of 44 (39%) patients; near complete (>95%) occlusion was noted in 27 of 44 (61%) patients. Direct transhepatic and transsplenic punctures were required in 11 of 43 (26%) and 3 of 43 (7%) cases, respectively. Technical success was 43 of 44 (98%) cases. At PVR-TIPS completion, persistence of MPV thrombus was noted in 33 of 43 (77%) cases. One-month TIPS venography demonstrated complete resolution of MPV thrombosis in 22 of 29 (76%) without anticoagulation. Thirty-six patients were listed for transplantation; 18 (50%) have been transplanted. Eighty-nine percent MPV patency rate and 82% survival were achieved at 5 years. Conclusions The PVR-TIPS may be considered for patients with obliterative PVT who are otherwise appropriate candidates for LT. The high rate of MPV patency post-TIPS placement suggests flow reestablishment as the dominant mechanism of thrombus resolution.

Cancer concepts and principles: Primer for the interventional oncologist - Part i

A sophisticated understanding of the rapidly changing field of oncology, including a broad knowledge of oncologic disease and the therapies available to treat them, is fundamental to the interventional radiologist providing oncologic therapies, and is necessary to affirm interventional oncology as one of the four pillars of cancer care alongside medical, surgical, and radiation oncology. The first part of this review intends to provide a concise overview of the fundamentals of oncologic clinical trials, including trial design, methods to assess therapeutic response, common statistical analyses, and the levels of evidence provided by clinical trials.

Validation of injection parameters for catheter-directed intraarterial gadolinium-enhanced MR angiography.

RATIONALE AND OBJECTIVES Catheter-directed intraarterial (IA) injections of gadolinium contrast agents may be used during endovascular interventions with magnetic resonance (MR) imaging guidance. Injection protocols require further validation. Using a flow phantom and swine, the authors aimed to (a) measure the optimal arterial gadolinium concentration ([Gd]) required for MR angiography and (b) validate a proposed IA injection protocol for gadolinium-enhanced MR angiography. MATERIALS AND METHODS For in vitro experiments, the authors placed a catheter in the aorta of an aorto-renal-iliac flow phantom. Injected [Gd], injection rates, and aortic blood flow rates were varied independently for 36 separate IA gadolinium injections. The authors performed 2D and 3D MR angiography with a fast spoiled gradient-recalled echo sequence. For subsequent in vivo experiments, they selectively placed catheters within the aorta, renal artery, or common iliac artery of three pigs. Injection rate and injected [Gd] were varied. The authors performed 32 separate IA gadolinium injections for 2D MR angiography. Signal-to-noise ratios (SNRs) were compared for the various combinations of injection rate and injected [Gd]. RESULTS In vitro, an arterial [Gd] of 2%-4% produced an optimal SNR for 2D MR angiography, and 3%-5% was best for 3D MR angiography. In swine, an arterial [Gd] of 1%-4% produced an optimal SNR. In the phantom and swine experiments, SNR was maintained at higher injection rates by inversely varying the injected [Gd]. CONCLUSION Dilute arterial [Gd] is required for optimal IA gadolinium-enhanced MR angiography. To maintain an optimal SNR, injection rates and injected [Gd] should be varied inversely. The postulated injection protocol was validated.

Filter-related, Thrombotic Occlusion of the Inferior Vena Cava Treated with a Gianturco Stent

The authors report a case of complete thrombotic occlusion of the inferior vena cava (IVC), which occurred 4 weeks after placement of an IVC filter (TrapEase; Cordis, Miami FL). Initial treatment with suction thrombectomy and thrombolysis was ineffective. Percutaneous removal of the filter was unsuccessful because of the long period of implantation. TrapEase filters (Cordis) are easily collapsible because of their symmetric design and composition (nitinol). An expandable metallic Gianturco Z stent (Cook, Bloomington, IN) was used to exclude the filter from the vessel lumen. In cases of persistent filter-related, thrombotic occlusion of the IVC, in which initial treatment has failed, the use of a Gianturco stent (Cook) to exclude the filter from the vessel lumen is a viable treatment option if the filter has a collapsible design.