S. Hunt

Percutaneous Renal Cryoablation: Short-Axis Ice-Ball Margin as a Predictor of Outcome.

PURPOSE To determine if CT characteristics of intraprocedural ice balls correlate with outcomes after cryoablation. MATERIALS AND METHODS A retrospective review was performed on 63 consecutive patients treated with renal cryoablation. Preprocedural and intraprocedural images were used to identify the size and location of renal tumors and ice balls as well as the tumor coverage and ice-ball margins. Review of follow-up imaging (1 mo and then 3-6-mo intervals) distinguished successful ablations from cases of residual tumor. RESULTS Patients who underwent successful ablation (n = 50; 79%) had a mean tumor diameter of 2.5 cm (range, 0.9-4.3 cm) and mean ice-ball margin of 0.4 cm (range, 0.2-1.2 cm). Patients with residual tumor (n = 13; 21%) had a mean tumor diameter of 3.8 cm (range, 1.8-4.5 cm) and mean ice-ball margin of -0.4 cm (range, -0.9 to 0.4 cm). Residual and undertreated tumors were larger and had smaller ice-ball margins than successfully treated tumors (P < .01). Ice-ball diameters were significantly smaller after image reformatting (P < .01). Ice-ball margins of 0.15 cm had 90% sensitivity, 92% specificity, and 98% positive predictive value for successful ablation. Success was independent of tumor location or number of cryoprobes. CONCLUSIONS Ice-ball margin and real-time intraprocedural reformatting could be helpful in predicting renal cryoablation outcomes. Although a 0.5-cm margin is preferred, a well-centered ice ball with a short-axis margin greater than 0.15 cm strongly correlated with successful ablation.

Antivascular Ultrasound Therapy Magnetic Resonance Imaging Validation and Activation of the Immune Response in Murine Melanoma

The purpose of this study was to investigate the treatment effects of antivascular ultrasound (US) with dynamic contrast‐enhanced magnetic resonance imaging (MRI), contrast‐enhanced sonography, and histopathologic analysis in a murine melanoma model.

Segmental Transarterial Embolization in a Translational Rat Model of Hepatocellular Carcinoma

PURPOSE To develop a clinically relevant, minimally invasive technique for transarterial embolization in a translational rat model of hepatocellular carcinoma (HCC). MATERIALS AND METHODS Oral diethylnitrosamine was administered to 53 male Wistar rats ad libitum for 12 weeks. Tumor induction was monitored using magnetic resonance imaging. Minimally invasive lobar or segmental transarterial embolization was performed through a left common carotid artery approach. Necropsy was performed to evaluate periprocedural mortality. Histologic analysis of tumors that received embolization was performed to assess percent tumor necrosis. RESULTS Severe cirrhosis and autochthonous HCCs were characterized in a cohort of rats composed of two groups of rats identically treated with diethylnitrosamine with median survival times of 101 days and 105 days (n = 10/group). A second cohort was used to develop minimally invasive transarterial embolization of HCCs (n = 10). In a third cohort, lobar embolization was successfully performed in 9 of 10 rats and demonstrated a high rate of periprocedural mortality (n = 5). Necropsy performed for periprocedural mortality after lobar embolization demonstrated extensive tissue necrosis within the liver (n = 3) and lungs (n = 2), indicating nontarget embolization as the likely cause of mortality. In a fourth cohort of rats, a segmental embolization technique was successfully applied in 10 of 13 rats. Segmental embolization resulted in a reduction in periprocedural mortality (P = .06) relative to selective embolization and a 19% increase in average tumor necrosis (P = .04). CONCLUSIONS Minimally invasive, segmental embolization mimicking the currently applied clinical approach is feasible in a translational rat model of HCC and offers the critical advantage of reduced nontarget embolization relative to lobar embolization.

Ischemia Induces Quiescence and Autophagy Dependence in Hepatocellular Carcinoma

Purpose To characterize hepatocellular carcinoma (HCC) cells surviving ischemia with respect to cell cycle kinetics, chemosensitivity, and molecular dependencies that may be exploited to potentiate treatment with transarterial embolization (TAE). Materials and Methods Animal studies were performed according to institutionally approved protocols. The growth kinetics of HCC cells were studied in standard and ischemic conditions. Viability and cell cycle kinetics were measured by using flow cytometry. Cytotoxicity profiling was performed by using a colorimetric cell proliferation assay. Analyses of the Cancer Genome Atlas HCC RNA-sequencing data were performed by using Ingenuity Pathway Analysis software. Activation of molecular mediators of autophagy was measured with Western blot analysis and fluorescence microscopy. In vivo TAE was performed in a rat model of HCC with (n = 5) and without (n = 5) the autophagy inhibitor Lys05. Statistical analyses were performed by using GraphPad software. Results HCC cells survived ischemia with an up to 43% increase in the fraction of quiescent cells as compared with cells grown in standard conditions (P < .004). Neither doxorubicin nor mitomycin C potentiated the cytotoxic effects of ischemia. Gene-set analysis revealed an increase in mRNA expression of the mediators of autophagy (eg, CDKN2A, PPP2R2C, and TRAF2) in HCC as compared with normal liver. Cells surviving ischemia were autophagy dependent. Combination therapy coupling autophagy inhibition and TAE in a rat model of HCC resulted in a 21% increase in tumor necrosis compared with TAE alone (P = .044). Conclusion Ischemia induces quiescence in surviving HCC cells, resulting in a dependence on autophagy, providing a potential therapeutic target for combination therapy with TAE.

Outcomes of Percutaneous Cholecystostomy in the Presence of Ascites

PURPOSE To evaluate whether the presence of ascites increases complications following placement of percutaneous cholecystostomy tubes (PCTs). MATERIALS AND METHODS Retrospective review of all transhepatic PCTs placed between January 2005 and June 2014 was performed: 255 patients were included (median age of 65 y; range, 20-95 y). Of these patients, 97 had ascites and 158 had no ascites or only pelvic fluid. In all, 115 patients had calculous cholecystitis (45%), 127 had acalculous cholecystitis (50%), and 13 had common bile duct obstruction (5%). The primary outcome of interest was all complications, including bile peritonitis, pericatheter leakage requiring PCT change, pericholecystic abscess formation, drain dislodgment, or death from biliary sepsis within 14 days of initial PCT insertion. RESULTS The overall complication rate was 11% among patients with ascites (n = 11), compared with 10% in those without (n = 16; P = .834). No difference was found between the two groups in any one complication. The overall outcome of PCT drainage differed between groups, with significantly shorter survival times in patients with ascites. Patients with ascites underwent cholecystectomy less often than patients without ascites (21% vs 39%; P = .002). Likewise, patients with ascites were more likely than those without ascites to die with the PCT in place (49% vs 25%; P = .001). CONCLUSIONS Frequencies of complications following PCT insertion were similar in patients with and without ascites. Additionally, the overall complication rate was low and not significantly different between the two groups. These observations support the use of PCT placement in patients with ascites.

Can Precision Medicine Reduce Overdiagnosis

Precision Medicine promises to get the right patient, the right test, the right diagnosis, the right treatment, and in the right amount. Is this hope or hype?

Magnetic Resonance–Monitored Coaxial Electrochemical Ablation—Preliminary Evaluation of Technical Feasibility

PURPOSE To evaluate the technical feasibility of a coaxial electrode configuration to rapidly create a mechanically defined electrochemical ablation zone monitored by magnetic resonance (MR) imaging in real time. MATERIALS AND METHODS A direct current generator supplied the nitinol cathode cage and central platinum anode for coaxial electrochemical ablation. Safety and efficacy were evaluated by measuring local pH, temperature, and current scatter in saline solutions. Ablation zone diameters of 3-6 cm (n = 72) were created on ex vivo bovine liver and verified by gross pathology. Feasibility of MR monitoring was evaluated using 8 swine livers to create ablations of 3 cm (n = 12), 4 cm (n = 4), and 5 cm (n = 4) verified by histology. RESULTS Local pH was 3.2 at the anode and 13.8 at the cathode. Current scatter was negligible. Ablation progress increased relative to local ion concentration, and MR signal changes corresponded to histologic findings. In the ex vivo model, the times to achieve complete ablation were 15 minutes, 20 minutes, 35 minutes, and 40 minutes for diameters of 3 cm, 4 cm, 5 cm, and 6 cm, respectively. Ablation times for the in situ model were 15 minutes, 35 minutes, and 50 minutes for 3 cm, 4 cm, and 5 cm, respectively. CONCLUSIONS The coaxial configuration mechanically defined the electrochemical ablation zone with times similar to comparably sized thermal ablations. MR compatibility allowed for real-time monitoring of ablation progress.

Definitive locoregional therapy (LRT) versus bridging LRT and liver transplantation with wait-and-not-treat approach for very early stage hepatocellular carcinoma

PURPOSE Since the change in the United Network for Organ Sharing (UNOS) policy excluding patients with very early stage hepatocellular carcinoma (veHCC, single tumor nodule <2 cm) from receiving Model for End-stage Liver Disease (MELD) exception points, patients eligible to receive liver transplantation (LT) who fall in this category are commonly treated with locoregional therapy (LRT) after progression to UNOS T2 stage (1 nodule of 2-5 cm or up to 3 nodules, none above 3 cm). The aim of the current study is to compare the outcomes of patients treated with bridging LRT and LT with wait-and-not-treat approach with patients treated with definitive LRT. METHODS A retrospective study has been performed on patients with veHCC evaluated in multidisciplinary liver tumor clinic of a large academic center between 2004-2011. Patients eligible for LT were assigned to the wait-and-not-treat group while patients who were not eligible were assigned to the definitive LRT group. Tumor size, time to treatment, severity of liver disease, recurrence and survival from time of detection were reviewed and recorded. RESULTS A total of 19 patients were identified and treated with definitive LRT while 57 patients were treated with bridging LRT prior to LT after disease progression to T2 stage. Patients in the definitive LRT group were older (70.4±10.2 years vs. 58.7±5.9 years, P < 0.001) and had more comorbid conditions compared with the wait-and-not-treat group. Mean survival for definitive LRT group at the end of 5 years was 34.3±6.0 months with a median of 30.3 months (95% CI, 5.7-55.0 months) compared with 48.7±2.6 months for the wait-and-not-treat group, respectively (median not reached). The 3- and 5-year survival rates were 53.3% and 33.3% for the definitive LRT group compared with 78.9% and 68.4% for the patients in the wait-and-not-treat group. Survival rate at the end of 5 years was significantly better for the wait-and-not-treat group (P = 0.013). CONCLUSION Based on the findings of current retrospective study, treating veHCC (UNOS T1 stage) patients listed for LT with bridging LRT after disease progression to T2 stage appears to be safe and effective with high 5-year survival rates.

On factors impacting subharmonic aided pressure estimation (SHAPE)

Subharmonic aided pressure estimation (SHAPE) uses ultrasound contrast agents (UCAs) to estimate hydrostatic pressure by transmitting at one frequency, receiving at its subharmonic frequency and then monitoring the subharmonic amplitude variations. The subharmonic response of the UCAs has an inverse linear relationship with the ambient pressure. In order to optimize SHAPE, we studied the impact of varying input acoustic output (IAO), UCA concentration and hematocrit concentrations. The current IAO selection algorithm is prone to noise, due to motion. A modified Logiq 9 ultrasound scanner with a 4C curvi-linear probe (GE, Milwaukee, WI) was used to acquire SHAPE data from Sonazoid (GE Healthcare, Oslo, Norway) transmitting at 2.5 MHz and receiving subharmonic signals at 1.25 MHz. The new selection algorithm provided improved or similar correlation between the SHAPE signal and hydrostatic pressure for all setups (r ranging from −0.85 to −0.95 vs −0.39 to −0.98). Also, it is important to study the effect of hematocrit, since the clinical population presents with a wide range of values. Additionally, the effect on SHAPE of varying UCA concentration was studied in vitro. The reduction in subharmonic amplitude as the pressure increased from 10 to 40 mmHg remained almost the same (Δ0.00–0.01 dB, p=0.18) with no significant change as the hematocrit concentration was tripled (from 1.8 to 4.5 ml/l). Likewise, the SHAPE gradient changed only slightly (Δ 0.02–0.05 dB, p=0.75) as the UCA concentration was increased from 0.2 to 1.2 ml/l. In conclusion the relative change in the subharmonic signal is independent of hematocrit and UCA concentration. An improved algorithm for identifying optimum IAO levels correctly should make SHAPE more sensitive and accurate.

Improved selection of optimal acoustic output power for subharmonic aided pressure estimation of portal hypertension

Subharmonic aided pressure estimation (SHAPE) is based on the inverse relationship between the subharmonic amplitude of contrast microbubbles and the ambient pressure. A noninvasive ultrasound based pressure estimation procedure would be a major development in the diagnosis of portal hypertension and less invasive than the current hepatic venous pressure gradient (HVPG) measurement. The hypothesis of this study was that portal vein pressures could be monitored and quantified noninvasively in humans using SHAPE. For maximum SHAPE sensitivity, the optimum acoustic power is currently selected using an algorithm, which collects subharmonic data at power levels increasing from 0 % to 100 % in 8 cine clips. The ROI is selected on a common Maximum Intensity Projection (MIP) for all these 8 clips, data is plotted against the power levels and the point of maximum inflection gives the optimum power. However, this algorithm is prone to motion due to breathing and can greatly affect the results, hence was improved to minimize the error.