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Biomedical subjects

S N Goldberg

Publications and source records attributed to S N Goldberg.

At least 19 recordsLinked to original sources

RF tumour ablation: computer simulation and mathematical modelling of the effects of electrical and thermal conductivity.

This study determined the effects of thermal conductivity on RF ablation tissue heating using mathematical modelling and computer simulations of RF heating coupled to thermal transport. Computer simulation of the Bio-Heat equation coupled with temperature-dependent solutions for RF electric fields (ETherm) was used to generate temperature profiles 2 cm away from a 3 cm internally-cooled electrode. Multiple conditions of clinically relevant electrical conductivities (0.07-12 S m-1) and 'tumour' radius (5-30 mm) at a given background electrical conductivity (0.12 S m-1) were studied. Temperature response surfaces were plotted for six thermal conductivities, ranging from 0.3-2 W m-1 degrees C (the range of anticipated clinical and experimental systems). A temperature response surface was obtained for each thermal conductivity at 25 electrical conductivities and 17 radii (n=425 temperature data points). The simulated temperature response was fit to a mathematical model derived from prior phantom data. This mathematical model is of the form (T=a+bRc exp(dR) s(f) exp(g)(s)) for RF generator-energy dependent situations and (T=h+k exp(mR)+n?exp(p)(s)) for RF generator-current limited situations, where T is the temperature (degrees C) 2 cm from the electrode and a, b, c, d, f, g, h, k, m, n and p are fitting parameters. For each of the thermal conductivity temperature profiles generated, the mathematical model fit the response surface to an r2 of 0.97-0.99. Parameters a, b, c, d, f, k and m were highly correlated to thermal conductivity (r2=0.96-0.99). The monotonic progression of fitting parameters permitted their mathematical expression using simple functions. Additionally, the effect of thermal conductivity simplified the above equation to the extent that g, h, n and p were found to be invariant. Thus, representation of the temperature response surface could be accurately expressed as a function of electrical conductivity, radius and thermal conductivity. As a result, the non-linear temperature response of RF induced heating can be adequately expressed mathematically as a function of electrical conductivity, radius and thermal conductivity. Hence, thermal conductivity accounts for some of the previously unexplained variance. Furthermore, the addition of this variable into the mathematical model substantially simplifies the equations and, as such, it is expected that this will permit improved prediction of RF ablation induced temperatures in clinical practice.

Catheter Ablation↗

Combination radiofrequency thermal ablation and adjuvant IV liposomal doxorubicin increases tissue coagulation and intratumoural drug accumulation.

There has been marked interest in minimally-invasive, image-guided radiofrequency (RF) tumour ablation (i.e. coagulating tumour using short duration heating ( < 15 min) by directly applying temperatures > 50 degrees C via needle electrodes) to treat focal liver, renal, breast, bone and lung tumours. In spite of advances in RF technology and improved understanding of tumour biophysiology that now enable experimental treatment of tumours up to 5cm, investigators have been unable to achieve complete ablation in many cases, particularly at the tumour margins and adjacent to blood vessels. One strategy for overcoming these limitations has been to take advantage of complementary interactions between RF thermal ablation and chemotherapy, particularly liposomal doxorubicin preparations, to attempt more complete tumour destruction. This paper will review published laboratory investigations demonstrating that this combined treatment paradigm has the unique potential both to potentiate preferential delivery of cytotoxic agents in liposome vehicles and to maximize the completeness of ablation of a treated tumour. New confirmatory data describing increased tumour destruction with RF ablation combined with different liposome preparations, documenting increased lipid peroxidation and expanding on previously published tumour growth studies is presented. Additionally, early clinical data including a randomized, pilot clinical study on 10 patients with primary and metastatic liver tumours, in which a non-optimized combination of RF ablation and IV liposomal doxorubicin (Doxil) increased the volume of tumour destruction 25-30% compared to RF alone, will also be described in detail.

Antibiotics, Antineoplastic↗

Radiofrequency tumor ablation: principles and techniques.

Radiofrequency (RF) tumor ablation has been demonstrated as a reliable method for creating thermally induced coagulation necrosis using either a percutaneous approach with image-guidance or direct surgical placement of thin electrodes into tissues to be treated. Early clinical trials with this technology have studied the treatment of hepatic, cerebral, and bony malignancies. However, more recently this technology has been used to treat a host of malignant processes throughout the body. This article will discuss the principles and technical considerations of RF ablation with the goal of defining optimal parameters for the therapy of focal lesions. This includes technologic innovations that permit large volume tumor ablation (i.e., hooked and internally cooled electrodes), as well as methods and adjuvant therapies that can modulate tumor biophysiology to permit improved tumor destruction (i.e, altered tissue conductivity and blood flow). Potential biophysical limitations to RF induced coagulation, such as perfusion mediated tissue cooling (vascular flow) will likewise be discussed. Lastly, the principles governing safe usage of the system, such as proper grounding pad placement, will be adressed.

Animals↗

Cost-effectiveness of percutaneous radiofrequency ablation for malignant hepatic neoplasms.

PURPOSE: Percutaneous radiofrequency (RF) ablation is a promising technique for the treatment of hepatic malignancies. However, its cost-effectiveness has not been established. The purpose of this study is to determine the cost-effectiveness of RF ablation compared to palliative care in the treatment of hepatocellular cancer and colorectal liver metastases. This study also seeks to evaluate the effects of transition from traditional to newly implemented prospective outpatient reimbursement mechanisms on RF ablation cost-effectiveness. MATERIALS AND METHODS: The marginal direct costs of a percutaneous RF ablation treatment strategy were compared to palliative care over a range of survival benefits with use of a cost-effectiveness model built from the perspective of the payer. Variables used in the model, including complication rates and procedure efficacy, were obtained from the literature and the authors' experience with 46 consecutive patients. RESULTS: The cost-effectiveness of a standardized percutaneous RF ablation treatment strategy compared to palliative care was $20,424, $11,407, $5,034, and $3,492, respectively, per life-year (LY) gained when marginal median survival conferred by RF ablation is 6 months, 1 year, 3 years, and 5 years. The RF ablation treatment strategy would be required to generate 6.14, 2.26, and 1.10 months of marginal median survival benefit to achieve strict ($20,000/LY gained), moderate ($50,000/LY gained), and generous ($100,000/LY gained) cost-effectiveness thresholds. Cost-effectiveness was sensitive to the number of lifetime treatments, hours of observation time, frequency of follow-up evaluations, cost of abdominal computed tomography, and decision to perform RF ablation as an inpatient or outpatient. CONCLUSION: Percutaneous RF ablation is a cost-effective treatment strategy compared to palliative care and has likely already achieved the survival benefit required to meet even a strict cost-effectiveness criterion. Dependence on reimbursement mechanism highlights the importance of concordance between policy and RF ablation technology. The results of this study allow flexible application of cost-effectiveness data despite current uncertainties in treatment and survival data and heterogeneity in treatment populations.

Catheter Ablation↗

Dynamic intrahepatic flow and cellular alterations during radiofrequency ablation of liver tissue in mice.

PURPOSE: The purpose of this study was to identify microvascular and other associated changes that occur in the liver during focal heating with monopolar radiofrequency (RF). MATERIALS AND METHODS: Intravital video microscopy was performed on exteriorized transilluminated livers of 15 live mice during RF-induced heating of liver parenchyma. Microvascular flow parameters, flow reversibility, microbubble formation, phagocytic activity, and endothelial permeability were recorded throughout a range of tip temperatures (40 degrees C-95 degrees C). RESULTS: During RF application, five discrete zones extended outward from the electrode surface: (i) tissue coagulation, (ii) cellular edema/necrosis, (iii) sinusoidal stasis, (iv) parenchymal shunting, and (v) normal liver tissue. Reversal of stasis in sinusoids and small (<25 microm) vessels occurred at tip temperatures below 50 degrees C. This zone of stasis corresponded to the hyperemic zone on histologic analysis. Although alterations in permeability and phagocytic activity were first identified at 43 degrees C, tip temperatures higher than 55 degrees C always produced local endothelial leakiness to carbon microparticles at the periphery and always inhibited phagocytic activity. At tip temperatures higher than 95 degrees C, microbubble formation occurred with bubbles ultimately tracking through necrotic tissue into patent sinusoids. Larger peripheral vessels (>30 microm) limited extension of coagulation. CONCLUSION: Although coagulation occurs at tip temperatures higher than 50 degrees C, RF heating induced reversible microvascular stasis at temperatures lower than 50 degrees C. Increased sinusoidal endothelial permeability occurs at near-coagulative temperatures. Therefore, targeted endovascular microparticle delivery through this leaky endothelium may provide an additional and complimentary adjunct for RF ablation therapy.

Animals↗

Essential techniques for successful radio-frequency thermal ablation of malignant hepatic tumors.

Radio-frequency thermal ablation is one of the most promising minimally invasive techniques for the treatment of nonresectable hepatic tumors. Essential technical tips to successful radio-frequency ablation therapy were collected from five international experts. They were organized into five categories: understanding the mechanisms and principles of radio-frequency ablation, modulation of tissue physiologic characteristics to increase tumor destruction, strategies of overlapping ablations, strategies to improve ablation according to tumor location, and imaging strategies after ablation to ensure adequate therapy. Established factors for optimal ablation, as well as emerging technical tips, are addressed with illustrations in each section. These essential tips will be very helpful for physicians performing radio-frequency ablation of hepatic tumors.

Catheter Ablation↗

Percutaneous radio-frequency ablation of hepatic metastases from colorectal cancer: long-term results in 117 patients.

PURPOSE: To describe the results of an ongoing radio-frequency (RF) ablation study in patients with hepatic metastases from colorectal carcinoma. MATERIALS AND METHODS: In 117 patients, 179 metachronous colorectal carcinoma hepatic metastases (0.9-9.6 cm in diameter) were treated with RF ablation by using 17-gauge internally cooled electrodes. Computed tomographic follow-up was performed every 4-6 months. Recurrent tumors were retreated when feasible. Time to new metastases and death for each patient and time to local recurrence for individual lesions were modeled with Kaplan-Meier analysis. Modeling determined the effect of number of metastases on the time to new metastases and death and effect of tumor size on local recurrence. RESULTS: Estimated median survival was 36 months (95% CI; 28, 52 months). Estimated 1, 2, and 3-year survival rates were 93%, 69%, and 46%, respectively. Survival was not significantly related to number of metastases treated. In 77 (66%) of 117 patients, new metastases were observed at follow-up. Estimated median time until new metastases was 12 months (95% CI; 10, 18 months). Percentages of patients with no new metastases after initial treatment at 1 and 2 years were 49% and 35%, respectively. Time to new metastases was not significantly related to number of metastases. Seventy (39%) of 179 lesions developed local recurrence after treatment. Of these, 54 were observed by 6 months and 67 by 1 year. No local recurrence was observed after 18 months. Frequency and time to local recurrence were related to lesion size (P < or =.001). CONCLUSION: RF ablation is an effective method to treat hepatic metastases from colorectal carcinoma.

Adult↗

Radio-frequency thermal ablation with NaCl solution injection: effect of electrical conductivity on tissue heating and coagulation-phantom and porcine liver study.

PURPOSE: To characterize the effects of NaCl concentration on tissue electrical conductivity, radio-frequency (RF) deposition, and heating in phantoms and optimize adjunctive NaCl solution injection for RF ablation in an in vivo model. MATERIALS AND METHODS: RF was applied for 12-15 minutes with internally cooled electrodes. For phantom experiments (n = 51), the NaCl concentration in standardized 5% agar was varied (0%-25.0%). A nonlinear simplex optimization strategy was then used in normal porcine liver (n = 44) to determine optimal pre-RF NaCl solution injection parameters (concentration, 0%-38.5%; volume, 0-25 mL). NaCl concentration and tissue conductivity were correlated with RF energy deposition, tissue heating, and induced coagulation. RESULTS: NaCl concentration had significant but nonlinear effects on electrical conductivity, RF deposition, and heating of agar phantoms (P<.01). Progressively greater heating was observed to 5.0% NaCl, with reduced temperatures at higher concentrations. For in vivo liver, NaCl solution volume and concentration significantly influenced both tissue heating and coagulation (P<.001). Maximum heating 20 mm from the electrode (102.9 degrees C +/- 4.3 [SD]) and coagulation (7.1 cm +/- 1.1) occurred with injection of 6 mL of 38.5% (saturated) NaCl solution. CONCLUSION: Injection of NaCl solution before RF ablation can increase energy deposition, tissue heating, and induced coagulation, which will likely benefit clinical RF ablation. In normal well-perfused liver, maximum coagulation (7.0 cm) occurs with injection of small volumes of saturated NaCl solution.

Animals↗

Percutaneous radio-frequency ablation of liver metastases from breast cancer: initial experience in 24 patients.

PURPOSE: To evaluate the authors' initial experience in a consecutive series of 24 patients with breast cancer liver metastases treated with radio-frequency (RF) ablation. MATERIALS AND METHODS: Twenty-four consecutive patients with 64 metastases measuring 1.0--6.6 cm in diameter (mean, 1.9 cm) underwent ultrasonography-guided percutaneous RF ablation with 18-gauge, internally cooled electrodes. Treatment was performed with the patient under conscious sedation and analgesia or general anesthesia. A single lesion was treated in 16 patients, and multiple lesions were treated in eight patients. Follow-up with serial computed tomography ranged from 4 to 44 months (mean, 10 months; median, 19 months). RESULTS: Complete necrosis was achieved in 59 (92%) of 64 lesions. Among the 59 lesions, complete necrosis required a single treatment session in 58 lesions (92%) and two treatment sessions in one lesion (2%). In 14 (58%) of 24 patients, new metastases developed during follow-up. Ten (71%) of these 14 patients developed new liver metastases. Currently, 10 (63%) of 16 patients whose lesions were initially confined to the liver are free of disease. One patient died of progressive brain metastases. No major complications occurred. Two minor complications were observed. CONCLUSION: On the basis of preliminary study results, percutaneous RF ablation appears to be a simple, safe, and effective treatment for focal liver metastases in selected patients with breast cancer.

Adult↗

Percutaneous tumor ablation: increased necrosis with combined radio-frequency ablation and intratumoral doxorubicin injection in a rat breast tumor model.

PURPOSE: To determine whether a combination of intratumoral doxorubicin injection and radio-frequency (RF) ablation increases tumor destruction compared with RF ablation alone in an animal tumor model. MATERIALS AND METHODS: R3230 mammary adenocarcinoma 1.2-1.5-cm- diameter nodules (n = 110) were implanted subcutaneously in 84 female Fischer rats. For initial experiments (n = 46), tumors were treated with (a) conventional, monopolar RF (250 mA +/- 25 [SD] at 70 degrees C +/- 1 for 5 minutes) ablation alone; (b) direct intratumoral doxorubicin injection (volume, 250 microL; total dose, 0.5 mg) alone; (c) combined therapy (doxorubicin injection immediately followed by RF ablation); (d) RF ablation and injection of 250 microL of distilled water; or (e) no treatment. In subsequent experiments, amount of doxorubicin (0.02-2.50 mg; n = 40 additional tumors) and timing of doxorubicin administration (2 days before to 2 days after RF ablation; n = 24 more tumors) were varied. Pathologic examination, including staining for mitochondrial enzyme activity and perfusion, was performed, and the resultant tumor destruction from each treatment was evaluated. RESULTS: Coagulation diameter was 6.7 mm +/- 0.6 for tumors treated with RF ablation alone and 6.9 mm +/- 0.7 for those treated with RF ablation and water (P =.52), while intratumoral doxorubicin injection alone produced only 2.0-3.0 mm of coagulation (P <.001). Increased coagulation was observed only with combined doxorubicin injection and RF therapy (P <.001). Coagulation was dependent on concentration and timing of doxorubicin administration, with greatest coagulation (11.5 mm +/- 1.1) observed for doxorubicin administered within 30 minutes of RF ablation. CONCLUSION: Adjuvant intratumoral doxorubicin injection increases coagulation in solid tumors compared with RF ablation alone. Increased tumor destruction is also seen when doxorubicin is administered after RF ablation, which suggests that RF ablation may sensitize tumors to chemotherapy. Such combination therapies may, therefore, offer improved methods for ablating solid tumors.

Adenocarcinoma↗

Accuracy of volumetric measurements after virtual right hepatectomy in potential donors undergoing living adult liver transplantation.

OBJECTIVE: The purpose of this study was to evaluate accuracy for determining the total and lobar liver volumes using a multidetector CT scanner in potential donors undergoing living adult right lobe liver transplantation. SUBJECTS AND METHODS: Fifty-two adult donors underwent CT using a multidetector scanner after IV injection of 180 mL of contrast material. For volumetric determination, portal venous phase images were acquired at 60 sec. Hand-tracing was used to isolate the entire liver, and a curved hepatectomy plane was then identified in a manner simulating the surgical incision. Two observers performed hand-tracing of the entire liver to calculate total liver volume, and of the right lobe to calculate expected graft volume. RESULTS: The mean volume of the entire liver, right lobe, and left lobe was 1807 mL, 990 mL, and 817 mL, respectively, for observer 1, and 1788 mL, 1007 mL, and 781 mL, respectively, for observer 2. There was significant agreement between the two observers in determining total and lobar liver volumes (r = 0.996, 0.977, and 0.965 for total, right lobe, and left lobe volumes, respectively; p< 0.0001). There was no statistically significant difference between the two observers in measuring total or lobar liver volumes (p< 0.0001). There was significant agreement between right lobe volume measured by each observer and graft weight obtained in 14 donors at surgery (r = 0.898 and 0.879, for observers 1 and 2, respectively; p <0.001). CONCLUSION: Total and lobar volume determinations after virtual right hemihepatectomy provides accurate and reproducible information that is critical in selecting potential living liver donors.

Adolescent↗

Hepatocellular carcinoma treated with radiofrequency ablation: comparison of pulse inversion contrast-enhanced harmonic sonography, contrast-enhanced power Doppler sonography, and helical CT.

OBJECTIVE: The purpose of this study was to compare the efficacy of contrast-enhanced pulse inversion harmonic imaging with contrast-enhanced power Doppler sonography and helical CT to determine incomplete local treatment after radiofrequency ablation in patients with hepatocellular carcinoma. MATERIALS AND METHODS: Thirty-five consecutive patients (24 men and 11 women; mean age, 64 years) with 43 hepatocellular carcinomas (3.6 +/- 1.1 cm) were treated using internally cooled radiofrequency ablation therapy. Therapeutic response was evaluated at 4 months with dual-phase contrast-enhanced helical CT, conventional power Doppler Sonography, and pulse inversion harmonic imaging using a sonographic contrast agent (SH-508). CT and sonographic studies were reviewed separately in random order by four radiologists at different consensus conferences. Sensitivity and specificity of the sonographic methods were determined using CT as a gold standard and results were compared using the McNemar test. RESULTS: CT examinations identified residual tumor in 12 lesions (27.9%). Although conventional contrast-enhanced power Doppler sonography identified residual viable tumor foci in four incompletely treated lesions (9.3%), contrast-enhanced pulse inversion harmonic imaging identified residual tumoral enhancement in 10 lesions (23.3%). Thus, the sensitivity of pulse inversion harmonic imaging (83.3%) was significantly greater (p < 0.05) for detecting residual nonablated tumor compared with conventional contrast-enhanced power Doppler sonography. CONCLUSION: Our study suggests that contrast-enhanced pulse inversion harmonic imaging may enable the detection of residual nonablated tumor in more cases than contrast-enhanced power Doppler sonography and may ultimately prove to be a useful adjunct for percutaneous ablation therapies. Nevertheless, contrast-enhanced axial imaging (CT or MR imaging) is currently the most sensitive test for managing thermal ablation for patients with hepatocellular carcinoma.

Carcinoma, Hepatocellular↗