Method For Tumor Ablation Research Articles

Combination of Photodynamic Therapy and Specific Immunotherapy Efficiently Eradicates Established Tumors.

The efficacy of immunotherapy against advanced cancer may be improved by combination strategies. Photodynamic therapy (PDT) is a local tumor ablation method based on localized activation of a photosensitizer, leading to oxygen radical-induced tumor cell death. PDT can enhance antitumor immune responses by release of antigen and danger signals, supporting combination protocols of PDT with immunotherapy. We investigated the local and systemic immune effects of PDT after treatment of established tumors. In two independent aggressive mouse tumor models, TC-1 and RMA, we combined PDT with therapeutic vaccination using synthetic long peptides (SLP) containing epitopes from tumor antigens. PDT of established tumors using the photosensitizer Bremachlorin resulted in significant delay of tumor outgrowth. Combination treatment of PDT with therapeutic SLP vaccination cured one third of mice. Importantly, all cured mice were fully protected against subsequent tumor rechallenge, and combination treatment of primary tumors led to eradication of distant secondary tumors, indicating the induction of a systemic antitumor immune response. Indeed, PDT by itself induced a significant CD8(+) T-cell response against the tumor, which was increased when combined with SLP vaccination and essential for the therapeutic effect of combination therapy. We show that immunotherapy can be efficiently combined with PDT to eradicate established tumors, based on strong local tumor ablation and the induction of a robust systemic immune response. These results suggest combination of active immunotherapy with tumor ablation by PDT as a feasible novel treatment strategy for advanced cancer.

Percutaneous irreversible electroporation for treatment of locally advanced pancreatic cancer following chemotherapy or radiochemotherapy

BackgroundIrreversible electroporation (IRE) is a non-thermal based tumor ablation method used close to vessels and ducts and has the potential of treating locally advanced pancreatic cancer (LAPC). The aim of this study was to evaluate the efficacy and safety of IRE in patients with LAPC after chemo- and/or radio-chemotherapy. MethodTwenty-four patients with biopsy proven LAPC and who had received chemo- and/or radio-chemotherapy with no signs of metastases were included and treated with ultrasound guided percutaneous IRE under general anesthesia. ResultsThe median overall survival from diagnosis of LAPC was 17.9 months; this included 7.0 months after IRE. Median time from IRE was 6.1 months to local progression and 2.7 months to observation of metastases. Local control was observed in nine patients. IRE related complications were observed in 11 patients, three of which were serious complications. There was no IRE related mortality. ConclusionPercutaneous IRE is reasonably safe in LAPC after chemo-/radio-chemotherapy and with promising results regarding efficacy.

Endoscopic ultrasound-guided ethanol ablation of a large metastatic carcinoid tumor: success with a note of caution

Endoscopic ultrasonography with fine needle infusion (EUS-FNI) of alcohol is the most reported method for EUS-guided tumor ablation. Several studies have reported successful EUS-guided ablation of pancreatic neuroendocrine tumors. However, these tumors have been relatively small (< 3 cm). In this report, a 50-year-old man with a metastatic carcinoid tumor with a large porta hepatis mass was referred to our clinic for EUS-guided ethanol ablation. After two separate EUS-FNI ablations, there was a 36 % reduction in tumor size (9.0 × 11.4 cm to 6.7 × 9.8 cm) with associated tumor lysis syndrome. Chromogranin A levels decreased from 460 to 132 ng/mL. The patient reported complete resolution of abdominal pain within 2 weeks, but only mild improvement in flushing and diarrhea. In conclusion, large metastatic neuroendocrine tumors can be successfully treated with EUS-guided ethanol ablation. Evidence-based guidelines are needed with regard to the appropriate volume of ethanol injected in EUS-guided ablation to promote the efficacy and safety of this emerging procedure.

Irreversible electroporation: A novel pancreatic cancer therapy

Approximately 43,000 new cases of pancreatic ductal adenocarcinoma (PDAC) are identified yearly in the United States. Surgical resection offers the only chance for cure with 5-year survival rates approaching 20%. However, only 80% of patients are candidates for a potentially curative resection because of metastatic disease (50%) or locally advanced tumors (30%). Perhaps more than any other stage of pancreatic cancer, patients with stage III locally advanced or unresectable tumors derive the most benefit from amultidisciplinary team approach. A typical treatment regimen begins with systemic therapy to control micrometastatic disease followed by radiation for local control. At each step of treatment, the surgeon is involved in assessing the resectability. Unfortunately, “downstaging” is estimated to occur in only 10%-15% of patients, and despite multimodality therapy, the median survival remains only 8-12 months. As such, locally advanced pancreatic cancer presents a difficult problem for the multidisciplinary team. Patients with locally advanced, albeit unresectable disease, should theoretically benefit from maximal local therapy. However, currently, there are very few treatment options for aggressive localized therapy in these patients. In highly selected cases, aggressive operations such as pancreatectomy with en bloc resection of the celiac axis can be performed, but these types of operations are only possible in few patients. Until recently, modest improvements in the prognosis and quality of life for locally advanced PDAC have focused on systemic chemotherapy and radiation therapy. Recently, several reports have described the technique and the outcome of ablative techniques for locally advanced PDAC. This article focuses on irreversible electroporation (IRE), which is a novel method for focal tumor ablation in the pancreas. Until recently, locoregional cancer therapies focused on the application of thermal energy for tissue destruction, such as radiofrequency ablation, microwave ablation, and cryoablation. Although effective in other organs such as the liver or kidney, these technologies lack safety and efficacy in the pancreas owing to the risk of thermal damage to adjacent structures and significant thermal dissipation from large adjacent blood vessels. IRE applies short, high-voltage pulses to the tissue to permeabilize cell membranes and induce cellular apoptosis. As IRE relies on apoptosis to induce cell death, structures formed by proteins such as vascular elastin and collagenous structures are not damaged, which should lead to preservation of blood vessel scaffolding. In addition, as IRE is nonthermal, there should be no heat-cold sink effect. Both are

Calibration of Ultrasound Backscatter Temperature Imaging for High-Intensity Focused Ultrasound Treatment Planning

High-intensity focused ultrasound (HIFU) is rapidly gaining acceptance as a non-invasive method for soft tissue tumor ablation, but improvements in the methods of treatment delivery, planning and monitoring are still required. Backscatter temperature imaging (BTI) uses ultrasound to visualize heating-induced echo strain and may be used to indicate the position of the HIFU focal region using low-power “sub-lesioning” exposure. The technique may also provide a quantitative tool for assessing the efficacy of treatment delivery if apparent strain measurements can be related to the underlying temperature rise. To obtain temperature estimates from strain measurements, the relationship between these variables has to be either measured or otherwise assumed from previous calibrations in similar tissues. This article describes experimental measurements aimed at deriving the relationship between temperature rise and apparent strain in the laboratory environment using both ex vivo bovine liver tissue samples and normothermically perfused porcine livers. A BTI algorithm was applied to radiofrequency ultrasound echo data acquired from a clinical ultrasound scanner (Z.One, Zonare Medical Systems, Mountain View, CA, USA) where the imaging probe was aligned with the focal region of a HIFU transducer. Temperature measurements were obtained using needle thermocouples implanted in the liver tissue. A series of “non-ablative” HIFU exposures giving peak temperatures below 10°C were made in three separate ex vivo bovine livers, yielding an average strain/temperature coefficient of 0.126 ± 0.088 percentage strain per degree Celsius. In the perfused porcine livers at a starting temperature of 38°C (normal body temperature) the strain/temperature coefficients were found to be 0.040 ± 0.029 percentage strain per degree Celsius. The uncertainty in these results is directly linked to the precision of the strain measurement, as well as the naturally occurring variance between different tissue samples, indicating that BTI may lack the accuracy required to be implemented successfully in practice as a quantitative treatment planning technique at a sub-lesioning exposure level. This is because, to be of use in treatment planning, temperature-rise estimates may require an accuracy greater (<10%) than that offered by BTI measurement. BTI may, however, still play a role in ensuring the correct positioning of the focal region and as a treatment monitoring modality capable of detecting an increased rate of heating in tissue after HIFU ablation.

Abstract No. 129: Percutaneous irreversible electroporation (IRE) in the treatment of hepatocellular carcinoma (HCC) and metastatic colorectal cancer (mCRC) to the liver

Purpose: Pancreatic carcinoma is surgically unresectable and without distant metastatic disease in 30% of newly diagnosed cases. We present our initial safety experience with percutaneous IRE in unresectable pancreatic carcinoma. Materials and Methods: Four consecutive patients (3 male,1 female), age 49-78, with surgically unresectable pancreatic carcinoma (stage III) were treated under general anesthesia. Average Eastern Cooperative Oncology Group (ECOG) grade was 1.5 (range 0-3). American Society of Anesthesiology (ASA) class was 3 in all patients. Seven percutaneous ablations were performed of five primary pancreatic tumors. Clinical evaluation, laboratory and imaging was performed at baseline, 24 hours, 1 month and 3 months. Results: Seven technically successful ablations were performed in the four patients. No mortalities occurred at 30 days. No episodes of intraoperative arrhythmia occurred. Intraoperative transient hypertension occurred with all treatments (7/7). No patients had prolonged hypertension after completion of electroporation. There were no incidents of hemorrhage, infection, pancreatic fistula, or bowel injury. One treatment (1/7) was complicated by partial splenic infarction, which required no treatment. Average length of stay was 1.3 days. No patients required analgesics on discharge. Conclusion: Percutaneous pancreatic IRE appears to be a safe method for pancreatic tumor ablation. Further studies will be needed to evaluate efficacy.

Mikrowellenablation

The majority of patients with hepatic malignancies are not amenable to surgical resection. In some of these cases minimally invasive ablative therapies are a treatment option. Besides radiofrequency ablation, the most common ablative therapies are cryoablation, laser ablation and microwave ablation. The classic fields of application of microwave ablation are the treatment of malignancies of the liver, kidneys and lungs. Furthermore, cases of treatment of bone tumors and tumors of the adrenal gland have been reported as well as treatment of secondary hypersplenism. The manufacturers of microwave systems pursue different strategies to reach an optimal ablation zone, such as water or gas cooling of the antenna, the simultaneous use of different antennas or an automatic modulation of the microwave energy and frequency. In contrast to other tumor ablation methods microwave ablation causes a direct heating of a tissue volume, thus this method is less vulnerable to the cooling effect of vessels in the ablation zone. Moreover the electric conductivity of the treated tissue does not influence microwave radiation so that microwave ablation has advantages for the treatment of high-resistance organs, such as the lungs or bone. Some publications have shown that microwave ablation causes larger ablation zones in less time in comparison to radiofrequency ablation. Classic indications for microwave ablation are the treatment of malignancies of the liver, lungs and kidneys. Initial technical problems have been solved, so that an increasing significance of the microwave ablation among the ablative therapies is to be expected.

A liver-mimicking MRI phantom for thermal ablation experiments

To develop a liver-mimicking MRI gel phantom for use in the development of temperature mapping and coagulation progress visualization tools needed for the thermal tumor ablation methods, including laser-induced interstitial thermotherapy (LITT) and radiofrequency ablation (RFA). A base solution with an acrylamide concentration of 30 vol. % was prepared. Different components were added to the solution; among them are bovine hemoglobin and MR signal-enhancing contrast agents (Magnevist as T1 and Lumirem as T2 contrast agent) for adjustment of the optical absorption and MR relaxation times, respectively. The absorption was measured in samples with various hemoglobin concentrations (0%-7.5%) at different temperatures (25-80 degrees C) using the near-infrared spectroscopy, measuring the transmitted radiation through the sample. The relaxation times were measured in samples with various concentrations of T1 (0.025%-0.325%) and T2 (0.4%-1.6%) contrast agents at different temperatures (25-75 degrees C), through the MRI technique, acquiring images with specific sequences. The concentrations of the hemoglobin and contrast agents of the gel were adjusted so that its absorption coefficient and relaxation times are equivalent to those of liver. To this end, the absorption and relaxation times of the gel samples were compared to reference values, measured in an ex vivo porcine liver at different temperatures through the same methods used for the gel. For validation of the constructed phantom, the absorption and relaxation times were measured in samples containing the determined amounts of the hemoglobin and contrast agents and compared with the corresponding liver values. To qualitatively test the heat resistance of the phantom, it was heated with the LITT method up to approximately 120 degrees C and then was cut to find out if it has been melted. In contrast to liver, where the absorption change with temperature showed a sigmoidal form with a jump at T approximately equal 45 degrees C, the absorption of the gel varied slightly over the whole temperature range. However, the gel absorption presented a linear increase from approximately 1.8 to approximately 2.2 mm(-1) with the rising hemoglobin concentration. The gel relaxation times showed a linear decrease with the rising concentrations of the respective contrast agents. Conversely, with the rising temperature, both T1 and T2 increased linearly and showed almost the same trends as in liver. The concentrations of hemoglobin and T1 and T2 contrast agents were determined as 3.92 +/- 0.42 vol. %, 0.098 +/- 0.023 vol. %, and 2.980 +/- 0.067 vol. %, respectively. The measured ex vivo liver T1 value increased from approximately 300 to approximately 530 ms and T2 value from approximately 45 to approximately 52 ms over the temperature range. The phantom validation experiments resulted in absorption coefficients of 2.0-2.1 mm(-1) with variations of 1.5%-2.95% compared to liver below 50 degrees C, T1 of 246.6-597.2 ms and T2 of 40.8-67.1 ms over the temperature range of 25-75 degrees C. Using the Bland-Altman analysis, a difference mean of -6.1/1.9 ms was obtained for T1/T2 between the relaxation times of the phantom and liver. After heating the phantom with LITT, no evidence of melting was observed. The constructed phantom is heat-resistant and MR-compatible and can be used as an alternative to liver tissue in the MR-guided thermal ablation experiments with laser to develop clinical tools for real-time monitoring and controlling the thermal ablation progress in liver.

Treatment with high intensity focused ultrasound: Secrets revealed

For many decades open surgery remained the only way available for local control of body tumors. In order to decrease the patients' morbidity and mortality several image guided minimally invasive procedures have been adopted. High intensity focused ultrasound (HIFU) is an extracorporeal non invasive method for tumor ablation. High intensity ultrasonic waves can be focused to a focal point resulting in lethal elevation of the temperature at the target site with consequent damage of the tumoral cells. The advances in HIFU technology during the past two decades expanded the HIFU applications to include ablation of both benign and malignant tumors with different treatment strategies being implemented for each type. The aim of this review is to introduce the reader to the details of the treatment process including pretreatment preparation, treatment planning, different ablation strategies, patients' after care as well as the follow up regimens for the most common HIFU applications.

Intrahepatic Radiofrequency Ablation Versus Electrochemical Treatment Ex Vivo

Radiofrequency ablation (RFA) and electrochemical treatment (ECT) are two methods of local liver tumor ablation. A reproducible perfusion model allowed us to compare these methods when applied in proximity to vascular structures. In a porcine liver perfusion model, we used RFA (group A) and ECT (group B) to perform ablations under ultrasound guidance within 10 mm of a vessel and examined the induced necrosis macroscopically and histologically. We created 83 lesions (RFA: 59, ECT: 24) in 27 livers. In group A (mean liver weight: 2046 g), perfusion was macroscopically found to limit necrosis in 52.5% of the procedures. Histology demonstrated the destruction of only 30.4% of the vessel walls within the ablation areas. In group B (mean liver weight: 1885 g), we detected reproducible and sharply demarcated ablation areas both macroscopically and histologically. Necrosis was unaffected by nearby vessels. No viable cells were found perivascularly. Histology showed destruction of the vascular endothelium without any discontinuities. We measured pH values of 0.9 (range: 0.6-1.8) at the anode and 12.2 (range: 11.4-12.6) at the cathode. Treatment time was 100 min when a charge of 300 coulombs was delivered. Electrochemical treatment is a method of ablation that creates reproducible and predictable volumes of necrosis. It produces sharply demarcated areas of complete necrosis also in perivascular sites. ECT, however, requires much longer treatment times than RFA. In our model, the effects of RFA were considerably limited by perfusion, which caused incomplete areas of necrosis in proximity to vessels.

Tumor Ablation and Nanotechnology

Next to surgical resection, tumor ablation is a commonly used intervention in the treatment of solid tumors. Tumor ablation methods include thermal therapies, photodynamic therapy, and reactive oxygen species (ROS) producing agents. Thermal therapies induce tumor cell death via thermal energy and include radiofrequency, microwave, high intensity focused ultrasound, and cryoablation. Photodynamic therapy and ROS producing agents cause increased oxidative stress in tumor cells leading to apoptosis. While these therapies are safe and viable alternatives when resection of malignancies is not feasible, they do have associated limitations that prevent their widespread use in clinical applications. To improve the efficacy of these treatments, nanoparticles are being studied in combination with nonsurgical ablation regimens. In addition to better thermal effect on tumor ablation, nanoparticles can deliver anticancer therapeutics that show a synergistic antitumor effect in the presence of heat and can also be imaged to achieve precision in therapy. Understanding the molecular mechanism of nanoparticle-mediated tumor ablation could further help engineer nanoparticles of appropriate composition and properties to synergize the ablation effect. This review aims to explore the various types of nonsurgical tumor ablation methods currently used in cancer treatment and potential improvements by nanotechnology applications.

Image-guided Tumor Ablation: Standardization of Terminology and Reporting Criteria

The field of interventional oncology with use of image-guided tumor ablation requires standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison between treatments that use different technologies, such as chemical (ethanol or acetic acid) ablation, and thermal therapies, such as radiofrequency (RF), laser, microwave, ultrasound, and cryoablation. This document provides a framework that will hopefully facilitate the clearest communication between investigators and will provide the greatest flexibility in comparison between the many new, exciting, and emerging technologies. An appropriate vehicle for reporting the various aspects of image-guided ablation therapy, including classification of therapies and procedure terms, appropriate descriptors of imaging guidance, and terminology to define imaging and pathologic findings, are outlined. Methods for standardizing the reporting of follow-up findings and complications and other important aspects that require attention when reporting clinical results are addressed. It is the group's intention that adherence to the recommendations will facilitate achievement of the group's main objective: improved precision and communication in this field that lead to more accurate comparison of technologies and results and, ultimately, to improved patient outcomes. The intent of this standardization of terminology is to provide an appropriate vehicle for reporting the various aspects of image-guided ablation therapy.

Image-guided Tumor Ablation: Standardization of Terminology and Reporting Criteria

The field of interventional oncology with use of image-guided tumor ablation requires standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison between treatments that use different technologies, such as chemical (ethanol or acetic acid) ablation, and thermal therapies, such as radiofrequency (RF), laser, microwave, ultrasound, and cryoablation. This document provides a framework that will hopefully facilitate the clearest communication between investigators and will provide the greatest flexibility in comparison between the many new, exciting, and emerging technologies. An appropriate vehicle for reporting the various aspects of image-guided ablation therapy, including classification of therapies and procedure terms, appropriate descriptors of imaging guidance, and terminology to define imaging and pathologic findings, are outlined. Methods for standardizing the reporting of follow-up findings and complications and other important aspects that require attention when reporting clinical results are addressed. It is the group's intention that adherence to the recommendations will facilitate achievement of the group's main objective: improved precision and communication in this field that lead to more accurate comparison of technologies and results and, ultimately, to improved patient outcomes. The intent of this standardization of terminology is to provide an appropriate vehicle for reporting the various aspects of image-guided ablation therapy.

Open-configuration MR-guided microwave thermocoagulation therapy for metastatic liver tumors from breast cancer

Liver metastases from breast cancer are associated with a poor prognosis, however, local control with microwave thermocoagulation therapy has been used in certain subgroups of these patients in the past decade. In this study, open-configuration magnetic resonance (MR) -guided microwave thermocoagulation therapy was used for metastatic liver tumors from breast cancer, and the efficacy of this treatment was assessed. Between June 2000 and April 2004, we used MR-guided microwave thermocoagulation therapy on 11 nodules in 8 patients with metastatic liver tumors from breast cancer. The procedure was carried out under general anesthesia. A 0.5 T open-configuration MR system and a microwave coagulator were used. Near-real-time MR images and real-time temperature images were collected and displayed on the monitor. The MR-compatible thoracoscope was used and combined with MR imaging guidance. Navigation software, a 3D Slicer, was installed and customized. The customized navigation software displayed near-real-time MR images. The percutaneous puncture into the tumors was successful in all cases. No mortality or major complications occurred as a result of the procedures. Five of the 8 patients are alive with new metastatic foci with a mean observation period of 25.9 months. We developed several devices to allow safe, easy, and accurate MR-guided microwave thermocoagulation therapy of liver tumors. Open-configuration MR-guided microwave thermocoagulation therapy appears to be a feasible method for tumor ablation of metastatic liver tumors from breast cancer.

Treatment of hepatocellular carcinoma by percutaneous tumor ablation methods: Ethanol injection therapy and radiofrequency ablation

In Japan, approximately 30,000 patients died of hepatocellular carcinoma (HCC) in 2003. Ten percent had hepatitis B virus infection and 80% had hepatitis C virus (HCV) infection, indicating that viral hepatitis accounted for >90% of cases of HCC. In comparison, only 3% (1.5%, hepatitis B virus; 1.5%, HCV) of the general population is infected with these viruses. We treated 1238 patients between 1992 and the end of 2003 by means of percutaneous tumor ablation (PTA): 524 patients, by percutaneous ethanol injection therapy (PEIT); 85 patients, by percutaneous microwave coagulation therapy; and 629 patients, by radiofrequency ablation (RFA). Three-, 5-, 7-, and 10-year survival rates of the 1238 patients were 69%, 50%, 34%, and 19%, respectively. When limited to tumors </=3 cm in diameter and </=3 in number of cancer nodules (3-3 rule), 5-year survival rates reached 64.7% for PEIT. However, to achieve a 40% survival rate in year 5 after PEIT, the indication for treatment can be expanded to a 4 (size)-3 (number) rule or 5 (size)-1 (number) rule. The recent introduction of RFA may further change the rules. HCV-related HCC generally develops on the background of advanced fibrosis/cirrhosis. An issue of much concern is that it may subsequently recur in a location other than that of the primary lesion. We initiated a prospective controlled study to evaluate treatment with PTA and interferon. Results suggest that if the virus is eradicated, a 5-year survival rate as high as 80% can be expected.

Augmenting the Ablative Effect of Liver Electrolysis: Using Two Electrodes and the Pringle Maneuver

Several methods of liver tumor ablation have been investigated, and these include the novel technique of electrolysis. Electrolysis is slower than other forms of ablative therapy. This study determined methods of increasing the ablative effect of electrolysis. Domestic white pigs were divided. One group received electrolysis using two electrode catheters, and in the other group a concurrent intermittent Pringle maneuver was performed to induce intermittent ischemia. The effect of two electrode catheters versus a single electrode catheter was compared, and the effect of the Pringle maneuver versus no Pringle was examined with two electrode catheters. The livers were harvested, and the volume of each lesion was calculated. There was a linear relationship between the volume of hepatic necrosis and the electrolytic dose in (p< .005) in both the single-electrode-catheter and two-electrode-catheter groups. Comparison between the single- and multiple-electrode groups showed a highly significant difference in the dose response (p< .0000002) when more than one electrode was used. Use of the Pringle maneuver during electrolysis produced larger volumes of hepatic necrosis over all doses when using two electrode catheters. Rates of necrosis were 3.8 cm3/100 C for a single electrode catheter, 5.46 cm3/100 C for two electrode catheters without Pringle, and 6.17 cm3/100 C for electrolysis with two electrode catheters coupled with intermittent Pringle maneuver. Thus, electrolysis was both reliable and predictable in producing hepatic necrosis in a dose-dependent manner. The time delay in achieving tumor ablation via electrolysis can be overcome by using two electrodes combined with the Pringle maneuver to increase the volume of the lesion produced.

The physiologic effect of the pneumoperitoneum on radiofrequency ablation.

Radiofrequency ablation (RFA) is gaining widespread acceptance as a safe and effective method for liver tumor ablation. Complete tumor ablation is essential for the success of the procedure. Multiple modalities have been explored in an effort to increase the size of the lesion created by RFA. The purpose of this study was to determine the physiologic effects of the pneumoperitoneum on RFA lesion size. A total of 32 RFA lesions were created in eight pigs. After the induction of anesthesia, pneumoperitoneums of 2, 12, and 24 mmHg were established sequentially in each animal. After an equilibration period of 2 min, RF was administered with a constant saline-infused (0.9%) needle at 25 W for 3 min. In subsequent and complementary experiments, both before and during RF administration at each intraperitoneal pressure (IPP), Doppler flow was measured by laparoscopic ultrasound in the portal vein and hepatic artery while blood pressure was monitored by a femoral arterial line. The animals were then killed humanely and the livers were harvested. Measurements were taken in three dimensions of the ablated areas, and the volume was calculated. Statistical analyses were performed using analysis of variance (ANOVA) and repeated measures test. The average volumes of the lesions (in cm3) were 3.1 +/- 1.8, 5.2 +/- 1.7, and 6.7 +/- 3.3 for IPP of 2, 12 and 24 mmHg, respectively; there was a significant difference between the area of lesion at an IPP of 2 mmHg and an IPP of 24 mmHg ( p < 0.05). Blood flow in the portal vein also decreased significantly from 1.8 +/- 0.6, 0.98 +/- 0.5, and 0.43 +/- 0.2 at IPP of 2, 12, and 24 mmHg, respectively ( p < 0.001). Hepatic artery blood flow and peripheral blood pressure did not change significantly in the respective IPP groups. This study indicates that the volume of liver ablated by RF can be increased by augmenting the IPP. Our data support the theory that a decrease in portal blood flow results in decreased heat dissipation during RFA. The laparoscopic approach to RFA offers the advantage of allowing control of the IPP, which may result in a larger volume of ablated tissue per treatment than can be achieved with the percutaneous technique. These preliminary data on normal hepatic tissue must be confirmed clinically in the setting of hepatic tumors.

Radio-frequency ablation of renal cell carcinoma: early clinical experienc.

Purpose: To report the authors' early experience with radio-frequency (RF) ablation of renal cell carcinoma. Materials and Methods: Twenty-four percutaneous RF ablation treatments for nine tumors were performed in eight patients with renal cell carcinoma. Indications included coexistent morbidity, previous surgery, or solitary kidney in patients with a life expectancy shorter than 10 years. Smaller (⩽3-cm) peripheral lesions ( n = 3) were treated with single electrodes. All but one of the larger (>3 cm) and/or central lesions ( n = 6) were treated with cluster or multiple electrodes. Patients returned for a second treatment when follow-up imaging depicted tumor enhancement. Follow-up imaging was performed at 1 and 3 months and then at 6-month intervals, with a mean follow-up of 10.3 months. Seven patients were alive at least 6 months after their initial treatment. Results: All five exophytic tumors were free of enhancement. One of three central tumors was free of enhancement. One tumor had both central and exophytic components and was free of enhancement. Three tumors were 3 cm or smaller and free of enhancement. Of the six tumors larger than 3 cm, four were free of enhancement. Conclusion: Percutaneous RF ablation is a promising treatment for select patients with renal cell carcinoma. The ultimate role of this modality will continue to evolve and warrants further study. Commentary New minimally invasive technologies are currently being applied to the field of nephron-sparing surgery (NSS) for renal cell carcinoma (RCC) in an effort to decrease operative time, pain, morbidity and hospital stay. Methods of tumor ablation have included cryotherapy, radio-frequency ablation (RFA), high intensity focused ultrasound (HIFU), laser and microwave coagulation. These new modalities are currently being administered laparoscopically or percutaneously; ultimately, completely extracorporeal techniques may be feasible. The primary mechanism of tissue destruction with RFA is thermonecrosis. Radio-frequency energy causes high frequency current flow from the needle electrode into the surrounding tissue. This causes ionic agitation, molecular friction, cellular warming with rapid dessication and cell death. The size and configuration of the lesion are related to the amount of energy delivered, ablation time, tissue impedance, electrolyte content of the tissue and surface area of the electrode. It is a major technical challenge to control for each of these variables independently. The major concern with RFA and related ablative technologies is the ability to image the destructive process precisely as it is being administered, thereby minimizing injury to normal adjacent parenchyma while assuring complete tumor ablation. Since a surgical specimen is not removed for pathologic study, histologic documentation of complete tumor destruction and accurate tumor staging/grading are not available. Meticulous long-term clinical and radiographic follow-up of treated patients is ultimately needed to validate the efficacy of ablative techniques such as RFA for treating renal malignancy. Andrew C. Novick, M.D.

Selective internal radiation therapy with 90yttrium microspheres for extensive colorectal liver metastases

Increasing attention has been given to treatments for colorectal liver metastases ever since hepatic resection was established as being worthwhile. Given the high proportion of patients who die of colorectal cancer with liver-only disease, it seems appropriate to be developing and investigating methods of local liver tumor ablation. Selective internal radiation therapy (SIRT) is a relatively new, not widely used, modality suitable for use even in patients with extensive liver involvement. Fifty patients with advanced, nonresectable, colorectal liver metastases were treated with SIRT between February 1997 and June 1999. Estimated liver involvement was less than 25% in 30 patients, 25% to 50% in 13, and greater than 50% in seven. A single dose of between 2.0 and 3.0 GBq of 90yttrium microspheres was injected into the hepatic artery via a subcutaneous port and followed at 4-week intervals by regional chemotherapy with 5-fluorouracil. SIRT was well tolerated with no treatment-related mortality, although some treatment-related morbidity did occur including a 12% incidence of duodenal ulceration. Responses to SIRT were assessed by serial carcinoembryonic antigen (CEA) measurements and CT scans. Median CEA values 1 and 2 months after SIRT (expressed as percentage of initial CEA) were 19 and 13, respectively. Patients were assigned to one of two groups based on whether or not extrahepatic disease (EHD) developed within 6 months of SIRT. Median survival from SIRT for group 1 (EHD) (n = 26) was 6.9 months (range 1.3 to 18.8 months) and estimated survival ± standard error at 6, 12, and 18 months was 57.7 ± 3.8%, 23.1 ± 4.8%, and 0%, respectively. For group 2 (no EH) (n = 24), median survival was 17.5 months (range 1.0 to 30.3 months) with estimated survival at 6, 12, 18, 24, and 30 months of 79.2 ± 2.9%, 66.7 ± 3.6%, 55.9 ± 3.3%, 25.2 ± 4.4%, and 16.8 ± 5.0%, respectively. This difference is statistically significant by log-rank test ( P <0.010). SIRT is a highly effective and well-tolerated regional treatment for extensive colorectal liver metastases. Tumor marker data suggest that substantial destruction of liver tumors can be achieved in more than 90% of patients by a single treatment. Survival times, particularly for those who do not develop extrahepatic metastases for some time, appear to be extended. SIRT warrants further use and investigation in patients with advanced colorectal liver metastases.

Hepatocellular carcinoma: treatment with transcatheter arterial chemoembolization

This article presents a review of the literature regarding the use of transcatheter arterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC). There have been two different approaches to the treatment: (a) percutaneous tumor ablation methods which can be divided into injectable and thermal methods; percutaneous ethanol injection (PEI) is the most widely used method, and (b) TACE. PEI is the treatment of choice for single HCCs smaller or equal to 3 cm in size. For patients with large HCCs combined TACE and PEI is probably the most effective nonsurgical treatment. In the presence of multiple HCC nodules, TACE remains the treatment of choice.