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Annals of Surgical Oncology 9:594-598 (2002)
© 2002 Society of Surgical Oncology

ORIGINAL ARTICLES

Radiofrequency Ablation of the Porcine Liver With Complete Hepatic Vascular Occlusion

C.K. Chang, MD, Mary Pat Hendy, BS, J. Michael Smith, MD, Matthew H. Recht, MD and Richard E. Welling, MD

From the Department of Surgery (CKC, JMS, MHR, REW) and the E. Kenneth Hatton Institute for Research and Education (MPH), Good Samaritan Hospital, Cincinnati, Ohio.

Correspondence: Address correspondence and reprint requests to: Mary Pat Hendy, E. Kenneth Hatton Institute for Research and Education, 11 J, Good Samaritan Hospital, 375 Dixmyth Ave., Cincinnati, OH 45220; Fax: 513-872-1549; E-mail: marypat_hendy{at}trihealth.com


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
Background: We studied the effects of radiofrequency ablation, relative to hepatic blood flow, on the volume and shape of the resulting tissue necrosis. The extent of necrosis is directly proportional to the size of the electrode and inversely related to blood flow, which dissipates the heat generated.

Methods: Two areas of necrosis were created in each of eight porcine livers, which were assigned to four groups according to blood flow occlusion: no occlusion, occlusion of the hepatic artery and portal vein, occlusion of the hepatic veins, and complete hepatic vascular occlusion. After 25 minutes of liver reperfusion, the animals were euthanized, and the livers were examined.

Results: Complete vascular occlusion resulted in the greatest area of necrosis (28.6 ± 3.4 cm3), followed by occlusion of the hepatic artery and portal vein (19.2 ± 5.9 cm3), occlusion of hepatic veins (14.4 ± 2.6 cm3), and no occlusion (4.9 ± 1.5 cm3). The volume of the necrotic areas created during complete vascular occlusion were significantly greater than those created with no occlusion, as well as those created with only the hepatic artery and portal vein occluded (P < .05).

Conclusions: Complete vascular occlusion, combined with radiofrequency ablation, increases the volume of necrosis and creates a more spherical ablative area.

Key Words: Radiofrequency ablation • Liver neoplasms • Catheter ablation • Coagulative necrosis • Regional blood flow


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
Hepatic resection is the gold standard for treatment of both primary and secondary liver tumors. Unfortunately, only 5% to 20% of such tumors have clinical and pathologic features that are favorable for resection.1 Given its limited applicability, researchers have studied numerous alternatives, including chemotherapy, injection of alcohol, and local ablative therapies. Unfortunately, there has been very limited success with chemotherapy and alcohol injection. More promising are local ablative therapies, which include cryoablation and radiofrequency ablation (RFA).2–4

Cryoablation, although commonly used for unresectable hepatic tumors, is problematic for several reasons.3,5–7 Fortunately, the systemic complications associated with cryoablation5,6 have not been reported with RFA, which causes coagulative necrosis through the dissipation of heat to the surrounding tissue.3,8 The amount of tissue destroyed depends on the quantity of heat generated as well as the quantity of heat dissipated. One of the major factors that contribute to heat dissipation from a particular region is blood flow, which causes a "heat sink" phenomenon. To minimize this effect and increase the size of the necrotic area produced by the RFA probe, we evaluated the heat sink in relation to different vascular occlusion techniques.

We compared the areas of necrosis produced by RFA with those with normal hepatic blood flow, after occlusion of the inflow (hepatic artery and portal vein) via the Pringle maneuver, after occlusion of the outflow (hepatic veins), and after total hepatic vascular occlusion. To our knowledge, no other study investigating the effects of complete hepatic isolation has been performed in an in vivo model, which we believe is the only model that can be used to adequately represent total hepatic isolation.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
The radiofrequency (RF) apparatus included a generator (RITA Model 1500TM; RITA Medical Systems Inc., Mountain View, CA), two large grounding pads, and an RF electrode that closed the electrical circuit. The RF electrode (RITA StarBurst XLTM) was a 14-gauge needle with a 15-cm shaft. The StarBurst XL features nine electrodes, plus a live trocar tip, and provides real-time temperature feedback from five independent thermocouples within the array. The array size is adjustable to allow for an ablation zone of 3 to 5 cm.

The experimental protocol was approved by the Good Samaritan Hospital Institutional Animal Care and Use Committee. Animal care complied with the regulations of the Animal Welfare Act 9CFR of the Animal and Plant Health Inspection Service, US Department of Agriculture.

Two female domestic pigs were used in each study group, for a total of eight pigs. Two or three areas of necrosis were created in each swine liver, depending on its size. Two swine livers, ablated without any vascular occlusion, served as the control model. The next two were ablated with the blood inflow (via the portal vein and hepatic artery) occluded (Pringle maneuver). Another two were ablated with the blood outflow (via the hepatic veins) occluded (by using an atrial/caval shunt). The two remaining pig livers were ablated with complete occlusion of hepatic inflow and outflow. The pigs weighed 20 to 25 kg and were not fed the night before the procedure. Intramuscular ketamine was used for anesthetic induction before endotracheal intubation. General anesthesia was maintained with 2% isoflurane. The animals were monitored by continuous pulse oximetry and electrocardiography. Intravenous access was established with a femoral vein cut-down with infusion of lactated Ringer’s solution. Two large grounding pads were placed in the gluteal region and connected to the RF generator.

A standard laparotomy and median sternotomy was performed with use of sterile technique. Inflow occlusion was achieved by dissecting out the porta hepatis and encircling the portal and hepatic arteries with umbilical tape. These vessels were occluded with a Rummel tourniquet. Outflow occlusion was achieved by encircling the supradiaphragmatic inferior vena cava and suprarenal inferior vena cava with umbilical tape. The atrial/caval shunt was performed with a 20F chest tube with perforations above and below the hepatic veins. Rummel tourniquets were then tightened above and below the hepatic veins with the internal shunt (20F chest tube) in place to ensure complete outflow occlusion. Heparinization with 10,000 U was given to all pigs in which the atrial/caval shunts were performed. Total hepatic occlusion was confirmed with 200 mg of intravenous fluorescein that stained the heart without any staining on the liver.

The RF needle was placed into predetermined areas of the liver. The power was set at 150 W with a target temperature of 100°C. The electrodes were then deployed to 2 cm and heated to the target temperature. Once the target temperature was reached, deployment continued to 4 cm. At the 4-cm mark, ablation was sustained for 7 minutes. After deployment to 5 cm, another 7-minute cycle was performed. The target temperature was maintained during the transition from 4 to 5 cm. The temperature was also recorded after a 1-minute cool-down period, and in each group, the target temperature in each thermocouple was >50°C.

Whenever vascular occlusion techniques were used, reperfusion of the liver was performed after the 1-minute cool-down period. Twenty-five minutes after re-establishing blood flow, we removed the liver and placed it in a 10% buffered formalin solution. The areas of necrosis were sectioned serially along the length of the shaft of the probe and then examined. We measured the definite border of necrosis, excluding the hyperemic zone around the margins. The dimensions of necrosis were measured accordingly, along three planes (x, y, and z; Figs. 1 and 2). The formula for the area of an ideal sphere was then used to calculate volume9: Go


(1)



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  		FIG. 1. The maximum diameter of the sphere was along the shaft of the probe. Tangential cuts along the shaft were used to determine the depth and minimum diameter.

 


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  		FIG. 2. Schematic representation of an increased area of necrosis with variations in hepatic vessel occlusion.

 

   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 CONCLUSION
 REFERENCES
 
The generator allows the operator to delete any of the five thermocouple electrodes from the average temperature to achieve the target temperature of 100°C. We were able to reach the average target temperature of 100°C in each of the individual electrodes without the need to negate any thermocouple temperature. An individual thermocouple electrode will not reach target temperature if it is adjacent to a major blood vessel. The uniform distribution of heat throughout this experiment was also confirmed by each thermocouple temperature remaining >50°C after the 1-minute cool-down period.

There was no difference in the time, power, or impedance between groups. The average impedance was 59 {Omega} (range, 32–75 {Omega}). The average time to create an area of necrosis for all the groups was 18 minutes (range, 17–20 minutes). There was one complication during the entire procedure. One pig in the complete hepatic occlusion group experienced a burn around the grounding pads. Although the impedance during this particular ablative procedure reached 123 {Omega}, the target temperature was still achieved. When this ablative area was examined grossly, it had a maximal diameter of only 4 cm, and thus it was excluded from our data. The explanation for this high resistance and incomplete ablative necrosis was the inadequate adherence of the grounding pad. A second ablation in this same animal, with new grounding pads at different sites, resulted in lower impedance and complete necrosis.

Table 1 summarizes our results. The average volume in the control group was 4.9 cm3. These ablative areas tended to be more cylindrical in shape, with the maximum diameter of necrosis along the shaft of the RFA probe, forming an incomplete sphere. The energy generated through the electrodes was centered inward with an overlapping area of necrosis between electrodes (Fig. 1). The ablative areas created with hepatic outflow occlusion had an average volume of 14.4 cm3 (P < .05). Relative to the control group, the venous congestion created by occluding the hepatic veins was significantly larger, and the resulting areas of necrosis were more spherical. For the group in which the inflow was occluded, the areas of necrosis had an average volume of 19.3 cm3 (P < .05); they were also more spherical than the controls. Although these ablative areas tended to be larger than those created with outflow occlusion, the difference was not statistically significant. The largest areas of necrosis, an average of 28.6 cm3 (P < .05), occurred in the group in which complete hepatic vascular occlusion was performed. The volume of necrosis was significantly higher than the ablative areas in all other groups, including the group in which the Pringle maneuver was performed (P < .05), and these ablative areas were also more spherical than those in the other groups.


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  		TABLE 1. TABLE 1. Volume of RFA lesion based on hepatic vasculature
 
There were no deaths during our experiments. The longest hepatic ischemia time was only 20 minutes, allowing for reperfusion between each ablative cycle. After completion of the last ablative area, the liver was reperfused for 25 minutes while we looked for hemodynamic instability in case of major vascular injury after the heat-sink effect was eliminated.

All statistical analyses were performed with the BMDP New System 2.0TM Professional software (Statistical Solutions, Saugus, MA). Data were analyzed by using Student’s t-test; P < .05 was considered significant.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
CONCLUSION
 REFERENCES
 
RFA uses an alternating current at a frequency of 460 kHz. Heat is generated through ionic excitement as ions attempt to align themselves in the polarity of the field. Thus, the tissue surrounding the electrode serves as the heat generator rather than the electrode itself. Once the tissue surrounding the electrode approaches 50°C, irreversible cell death occurs.9,10 The extent of the coagulative necrosis is directly proportional to the size of the RF electrode and is inversely related to the blood flow.11 Blood flow through this region is able to dissipate the heat generated through convectional forces, creating a heat sink that limits the size and shape of the ablated area.

RFA can be performed percutaneously or laparoscopically or through an open surgical technique. The approach chosen depends on multiple factors, including the location and size of the tumor, the patient’s health, and the need for concurrent procedures, such as hepatic resection12 or insertion of hepatic artery pumps.13 The laparoscopic approach offers the advantage of being minimally invasive; when combined with laparoscopic ultrasonography, it offers accurate positioning of the RF electrodes. One of the disadvantages of both the percutaneous and laparoscopic approaches is the inability to control the portal vein and hepatic artery with the Pringle maneuver, a technique that minimizes the heat sink around the tumor. Despite earlier concerns that elimination of the heat sink may damage vessels surrounding the ablative area, Curley et al.14 were able to show that these vessels are not affected. Eight to 13% of patients developed complications after RFA, including hemorrhage, hematoma, bilomas, biliary strictures, abscess, pseudoaneurysms, and pleural effusions.8,15

One of the potential benefits of the heat-sink effect is to protect large vessels, as well as the biliary ducts, from thermal injury. Removal of the heat sink by inflow and outflow occlusion or total hepatic isolation may leave large vessels and biliary ducts susceptible to injury. However, Curley et al. used RFA with inflow occlusion irrespective of tumor location, including tumors abutting major portal veins, hepatic vessels, and the inferior vena cava,4 and reported a complication rate of only 2.4%. Their only exclusion criteria were large size and tumors adjacent to major biliary ducts.

At present, biliary duct injury is the major drawback to RFA. Although this complication is being addressed by the use of hepatic stents16 and intraductal cooling17 of major bile ducts, these techniques are currently in their infancy. Biliary injury could also be minimized by selecting tumors that are not adjacent to hepatic ducts.

McGahan et al.10 and Rossi et al.18 first introduced the use of RFA for hepatic tumors under ultrasound guidance in the early 1990s. They were able to produce clearly demarcated areas of necrosis with ultrasound images that correlated with pathologic specimens. Multiple studies on animal models have shown that an increase in volume can be achieved when hepatic inflow is occluded.9,19–21 Patterson et al.9 were able to show a 5-fold increase in volume when both the hepatic artery and portal vein were occluded with the Pringle maneuver. Rossi et al.19 compared various in vivo hepatic isolation techniques with that of complete hepatic isolation in an ex vivo model. The dimensions of the ablative areas in in vivo models with only inflow or outflow occlusion were similar to the dimensions of ablative areas in the ex vivo model representing total hepatic isolation. Our model looked at total hepatic isolation in an in vivo, rather than ex vivo, model. It is our belief that only the in vivo model adequately represents total hepatic isolation. A recent study by Chinn et al.20 demonstrated a significant increase in the ablative area with occlusion of the hepatic artery alone (7.6 vs. 4.3 cm3). Although the greatest volume was achieved in ablative areas in which the Pringle maneuver was performed, they concluded that most of the vascular isolation could be accomplished with hepatic artery occlusion alone. Therefore, RFA could be used from a percutaneous approach alone with balloon occlusion of the hepatic artery.

In our study, we were also able to demonstrate an increase in volume by comparing areas of necrosis in the inflow occlusion group versus the control group (19.3 vs. 4.9 cm3; P < .05). The shape of the ablative areas in the inflow occlusion group was consistently more spherical relative to the cylindrical-shaped ablative areas in the control group. There was also a significant increase in volume with outflow occlusion alone versus the control group (14.4 vs. 4.9 cm3; P < .05). The passive congestion caused by occlusion of the hepatic veins did not produce any significant increases in volume when compared with that of the inflow occlusion group (14.4 vs. 19.3 cm3; P > .05). The largest ablative areas were formed in the group that had total occlusion of hepatic blood flow. These areas of necrosis were significantly larger than those in the control group (28.6 vs. 4.9 cm3; P < .05), the inflow occlusion group (28.6 vs. 19.3 cm3; P < .05), and the outflow occlusion group (28.6 vs. 14.4 cm3; P < .05). Therefore, by completely eliminating the blood flow heat sink in our porcine model, we were able to demonstrate larger volumes and consistent shapes.


   CONCLUSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
REFERENCES
 
Complete hepatic isolation can be performed safely to improve the shape and volume of areas of necrosis created through RFA. Occlusion of the hepatic veins in the clinical setting can be achieved through an external veno/veno bypass circuit.


   Acknowledgments
 
Supported by a grant from the Good Samaritan Hospital Education and Research Foundation, Cincinnati, OH. An RF generator was supplied by RITA Medical Systems, Inc. The authors thank Cecelia Franz-Berg for her editorial expertise.


   Footnotes
 
Presented at the 55th Annual Cancer Symposium of the Society of Surgical Oncology, Denver, Colorado, March 14–17, 2002.

Received for publication October 22, 2001. Accepted for publication March 29, 2002.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 

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  7. Seifert JK, Morris DL. Prognostic factors after cryotherapy for hepatic metastases from colorectal cancer. Ann Surg 1998; 228: 201–8.[CrossRef][Medline]
  8. Wood TF, Rose DM, Chung M, Allegra DP, Foshag LJ, Bilchik AJ. Radiofrequency ablation of 231 unresectable hepatic tumors: indications, limitations, and complications. Ann Surg Oncol 2000; 7: 593–600.[Abstract]
  9. Patterson EJ, Scudamore CH, Owen DA, Nagy AG, Buczkowski AK. Radiofrequency ablation of porcine liver in vivo: effects of blood flow and treatment time on lesion size. Ann Surg 1998; 227: 559–65.[CrossRef][Medline]
  10. McGahan JP, Brock JM, Tesluk H, Gu WZ, Schnieder P, Browning PD. Hepatic ablation with use of radio-frequency electrocautery in the animal model. J Vasc Interv Radiol 1992; 3: 291–7.[Medline]
  11. Strohbehn JW. Temperature distributions from interstitial rf electrode hyperthermia systems: theoretical predictions. Int J Radiat Oncol Biol Phys 1983; 9: 1655–67.[Medline]
  12. Scudamore CH, Lee SI, Patterson EJ, et al. Radiofrequency ablation followed by resection of malignant liver tumors. Am J Surg 1999; 177: 411–7.[CrossRef][Medline]
  13. Kainuma O, Asano T, Aoyama H, et al. Combined therapy with radiofrequency thermal ablation and intra-arterial infusion chemotherapy for hepatic metastases from colorectal cancer. Hepatogastroenterology 1999; 46: 1071–7.[Medline]
  14. Curley SA, Davidson BS, Fleming RY, et al. Laparoscopically guided bipolar radiofrequency ablation areas of porcine liver. Surg Endosc 1997; 11: 729–33.[CrossRef][Medline]
  15. Curley SA, Izzo F, Ellis LM, Nicolas Vauthey J, Vallone P. Radiofrequency ablation of hepatocellular cancer in 110 patients with cirrhosis. Ann Surg 2000; 232: 381–91.[CrossRef][Medline]
  16. Bilchik AJ, Wood TF, Allegra DP. Radiofrequency ablation of unresectable hepatic malignancies: lessons learned. Oncologist 2001; 6: 24–33.[Abstract/Free Full Text]
  17. Dominique E, El Otmany A, Goharin A, Attalah D, de Baere T. Intraductal cooling of the main bile ducts during intraoperative radiofrequency ablation. J Surg Oncol 2001; 76: 297–300.[CrossRef][Medline]
  18. Rossi S, Fornari F, Pathies C, Buscarini L. Thermal lesions induced by 480 kHz localized current field in guinea pig and in pig liver. Tumori 1990; 76: 54–7.[Medline]
  19. Rossi S, Garbagnati F, De Francesco I, et al. Relationship between the shape and size of radiofrequency induced thermal lesions and hepatic vascularization. Tumori 1999; 85: 128–32.[Medline]
  20. Chinn SB, Lee FT Jr, Kennedy GD, et al. Effect of vascular occlusion on radiofrequency ablation of the liver: results in a porcine model. AJR Am J Roentgenol 2001; 176: 789–95.[Abstract/Free Full Text]
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