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Radiofrequency Ablation of Hepatic Tumors Adjacent to the Gallbladder: Feasibility and Safety

¹ All authors: Department of Radiology, Mail Code 7800, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio TX 78229.

Received February 1, 2002; accepted after revision August 20, 2002.

 
Address correspondence to S. Chopra.

Abstract

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OBJECTIVE. This study was performed to assess the feasibility and safety of radiofrequency ablation of hepatic tumors adjacent to the gallbladder.

MATERIALS AND METHODS. Of the 83 patients who underwent radiofrequency ablation of hepatic tumors at our institution between December 1997 and August 2000, we identified eight patients—four men and four women who were 42-85 years old (mean age, 67 years)—who had tumors adjacent to the gallbladder. All ablations were performed with curative intent. We reviewed the patients' preablation imaging, radiofrequency ablation parameters, and course after ablation. Follow-up ranged from 3 to 22 months (mean, 8 months).

RESULTS. Six patients with colorectal carcinoma and two with hepatocellular carcinoma had a total of 14 tumors adjacent to the gallbladder. Of the 14 tumors, nine (64%) were metastases and five (36%) were hepatocellular carcinoma. Eleven tumors (79%) were located directly adjacent to the gallbladder and three (21%) were located within 1 cm of the gallbladder. Tumor size ranged from 0.9 to 4.5 cm (mean, 3.6 cm). The number of radiofrequency ablations performed on each tumor ranged between one and six (mean, three ablations). Right upper quadrant pain developed in the immediate postablation period (within 7 days after the ablation) in six patients (75%) and ranged in duration from 5 to 21 days (mean, 7 days). Fever developed in four patients (50%), with a mean duration of 5 days. Arthralgia and right shoulder pain developed in one patient (12%). No deaths were noted in the immediate period after ablation. Complete ablation of all tumors visible on CT was achieved in seven patients. Of these, one patient (14%) had local tumor recurrence after 11 months.

CONCLUSION. Radiofrequency ablation of tumors adjacent to the gallbladder is feasible and appears to be safe. Self-limited morbidity after ablation is noted in most patients and is probably related to a mild iatrogenic cholecystitis.

Introduction

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Radiofrequency ablation is one of the newer modalities used in minimally invasive treatment of hepatic neoplasms. The relative benefits of radiofrequency therapy include low morbidity, few complications, performance on an outpatient basis, and the ability to repeat the procedure as necessary to treat recurrence. Various studies have established the effectiveness of radiofrequency ablation in the treatment of primary and metastatic hepatic tumors [1, 2, 3, 4, 5, 6, 7, 8]. In general, the reported complication rate of radiofrequency ablation of the hepatic tumors is 5-25% for minor complications (e.g., postprocedure pain) and anecdotal (no percentages are given) for major complications [2, 5, 6, 7, 8, 9, 10, 11]. Some authors have recommended that percutaneous radiofrequency ablation not be used to treat tumors adjacent to anatomic structures that might be inadvertently injured by the thermal process [4]. Although the same authors later treated such lesions without complications, it is still generally believed that tumors adjacent to the gallbladder should not be treated with radiofrequency ablation [9]. However, to our knowledge, apart from anecdotal reports as part of these studies, no study has validated this belief. In our clinical practice, we have treated a series of tumors adjacent to the gallbladder. We reviewed these patients to assess the feasibility and safety of radiofrequency ablation of hepatic tumors adjacent to the gallbladder.

Materials and Methods

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Between December 1997 and August 2000, we performed radiofrequency ablation on hepatic neoplasms in 83 patients at our institution. We searched our radiofrequency ablation database and identified eight patients—four men and four women who were 42-85 years old (mean age, 67 years)—in whom the treated tumors were in the vicinity of the gallbladder. We reviewed the patients' charts for demographic details, the presence of preexisting gallbladder disease, type of tumors, ablation parameters, and course after ablation. The patient demographics, tumor characteristics, and ablation parameters are shown in Table 1. None had known preexisting gallbladder disease. Six patients had a total of nine hepatic metastases from colorectal carcinoma and two patients had five foci of hepatocellular carcinoma. Thus, our review included a total of 14 tumor nodules in eight patients. Eight tumor nodules were located in Couinaud segment V and three in segment IV, two spanned segments IV and V, and one spanned segments III and IV. Eleven tumor nodules were located directly adjacent to the gallbladder and three were within 1 cm of the gallbladder. Tumor size ranged from 0.9 to 4.5 cm in largest diameter. One tumor, located in an 8-cm area of segment V, was multifocal.

The aim of performing radiofrequency ablation in all patients was complete destruction of the lesion with a 5- to 10-mm-wide tumor-free margin around all possible aspects of each tumor. The radiofrequency ablations were performed in 14 sessions in the eight patients. Five sessions constituted repeated ablation. All radiofrequency ablation was performed after the patient fasted overnight. Conscious sedation and local anesthesia were used every time. Radiofrequency devices used were a model 500 generator with a 3-cm multiprong retractable electrode model 30 or model 70 (RITA Medical Systems, Mountain View, CA) and a model CC-1 generator with a cluster, three-prong, 2.5-cm tip electrode (model PE3D 2.5K; Radionics, Burlington, MA). All ablations were carried out percutaneously using sonographic guidance. Strict asepsis was maintained throughout the procedures. The ablations were performed and monitored according to the recommendations of the equipment manufacturers. The number of ablations performed at each session ranged from one to six (mean, three ablations), the greater number being required in the larger tumors. The aim of ablation in all patients was a cure.

All patients were treated on an outpatient basis and were observed for 6 hr after treatment for complications. No antibiotics were given before or after the ablation. Complete blood count, serum bilirubin liver enzyme levels, and CT immediately after ablation were performed before discharge. The reasons for performing CT immediately after ablation were to assess the completeness of ablation, to obtain a baseline image of the radiofrequency lesion, and to detect any immediate complications. Patients were followed up by telephone for 1 week or until the remission of symptoms, whichever occurred later. All symptoms were documented in the patient chart after recovery and during the ablation follow-up period. Repeated CT was performed every 3 months to monitor tumor recurrence. As part of this study, the CT scans obtained before and immediately after ablation and subsequently were jointly reviewed by three board-certified radiologists, with a consensus of opinion reached for the presence of gallbladder wall thickening of more than 2 mm, abnormal gallbladder wall enhancement, and pericholecystic fluid. Any conflict of opinion was resolved by consensus.

Results

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Symptoms After Ablation
Of eight patients undergoing 14 ablation sessions, six patients developed symptoms after eight ablation sessions (Table 2). Abdominal pain was noted in all eight instances. The pain was localized to the site of needle entry after five and to the right upper quadrant after three of eight ablation sessions. One patient also developed right shoulder pain. The severity of pain was described as mild after four sessions, moderate after two, and severe after two. The duration of pain ranged from 5 to 21 days (mean, 7 days). Fever with malaise and chills was reported after five ablation sessions. The highest temperature was 101-102°F (38-39°C). The duration of fever was 2-13 days. Nausea and vomiting occurred in one instance for 2 hr and were relieved with antiemetic agents.

CT Findings
No patient had gallbladder wall thickening on the preablation CT scans (Fig. 1A). Gallbladder wall thickening was noted on the immediate postprocedure CT scans after six sessions in four patients (Fig. 1B). All six instances of gallbladder wall thickening after ablation were associated with symptoms. A small perihepatic hematoma was noted in one patient after each of two ablation sessions. In one instance, the hematoma was asymptomatic; in the other, it was associated with focal gallbladder wall thickening and local pain. No gallbladder wall thickening was observed after the eight sessions in the remaining four patients (Fig. 2A, 2B, 2C). Symptoms were seen in only three instances in two of the four patients with gallbladder wall thickening. The remaining two patients were completely asymptomatic. One had severe ascites before and after the ablations.

View larger version (138K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A. —72-year-old man with hepatic metastases in Couinaud's segment V. Contrast-enhanced CT image shows multiple hypoattenuating tumor nodules (arrow) adjacent to gallbladder.

View larger version (134K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B. —72-year-old man with hepatic metastases in Couinaud's segment V. Contrast-enhanced CT image immediately after radiofrequency ablation shows area of radiofrequency-induced coagulation necrosis (short arrow) and gallbladder wall edema (long arrow).

View larger version (162K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2A. —85-year-old man with hepatic metastases in Couinaud's segment IVb. Contrast-enhanced CT image shows tumor mass (long arrow) and incidental right adrenal adenoma (short arrow).

View larger version (173K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2B. —85-year-old man with hepatic metastases in Couinaud's segment IVb. Contrast-enhanced CT image immediately after radiofrequency ablation shows radiofrequency-induced coagulation necrosis (arrow).

View larger version (181K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2C. —85-year-old man with hepatic metastases in Couinaud's segment IVb. Contrast-enhanced CT image inferior to B shows normal gallbladder wall (arrow).

Laboratory Findings
Both before and after ablation, WCCs were available in 13 instances. The counts were normal (mean, 4.94 x 10³/µL; range, 2.7-9 x 10³/µL) before ablation in all instances and remained normal after ablation in all but one instance (mean, 6.6 x 10³/µL; range, 2.7-14 x 10³/µL). In one instance, a transient increase of the WCC to 14 x 10³/µL was noted. Serum bilirubin levels before and after ablation were available in 10 instances. Serum bilirubin levels before ablation were normal (mean, 0.76 mg/dL; range, 0.4-1 mg/dL) in all cases. Serum bilirubin values after ablation were abnormal (mean, 1.73 mg/dL; range, 0.8-3.6 mg/dL) in eight instances. Alkaline phosphatase levels before and after ablation were available in 10 instances. The mean alkaline phosphatase level before ablation was 100 U/L (range, 64-133 U/L) and after ablation was 87.9 U/L (range, 49-125 U/L). The alkaline phosphatase level was abnormal in one instance before ablation and in no instances after ablation. Aspartate aminotransferase levels were available in 10 instances before and after ablation. The mean aspartate aminotransferase level before ablation was 55.5 U/L (range, 15-155 U/L) and after ablation was 263 U/L (range, 29-1176 U/L). Aspartate aminotransferase levels were normal before and high after ablation in six instances, high both before and after ablation in three instances, and normal both before and after ablation in one instance. Alanine aminotransferase levels were available before and after ablations in six instances. The mean alanine aminotransferase level before ablation was 53.8 U/L (range, 22-323 U/L) and after ablation was 263 U/L (range, 34-718 U/L). The alanine aminotransferase levels were normal before and high after ablation in two instances, high both before and after ablation in three instances, and normal both before and after ablation in one instance.

Completeness of Ablation and Follow-Up
Of the eight patients, the ablations were considered complete (no detectable remaining tumor on CT) in seven (87%). In the remaining patient, the lesion could not be completely ablated even after two sessions. As shown in Table 3, the follow-up times ranged from 3 to 22 months (mean, 8 months) in the patients with completed ablations. One patient had local recurrence at 11 months. The remaining six patients showed no local recurrence at the end of the follow-up period. None of the patients showed evidence of gallbladder disease.

Discussion

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The proximity of a normal structure to an ablation site raises two issues: the effect of ablation on the integrity of the structure, and the effect of the proximity of the structure on the quality of ablation. The effect of ablation on the integrity of a normal structure contributes to the potential for complications. Various authors have considered the effect of interstitial heating by radiofrequency or laser on normal structures in the liver. The lack of effect on large hepatic blood vessels is the most prominent observation, both experimentally [12] and clinically [1]. These large vessels act as "heat sinks," producing dispersion of heat that on the one hand makes these vessels safe from heat-induced thrombosis and on the other hand may lead to incomplete tumor destruction. The biliary system as bystander victim has also been mentioned. Bilchik et al. [13] noted a patient who, after radiofrequency ablation, developed a bile duct stricture requiring endoscopic stent placement. Livraghi et al. [8] noted a patient who developed cholecystitis after radiofrequency ablation of a neoplasm near the gallbladder. However, to our knowledge, little information exists about the feasibility of successful and safe ablation next to the gallbladder. Therefore, we undertook this study to determine the safety of radiofrequency ablation of hepatic lesions adjacent to the gallbladder.

Our experience as indicated in this study suggests that the radiofrequency ablation of lesions in the gallbladder fossa is safe. Although most patients developed symptoms referred to the gallbladder after ablation, the symptoms were self-limited in all and did not require any intervention other than analgesic medication. The main symptoms were right upper quadrant pain with or without nausea, vomiting, and fever. Symptoms of right upper quadrant pain or fever, nausea, and vomiting developed in 75% of patients and after 57% of ablation sessions. The frequency of symptoms after ablation was higher in this subgroup of patients than the frequency of symptoms observed after radiofrequency ablation of tumors that are not in the proximity of the gallbladder, which is approximately 25% [10, 11].

Mild discomfort of short duration at the ablation site after radiofrequency ablation anywhere in the liver may be caused by stretching of the hepatic capsule overlying the ablation site, by subcapsular hematoma, or by intraperitoneal hemorrhage. We observed that in patients with ablation of lesions in the gallbladder fossa, the sites and characteristics of pain are similar to those of pain from acute cholecystitis, and the pain is more prolonged than that experienced after radiofrequency ablation of liver tumors remote from the gallbladder.

We believe that the proximity of the ablation margin to the gallbladder induces focal thermal injury of the gallbladder wall and results in mild cholecystitis. This hypothesis is supported in our study by the observation that on CT performed immediately after ablation, some patients had focal edema of the gallbladder wall adjacent to the ablation margin. However, this thermally induced cholecystitis is mild enough not to cause leukocytosis. Second, in one patient with cirrhosis, the gallbladder was separated from the ablation site by ascitic fluid in the widened interlobar fissure, and no symptoms related to the gallbladder were observed after ablation. In this patient, the gallbladder was probably protected from thermal injury by the cooling effect of ascitic fluid. Additionally, we detected an elevation of the levels of the serum bilirubin and liver enzymes in our patients. However, the severity of the elevation was no greater than that reported for the ablation of liver tumors remote from the gallbladder [9].

Our experience with radiofrequency ablation of hepatic lesions abutting the gallbladder has led us to some insights regarding the technique. In our opinion, the choice and placement of the needle are of utmost importance in ensuring the safety of this procedure. It is essential that the gallbladder wall itself not be traversed by the radiofrequency needle probe for fear of perforation. Keeping that in mind, one can advance the tip of the needle probe to within a few millimeters of the gallbladder wall without compromising the safety of the procedure. A straight needle probe is the easiest to place and can be placed either perpendicular or parallel to the gallbladder wall. The umbrella probe should always be placed perpendicular to the gallbladder wall. We do not recommend the use of the Star-burst probes (RITA Medical Systems, Mountain View, CA) because of difficulty in predicting the positions of the deployed prongs in relation to the needle tip. For accuracy in placement, we recommend that a real-time guidance technique like sonography or CT fluoroscopy be used to place the needle.

The presence of a bile-filled gallbladder may have a potential effect on the completeness of ablation and therefore on the probability of local recurrence. In our study, 86% of patients were free of local recurrence at the end of the follow-up. As shown in Table 3, five of the seven patients with complete ablation were followed up for less than 6 months. These short follow-up periods resulted from patient attrition for various reasons. Therefore, it is important to note that the number of patients in our study is too small and the follow-up periods are too short for the data on recurrence to be applicable. Only larger studies will clarify this issue.

Apart from the limitations we have mentioned, no pathologic proof of changes in the gallbladder after ablation is available. The description of changes in the gallbladder after ablation is based solely on CT appearances. The presence of thermally induced cholecystitis can only be surmised.

In conclusion, on the basis of the observations made in this study, it appears that radiofrequency ablation of hepatic tumors adjacent to the gallbladder is feasible and potentially safe.

References

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