HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by de Baère, T. Articles by Elias, D. Search for Related Content PubMed PubMed Citation Articles by de Baère, T. Articles by Elias, D. Social Bookmarking                      What's this?

Adverse Events During Radiofrequency Treatment of 582 Hepatic Tumors

¹ Departement d'Imagerie Medicale et de Chirurgie, Institut Gustave Roussy, 39 Rue Camille Desmoulins, Villejuif 94805, France.
² Service de Radiologie et de Chirurgie Générale et Digestive, CHU Michallon, Grenoble, France.

Received December 30, 2002; accepted after revision April 1, 2003.

 
Address correspondence to T. de Baère.

Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
OBJECTIVE. We describe the rates and potential risk factors of complications of radiofrequency ablation of hepatic tumors.

SUBJECTS AND METHODS. Over a 5-year period, 312 patients underwent 350 sessions of radiofrequency ablation (124 intraoperative and 226 percutaneous) for treatment of 582 liver tumors including 115 hepatocellular carcinomas and 467 metastatic tumors. The chi-square test was used for a group-to-group comparison of the occurrence of adverse events.

RESULTS. Thirty-seven (10.6%) adverse events and five (1.4%) deaths were related to radiofrequency treatment. The deaths were caused by liver insufficiency (n = 1), colon perforation (n = 1), and portal vein thrombosis (n = 3). Portal vein thrombosis was significantly (p < 0.00001) more frequent in cirrhotic livers (2/5) than in noncirrhotic livers (0/54) after intraoperative radiofrequency ablation performed during a Pringle maneuver. Liver abscess (n = 7) was the most common complication. Abscess occurred significantly (p < 0.00001) more frequently in patients bearing a bilioenteric anastomosis (3/3) than in other patients (4/223). We encountered five pleural effusions, five skin burns, four hypoxemias, three pneumothoraces, two small subcapsular hematomas, one acute renal insufficiency, one hemoperitoneum, and one needle-tract seeding. The 6.3% of minor complications did not require specific treatment or a prolonged hospital stay. Among the 5.7% major complications, 3.7% required less than 5 days of hospitalization for treatment or surveillance and 2% required more than 5 days for treatment.

CONCLUSION. Radiofrequency ablation of liver tumors is a well-tolerated technique, but caution should be exercised when treating patients with a bilioenteric anastomosis, and radiofrequency ablation during vascular occlusion in cirrhotic livers should be avoided.

Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Radiofrequency ablation is one of the most promising imaging-guided thermal ablation techniques used to treat primary or metastatic liver tumors. It is used either percutaneously in patients in whom surgery is contraindicated [1-3], during open surgery as an adjunct to liver resection to destroy unresectable tumors [4, 5], or, less frequently, during laparoscopy [6, 7]. To date, more than 5000 radiofrequency ablation procedures have been reported in the literature. Although the technique is considered relatively safe, the rate of adverse events is probably approximate because of the type of articles that have focused on this topic. These articles are often short series or case reports [8-12], are based on questionnaires sent to a large number of centers [13], or are reviews from the literature [14]. To overcome the intrinsic weaknesses of questionnaire studies or literature reviews, this study was designed to precisely evaluate the rate of adverse events arising during radiofrequency ablation of liver tumors and to define a subset of high-risk situations through the analysis of complete patient files prospectively registered for radiofrequency complications in two centers.

Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Over a 5-year period in two medical centers, adverse events related to radiofrequency ablation were prospectively recorded in 312 consecutive patients treated for liver tumors. For major and minor complications, we used the definition of the Society of Cardiovascular and Interventional Radiology [15], which states that a major complication is one that, if left untreated, might threaten the patient's life, lead to substantial morbidity and disability, or result in a lengthened hospital stay. All other complications were considered minor.

Our study population included 131 women and 181 men who were 62 ± 14 (mean ± SD) years old bearing 582 tumors including 115 hepatocellular carcinomas and 467 metastatic tumors, mostly from colorectal cancer. The tumors were treated during 350 procedures. Two hundred twenty-six procedures were percutaneous, and 124 were intraoperative. Twenty-seven patients underwent multiple radiofrequency procedures: two in 18 patients, three in seven patients, and four in two patients. Intraoperative radiofrequency ablation was always performed during open surgery, and no treatment was performed laparoscopically. Intraoperative radiofrequency ablation was combined with liver resection in 118 patients; radiofrequency ablation was the only treatment performed during laparotomy in the remaining six patients. A mean of 2.1 ± 1.92 tumors were treated during intraoperative radiofrequency ablation, and a mean of 1.32 ± 0.76 tumors were treated percutaneously. The largest tumor dimensions ranged from 5 to 55 mm with a mean value of 26 mm. An international normalized ratio below 1.5 and a platelet count above 75 x 10³/µL were required before percutaneous radiofrequency treatment. Most radiofrequency treatments were performed using single or cluster cooled-tip needles (Cool-Tip Cluster, Radionics, Burlington, MA) or 3- or 4-cm diameter expandable array needles (LeVeen, Radiotherapeutics, Sunnyvale, CA). Radiofrequency systems were used according to the manufacturer's recommendations. The Radionics radiofrequency generator was activated for 15 min in the automatic mode allowing pulsed radiofrequency delivery while the needle was being cooled with chilled saline, as described elsewhere [1, 16]. The Radiotherapeutics system started radiofrequency delivery at low power with incremental power increases every minute, until a major increase in impedance, called roll-off, was obtained. One to four grounding pads were used and positioned according to the manufacturer's recommendations, which varied with time because needle designs have changed. All the intraoperative and 208 of the 226 percutaneous treatments were performed under sonographic guidance, and the remaining 18 treatments were performed under CT guidance because tumor visualization was poor with sonography or because a transpulmonary approach was required to target highly located tumors. General anesthetic was used for all intraoperative radiofrequency procedures and for 199 of the 226 percutaneous procedures. Needle-tract cauterization was not systematically performed.

The Pringle maneuver (clamping of the porta hepatis, thus interrupting hepatic arterial and portal venous flow to the liver) was applied in 59 (47%) of 126 intraoperative radiofrequency treatments, including those in five patients with hepatocellular carcinoma in the cirrhotic liver and in 54 patients with metastases. The Pringle maneuver was used either because the tumor exceeded 25 mm or because it was in contact with vessels larger than 4 mm. Intraductal cooling of the main bile duct with chilled saline was used in eight intraoperative radiofrequency treatments modeled after a technique described elsewhere [17]. Temporary vascular balloon occlusion was used in 25 of the 226 percutaneous treatments according to a technique reported elsewhere [18]. These balloon occlusions were used percutaneously when treating metastases in contact with vessels larger than 4 mm or metastases with diameters that exceeded 35 mm. The occluded vessels were one hepatic vein in 18 patients, two hepatic veins in two patients, and one segmental portal branch in five patients. Selective arterial embolization was used in addition to percutaneous radiofrequency treatment of hepatocellular carcinoma in six patients whose tumors exceeded 35 mm.

Two hundred ninety-nine of the 312 patients in this study were followed up for at least 4 months. The examinations included CT and a blood test every 2 or 3 months for 6 months in all patients whom we were able to follow up, except for four patients with an increased serum creatinine level. These four patients were followed up with MRI. Fifty additional patients underwent both CT and MRI follow-up because they were enrolled in a prospective study for follow-up evaluation. All CT and MRI included dynamic enhanced imaging. Follow-up imaging was interpreted by senior radiologists who were not in charge of the radiofrequency ablation, and clinical follow-up was performed by the physician who performed the radiofrequency ablation. Any image changes except the usual area of devascularization seen after radiofrequency ablation or tumor progression were considered as complications. Any rehospitalization or consultation in addition to the scheduled ones was considered complications. Seven patients died within the 4 months after treatment, and six were lost to follow-up imaging. In these six patients, medical files from other centers were available 2 months after radiofrequency ablation. Prophylactic antibiotic therapy with a single 1-g dose of ceftriaxone was administered to all patients who were treated during surgery. Prophylactic antibiotic therapy with an IV injection of amoxicillin and clavulanate (2 g) immediately before the radiofrequency ablation procedure and oral administration of the same antibiotic (2 g/day) over 2 days was given for percutaneous radiofrequency treatments. The three patients with a bilioenteric anastomosis received a 5-day course of amoxicillin and clavulanate, and the patient with a metallic biliary stent received ceftriaxone (2 g/day) and metronidazole (0.5 g/day) over 5 days.

Percutaneous radiofrequency ablation was performed on the basis of a one- or two-night hospital stay, with a blood test obtained the day after radiofrequency ablation for all patients. No systematic imaging was performed during the hospital stay after radiofrequency ablation unless unusual findings such as pain, jaundice, or dyspnea revealed at the postoperative clinical examination or a blood test revealing unusual major modifications.

The chi-square test was used for a group-to-group comparison of occurrence of adverse events with a significant p value below 0.05.

Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The mortality rates for radiofrequency procedures were 1.4% (5/350) and 1.6% (5/312) for patients. The mortality rate of intraoperative radiofrequency delivery of 2.4% (3/123) was not significantly different (p = 0.9) from the percutaneous delivery of 0.9% (2/216). The adverse event rate was 12% (42/350) including the five deaths. Among these adverse events, 22 (6.3%) were minor and 20 (5.7%) were major complications, including 13 requiring less than 5 days of hospitalization for treatment and seven requiring more than 5 days. Details of the 42 adverse events including time of discovery and length of hospital stay required for treatment are given in Table 1.

Eleven vascular thromboses occurred, which included five hepatic veins and three segmental portal branches imaged at direct venography at the end of radiofrequency treatment performed during percutaneous balloon occlusion. These eight thrombotic events involved only the balloon occluded vessel without upstream extension and did not induce clinical symptoms or unusual modifications on blood tests performed on day 1. None of the thromboses previously mentioned were revealed on follow-up CT scans and MRIs obtained 2 or 3 months after treatment. The three patients with complete and extensive portal vein thromboses who presented with abdominal pain, ascites, and a major increase in bilirubin level were diagnosed on CT performed at day 1 or 2. Two of these portal vein thromboses occurred in a patient with cirrhosis who was undergoing liver resection and intraoperative radiofrequency ablation associated with the Pringle maneuver for unresectable hepatocellular carcinoma. One of these two patients underwent one radiofrequency delivery during a 10-min Pringle maneuver, and the other underwent two radiofrequency deliveries during a 5- and 7-min Pringle maneuver. The third portal vein thrombosis occurred after percutaneous treatment of a single metastasis in a patient who had already undergone two liver operations and one percutaneous radiofrequency treatment. Two of the three patients who developed portal vein thromboses after radiofrequency ablation died within 7 days after the discovery. The third patient returned home with an increase in the Child-Pugh score from B7 preoperatively to C10 postoperatively and died 4 months later.

The seven liver abscesses were discovered 13 days to 2 months after percutaneous radiofrequency treatment (Figs. 1A, and 1B). Three abscesses that were asymptomatic caused low-grade fever, and therefore the patients were not referred to the hospital before the scheduled 2-month follow-up imaging when gas collections were found on CT or MRI. Two other abscesses were discovered 3 and 4 weeks after radiofrequency on CT that was performed for unusual abdominal pain and fever. These five abscesses were punctured under sonographic guidance and drained over 3 days before removal of the drain. Cultures were positive for Escherichia coli and Streptococcus faecalis. A combination of amoxicillin and clavulanate (2 g/day) was initiated before draining the abscess and continued for 15 days; the patients recovered uneventfully. The last two of the seven abscesses caused septicemia and septic shock. The first of these last two patients underwent radiofrequency ablation for a single metastasis from colon cancer that was high-seated in a remnant liver after a previous right hepatectomy. This patient had undergone biliary drainage for 3 months because of a postoperative fistula and was finally treated with a metallic stent 2 months before radiofrequency ablation for persistent stenosis of the common bile duct. Six weeks after radiofrequency ablation, a CT scan revealed a hepatic abscess extending to the mediastinum through a perforation in the diaphragm. The second severe abscess occurred in a patient operated on for duodenopancreatic resection 4 months before radiofrequency ablation for a single metastasis from pancreatic adenocarcinoma. Two weeks after radiofrequency treatment, chemotherapy combining gemcitabine and docetaxel was begun. Three weeks after the first course of chemotherapy, three large hepatic abscesses were found on CT. Both patients with septicemia and abscesses were managed with percutaneous drainage. Drain cultures revealed Clostridium organisms and E. coli, which were treated with antibiotics. Hospitalization for these two patients lasted 41 and 42 days. Both patients died of widespread metastatic disease, 5 and 7 months, respectively, after radiofrequency ablation. Among the 350 radiofrequency procedures, an abscess occurred in all three patients with bilioenteric anastomoses.

View larger version (142K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A. —Asymptomatic 63-year-old woman. MRI obtained 2 months after radiofrequency ablation shows air-fluid level corresponding to liver abscess in location of radiofrequency ablation.

View larger version (160K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B. —Asymptomatic 63-year-old woman. MRI obtained 6 months after drainage and antibiotic therapy shows only small scar (arrow).

Lung and pleural-related complications included five pleural effusions, three pneumothoraces, and four cases of dyspnea with hypoxemia. The pleural effusions were discovered on chest radiography performed for unusual pain 1 day after percutaneous radiofrequency ablation. Four were mild and resolved spontaneously before day 7. The last one was mild on day 1 but increased in volume by day 7 and then required a thoracocentesis. The plural effusion three times during the next 2 months and required three additional thoracocenteses but finally resolved. Two of the three cases of pneumothoraces were expected because a CT-guided transpulmonary approach had been chosen to gain access to a highly located tumor. One occurred unexpectedly during sonographically guided treatment of a highly located tumor. This last one was discovered on a chest radiograph obtained to investigate right shoulder pain, which had started in the recovery room. None of the pneumothorax cases required treatment. They all resolved spontaneously, and the patients were discharged from the hospital on day 1. Dyspnea and hypoxemia were observed at day 1 in four patients after percutaneous (n = 2) and intraoperative (n = 2) radiofrequency ablation. Because these conditions mimic pulmonary embolism, single-detector helical CT was performed to rule out pulmonary embolism. No cause was found to explain the symptoms, and the hypoxemia resolved spontaneously after 2-4 days, therefore slightly prolonging the hospital stay of the two patients who were treated percutaneously.

The five skin burns were first- and third-degree burns in four patients and in one patient, respectively. The burns occurred at the edge of one of the grounding pads facing the active electrode when the maximal power of the generator was used. Treatment lasted for at least 30 min using multiple overlapping deliveries with the larger needles—that is, the Radionics Cluster or the LeVeen 4.0-cm needle.

The patient with a colon perforation was discharged from the hospital 2 days after radiofrequency treatment with no abnormal clinical findings and no pain. He returned to another hospital on the day 4 with abdominal pain and was treated with antibiotics and steroids at home for 3 days. When the patient was referred again to our hospital 8 days after radiofrequency ablation, he had obvious peritonitis with a gas-containing peritoneal effusion. At laparotomy, right colon perforation adjacent to the subcapsular liver radiofrequency destruction was found to be the cause of peritonitis. The patient died of multiorgan failure after 7 weeks in the intensive care unit.

Another patient had a peritoneal effusion that was discovered on sonography, which was performed in the recovery room because the patient had severe abdominal pain 1 hr after the percutaneous radiofrequency treatment with a 17-gauge single needle of five neuroendocrine tumors measuring less than 1 cm. The patient underwent an emergency laparotomy. Bile and blood leakage was discovered at one of the five puncture sites. The patient recovered uneventfully, without the need for a blood transfusion, after 2 days of peritoneal drainage. He was discharged from the hospital 5 days after radiofrequency ablation. He is still alive and tumor-free 3 years later.

Postoperative hepatic failure occurred in a patient treated for 13 hepatic metastases from colon cancer, including 12 metastases in the right liver lobe. He underwent a right hepatectomy, partially extended to segment IV, associated with a single radiofrequency delivery for treatment of a segment III metastasis, without the Pringle maneuver. On day 3, a small, hard remnant liver with a large area of radiofrequency destruction was found at laparotomy that was performed to investigate liver failure shown on a blood test and clinical examination. However, CT findings were normal. Hepatic failure without portal thrombosis led to the patient's death on day 6.

Transient renal failure occurred in one patient after radiofrequency treatment of a 55-mm hepatocellular carcinoma lesion requiring 10 radiofrequency deliveries with a LeVeen 4.0-cm needle after superselective hepatic artery embolization was performed. The renal failure resolved after one course of dialysis, and the patient was discharged from the hospital 4 days after radiofrequency ablation. This patient was still tumor-free at the last follow-up CT performed 8 months after radiofrequency treatment.

Tumor seeding of the abdominal wall was discovered in another patient on follow-up MRI, 4 months after treatment of a subcapsular hepatocellular carcinoma measuring 5 cm in diameter that required three punctures to achieve radiofrequency needle placements for five radiofrequency deliveries.

Concerning the two subcapsular hematomas, one was seen on a sonogram obtained immediately after radiofrequency ablation and confirmed on a CT scan obtained 24 hr later, and the other was found on a CT scan obtained 24 hr later for pain. Both hematomas were less than 5 mm thick and did not induce any drop in hemoglobin level. They both resolved spontaneously and were no longer seen on the CT at 2-month follow-up.

Incidental findings on follow-up imaging, such as segmental or subsegmental biliary tract dilatation upstream of the radiofrequency area of destruction or arterioportal shunts, were not considered as adverse events because they have been reported as usual consequences of radiofrequency liver ablation [19, 20]. Pneumothoraces occurring after a transpleurodiaphragmatic surgical approach were not taken into account because they are expected after a thoracotomy [21]. In the same manner, mild pleural effusion occurring after intraoperative radiofrequency was not taken into account because it is a common occurrence after laparotomy for hepatectomy.

Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
In our experience, abscess was the more frequent clinically symptomatic complication after radiofrequency ablation, as reported by others [22] and in a review of the literature [14]. Abscesses occurred later, at least 13 days after radiofrequency, and this is consistent with recent articles that have reported an interval ranging from 8 days to 5 months [8, 22]. Prophylactic antibiotics used during percutaneous radiofrequency ablation did not prevent formation of seven abscesses in the 226 procedures when compared with no abscesses after 124 intraoperative radiofrequency ablations. However, we can hardly compare the two groups that were receiving radiofrequency treatment via different accesses at the same time with those groups receiving different antibiotics. Furthermore, in our experience, there is no scientific or published proof that prophylactic antibiotic therapy is of any benefit. Consequently, further comparative trials on the value and the type of prophylactic antibiotic therapy are needed. Concerning the percutaneously treated patients, we found a highly significant difference (p < 0.00001) between the rate of abscess for patients with (3/3) and without (4/223) a bilioenteric anastomosis. Accordingly, Livraghi et al. [13] found two patients with a bilioenteric anastomosis in the six abscesses that occurred after radiofrequency ablation. Moreover, in our experience, patients with bilioenteric anastomosis developed an abscess despite prolonged administration of antibiotics. This extended antibiotic regimen for prophylaxis was based on previously published warnings of an increased risk of septic complications after transarterial chemoembolization or ethanol injection in patients with bilioenteric anastomoses [23-25]. Bilioenteric anastomosis should be considered a major risk factor for septic complications when performing radiofrequency ablation because it is a risk factor for transarterial chemoembolization or percutaneous ethanol injection in the liver. If radiofrequency ablation is mandatory in patients with a bilioentric anastomosis, a regimen of antibiotic prophylaxis should be tailored for them. Geschwind et al. [26] recently reported uneventful transarterial chemoembolization in patients with bilioenteric anastomosis. The regimen of antibiotic prophylaxis consisted of 10 g/day of IV tazobactam sodium or piperacillin sodium for 3 days with a bowel preparation of 45 mL of oral phosphosoda, 1 g of oral neomycin, and 1 g of oral erythromycin (three doses per day). Furthermore, the late occurrence of abscesses indicates that there should probably be an interval between radiofrequency treatment and the administration of any subsequent immunodepressive treatment such as chemotherapy, even if it is difficult to give precise recommendations concerning the duration of this interval.

Thrombosis and coagulation of vessels smaller than 3 mm in diameter is a common occurrence after radiofrequency ablation [27]. Indeed, whenever radiofrequency ablation is performed, numerous small vessels are coagulated, but the image-monitoring technique we use cannot detect this in most patients. In contrast, thrombosis of vessels larger than 4 mm after radiofrequency ablation is uncommon, provided that normal flow is maintained through these vessels. In our experience, thromboses of large vessels were always linked to vascular occlusion when it was used as an adjunct to radiofrequency ablation, except in one patient. One third of the percutaneous radiofrequency procedures performed during temporary vessel balloon occlusion led to complete thrombosis limited to the ballooned vessel, either segmental portal branches or hepatic veins. Although these thromboses always remained asymptomatic and vessels were recanalized thereafter on 2-month follow-up imaging, one should keep in mind that before targeting a vessel for balloon occlusion, one should be sure that the patient can sustain temporary thrombosis of the targeted vessel. This means, for example, that it could be dangerous to treat a remnant liver with a single hepatic vein during balloon occlusion of this vessel. The rate of portal vein thromboses after radiofrequency ablation performed during Pringle maneuvers in cirrhotic patients (2/5) was significantly higher (p < 0.00001) than the rate in noncirrhotic livers (0/54). Moreover, these thromboses occurred despite the Pringle maneuver applied for less than 10 min for treatment of tumors at a distance from the portal trunk. In conclusion, vascular occlusion combined with radiofrequency ablation appears to be safe, except in patients with cirrhosis, even if of short duration.

In our experience, tumor seeding was rare, but a follow-up of 4 months is too short to detect all seeding. However, the rate of 0.5% during percutaneous treatment is akin to that reported by most teams with considerable radiofrequency ablation experience [28, 29], although a rate up to 12% has been reported by one center with limited experience [30]. The only seeding that we experienced occurred in a patient who had known risk factors (primary tumor; poorly differentiated, subcapsular location; and multiple needle insertions). In such patients, we would recommend first trying a route traversing nontumorous parenchyma—limiting the number of needle insertions as much as possible—and then delivering radiofrequency treatment through a guiding needle and cauterizing the tract with the radiofrequency device at the end of the radiofrequency procedure. In addition, even if cauterization remains unproven, we believe that this procedure must also be applied before any repositioning of the needle or opening of the array if one had been in contact with the tumor. Besides the increased risks of seeding, subcapsular location of the radiofrequency-targeted tumor inside the liver might be of paramount importance in terms of potential complications to adjacent organs. Because radiofrequency is supposed to destroy the tumor with a safety margin of 0.5-1 cm of healthy parenchyma, this means that organs or the liver structure located less than 0.5-1 cm from the tumor margin will be heated. To what extent adjacent organs or vital liver structures tolerate heat is not well documented. Of the adjacent organs, the colon is probably the most sensitive to heat because of its thin wall, and colon perforation is the most frequently reported complication involving adjacent organs [13, 14]. Furthermore, a history of previous colon resection was revealed by Livraghi et al. [13] in five of six patients who developed colon perforation after radiofrequency ablation, supporting the role of postoperative adhesions and the lack of peristalsis. Therefore, it is probably not advisable to percutaneously treat liver tumors that are less than 1 cm from the colon. On the contrary, thermal damage to the right kidney does not appear to give rise to complications, and this is easy to understand because radiofrequency treatment of peripheral renal tumors has been shown to be safe [31, 32]. The abdominal wall and the diaphragm also seem to be relatively resistant to thermal damage, even if few diaphragmatic perforations have been reported [22]. Radiofrequency ablation of tumors adjacent to the gallbladder has been recently reported to be safe, with a self-limited morbidity related to mild iatrogenic cholecystitis [33].

Surprisingly, we encountered four patients with self-resolved hypoxemias after radiofrequency that were never reported previously. No abnormal imaging findings were found. Although the explanation for this condition remains obscure, acute lung injury as a result of systemic inflammatory response syndrome giving rise to overexpression of cytokines is plausible. Indeed, a major increase in the blood levels of cytokines, such as TNF- (tumor necrosis factor-alpha) and MIP-2 (macrophage inflammatory protein-2), and severe lung inflammation have been described experimentally after cryotherapy to the liver [34], which partially explains the cryoshock sometimes encountered after cryotherapy in clinical practice. In the same experimental study, a smaller increase in the same cytokines and occasional mild patchy congestive lung edema were reported after radiofrequency ablation to the liver. We hypothesize that the release of cytokines and degradation products during radiofrequency ablation may have been potentially toxic to the lung in four of our patients, in a manner similar to that found after cryotherapy. Also, myoglobinuria, known to occur after cryotherapy, was only recently reported after radiofrequency ablation [35]. As reported in another article [12], myoglobinuria might be responsible for the renal insufficiency in the patient in our study who received the highest number of radiofrequency deliveries for a single tumor in this series. However, contrast material that is administered during associated arterial embolization could account for renal toxicity.

Most of the pad burns occurred in our early experience with radiofrequency treatment because we used only one pad for small electrodes and two pads for larger electrodes. Increasing the number of pads according to the manufacturer's recommendations lowered the occurrence of burns. In addition, adequate skin preparation, pads positioned equidistant from the active electrode, and advice proffered in an excellent experimental study [36] can be of great help in limiting these burns. Finally, careful and regular checking of the local temperature at the edges of the pad closest to the electrode, using chilled saline to cool the edges locally if needed, or changing position for subsequent radiofrequency deliveries can be helpful to avoid burns.

Our study has several limitations. One is the heterogeneity of the tumors treated, both hepatocellular carcinomas and metastatic tumors. The second is the heterogeneity of the treatment procedures including percutaneous and intraoperative radiofrequency ablation, cooled needles, and expandable arrays. This heterogeneity allows a group-to-group comparison in a series of patients treated by the same teams with the same techniques. In this regard, we could show differences in terms of the rate of portal thrombosis after the Pringle maneuver and the rate of abscess after ablation according to technique or population. However, the series remains too small to find differences in many variables.

Another limitation of this study is that except for the blood tests and clinical examinations, no systematic examinations were performed in the early days after radiofrequency ablation. This probably lowered the number of asymptomatic adverse events such as small pleural effusions or small subcapsular hematomas, which had resolved on the systematic follow-up CT performed at 2 months. We believe that prospective registration of adverse events in our two centers, in which radiologists were trained in radiofrequency ablation since the early days of the technique, allowed us to acquire more precise data than would a questionnaire or a review of the literature, which contains most of the published articles or abstracts focused on this topic.

Radiofrequency treatment of liver tumors is most often well tolerated. Adverse events that required treatment occurred in 5.7% of procedures including death in 1.4% of procedures. These events were experienced at our two medical centers early in our learning curves. Abscesses rank first among complications for which prophylactic antibiotics may play a role that remains to be defined. Avoiding the Pringle maneuver during radiofrequency ablation in cirrhotic patients, exercising extreme caution when treating patients with bilioenteric anastomosis, or having a tumor less than 1 cm from adjacent organs, especially the colon, should help to lower the rate of complications after radiofrequency treatment of liver tumors.

References

Top Abstract Introduction Subjects and Methods Results Discussion References

 

1. de Baère T, Elias D, Dromain C, et al. Radiofrequency ablation of 100 hepatic metastases with a mean follow-up of more than 1 year. AJR 2000;175:1619 -1625[Abstract/Free Full Text]
2. Livraghi T, Goldberg SN, Lazzaroni S, et al. Small hepatocellular carcinoma: treatment with radiofrequency ablation versus ethanol injection. Radiology1999; 210:655 -661[Abstract/Free Full Text]
3. Solbiati L, Livraghi T, Goldberg SN, et al. Percutaneous radio-frequency ablation of hepatic metastases from colorectal cancer: long-term results in 117 patients. Radiology2001; 221:159 -166[Abstract/Free Full Text]
4. Curley SA, Izzo F, Ellis LM, Nicolas Vauthey J, Vallone P. Radiofrequency ablation of hepatocellular cancer in 110 patients with cirrhosis. Ann Surg2000; 232:381 -391[Medline]
5. Elias D, de Baère T, Mutillo I, et al. Intraoperative use of radiofrequency treatment allows an increase in the rate of curative liver resection. J Surg Oncol1998; 67:190 -191[Medline]
6. Cuschieri A, Bracken J, Boni L. Initial experience with laparoscopic ultrasound-guided radiofrequency thermal ablation of hepatic tumours. Endoscopy1999; 31:318 -321[Medline]
7. Siperstein A, Garland A, Engle K, et al. Laparoscopic radiofrequency ablation of primary and metastatic liver tumors: technical considerations. Surg Endosc2000; 14:400 -405[Medline]
8. Zagoria RJ, Chen MY, Shen P, Levine EA. Complications from radiofrequency ablation of liver metastases. Am Surg2002; 68:204 -209[Medline]
9. Francica G, Marone G, Solbiati L, D'Angelo V, Siani A. Hemobilia, intrahepatic hematoma and acute thrombosis with cavernomatous transformation of the portal vein after percutaneous thermoablation of a liver metastasis. Eur Radiol2000; 10:926 -929[Medline]
10. Shibata T, Yamamoto N, Ikai I, et al. Choledochojejunostomy: possible risk factor for septic complications after percutaneous hepatic tumor ablation. AJR2000; 174:985 -986[Free Full Text]
11. Yamagami T, Nakamura T, Kato T, Matsushima S, Iida S, Nishimura T. Skin injury after radiofrequency ablation for hepatic cancer. AJR 2002;178:905 -907[Free Full Text]
12. Keltner JR, Donegan E, Hynson JM, et al. Acute renal failure after radiofrequency liver ablation of metastatic carcinoid tumor. Anesth Analg 2001;93:587 -589[Abstract/Free Full Text]
13. Livraghi T, Solbiati L, Meloni MF, et al. Treatment of focal liver tumors with percutaneous radio-frequency ablation: complications encountered in a multicenter study. Radiology2003; 226:441 -451[Abstract/Free Full Text]
14. Mulier S, Mulier P, Ni Y, et al. Complications of radiofrequency coagulation of liver tumours. Br J Surg2002; 89:1206 -1222[Medline]
15. Burke DR, Lewis CA, Cardella JF, et al. Quality improvement guidelines for percutaneous transhepatic cholangiography and biliary drainage: Society of Cardiovascular and Interventional Radiology. J Vasc Interv Radiol 1997;18:677 -681
16. Goldberg SN, Stein MC, Gazelle GS, et al. Percutaneous radiofrequency tissue ablation: optimization of pulsed-radiofrequency technique to increase coagulation necrosis. J Vasc Interv Radiol 1999;10:907 -916[Medline]
17. Elias D, El Otmany A, Goharin A, Attalah D, de Baère T. Intraductal cooling of the main bile ducts during intraoperative radiofrequency ablation. J Surg Oncol2001; 76:297 -300[Medline]
18. de Baère T, Bessoud B, Dromain C, et al. Percutaneous radiofrequency ablation of hepatic tumors during temporary venous occlusion. AJR 2002;178:53 -59[Abstract/Free Full Text]
19. Dromain C, de Baère T, Elias D, et al. Hepatic tumors treated with percutaneous radiofrequency ablation: CT and MR imaging follow-up. Radiology2002; 223:255 -262[Abstract/Free Full Text]
20. Lim HK, Choi D, Lee WJ, et al. Hepatocellular carcinoma treated with percutaneous radio-frequency ablation: evaluation with follow-up multiphase helical CT. Radiology2001; 221:447 -454[Abstract/Free Full Text]
21. Elias D, de Baère T, Goharin A, Lasser P, Roche A. Transpleurodiaphragmatic radiofrequency thermoablation of a liver metastasis. J Am Coll Surg2000; 191:683 -685[Medline]
22. Wood TF, Rose DM, Chung M, et al. Radiofrequency ablation of 231 unresectable hepatic tumors: indications, limitations, and complications. Ann Surg Oncol2000; 7:593 -600[Abstract]
23. Kim W, Clark TW, Baum RA, Soulen MC. Risk factors for liver abscess formation after hepatic chemoembolization. J Vasc Interv Radiol 2001;12:965 -968[Medline]
24. Song SY, Chung JW, Han JK, et al. Liver abscess after transcatheter oily chemoembolization for hepatic tumors: incidence, predisposing factors, and clinical outcome. J Vasc Interv Radiol2001; 12:313 -320[Medline]
25. de Baère T, Roche A, Amenabar JM, et al. Liver abscess formation after local treatment of liver tumors. Hepatology1996; 23:1436 -1440[Medline]
26. Geschwind JF, Kaushik S, Ramsey DE, et al. Influence of a new prophylactic antibiotic therapy on the incidence of liver abscesses after chemoembolization treatment of liver tumors. J Vasc Interv Radiol 2002;13:1163 -1166[Medline]
27. Lu DS, Raman SS, Vodopich DJ, Wang M, Sayre J, Lassman C. Effect of vessel size on creation of hepatic radiofrequency lesions in pigs: assessment of the "heat sink" effect. AJR2002; 178:47 -51[Abstract/Free Full Text]
28. de Sio I, Castellano L, De Girolamo V, et al. Tumor dissemination after radiofrequency ablation of hepatocellular carcinoma. Hepatology2001; 34:609 -610
29. Goldberg SN, Solbiati L. Tumor dissemination after radiofrequency ablation of hepatocellular carcinoma. (letter) Hepatology2001; 34:609
30. Llovet JM, Vilana R, Bru C, et al. Increased risk of tumor seeding after percutaneous radiofrequency ablation for single hepatocellular carcinoma. Hepatology2001; 33:1124 -1129[Medline]
31. de Baère T, Kuoch V, Smayra T, et al. Radiofrequency ablation of renal cell carcinoma: preliminary experience. J Urol 2002;167:1961 -1964[Medline]
32. Wood BJ, Ramkaransingh JR, Fojo T, Walther MM, Libutti SK. Percutaneous tumor ablation with radiofrequency. Cancer 2002;94:443 -451[Medline]
33. Chopra S, Dodd GD 3rd, Chanin MP, Chintapalli KN. Radiofrequency ablation of hepatic tumors adjacent to the gallbladder: feasibility and safety. AJR2003; 180:697 -701[Abstract/Free Full Text]
34. Chapman WC, Debelak JP, Wright Pinson C, et al. Hepatic cryoablation, but not radiofrequency ablation, results in lung inflammation. Ann Surg 2000;231:752 -761[Medline]
35. Shankar S, Tuncali K, vanSonnenberg E, Seifter JL, Silverman SG. Myoglobinemia after CT-guided radiofrequency ablation of a hepatic metastasis. AJR 2002;178:359 -361[Free Full Text]
36. Goldberg SN, Solbiati L, Halpern EF, Gazelle GS. Variables affecting proper system grounding for radiofrequency ablation in an animal model. J Vasc Interv Radiol2000; 11:1069 -1075[Medline]

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				J.-R. Garbay, M.-C. Mathieu, M. Lamuraglia, N. Lassau, C. Balleyguier, and R. Rouzier Radiofrequency Thermal Ablation of Breast Cancer Local Recurrence: A Phase II Clinical Trial Ann. Surg. Oncol., November 1, 2008; 15(11): 3222 - 3226. [Abstract] [Full Text] [PDF]

				T. de Baere, F. Deschamps, P. Briggs, C. Dromain, V. Boige, L. Hechelhammer, M. Abdel-Rehim, A. Auperin, D. Goere, and D. Elias Hepatic Malignancies: Percutaneous Radiofrequency Ablation during Percutaneous Portal or Hepatic Vein Occlusion Radiology, September 1, 2008; 248(3): 1056 - 1066. [Abstract] [Full Text] [PDF]

				I. H. Lee, Y. C. Yoon, E. Y. Cho, J. W. Kwon, and S. T. Kwon Perineural Air Injection as a Means of Prevention of Thermal Injury of the Sciatic Nerve During Radio Frequency Ablation: A Preliminary Experimental Study in Rabbits J. Ultrasound Med., August 1, 2008; 27(8): 1221 - 1227. [Abstract] [Full Text] [PDF]

				S. Sartori, P. Tombesi, F. Macario, I. Nielsen, D. Tassinari, M. Catellani, and V. Abbasciano Subcapsular Liver Tumors Treated with Percutaneous Radiofrequency Ablation: A Prospective Comparison with Nonsubcapsular Liver Tumors for Safety and Effectiveness Radiology, August 1, 2008; 248(2): 670 - 679. [Abstract] [Full Text] [PDF]

				E. J. Lee, H. Rhim, H. K. Lim, D. Choi, W. J. Lee, and K. S. Min Effect of Artificial Ascites on Thermal Injury to the Diaphragm and Stomach in Radiofrequency Ablation of the Liver: Experimental Study with a Porcine Model Am. J. Roentgenol., June 1, 2008; 190(6): 1659 - 1664. [Abstract] [Full Text] [PDF]

				M.-h. Park, H. Rhim, Y.-s. Kim, D. Choi, H. K. Lim, and W. J. Lee Spectrum of CT Findings after Radiofrequency Ablation of Hepatic Tumors RadioGraphics, March 1, 2008; 28(2): 379 - 390. [Abstract] [Full Text] [PDF]

				J. Lee, H. Rhim, Y. H. Jeon, H. K. Lim, W. J. Lee, D. Choi, and Y.-s. Kim Radiofrequency Ablation of Liver Adjacent to Body of Gallbladder: Histopathologic Changes of Gallbladder Wall in a Pig Model Am. J. Roentgenol., February 1, 2008; 190(2): 418 - 425. [Abstract] [Full Text] [PDF]

				H. W. Head, G. D. Dodd III, N. C. Dalrymple, S. R. Prasad, F. M. El-Merhi, M. W. Freckleton, and L. G. Hubbard Percutaneous Radiofrequency Ablation of Hepatic Tumors against the Diaphragm: Frequency of Diaphragmatic Injury Radiology, June 1, 2007; 243(3): 877 - 884. [Abstract] [Full Text] [PDF]

				E. Liapi and J.-F. H. Geschwind Transcatheter and Ablative Therapeutic Approaches for Solid Malignancies J. Clin. Oncol., March 10, 2007; 25(8): 978 - 986. [Abstract] [Full Text] [PDF]

				R. T. P. Poon Optimal Initial Treatment for Early Hepatocellular Carcinoma in Patients with Preserved Liver Function: Transplantation or Resection? Ann. Surg. Oncol., February 1, 2007; 14(2): 541 - 547. [Abstract] [Full Text] [PDF]

				K. E. Maturen, H. V. Nghiem, J. A. Marrero, H. K. Hussain, E. G. Higgins, G. A. Fox, and I. R. Francis Lack of tumor seeding of hepatocellular carcinoma after percutaneous needle biopsy using coaxial cutting needle technique. Am. J. Roentgenol., November 1, 2006; 187(5): 1184 - 1187. [Abstract] [Full Text] [PDF]

				I. Bricault, R. Kikinis, P. R. Morrison, E. vanSonnenberg, K. Tuncali, and S. G. Silverman Liver Metastases: 3D Shape-based Analysis of CT Scans for Detection of Local Recurrence after Radiofrequency Ablation Radiology, October 1, 2006; 241(1): 243 - 250. [Abstract] [Full Text] [PDF]

				K. Takayasu, Y. Muramatsu, Y. Mizuguchi, T. Okusaka, K. Shimada, T. Takayama, and M. Sakamoto CT Evaluation of the progression of hypoattenuating nodular lesions in virus-related chronic liver disease. Am. J. Roentgenol., August 1, 2006; 187(2): 454 - 463. [Abstract] [Full Text] [PDF]

				F. H. van Duijnhoven, M. C. Jansen, J. M. C. Junggeburt, R. van Hillegersberg, A. M. Rijken, F. van Coevorden, J. R. van der Sijp, T. M. van Gulik, G. D. Slooter, J. M. Klaase, et al. Factors Influencing the Local Failure Rate of Radiofrequency Ablation of Colorectal Liver Metastases Ann. Surg. Oncol., May 1, 2006; 13(5): 651 - 658. [Abstract] [Full Text] [PDF]

				A. Shibuya, T. Nakazawa, K. Saigenji, K. Furuta, and K. Matsunaga Diaphragmatic hernia after radiofrequency ablation therapy for hepatocellular carcinoma. Am. J. Roentgenol., May 1, 2006; 186(5 Suppl): S241 - S243. [Full Text] [PDF]

				Y. K. Cho, H. Rhim, Y. S. Ahn, M. Y. Kim, and H. K. Lim Percutaneous radiofrequency ablation therapy of hepatocellular carcinoma using multitined expandable electrodes: comparison of subcapsular and nonsubcapsular tumors. Am. J. Roentgenol., May 1, 2006; 186(5 Suppl): S269 - S274. [Abstract] [Full Text] [PDF]

				P. Cabassa, F. Donato, F. Simeone, L. Grazioli, and L. Romanini Radiofrequency ablation of hepatocellular carcinoma: long-term experience with expandable needle electrodes. Am. J. Roentgenol., May 1, 2006; 186(5 Suppl): S316 - S321. [Abstract] [Full Text] [PDF]

				G E N E (Gruppo Epatocarcinoma Nord-Est Hepatocarc, C Angonese, A Baldan, U Cillo, A D'Alessandro, M De Antoni, M De Giorgio, A Masotto, D Marino, M Massani, et al. Complications of radiofrequency thermal ablation in hepatocellular carcinoma: what about "explosive" spread? Gut, March 1, 2006; 55(3): 435 - 436. [Full Text] [PDF]

				K. K. Ng, C. M. Lam, R. T. Poon, T. W. Shek, D. W. Ho, and S. T. Fan Safety limit of large-volume hepatic radiofrequency ablation in a rat model. Arch Surg, March 1, 2006; 141(3): 252 - 258. [Abstract] [Full Text] [PDF]

				A. Giorgio, G. Ferraioli, D. Choi, and H. K. Lim Liver Abscess Formation After Radiofrequency Ablation in Patients with Hepatocellular Carcinoma Am. J. Roentgenol., February 1, 2006; 186(2): 582 - 583. [Full Text] [PDF]

				T. M. Wah, R. S. Arellano, D. A. Gervais, C. A. Saltalamacchia, J. Martino, E. F. Halpern, M. Maher, and P. R. Mueller Image-guided Percutaneous Radiofrequency Ablation and Incidence of Post-Radiofrequency Ablation Syndrome: Prospective Survey Radiology, December 1, 2005; 237(3): 1097 - 1102. [Abstract] [Full Text] [PDF]