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Published online before print June 2, 2008, 10.1148/radiol.2482071690

(Radiology 2008;248:670.)

A more recent version of this article appeared on August 1, 2008
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© RSNA, 2008

Vascular and Interventional Radiology

Subcapsular Liver Tumors Treated with Percutaneous Radiofrequency Ablation: A Prospective Comparison with Nonsubcapsular Liver Tumors for Safety and Effectiveness1

Sergio Sartori, MD, Paola Tombesi, MD, Francesca Macario, MD, Ingrid Nielsen, MD, Davide Tassinari, MD, Mirella Catellani, MD, and Vincenzo Abbasciano, MD

1 From the Section of Interventional Ultrasound, Department of Internal Medicine (S.S., P.T., I.N., M.C., V.A.), and Gastroenterology Unit (F.M.), St Anna Hospital, corso Giovecca 203, 44100 Ferrara, Italy; and Oncology Unit, City Hospital, Rimini, Italy (D.T.). Received September 25, 2007; revision requested November 14; revision received November 22; accepted January 15, 2008; final version accepted January 30. Address correspondence to S.S. (e-mail: srs{at}unife.it).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATIONS FOR PATIENT CARE
 References
 
Purpose: To assess the safety and effectiveness of percutaneous radiofrequency (RF) ablation of subcapsular liver tumors.

Materials and Methods: The study protocol was approved by the institutional review board, and all patients gave written informed consent. One hundred eighty-one patients (79 men, 102 women; age range, 36–85 years) underwent ultrasonographically (US) guided percutaneous RF ablation of 361 primary or secondary (metastatic) liver tumors. Forty-four patients had one or more subcapsular nodules (group 1), and 137 had nonsubcapsular nodules only (group 2). Overall, 80 nodules were subcapsular and 281 were nonsubcapsular. The completeness of the ablation was assessed with contrast material–enhanced computed tomography (CT) 1 month after RF ablation. If residual tumor was documented, RF ablation was repeated. All patients in whom the ablation was complete after the first or second ablation session were monitored with CT or contrast-enhanced US every 3 months. Major complication, complete ablation, and local tumor progression rates were compared by using the {chi}2 test or Fisher exact test.

Results: Three (7%) major complications (intraperitoneal bleeding, skin burn, and tumor seeding) occurred in group 1, and two (1.5%) cases of tumor seeding occurred in group 2 (P = .093). No RF ablation–related deaths occurred. The complete ablation rate was 98% (43 of 44 patients) in group 1 and 98.5% (135 of 137 patients) in group 2 (P = .756). The local tumor progression rate after a median follow-up of 25 months (range, 13–54 months) was 16% (seven of 43 patients) in group 1 and 9.6% (13 of 135 patients) in group 2 (P = .355).

Conclusion: The difference in major complication rate between the subcapsular and nonsubcapsular liver tumors was not significant. The safety of RF ablation of subcapsular tumors seems acceptable, and the effectiveness is comparable to that of RF ablation of nonsubcapsular tumors.

© RSNA, 2008


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATIONS FOR PATIENT CARE
 References
 
Percutaneous radiofrequency (RF) ablation is widely accepted as an effective treatment for liver tumors when surgery is not indicated. It provides excellent local tumor control and has a good safety profile (1–7). Some years ago, a high prevalence (12.5%) of tumor seeding in the needle track in patients with subcapsular lesions was reported (8). Although this report was widely questioned (9–12), other studies have suggested that subcapsular tumors and tumors abutting hollow viscera are associated with an increased rate of major complications (13–17). Conversely, investigators in a retrospective study reported a low risk of seeding in a nonselect group of patients (18), and a prospective study showed comparable morbidity after RF ablation between subcapsular and nonsubcapsular tumors (19). On the basis of these conflicting reports, the indications for RF ablation are not yet clearly established, and a subcapsular tumor location is considered a contraindication to RF ablation by some groups, whereas other groups do not exclude subcapsular tumors for RF ablation.

Before December 2002, in our internal medicine department RF ablation was performed in only those patients with nonsubcapsular tumors, and no major complications were observed. In 2003, less strict criteria for performing RF ablation were adopted, and we planned a prospective study, the purpose of which was to evaluate the safety and effectiveness of percutaneous RF ablation of subcapsular liver tumors.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATIONS FOR PATIENT CARE
 References
 
Patient Selection
The study protocol was approved by the institutional review board of St Anna Hospital, and all patients gave written informed consent before being enrolled. Between January 2003 and June 2006, 181 consecutive patients with inoperable hepatocellular carcinoma (HCC) or metastasis to the liver who were selected to undergo percutaneous RF ablation were assigned to one of two groups: Group 1 included those patients with one or more subcapsular nodules near the stomach, bowel, liver dome, diaphragm, and/or abdominal wall. Subcapsular nodule was defined as a lesion located less than 1 cm from the liver edge. This group also included some patients who had other, nonsubcapsular lesions in addition to the subcapsular nodules and underwent RF ablation. Patients in group 2 had nonsubcapsular nodules only.

The diagnosis of malignancy was obtained by using two imaging techniques—usually triphasic contrast material–enhanced computed tomography (CT) and low mechanical index contrast-enhanced ultrasonography (US)—with concordant findings. The contrast-enhanced CT and US images were interpreted by physicians and radiologists (S.S., P.T., F.M.) with at least 5 years experience with these modalities. When the CT and US findings were not concordant, biopsy of the lesion(s) was performed to obtain the diagnosis. The criteria for RF ablation eligibility were as follows: up to three nodules with diameters of up to 5 cm; tumor location at least 0.5 cm from the gallbladder, the main, left, or right hepatic duct, or the main vessels; no evidence of adhesions to hollow viscera; Child-Pugh class A or B liver cirrhosis; absence of neoplastic portal venous thrombosis, refractory ascites, and extrahepatic disease; platelet count greater than or equal to 50 000 cells per cubic millimeter and prothrombin activity of greater than or equal to 50%; age younger than 85 years; and written informed consent for RF ablation.

RF Ablation Technique
Before performing RF ablation, we assessed tumor vascularity with contrast-enhanced US so that we could compare the vascularity patterns seen before the ablation with those seen at the end of ablation. Vascularity was subjectively quantified on the basis of the intensity of arterial phase enhancement of the tumor compared with that of the surrounding parenchyma (hypervascular, isovascular, or hypovascular), and the pattern of enhancement was classified as diffuse (either homogeneous or heterogeneous) or rim. An 8 µL/mL solution of BR1 (SonoVue; Bracco, Milan, Italy), sulfur hexafluoride microbubbles stabilized by a phospholipid shell, was used as the US contrast agent. After a bolus injection of 2.4 mL of BR1 followed by a 5-mL saline flush, contrast-enhanced US was performed with a contrast-specific nonlinear technique by using an Esaote Esatune system (Esaote, Genova, Italy) according to the standard protocol recommended by the European Federation of Societies for Ultrasound in Medicine and Biology (20). RF ablation was usually performed after local anesthesia and conscious sedation were induced in the patient by means of intravenous administration of midazolam combined with ramifentanil. General anesthesia was reserved for patients whose tumors were strictly abutting the capsular surface of the liver to avoid the risk of interrupting the procedure because of intolerable pain.

All RF ablation procedures were performed with US (SSA-370; Toshiba Medical Systems, Tokyo, Japan) guidance by one of three experienced physicians (S.S., P.T., or F.M.) who had at least 3 years training in US-guided ablation of liver tumors. All treatments were performed according to a standard protocol by using a cool-tip RF system (Radionics, Burlington, Mass). An internally cooled 17-gauge electrode needle with a 2- or 3-cm exposed tip was used to treat tumors up to 3 cm in diameter. Multiple overlapping ablations with the 3-cm exposed tip were performed when the tumor diameter exceeded 3 cm, with a 3-cm diameter of necrosis estimated for each single ablation. A safety margin of 1 cm beyond the lesion's edge was planned for all lesions that did not meet our definition of subcapsular nodule (ie, less than 1 cm from the liver capsule). We maintained a temperature lower than 20°C at the electrode tip by continuously infusing the needle lumen with cold saline. The ablations were performed in an automatic impedance control mode, in which the RF current was adjusted according to the impedance measured at the needle tip. Each ablation cycle lasted 10–12 minutes. The tumors were punctured obliquely through a layer of nontumorous tissue, whenever the lesion location made it possible.

After ablation, the needle was withdrawn slowly (for 5–10 seconds) and the needle track was thermocoagulated by continuing the RF current. If the tumor location did not allow the needle to be passed through a layer of nontumorous tissue, the needle track was not thermocoagulated. If the tumor was adjacent to hollow viscera (Fig 1a) and could not be displaced with a safe margin of at least 2 cm by positioning the patient in an oblique or lateral position, 5% dextrose was intraperitoneally instilled around the liver to displace the hollow viscera (Fig 1b) (6,17). Patients who had diabetes or a condition predisposing them to biliary tract colonization were given prophylactic intravenous cefoperazone (2 g) 2 hours before the RF ablation. The completeness of the ablation was assessed with contrast-enhanced US within 10 minutes after the end of RF ablation (Fig 2). If residual viable foci were identified (Fig 3a), the electrode needle was inserted into the foci with US guidance and the foci were ablated as previously described (Fig 3b, 3c).


Figure 1A
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  		Figure 1a: Oblique subcostal sonograms of left liver lobe show exophytic nodule (arrows) of liver segment II abutting transverse colon. (a) A small ascites is present, but it is not enough to achieve a safe margin between the nodule and the colon. (b) After intraperitoneal instillation of 5% dextrose, the nodule is surrounded by a large ascites and thus can be ablated without risk of thermal injury to the colon.

 

Figure 1B
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  		Figure 1b: Oblique subcostal sonograms of left liver lobe show exophytic nodule (arrows) of liver segment II abutting transverse colon. (a) A small ascites is present, but it is not enough to achieve a safe margin between the nodule and the colon. (b) After intraperitoneal instillation of 5% dextrose, the nodule is surrounded by a large ascites and thus can be ablated without risk of thermal injury to the colon.

 

Figure 2A
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  		Figure 2a: Oblique subcostal contrast-enhanced sonograms of right liver lobe obtained during arterial phase. (a) On sonogram obtained before RF ablation, an enhancing HCC (arrows) is visible in liver segment VII. (b) Sonogram obtained 5 minutes after RF ablation shows large area of complete absence of enhancement (arrows), which indicates complete ablation.

 

Figure 2B
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  		Figure 2b: Oblique subcostal contrast-enhanced sonograms of right liver lobe obtained during arterial phase. (a) On sonogram obtained before RF ablation, an enhancing HCC (arrows) is visible in liver segment VII. (b) Sonogram obtained 5 minutes after RF ablation shows large area of complete absence of enhancement (arrows), which indicates complete ablation.

 

Figure 3A
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  		Figure 3a: Oblique subcostal contrast-enhanced sonograms of right liver lobe obtained after RF ablation of HCC in liver segment VI. (a) Arterial phase sonogram shows residual enhancing viable area (arrows) at periphery of ablated lesion (outlined). (b) Arterial phase sonogram shows electrode needle (arrows) inserted into viable area. (c) Sonogram obtained 5 minutes after RF ablation of residual viable area shows complete absence of enhancement (arrows).

 

Figure 3B
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  		Figure 3b: Oblique subcostal contrast-enhanced sonograms of right liver lobe obtained after RF ablation of HCC in liver segment VI. (a) Arterial phase sonogram shows residual enhancing viable area (arrows) at periphery of ablated lesion (outlined). (b) Arterial phase sonogram shows electrode needle (arrows) inserted into viable area. (c) Sonogram obtained 5 minutes after RF ablation of residual viable area shows complete absence of enhancement (arrows).

 

Figure 3C
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  		Figure 3c: Oblique subcostal contrast-enhanced sonograms of right liver lobe obtained after RF ablation of HCC in liver segment VI. (a) Arterial phase sonogram shows residual enhancing viable area (arrows) at periphery of ablated lesion (outlined). (b) Arterial phase sonogram shows electrode needle (arrows) inserted into viable area. (c) Sonogram obtained 5 minutes after RF ablation of residual viable area shows complete absence of enhancement (arrows).

 
After RF ablation, all patients remained in the hospital overnight and their vital signs were monitored. The next morning clinical examination, complete blood cell count, and US examination of the abdomen and pleural space (to exclude the presence of pleural effusion or pneumothorax) were performed, and if the patient was considered to be well, he or she was discharged in the afternoon.

Data Collection and Outcome Measures
All patients were followed up until death, study dropout, or time of data analysis (July 31, 2007). The patients underwent contrast-enhanced CT 1 month after RF ablation and were successively monitored with alternating CT and contrast-enhanced US every 3 months. A high level of concordance between contrast-enhanced US and CT findings, especially those seen during the arterial phase, has been reported recently (21). Moreover, contrast-enhanced US seems to be more accurate than contrast-enhanced CT in depicting the portal venous phase washout of contrast material in some malignant lesions (21,22) and is considered a cost-effective imaging method for assessing the therapeutic response to percutaneous ablative therapies (23).

Major complication, complete ablation, and local tumor progression rates; treatment-related mortality; and distant intra- and extrahepatic recurrences were recorded. Major complications were defined as complications that may threaten the patient's life, lead to substantial morbidity and/or disability, result in hospital admission, or substantially lengthen hospital stay (16,24). Treatment-related mortality was defined as any death due to RF ablation–related complications. Complete ablation was defined as the absence of any enhancing lesion (indicating residual tumor) at the ablation site, as assessed at CT performed 1 month after RF ablation. The patients with incomplete ablation underwent repeat RF ablation. If complete ablation was then achieved, the patients continued to be monitored. If complete ablation was not achieved, the patients underwent other treatments and were excluded from further analysis. Local tumor progression was defined as the appearance of viable tumor foci within or at the periphery of the ablated lesion at contrast-enhanced CT or US after complete ablation was documented at the first CT examination performed after the initial or repeat ablation. Distant intra- or extrahepatic recurrences that occurred without evidence of local progression were treated with RF ablation or other therapies, and monitoring was continued according to the study design, until documentation of local progression or death.

Statistical Analyses
The patient and tumor characteristics of the two groups were compared by using the Fisher exact test if the characteristics were considered categorical variables. If the characteristics were continuous data, they were expressed as medians and ranges and were compared by using the Mann-Whitney test. All outcome measures were compared between the two groups by using the {chi}2 test or Fisher exact test, where appropriate. Comparisons were made by considering HCCs and metastases together in an overall analysis or by analyzing the HCCs and metastases separately. Moreover, comparisons were made by considering either the number of patients or the number of nodules. Distant recurrence-free survivals were computed by using the Kaplan-Meier method and were compared between the two groups by using the log-rank test. All statistical analyses were performed by using a statistical software program (SPSS10; SPSS, Chicago, Ill). P < .05 was considered to indicate a significant difference.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATIONS FOR PATIENT CARE
 References
 
One hundred eighty-one patients with 361 nodules were enrolled in the study. Forty-four patients were included in group 1, and 137 patients were included in group 2. In 31 (17.1%) patients, the CT and contrast-enhanced US findings were not concordant and the diagnosis of malignancy was obtained at US-guided biopsy. Biopsy was performed in seven patients in group 1 and in 24 patients in group 2 (P = .916). Overall, 80 nodules were subcapsular and 281 nodules were nonsubcapsular. Patient and tumor characteristics are detailed in Tables 1 and 2, respectively. The two patient groups were well matched in age, sex, proportions of HCC and metastatic lesions, and proportions of solitary and multiple tumors. No significant differences in tumor size, number of tumors greater than 3 cm in diameter that required additional overlapping ablations, or proportions of HCC and metastatic lesions were observed between the subcapsular and nonsubcapsular nodules. In three cases, an artificial ascites was needed to displace hollow viscera. The needle track could be thermocoagulated for 63 of the 80 subcapsular tumors and for all 281 nonsubcapsular tumors. The needle track could not be thermocoagulated for 17 subcapsular lesions, which were located in the lateral and superficial surfaces of the liver. General anesthesia was induced in two patients in group 1 and one patient in group 2; this subject refused conscious sedation (P = .147).


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  		Table 1. Baseline Characteristics of Patients in Groups 1 and 2

 

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  		Table 2. Characteristics of Tumor Nodules

 
Five major complications were observed in five (2.8%) patients: One case of intraperitoneal bleeding and two cases of subcutaneous tumor seeding occurred in three patients with HCC, and one case each of skin burn and peritoneal tumor seeding occurred in two patients with metastasis from colon cancer (P = .889). One case each of intraperitoneal bleeding, skin burn, and subcutaneous seeding occurred in three (7%) of the 44 patients in group 1. One case each of subcutaneous tumor seeding and peritoneal tumor seeding occurred in two (1.5%) of the 137 patients in group 2 (Table 3). We observed no significant differences between the two groups either when we analyzed major complications according to group or when we compared the HCC and metastatic lesions.


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  		Table 3. Major Complications Observed in Two Patient Groups

 
Intraperitoneal bleeding occurred in a patient with a 5-cm-diameter exophytic mass of the right lobe (Fig 4). In this patient, complete ablation required three needle insertions and the needle tracks could not be thermocoagulated. The bleeding was self limiting and was managed by transfusing three units of packed red blood cells. A patient with a superficial lesion of the right lobe had a skin burn, which was treated conservatively and healed after 20 days. We found it surprising that the burn did not occur at the grounding pad site but rather adjacent to the metallic needle guide bracket attached to the transducer. This device had previously been used uneventfully in many procedures; however, after the skin burn occurred, it was replaced with nonmetallic brackets. One case of tumor seeding occurred after the RF ablation of a superficial tumor for which needle track thermocoagulation could not be achieved. Two cases of seeding occurred even though the needle track was thermocoagulated. All tumor seedings were surgically removed.


Figure 4
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  		Figure 4: Oblique subcostal contrast-enhanced sonogram of right liver lobe obtained the day after RF ablation of large exophytic nodule encompassing liver segments IV and V. Complete ablation required three electrode needle insertions, and two needle tracks (arrows) were still highly visible in the nodule. It was not possible to puncture the tumor through a layer of nontumorous tissue, so the needle tracks could not be thermocoagulated after ablation. Self-limiting intraperitoneal bleeding developed 3 hours after RF ablation.

 
No treatment-related deaths occurred in either nodule group. The overall major complication rate was 1.4% (five of 361 nodules), and the difference between the subcapsular (three [4%] of 80) and nonsubcapsular (two [0.7%] of 281) tumors approached but did not reach significance (P = .074). No significant difference in major complication rate was observed when the HCC and metastatic lesions were analyzed separately (P = .177 and P = .560, respectively).

Contrast-enhanced US performed immediately after RF ablation depicted residual viable foci in 13 (16%) of the 80 subcapsular tumors and 39 of the 281 (13.9%) nonsubcapsular tumors (P = .863). These residual viable foci were immediately treated with additional contrast-enhanced US-guided RF ablation. Complete ablation was depicted in 39 of the 44 patients in group 1 and in 128 of the 137 patients in group 2 at CT performed 1 month after RF ablation (P = .477). No significant difference in complete ablation rate was observed at comparison of the high-risk (subcapsular) and low-risk (nonsubcapsular) nodules (P = .180). With repeat treatment in the patients with incomplete ablation (five patients in group 1, nine patients in group 2), overall complete ablation was achieved in 43 of the 44 patients in group 1 and in 135 of the 137 patients in group 2 (P = .756), yielding a total of 79 high-risk and 276 low-risk nodules (Table 4). The mean number of treatment sessions was 1.11 for group 1 and 1.07 for group 2; corresponding mean numbers of electrode placements were 2.85 ± 1.43 (standard deviation) and 2.94 ± 1.52, respectively.


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  		Table 4. Complete Ablation Rates in Patient and Nodule Groups after Initial Complete Ablation or Re-treatment of Residual Foci

 
The overall median follow-up period was 25 months (range, 13–54 months), with median follow-up periods of 24 months (range, 13–50 months) and 26 months (range, 13–54 months) for groups 1 and 2, respectively (P = .80). By the time of data analysis, local tumor progression had occurred in 20 of 178 patients: seven in group 1 and 13 in group 2 (P = .355). Local tumor progression was observed in nine subcapsular and 22 nonsubcapsular nodules (P = .469) (Table 5). The median time to distant intra- and extrahepatic progression was 28 months (range, 3–50 months) in group 1 and 27 months (range, 7–54 months) in group 2 (P = .74) (Fig 5). No significant difference in time to tumor progression was observed when the patients with HCC (P = .54) (Fig 6) and the patients with metastasis (P = .71) (Fig 7) were analyzed separately.


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  		Table 5. Local Tumor Progression Rates in Patient and Nodule Groups after Initial Complete Ablation or Retreatment of Residual Foci

 

Figure 5
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  		Figure 5: Graph shows distant intra- and extrahepatic tumor recurrence curves for patients with one or more subcapsular tumors (group 1) and patients with nonsubcapsular tumors only (group 2) (P = .74).

 

Figure 6
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  		Figure 6: Graph shows distant intra- and extrahepatic tumor recurrence curves for patients with subcapsular HCCs and patients with nonsubcapsular HCCs (P = .54).

 

Figure 7
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  		Figure 7: Graph shows distant intra- and extrahepatic tumor recurrence curves for patients with subcapsular metastases and patients with nonsubcapsular metastases (P = .71).

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
ADVANCES IN KNOWLEDGE
 IMPLICATIONS FOR PATIENT CARE
 References
 
Percutaneous RF ablation is a valid treatment for nonresectable liver tumors because of its effectiveness and safety. Major complication rates reportedly range from 2.2% to 10.6%, and mortality rates range from 0.09% to 1.45% (14,16,25,26). Our results—a major complication rate of 2.8% and a mortality rate of 0%—confirm the good safety profile of RF ablation. Subcapsular tumors and tumors abutting hollow viscera are considered to be associated with an increased risk of complications (5,8,13,14–16,24,27). The inability to thermocoagulate the needle track after RF ablation of some subcapsular nodules may be associated with a risk of bleeding and tumor seeding (9,16,19,24,27). Thermal injury and difficulty placing the electrode needle correctly in tumors strictly abutting the liver dome may increase the risk of thoracic and diaphragmatic complications (16,24). The thermal injury that results from treating subcapsular lesions adjacent to hollow viscera may cause gastrointestinal perforation (15,16,17,24). For subcapsular tumors, many authors recommend using open or laparoscopic approaches as safer alternatives to percutaneous RF ablation (16,19,24). However, the open approach is invasive and requires general anesthesia, which can be detrimental to patients with impaired liver function (5,28–30). The laparoscopic approach, although minimally invasive, can be technically demanding during electrode placement because of limited access (5).

The problem of treating liver tumors located in "risky" areas has been downsized in some reports. Investigators in a multicenter study reported a low rate of tumor seeding (12 [0.9%] seedings in 1314 treated patients) in a large series of nonselect patients, and they did not identify subcapsular location as a risk factor for seeding (18). In one study (30), no procedure-related mortality and a major complication rate of 2.4% (1 of 41 tumors) were observed after RF ablation of HCC abutting the gastrointestinal tract, and in another investigation (31), no difference in major complication rate was observed between 12 subcapsular HCCs and 31 nonsubcapsular HCCs. However, these studies were weakened by their retrospective design, and the latter one (31) was also limited by a small sample.

Similar RF ablation–related morbidity with subcapsular and nonsubcapsular HCCs was reported in a prospective study (19), but the major complication rate in both HCC groups was higher (15% [seven of 48 tumors] and 16% [five of 32 tumors], respectively) than those reported by most authors (14,16,25,26). Moreover, 36 (75%) of 48 subcapsular tumors and 20 (62%) of 32 nonsubcapsular tumors were ablated with open or laparoscopic RF ablation, and this discrepancy in ablation approaches might have biased the results. It follows that the role and safety of percutaneous RF ablation of subcapsular liver tumors are not yet clearly established and need to be refined. Our prospective study made some contributions in this regard.

Although both tumor groups (subcapsular and nonsubcapsular) included HCCs and metastases, they were well matched in tumor characteristics, and all procedures were performed percutaneously by using the same technique with US guidance. Moreover, the numbers of treatment sessions and electrode placements, which are considered risk factors for complications (14,16,24,27), were similar in the two groups. No procedure-related deaths occurred, and no significant difference in major complication rate between the two groups was observed. However, unlike mortality, which should always be reported on a per-patient basis, morbidity is more appropriately reported on the basis of the number of ablation sessions or ablated nodules (32,33). Given the number of ablated nodules in our study, the subcapsular tumors showed a trend toward a higher major complication rate compared with the nonsubcapsular tumors, and it is likely that this difference was not significant because the sample was too small. Nevertheless, the prevalence of major complications among the subcapsular tumors (4% [three of 80]) was acceptable and similar to that reported in many studies in which only patients with nonsubcapsular tumors or nonselect patients were enrolled (14,16,25,26).

The complete ablation rate after the first session of RF ablation was slightly but not significantly lower in group 1—probably because of the greater difficulty inserting the needle into the desired position of the subcapsular tumors abutting the liver dome. However, in a prior study (19), the complete ablation rate was quite similar between the subcapsular and nonsubcapsular tumor groups after the second session of treatment.

In addition to facilitating an increased risk of complications, subcapsular tumors and tumors abutting hollow viscera are associated with a higher rate of local tumor progression after RF ablation because of the inability to achieve a 0.5–1.0-cm tumor-free margin (34–36). However, subcapsular location has never been reported as a risk factor of recurrence after surgical resection (37), and there currently is no definitive evidence that the absence of a safety margin on the capsular side of a peripheral tumor increases the local progression rate after RF ablation. A local recurrence rate of 11% (4 of 38 tumors) was reported after RF ablation of HCC abutting the gastrointestinal tract (30), and no substantial difference in local tumor progression was observed in either of two comparisons between subcapsular and nonsubcapsular tumors (19,31). Our study results confirm these findings, although we observed a fairly but not significantly higher local tumor progression rate among the tumors in risky locations.

Reported prevalences of local tumor progression after RF ablation vary—ranging from 1.8% to 26.0% (1,19,30,31,34,35)—probably because there is no standardization of terminology, reporting criteria, or follow-up duration (33). In many previous reports (19,30,31,34,35,38), median follow-ups have ranged from 7 to 18 months, and the highest local tumor progression rate was observed when local tumor progression was loosely defined as any tumor recurrence in the same segment of the ablated nodule (34). By using the definition recommended by the International Working Group on Image-guided Tumor Ablation (33), we calculated an overall local tumor progression rate of 8.7% (31 of 355 nodules) and a rate of 11% (nine of 79 nodules) among the subcapsular nodules. Investigators in a prior study reported a local tumor progression rate of 4% (two of 47 nodules) after RF ablation of subcapsular tumors (19), but the median follow-up duration was shorter than that in our study (13 vs 25 months) and most patients underwent open or laparoscopic RF ablation.

It is unlikely that the presence of both HCCs and metastases in our series influenced the local tumor progression rate. Although RF ablation is considered more effective for HCC than for metastasis (5,6), we observed no substantial difference in local progression between the primary and metastatic tumors in either subcapsular or nonsubcapsular locations. We paid particular attention to obtain a wide tumor-free margin of ablation whenever the tumor location made it possible, whereas most studies reporting a higher local tumor progression rate with metastases were conducted in the late 1990s, when the potential usefulness of a safety margin was not yet fully understood (38–41). In a more recent report, no difference in local tumor progression rate was observed between HCCs and metastases (42).

Our study had some limitations. First, we could not determine whether the two groups were well matched for tumor grade because not all patients underwent biopsy. Because needle track seeding may be related to poor tumor differentiation (8), we could not exclude some degree of bias in the comparison of track seeding rates. Second, although our median follow-up period was fairly long (25 months), follow-up periods ranged from 13 to 54 months. Consequently, in some cases the follow-up period may not have been long enough for the seedings to grow to a detectable size. Finally, overall survival was not included in the analysis of outcome measures because the aim of our study was to evaluate the safety and effectiveness of percutaneous RF ablation of subcapsular liver tumors. Technique effectiveness is determined on the basis of the rate of local tumor progression (33), and local tumor progression is largely determined on the basis of the completeness of ablation (5). Overall survival, on the other hand, depends on many other additional variables, such as biologic features of the tumor, development of distant intra- and extrahepatic recurrences, response to alternative or combined treatments, comorbidity, and residual liver function.

In conclusion, our study results suggest that the subcapsular location (less than 1 cm from the capsule) of a liver tumor—whether an HCC or a metastasis—should not be considered a contraindication to percutaneous RF ablation, provided it is performed by physicians who are well experienced in the RF ablation of hepatic lesions. Major complication and local tumor progression rates may be higher with subcapsular tumors than with nonsubcapsular tumors, but they are acceptable. Further prospective studies are needed to determine whether the clinical benefit of the local tumor control achieved with percutaneous RF ablation in these settings is comparable to that achieved with other recommended approaches, such as open and laparoscopic RF ablation.


   ADVANCES IN KNOWLEDGE
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
IMPLICATIONS FOR PATIENT CARE
 References
 


   IMPLICATIONS FOR PATIENT CARE
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATIONS FOR PATIENT CARE
References
 


   FOOTNOTES
 

Abbreviations: HCC = hepatocellular carcinoma • RF = radiofrequency

Author contributions: Guarantors of integrity of entire study, S.S., P.T.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, S.S., P.T., I.N., D.T., M.C.; clinical studies, S.S., P.T., F.M., I.N., M.C., V.A.; statistical analysis, D.T.; and manuscript editing, S.S., P.T., F.M.

Authors stated no financial relationship to disclose.


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATIONS FOR PATIENT CARE
 References
 

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