Percutaneous treatment of hepatocellular carcinoma in patients with cirrhosis: A comparison of the safety of cryoablation and radiofrequency ablation

Materials and methods: This retrospective HIPAA-compliant study received institutional review board approval. Forty-two adult patients with cirrhosis underwent image-guided percutaneous ablation of hepatocellular carcinoma from 2003 to 2011.

 

Ruth M. Dunnea, Paul B. Shyna,∗, Jeffrey C. Sunga, Servet Tatlia, Paul R. Morrisona,

Paul J. Catalanob,c, Stuart G. Silvermana

a Division of Abdominal Imaging and Intervention, Department of Radiology, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115,

United States

b Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, 450 Brookline Avenue, CLSB 11007, Boston, MA 02215, United States

c Department of Biostatistics, Harvard School of Public Health, Boston, MA 02215, United States

 

Articleinfo

 

Article history:

Received 12 September 2013 Received in revised form

31 December 2013

Accepted 3 January 2014

 

Keywords:

Ablation techniques Carcinoma, Hepatocellular Liver cirrhosis

 

Abstract

 

Purpose: To compare the safety of image-guided percutaneous cryoablation and radiofrequency ablation in the treatment of hepatocellular carcinoma in patients with cirrhosis.

Materials and methods: This retrospective HIPAA-compliant study received institutional review board approval. Forty-two adult patients with cirrhosis underwent image-guided percutaneous ablation of hepatocellular carcinoma from 2003 to 2011. Twenty-five patients underwent 33 cryoablation proce- dures to treat 39 tumors, and 22 underwent 30 radiofrequency ablation procedures to treat 39 tumors. Five patients underwent both cryoablation and radiofrequency ablation procedures. Complication rates and severity per procedure were compared between the ablation groups. Potential confounding patient, procedure, and tumor-related variables were also compared. Statistical analyses included Kruskal–Wallis, Wilcoxon rank sum, and Fisher’s exact tests. Two-sided P-values <0.05 were considered significant.

Results: The overall complication rates, 13 (39.4%) of 33 cryoablation procedures versus eight (26.7%) of 30 radiofrequency ablation procedures and severe/fatal complication rates, two (6.1%) of 33 cryoab- lation procedures versus one (3.3%) of 30 radiofrequency ablation procedures, were not significantly different between the ablation groups (both P = 0.26). Severe complications included pneumothoraces requiring chest tube insertion during two cryoablation procedures. One death occurred within 90 days of a radiofrequency ablation procedure; all other complications were managed successfully.

Conclusion: No significant difference was seen in the overall safety of image-guided percutaneous cryoab- lation and radiofrequency ablation in the treatment of hepatocellular carcinoma in patients with cirrhosis.

 

© 2014 Elsevier Ireland Ltd. All rights reserved.

 

1. Introduction

 

Hepatocellular carcinoma (HCC) is the fifth most common can- cer worldwide leading to an estimated 500,000 deaths per year [1]. Surgical resection or liver transplantation is the preferred treat- ment for HCC but is often precluded by advanced tumor stage, comorbid diseases, or decreased hepatic reserve from coexisting cirrhosis. Transplantation is limited by donor organ availability and tumor-related exclusion criteria [2].

Open, surgical cryoablation was introduced as a treatment option for patients with unresectable liver tumors [3]. However, it was associated with severe complications including hepatic frac- ture leading to hemorrhage and bile leaks, or cryoshock leading to multi-organ failure and disseminated intravascular coagulation [4]. More recently, non-surgical therapies, including percutaneous image-guided thermal ablation have emerged as important alter- native treatments either for definitive therapy or as a bridge to transplantation [5]. As a result, according to the Barcelona Clinic Liver Cancer staging system, percutaneous image-guided tumor ablation is recommended in patients with early-stage HCC, defined as patients with preserved liver function (Child–Pugh A and B) and solitary or up to three HCC nodules, each less than or equal to 3 cm in size, who are unsuitable for surgical resection [6].

Radiofrequency ablation has been the most widely utilized percutaneous ablative technology in the liver [5]. However, improvements in percutaneous cryoablation technology including small diameter (13–17 gauge) cryoablation applicators and the use of intra-procedural CT or MRI monitoring have been realized [7,8]. Despite these developments, a recent review concluded that there was insufficient experience to recommend the use of percutaneous cryoablation in the treatment of HCC [9].

Complications reported following open, surgical cryoablation have led to reluctance in using percutaneous cryoablation to treat HCC [5,10,11].

Potential advantages of cryoablation relative to radiofrequency ablation include precise intraprocedural monitoring of iceball for- mation and dynamic adjustment of iceball shape and size to ensure adequate tumor coverage while avoiding excessively large abla- tion volumes or iceball propagation into adjacent critical structures [7,8]. Also, percutaneous cryoablation may induce less diaphrag- matic injury and post procedural pain when treating hepatic dome tumors [12].

Whether cryoablation or radiofrequency ablation is used, com- plications are of particular concern in patients with cirrhosis who have an increased incidence of hepatic or renal insufficiency and bleeding diatheses [13,14].

To the best of our knowledge a comparative analysis of percuta- neous cryoablation and radiofrequency ablation for the treatment of HCC in patients with underlying cirrhosis has not been reported. More specifically, the perception that percutaneous cryoablation in cirrhotic patients is less safe compared to radiofrequency abla- tion deserves scientific scrutiny given the potential advantages of cryoablation. The purpose of our study was to compare the safety of image-guided percutaneous cryoablation and radiofrequency abla- tion in the treatment of HCC in patients with cirrhosis.

 

2. Materials and methods

 

2.1 Patients and procedures

 

Approval of our institutional review board was obtained for this retrospective study and was conducted in compliance with the Health Insurance Portability and Accountability Act. The need for informed consent was waived.

Initial review of our Division’s liver ablation database from January 2003 to July 2011 identified 273 hepatic ablation proce- dures. Ninety-four ablation procedures were performed to treat HCC. Seventeen ethanol and three microwave ablation procedures were excluded. Of the remaining 74 cryoablation or radiofrequency ablation procedures, 11 were excluded because more than one ther- apeutic technique was used in the same treatment session, e.g. radiofrequency ablation and ethanol or radiofrequency ablation and transarterial chemoembolization. The final cohort included 42 patients (31 men, 11 women) undergoing 63 ablation proce- dures; 33 cryoablation procedures were used to treat 39 tumors in 25 patients and 30 radiofrequency ablation procedures were used to treat 39 tumors in 22 patients. Five patients underwent non- concurrent cryoablation and radiofrequency ablation procedures during the study period and thus were included in both groups. The diagnosis of HCC was based on pathology (n = 37) or imaging criteria as defined by the American Association for the Study of Liver Diseases (n = 5) [15]. All patients had cirrhosis and the diagno- sis of cirrhosis was based on pathology in 22 patients and imaging features in 20 patients [16].

 

Table 1

Comparison of cryoablation and radiofrequency ablation procedures in the percuta- neous image-guided ablation of hepatocellular carcinoma in patients with cirrhosis.

 

All procedures were performed with the intention to completely ablate the targeted tumors. Fifty-two procedures were performed in patients who were not surgical candidates due to unresectable tumor or underlying comorbidities. The remaining 11 procedures were performed for “bridging” to liver transplantation.

Before ablation, laboratory tests were performed to ensure a blood platelet count of 50 109 L–1 or greater and an International Normalized Ratio of 1.5 or less. When indicated, appropriate trans- fusions were administered to correct coagulopathy. Antiplatelet agents were withheld for at least 5 days before intervention.

All tumor ablation procedures were performed by one of three attending abdominal interventional radiologists with 7–12 years ablation experience. Procedures were performed using general anesthesia or moderate intravenous sedation (Table 1). Proce- dures were guided by CT (LightSpeed, GE Healthcare, Milwaukee, WI) or MRI (0.5 T open-configuration Signa SP, GE Healthcare). The cryoablation procedures were performed using an argon- based cryoablation system (CryoHit, Galil Medical, Yokneam, Israel) and 13-gauge or 17-gauge cryoablation applicators. One to seven (median = 3.6) applicators were used to achieve an iceball that com- pletely encompassed the tumor with a 5 mm or greater margin of liver beyond the tumor. Two 15-min freezes separated by a 10-min passive thaw were applied.

The radiofrequency ablation procedures were performed using a 200-W impedance-controlled pulsed-current radiofrequency abla- tion generator (Cool-tip, Covidien, Boulder, CO) and internally cooled 17-gauge electrodes or cluster electrodes in all but one radiofrequency ablation procedure. One radiofrequency ablation was performed using a 200-W radiofrequency ablation generator with an impedance-based feedback system and a single, MR- compatible, 15-gauge electrode (Boston Scientific, Boston, MA). For all radiofrequency ablation procedures, single or multiple overlap- ping 12-min ablations were performed to treat the entire tumor and a minimum 5 mm margin.

All patients were observed overnight. Laboratory testing includ- ing a complete blood count, serum creatinine, aminotransferases, bilirubin and myoglobin at 2, 12, and 24 h after each procedure were obtained. If post-procedural serum myoglobin increased above 1000 µg/L, then d-mannitol (Abbott Laboratories, North Chicago, IL), 0.3 g/kg, and sodium bicarbonate, 150 mEq, in 1 L 5% dextrose water at 150 ml/h were administered for 24 h.

 

2.2 Pre and post-procedure imaging

 

MRI of the abdomen (Signa 1.5 or 3.0 T, GE Healthcare) was performed within one month prior to ablation; and at 24 h, three months, and every 3–6 months after the ablation. MRI sequences included T2-weighted single-shot fast spin-echo, T1-weighted dual-echo fast spoiled gradient-echo (FSGE), and breath-hold three-dimensional FSGE images before and after intravenous injection of 20 ml gadopentetate dimeglumine (Magnevist, Berlex Laboratories, Wayne, NJ). In three patients with renal insuffi- ciency, unenhanced MR images were obtained. CT (LightSpeed, GE Healthcare; or Somatom Volume Zoom, Sensation 16 or 64, Siemens Medical Solutions, Erlangen, Germany) following injec- tion of 80 ml of intravenous contrast material (Ultravist 370 mgI/ml, Bayer Healthcare Pharmaceuticals, Wayne, NJ) was performed in three patients with contraindications to MRI.

 

Table 2

Classification of post-procedural complications following percutaneous ablation of HCC in patients with cirrhosis using accordion severity grading system: contracted classification [22].

 

2.3.Safety assessment

Complication rates and severity were based on the single most severe complication encountered after each procedure. Complications were classified using the Accordion Severity Classi- fication of Postoperative Complications, an updated version of the Clavien–Dindo surgical complication classification (Table 2) [17]. We used this surgical classification system rather than the Soci- ety of Interventional Radiology (SIR) complication classification for image-guided interventional procedures to allow better descrip- tion of the complications we encountered in our study [18,19]. Using this classification system, complications were classified into four categories: mild, moderate, severe, and death; the SIR compli- cation classification scheme has only minor and major complication categories [19]. Also, although the primary outcome of our study was to compare the complication rates and severity of percuta- neous cryoablation to those following radiofrequency ablation in treatment of HCC, the use of a surgical classification system allowed comparison of our results with historical surgical data.

 

2.4 Patient, procedure, and tumor-related variables

 

Patient, procedure, and tumor-related variables that could potentially confound the comparison of safety between cryoab- lation and radiofrequency ablation cohorts were recorded (Tables 3 and 4). Portal hypertension was defined by the presence of at least two of the following imaging criteria: splenomegaly, ascites, varices or dilation of the portal vein exceeding 1.3 cm [20]. To investigate whether complication rates were related to the aggressiveness of the ablations or the extent to which the tumors were ablated, we evaluated post-procedural imaging at 24 h and three months following the procedures. Twenty-four hour post-procedure imaging was evaluated for ablation zone coverage of the tumor with a 5 mm or greater margin of surrounding liver on MRI or CT at 24 h [18]. The region of absent enhancement following radiofrequency ablation or cryoablation was defined as the abla-tion zone. The maximum cross-sectional area of the ablation zone on trans-axial MRI or CT images obtained at 24 h was calculated using the ellipsoid area formula (π × r1 × r2; r1 = long axis radius, r2 = perpendicular short-axis radius). Three month post-procedure imaging was evaluated for evidence of local tumor progression

defined by new or recurrent enhancing nodules in or contiguous with the ablation zone on MRI or CT [18]. The mean clinical follow- up after ablation was 500.7 days SD 84.7, median 361; range 8–1429.

 

Table 3

Comparison of patient-related variables with the potential to impact the safety of percutaneous image-guided ablation of hepatocellular carcinoma in patients with cirrhosis.

 

RF, radiofrequency; HCC, hepatocellular carcinoma; MELD, model for end-stage liver disease; eGFR, estimated glomerular filtration rate; INR, international normalized ratio (prothrombin time).

 

Medication-related coagulopathy indicates patients receiving antiplatelet medication (acetylsalicylic acid 81 mg, Bayer Medical) at the time of procedure. Values are denoted as numbers or fractions with percentages in parentheses.

For categorical variables, percentages were calculated per patient. For continuous variables, percentages were calculated per procedure.

a Values represent mean ± standard deviation.

 

Table 4

Comparison of tumor-related variables with the potential to impact the safety of percutaneous image-guided ablation of hepatocellular carcinoma in patients with cirrhosis.

 

RF, radiofrequency.

Values are numbers or fractions with percentages in parentheses.

a Values represent mean standard deviation.

** Values indicate statistical significance.

 

2.5. Statistical analysis

 

Comparative analyses were performed to evaluate differences in complication rates, severity and type, and to correlate complication rates with 24-h and three month imaging results. Potentially con- founding patient, procedure, and tumor-related variables between the two groups were compared.

The Kruskal–Wallis one-way analysis of variance for multiple groups and Wilcoxon rank sum for two groups were used to com- pare continuous variables including patient age, Child–Pugh and Model for End-Stage Liver Disease (MELD) scores, tumor size and distance to critical structures, ablation area, and complication rates. Fisher’s exact test was used to compare categorical variables such as patient gender, co-morbidities, presence of portal hypertension, and previous local liver-directed therapies. Unadjusted compli- cation risk factor analysis was performed using Fischer’s exact test. Multivariate logistic regression analyses were used to analyze potential contributing risk factors for each complication indepen- dent of ablation group for a statistically significant association. All statistical analyses were performed using Stata statistical software package (version 12). A P-value <0.05 was considered significant.

 

Table 5

Comparison of complication rates following percutaneous image-guided ablation of hepatocellular carcinoma in patients with cirrhosis.

RF, radiofrequency.

Values are fractions with percentages in parentheses.

a Values represent mean standard deviation.

b Biliary injuries, thrombocytopenia and pulmonary edema were compared cumulatively between the two groups. 100-Day follow-up was not available following one cryoablation and two radiofrequency ablation procedures.

 

3.Results

 

3.1.Safety assessment

No significant differences were observed in the overall compli- cation rates, complication rates by severity, or specific complication types between the cryoablation and radiofrequency ablation groups (Table 5). The most common mild complications were myo- globulinemia >1000 µg/L and biliary injury. Myoglobulinemia was seen following three (9%) of 33 cryoablation procedures; all three patients received d-mannitol and sodium bicarbonate prophylac- tically per protocol. Of these patients, two developed transient acute renal insufficiency with post-procedure peak serum creat- inine of 2.01 mg/dl in one patient, and 2.12 mg/dl in the other; both patients’ laboratory values normalized within two days. Myo- globulinemia was not observed following radiofrequency ablation. Three patients developed biliary injury (strictures or biloma), two following radiofrequency ablation and one following cryoablation. All biliary injuries were diagnosed three months after the ablation in asymptomatic patients with normal serum bilirubin values and required no treatment.

Thrombocytopenia ranging from 51 to 86 109 L–1 occurred fol-lowing four (12%) of 33 cryoablation procedures and one (3%) of 30 radiofrequency ablation procedures. Although these patients were asymptomatic with no evidence of hemorrhage, platelet transfu- sions were administered. The decrease in serum platelet counts from pre-procedure levels prompting post-procedure platelet transfusions ranged from 13 to 50 109 L–1.

Pneumothorax was observed in three (9%) of 33 cryoablation procedures and none of the radiofrequency ablation procedures. In one procedure, the pneumothorax occurred immediately followed cryoablation applicator removal and a chest tube was inserted pro- phylactically; external air had entered the pleural space through the applicator track. In the other two cases, intra-procedural pneu- mothoraces were potentially related to lung puncture and required chest tube insertion.

 

One death occurred in a patient with Child–Pugh C cirrho- sis 70 days following radiofrequency ablation. The patient had Child–Pugh B cirrhosis during pre-procedure assessment, how- ever, the patient’s bilirubin rose to 11.7 mg/dl in the interval between the initial assessment and the ablation procedure. The patient’s post-procedure bilirubin rose to 18 mg/dl, then returned to 10.2 mg/dl five weeks after the procedure. Although the patient’s death occurred within 90 days of the procedure and was included as a complication, the death was caused by multi-organ failure due to sepsis following lower extremity osteomyelitis and not by the ablation procedure.

 

3.2.Patient, procedure, and tumor-related variables

There were no significant differences in the patient-related vari- ables between groups (Table 3). With respect to tumor-related variables, the mean tumor size and mean cross-sectional ablation area of the cryoablated tumors were significantly larger than those treated with radiofrequency ablation. The minimum applicator tra- jectory distance to aerated lung was within 2 cm in more tumors treated with cryoablation than with radiofrequency ablation, per- haps explaining the higher pneumothorax rate in the cryoablation group. However, no other significant difference was observed in tumor-related variables between groups (Table 4).

Complication rates were not affected by the extent of tumor treatment between the ablation groups. There was no signifi- cant difference in the number of procedures that demonstrated complete ablation zone coverage between the cryoablation group (38 [97.4%] of 39 tumors treated) and the radiofrequency abla- tion group (36 [92.3%] of 39 tumors treated, P = 0.615). There was also no significant difference in the number of procedures that demonstrated absence of local tumor progression at three months between the cryoablation group (32 [86.5%] of 37 tumors treated) and the radiofrequency ablation group (28 [82.4%] of 34 tumors treated, P = 0.747). Three-month imaging was not available for two tumors treated with cryoablation and for five tumors treated with radiofrequency ablation.

Because the incidence of each individual complication was low, multivariate analysis of potential contributing risk factors associ- ated with specific complications was limited. However, patient, procedure, and tumor-related variables were analyzed as poten- tial contributing risk factors for the most common complications including biliary injury, thrombocytopenia, and pneumothorax. Biliary injury was statistically more likely to occur in tumors less than one centimeter from 1st, 2nd or 3rd order portal vessels and bile ducts (P = 0.009). There was a significant relationship between post-procedure thrombocytopenia and a pre-procedure platelet count of less than 100 109 L–1 (P = 0.033), a relationship that held when adjusted for ablation group (P = 0.01). There was no significant relationship between the incidence of pneumothorax following cryoablation and tumor distance to diaphragm (P = 1.0) or applicator trajectory distance to aerated lung (P = 1.0).

 

4.Discussion

The use of percutaneous cryoablation to treat HCC in cir- rhotic patients has been limited largely by concerns regarding safety. These concerns have been based primarily on data derived from open, surgical cryoablations [4]. One study of open, surgical ablations reported higher complication rates following cryoab- lation (40.7%) compared to radiofrequency ablation (3.3%) [21]. One retrospective study demonstrated similar complication rates following percutaneous cryoablation (29%) compared to percuta- neous radiofrequency ablation (24%), but included both HCC and metastatic liver tumors [22]. This study did not stratify complica- tions based on tumor type or presence of cirrhosis. Moreover, this study, performed over ten years ago, does not reflect improvements in ablation technology that have since occurred including smaller applicator sizes (11-gauge cryoablation applicators and 14-gauge radiofrequency ablation electrodes compared to 17-gauge cryoab- lation applicators and 17-gauge radiofrequency electrodes in our study) and increased radiofrequency ablation generator power (50- W compared to 200-W in our study). As such, our study, including 78 HCC tumors is the largest series that compares percutaneous cryoablation and radiofrequency ablation in patients with proven cirrhosis and HCC.

Our overall complication rates (39.4% versus 26.7%) and rates of severe complications including death (6% versus 3.3%) were similar for the cryoablation and radiofrequency ablation groups, respec- tively. These results are comparable to previously published studies reporting overall complication rates of 8–41% for cryoablation and 19–24% for RF ablation [8,22–24].

The one death observed in this study occurred following radiofrequency ablation in the only patient with Child–Pugh C cir- rhosis. Because of poor hepatic reserve, liver failure and death have previously been reported in patients with Child–Pugh B and C cir- rhosis following a single radiofrequency ablation session [25]. As a result, Child–Pugh C cirrhosis remains a relative contraindica- tion to ablation [25]. While our patient’s death occurred within 90 days of the procedure and was considered a procedure-related complication, the cause of death was not related to the ablation procedure.

One particular concern regarding the use of cryoablation in treating patients with HCC and cirrhosis has been a perceived increased risk of hemorrhage in this potentially coagulopathic pop- ulation. However, we observed no bleeding complications after cryoablation. One animal study identified no significant difference in the degree of hemorrhage encountered after ablation with a sin- gle cryoablation applicator compared to a single radiofrequency applicator [26]. While hepatic fracture and associated hemorrhage have been reported following percutaneous cryoablation, it was not observed in our study and hence the incidence is likely much lower than what has been reported after cryosurgery [4].

When evaluating individual complication types, pneumothorax was more common in the cryoablation group (9.1%) compared to the radiofrequency ablation group (0%). While not statistically sig- nificant, this difference may have been due to the fact that the minimum applicator trajectory distance to aerated lung of 2 cm or less was observed in significantly more tumors treated with cryoablation than with radiofrequency ablation (P = 0.02).

While all patients maintained post-procedure platelet counts above 50 109 dl–1 without signs of hemorrhage, five patients received platelet transfusions as a prophylactic measure for post- procedure platelet count declines ranging from 13 109 L–1 to

50 109 L–1. Thrombocytopenia following cryoablation is thought to reflect a systemic inflammatory response and perhaps platelet sequestration within the cryoablation zone [27]. The severity of thrombocytopenia correlates with the volume of normal liver ablated and the post-procedure serum aspartate aminotransferase (AST) level, a surrogate measure for the degree of hepatocel- lular injury [27]. Thrombocytopenia following radiofrequency ablation is less common but can occur, especially in the set- ting of a preprocedure platelet count of less than 120 109 L–1 [28].

Myoglobulinemia was observed only following cryoablation in our study. Myoglobulinemia can occur after both cryoablation and radiofrequency ablation, but has been thought to be more common after cryoablation with the severity correlating with abla- tion volume [27,28]. While renal failure is an uncommon sequela, early identification and prophylaxis is important especially in patients with cirrhosis and potentially compromised renal function [14].

No cases of cryoshock occurred in our study; this syndrome has a reported incidence of 1% following cryosurgery leading to death in approximately 33% of afflicted patients [4]. Cryoshock is an inflammatory cytokine mediated complication, thought to be unique to cryoablation that consists of pleural effusions, throm- bocytopenia with hemorrhage, myoglobinemia with acute renal failure, and acute respiratory distress syndrome. Cryoshock is likely related to the ablation of large tumors with large ablation volumes. Indeed, cryosurgical series in which cryoshock occurred included the treatment of 10 cm tumors [29]. Our cohort consisted of much smaller tumors with a median axial tumor diameter 2.8 cm, and a range of 1.5–4.9 cm.

Although not statistically significant, biliary injury was more common following radiofrequency ablation than cryoablation. None of the biliary injuries resulted in adverse events or required treatment. Their incidence was significantly associated with prox- imity of the tumor to major bile ducts, a recognized risk factor for biliary injury during both cryoablation and radiofrequency abla- tions [30].

We used a standardized surgical classification scheme instead of the Society of Interventional Radiology (SIR) complication classi- fication for image-guided interventional procedures for two main reasons [17–19]. First, the SIR scheme has only minor and major complication categories and thus the major complication rate would be higher than what we reported and misleading [18,19]. For example, using the SIR classification, overnight observation is considered a minor complication, and a greater than 24-h hospi- talization a major complication. However, we typically admit our patients for overnight observation as a precaution. Furthermore, some of our patients were kept in hospital to manage medical conditions unrelated to the procedure. In addition, blood prod- uct administration is considered a major complication in the SIR classification. However, all patients who developed thrombocy-topenia in our study had platelet levels above 50 109 dl–1 without

signs of hemorrhage, but were administered platelet transfusions prophylactically. Second, the use of the surgical complication clas- sification scheme facilitated comparisons between percutaneous ablative procedures and surgical procedures. Indeed, it has been the experience following open cryosurgery that has largely led to the concerns of the safety of cryoablation relative to radiofrequency ablation.

We acknowledge several limitations of our study. First, our sample size was small, and hence the statistical power was limited. A larger study may have provided the statistical power to better analyze the specific complications and their relation to potential risk factors. However, our study is the only study which specifically compares the safety of percutaneous cryoab- lation and radiofrequency ablation in a focused population of patients with proven cirrhosis and HCC, a group at potentially greater risk of complications. Second, our study was retrospective and therefore subject to selection bias. However, we conducted a thorough analysis of potentially confounding patient, pro- cedure, and tumor-related variables. Despite the larger mean tumor size and corresponding mean ablation zone area in the cryoablation group, a factor that would be expected to result in more complications within the cryoablation group, there was no significant difference in the complication rates. Imaging indicators of treatment aggressiveness based on adequacy of tumor ablation coverage at 24 h and local tumor progression rates at three months also were not significantly different between the two groups. Tumor proximity to the diaphragm or other critical structures, where precise monitoring of the iceball could be advantageous, were expected factors favoring the selection of cryoablation. How- ever, analysis of these and all other potentially confounding patient, procedure, and tumor-related variables revealed that patient selec- tion did not affect our conclusion that the safety of the two procedures was not significantly different. We acknowledge that there may have been other unrecognized confounding variables. Finally, as our cohort included only tumors smaller than 5 cm, we cannot claim that there is no difference in safety between cryoab- lation and radiofrequency ablation when treating larger tumors.

Our current algorithm for ablating HCC tumors in patients with cirrhosis prioritizes the use of RFA or MWA due to shorter aver- age procedure times and lower costs. RFA or MWA is used in patients with baseline renal insufficiency or thrombocytopenia. RFA or MWA is also used to treat multiple tumors or single tumors larger than 5 cm in a single session. Cryoablation is selected when ablation beyond the liver capsule and into the diaphragm or body wall is needed to achieve adequate margins but techniques such as artificial ascites are not feasible, as in the case of tumors near the bare area of liver or when postsurgical adhesions are anticipated. Cryoablation, with its advantage of excellent ice ball visibility on CT or MR, is also preferred when precise monitoring of the abla- tion zone is required to avoid injury to non-displaceable adjacent critical structures such as bowel or large bile ducts. In conclusion, percutaneous cryoablation and radiofrequency ablation can both be performed with a similar degree of safety in the treatment of HCC in patients with cirrhosis. When treating these patients, our data may be helpful in choosing the ablative technology and in post-procedure care.

 

Conflicts of interest

 

The authors or authors’ institutions have no conflicts of interest.

 

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