European Journal of Radiology 83 (2014) 632–638
Contents lists available at ScienceDirect
European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Percutaneous treatment of hepatocellular carcinoma in patients with cirrhosis: A comparison of the safety of cryoablation and radiofrequency ablation Ruth M. Dunne a , Paul B. Shyn a,∗ , Jeffrey C. Sung a , Servet Tatli a , Paul R. Morrison a , Paul J. Catalano b,c , Stuart G. Silverman a 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
a r t i c l e
i n f o
Article history: Received 12 September 2013 Received in revised form 31 December 2013 Accepted 3 January 2014 Keywords: Ablation techniques Carcinoma, Hepatocellular Liver cirrhosis
a b s t r a c t 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 procedures 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 1.5 (corrected) Thrombocytopenia 5 cm Tumor location Tumor location (Couinaud segments in relation to diaphragm) IVA, VII, VIII (near diaphragm) I, II, III, IVB, V, VI Minimum distance to 1st, 2nd, or 3rd order portal vessels and bile ducts 1 cm Minimum distance to diaphragm 2 cm Minimum distance of applicator to aerated lung 2 cm Ablation zone cross-sectional area Axial ablation areaa (cm2 ) Ablation area (cm2 , median, range)
39
39
1.0 0.34
28/33 (84.8) 4/33 (12.1) 1/33 (3)
22/30 (73.3) 7/30 (23.3) 1/30 (3.3)
2.9 ± 0.84 2.8, 1.5–4.9 27/39 (69.2) 12/39 (30.7) 0/39 (0)
2.3 ± 1.17 2, 0.4–6.3 30/39 (76.9) 8/39 (20.5) 1/39 (2.6)
26/39 (66.7) 13/39 (33.3)
18/39 (46.2) 21/39 (53.8)
9/39 (23.1) 30/39 (76.9)
7/39 (17.9) 32/39 (82.1)
19/39 (48.7) 20/39 (51.3)
18/39 (46.2) 21/39 (53.8)
20/39 (51.3) 19/39 (48.7)
9/39 (23.1) 30/39 (76.9)
19.24 ± 16.12 13.35, 1.98–60.04
13.92 ± 8.62 11.56, 4.71–51.15
0.0022** 0.61
0.11
0.78
1.0
0.02**
0.001**
RF, radiofrequency. Values are numbers or fractions with percentages in parentheses. a Values represent mean ± standard deviation. ** Values indicate statistical significance.
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 ablation 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 ( × 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 followup after ablation was 500.7 days ± SD 84.7, median 361; range 8–1429.
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 confounding 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 compare 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 complication 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 independent of ablation group for a statistically significant association. All statistical analyses were performed using Stata statistical software package (version 12). A P-value 1000 g/L and biliary injury. Myoglobulinemia was seen following three (9%) of 33 cryoablation procedures; all three patients received d-mannitol and sodium bicarbonate prophylactically per protocol. Of these patients, two developed transient acute renal insufficiency with post-procedure peak serum creatinine of 2.01 mg/dl in one patient, and 2.12 mg/dl in the other; both patients’ laboratory values normalized within two days. Myoglobulinemia 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 following 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 transfusions 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 prophylactically; external air had entered the pleural space through the applicator track. In the other two cases, intra-procedural pneumothoraces were potentially related to lung puncture and required chest tube insertion.
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R.M. Dunne et al. / European Journal of Radiology 83 (2014) 632–638
Table 5 Comparison of complication rates following percutaneous image-guided ablation of hepatocellular carcinoma in patients with cirrhosis. Parameter
Cryoablation
RF ablation
P-value
Procedures with complications (overall) Procedures with complications by highest severity (Accordion Complication Severity Scale) 1 = mild 2 = moderate 3 = severe 4 = death Number of hospital days in patients with complicationsa Specific complications grouped by severity Level 1: mild Periprocedural pain requiring additional day(s) of hospitalization Pulmonary edema Urinary retention Myoglobinemia Myoglobinemia and acute renal failure Frostbite at skin cryoprobe insertion Pneumothorax with prophylactic chest drain insertion (no lung puncture) Bile duct stricture Biloma Ascites Rectus sheath hematoma Level 2: moderate Thrombocytopenia
Contents lists available at ScienceDirect
European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Percutaneous treatment of hepatocellular carcinoma in patients with cirrhosis: A comparison of the safety of cryoablation and radiofrequency ablation Ruth M. Dunne a , Paul B. Shyn a,∗ , Jeffrey C. Sung a , Servet Tatli a , Paul R. Morrison a , Paul J. Catalano b,c , Stuart G. Silverman a 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
a r t i c l e
i n f o
Article history: Received 12 September 2013 Received in revised form 31 December 2013 Accepted 3 January 2014 Keywords: Ablation techniques Carcinoma, Hepatocellular Liver cirrhosis
a b s t r a c t 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 procedures 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 1.5 (corrected) Thrombocytopenia 5 cm Tumor location Tumor location (Couinaud segments in relation to diaphragm) IVA, VII, VIII (near diaphragm) I, II, III, IVB, V, VI Minimum distance to 1st, 2nd, or 3rd order portal vessels and bile ducts 1 cm Minimum distance to diaphragm 2 cm Minimum distance of applicator to aerated lung 2 cm Ablation zone cross-sectional area Axial ablation areaa (cm2 ) Ablation area (cm2 , median, range)
39
39
1.0 0.34
28/33 (84.8) 4/33 (12.1) 1/33 (3)
22/30 (73.3) 7/30 (23.3) 1/30 (3.3)
2.9 ± 0.84 2.8, 1.5–4.9 27/39 (69.2) 12/39 (30.7) 0/39 (0)
2.3 ± 1.17 2, 0.4–6.3 30/39 (76.9) 8/39 (20.5) 1/39 (2.6)
26/39 (66.7) 13/39 (33.3)
18/39 (46.2) 21/39 (53.8)
9/39 (23.1) 30/39 (76.9)
7/39 (17.9) 32/39 (82.1)
19/39 (48.7) 20/39 (51.3)
18/39 (46.2) 21/39 (53.8)
20/39 (51.3) 19/39 (48.7)
9/39 (23.1) 30/39 (76.9)
19.24 ± 16.12 13.35, 1.98–60.04
13.92 ± 8.62 11.56, 4.71–51.15
0.0022** 0.61
0.11
0.78
1.0
0.02**
0.001**
RF, radiofrequency. Values are numbers or fractions with percentages in parentheses. a Values represent mean ± standard deviation. ** Values indicate statistical significance.
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 ablation 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 ( × 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 followup after ablation was 500.7 days ± SD 84.7, median 361; range 8–1429.
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 confounding 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 compare 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 complication 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 independent of ablation group for a statistically significant association. All statistical analyses were performed using Stata statistical software package (version 12). A P-value 1000 g/L and biliary injury. Myoglobulinemia was seen following three (9%) of 33 cryoablation procedures; all three patients received d-mannitol and sodium bicarbonate prophylactically per protocol. Of these patients, two developed transient acute renal insufficiency with post-procedure peak serum creatinine of 2.01 mg/dl in one patient, and 2.12 mg/dl in the other; both patients’ laboratory values normalized within two days. Myoglobulinemia 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 following 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 transfusions 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 prophylactically; external air had entered the pleural space through the applicator track. In the other two cases, intra-procedural pneumothoraces were potentially related to lung puncture and required chest tube insertion.
636
R.M. Dunne et al. / European Journal of Radiology 83 (2014) 632–638
Table 5 Comparison of complication rates following percutaneous image-guided ablation of hepatocellular carcinoma in patients with cirrhosis. Parameter
Cryoablation
RF ablation
P-value
Procedures with complications (overall) Procedures with complications by highest severity (Accordion Complication Severity Scale) 1 = mild 2 = moderate 3 = severe 4 = death Number of hospital days in patients with complicationsa Specific complications grouped by severity Level 1: mild Periprocedural pain requiring additional day(s) of hospitalization Pulmonary edema Urinary retention Myoglobinemia Myoglobinemia and acute renal failure Frostbite at skin cryoprobe insertion Pneumothorax with prophylactic chest drain insertion (no lung puncture) Bile duct stricture Biloma Ascites Rectus sheath hematoma Level 2: moderate Thrombocytopenia
