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Keywords:

  • elderly patients;
  • hepatocellular carcinoma;
  • radiofrequency ablation;
  • survival rate

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

Aim:  This study was conducted to evaluate the efficacy and safety of radiofrequency ablation (RFA) therapy in elderly patients with hepatocellular carcinoma (HCC).

Methods:  Four hundred and sixty-one patients with naïve HCC, including 107 elderly (aged ≥75 years) patients, who were treated with RFA between 2000 and 2007, were enrolled. Baseline characteristics, survival/recurrence rates and complications after RFA were compared between elderly and non-elderly patients.

Results:  In the elderly group, the proportion of men, alcohol consumption, serum alanine aminotransferase and γ-glutamyl transpeptidase levels were significantly lower compared with those in the non-elderly group. There were no differences in Child–Pugh grade and tumor characteristics between the two groups. The cumulative survival rates in the elderly group were 82% at 3 years and 61% at 5 years, which was equivalent to the non-elderly group. Similarly, no differences were observed in recurrence rates. In multivariate analysis, Child–Pugh grade and tumor-related factors were significant factors associated with survival, but age was not. Although elderly patients had more extrahepatic comorbidities, their presence was not a factor associated with survival prognosis or complication after RFA.

Conclusion:  RFA treatment might be safe and effective in elderly patients, as well as non-elderly patients, with HCC.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

HEPATOCELLULAR CARCINOMA (HCC) is one of the most common malignancies worldwide. Hepatitis C virus (HCV) infection is the major cause of HCC in Europe, the USA and Japan.1–3 Among HCC patients investigated between 1992 and 2000, over 70% were HCV-positive. In addition, the proportion of elderly HCC patients is increasing and the average patient age in Japan is rising.4,5 The aging of patients with HCV is the most significant reason for the increasing number of elderly patients with HCC.6 These trends have led to a rising demand for studies of HCC treatment in elderly patients.

Current options for the treatment of HCC consist of surgical resection, transcatheter arterial embolization and percutaneous ablation therapy. Although surgical resection had been considered to be the first choice of treatment,7,8 it plays a limited role in the treatment of HCC because underlying cirrhosis or multiple lesions often contradict surgery. Liver transplantation may be effective in some cases,9 but its feasibility is restricted by the shortage of organ donors. Among various non-surgical therapies, radiofrequency ablation (RFA) was recently introduced and its use has been rapidly increasing worldwide.10–12 RFA therapy for early stage HCC is minimally invasive and highly curative and is a standard treatment along with hepatic resection.13

Elderly patients have a high incidence of comorbid illnesses and are usually considered a high-risk group for major surgery.14,15 RFA treatment may therefore be an acceptable alternative. Because few studies have addressed the outcome of RFA in elderly patients with HCC, we undertook a retrospective cohort study of 107 elderly (aged ≥75 years) patients with HCC who were treated with RFA to assess their clinical characteristics and prognoses.

METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

Study population

The study was conducted in accordance with the Declaration of Helsinki. Written informed consent on the use of clinical records for research purposes was obtained from all subjects. From January 2000 to December 2007, 1278 cases with HCC were treated with RFA in the Department of Internal Medicine, Saga Medical School Hospital and in the Department of Hepatology, Saga Prefectural Hospital. Eight hundred and five patients with recurrent HCC, who had received previous treatment, and 12 patients, who received non-curative RFA as palliative therapy or had any extrahepatic malignancies, were excluded. The remaining 461 patients (264 men, 197 women; age range 38–93 years; mean age 68.2 ± 8.7 years) were enrolled in this study. They consisted of 107 (23.2%) elderly subjects, aged 75 years or over, and 354 non-elderly subjects.

According to the estimate released by the National Cancer Center, Japan, the number of liver cancer mortalities in Japanese persons aged over 75 years increased, whereas that of subjects under 75 years decreased between 2004 and 2008.16 Additionally, the incidence of liver cancer continually increased in Japanese persons over 75 years until 2005, whereas the incidence in persons under 75 years reached its peak in 2003.17 Therefore, we divided subjects into two groups (those <75 years and those ≥75 years) to analyze and discuss the strategy of treatment for elderly HCC patients.

The indication for RFA treatment was that HCC consisted of five or fewer nodules, with each nodule having a maximum diameter of 30 mm, or that HCC consisted of a single tumor, regardless of size, and that hepatic function was not Child–Pugh grade C.

Radiofrequency ablation treatment was applied to cases (n = 226) that were not considered to be suitable for resection for the following reasons: (i) impairment of liver function, and (ii) an excessive number of tumors or cardiopulmonary dysfunction. In addition, we applied RFA in cases (n = 235) where patients chose ablation therapy even though surgery was also feasible. Exclusion criteria for RFA were: (i) total bilirubin concentration over 3 mg/dL; (ii) platelet count under 30 000/mm3; (iii) prothrombin activity under 50%; (iv) ascites that could not be controlled by nutritional therapy and diuretics; and (v) patients with portal vein tumor thrombosis or extrahepatic metastasis. When four or more nodules were detected or the largest nodule was over 3 cm, RFA was preceded by transcatheter arterial chemoembolization (TACE) using epirubicin and gelatin sponge particles.

Diagnosis of HCC

Using combined examinations from ultrasonography and dynamic computed tomography (CT) scans or dynamic magnetic resonance imaging (MRI) or CT during angiography, diagnosis of HCC was confirmed in cases where the contrast pattern of the nodule in CT or MRI was hypervascular in the arterial phase and hypovascular in the portal phase. If the nodules were not consistent with typical contrast patterns for HCC, a needle biopsy of the tumor was taken for pathological diagnosis. The American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) 6th edition staging system for HCC was used for Tumor–Node–Metastasis (TNM) classification.18

RFA

The following three RF systems were used. From January 2000 to March 2000, 25 patients underwent RFA treatment using an RF 2000 generator system (Radio Therapeutics, Mountain View, CA, USA). After a 15-G needle electrode (Le Veen; Boston Scientific, Natick, MA, USA) was inserted into the tumor, 10 expandable hook-shaped electrode tines were expanded and the output of the generator was increased from 50 W to a maximum of 90 W in increments of 10 W/min. Power was applied, either until a sufficient elevation of impedance was obtained or for 15 min. When the elevation of impedance was insufficient, the tip of the needle was moved slightly and then the power distribution was continued using the same method, starting at 70 W.

From April 2000 to August 2000, 65 patients underwent RFA treatment with a model 500PA generator system (Rita Medical Systems, Mountain View, CA, USA). A 15-G needle electrode was inserted into the tumor and four expandable hook-shaped electrode tines (Model 30) with a temperature sensor were expanded. The output was increased to 50 W starting from a default of 10 W in increments of 10 W/30 s. After the temperature of the four electrodes exceeded 80°C, power was applied for 8–10 min. When the increase in resistance was small, the tines were closed and the entire needle was rotated 45°. The tines were then expanded again to continue the power application.

From September 2000 to December 2007, 371 patients underwent RFA with a cool-tip RF system (Radionics, Burlington, MA, USA). A 17-G cooled-tip electrode with a 2- or 3-cm metallic tip was inserted into the tumor and power application was started at 40 W for a 2-cm tip or at 60 W for a 3-cm tip in an impedance control mode while refluxing cold water inside the needle. The electrode was left in place for a total of 12–14 min while the output was increased in increments of 20 W/min until the impedance rolled off or the output reached 140 W. When the impedance increased rapidly after the start of power application, the power application was minimized for 15 s and then restarted at a low output and then gradually increased. After the completion of power application, the refluxing of cold water inside the needle was stopped and the temperature of the tip was measured to confirm that the temperature of the cauterized tissues was at least 65°C. When the target nodule was larger than 2 cm in diameter, we performed multiple ablations.

Evaluation of treatment efficacy and follow up

Complete ablation of the lesion after RFA treatment was assessed in all patients using dynamic CT scans. A diagnosis of complete ablation was made when the lesion was observed as a low density area in both the arterial and portal venous phases on a dynamic CT scan and when the size of the ablated area was greater than the size of the pre-treatment lesion.19 If tumor ablation was incomplete, as determined by the presence of a contrast-enhanced area at an early phase, or if the size of the ablated area was smaller than the pre-treatment lesion, then the patients received an additional treatment until complete ablation of all lesions was confirmed. For follow up, we performed monthly blood tests to assess liver function and to monitor the levels of the tumor markers α-fetoprotein (AFP, latex agglutination method) and des-γ-carboxy-prothrombin (DCP, electro-chemiluminescence immunoassay method). Contrast CT or MRI was also performed every 3–4 months during the follow-up period. When recurrence was observed, appropriate treatment was performed immediately. Intrahepatic HCC recurrence was classified as either tumor recurrence at a site distant from the primary tumor or adjacent to the treated site (local tumor progression).

Comorbidity and complications

Extrahepatic comorbidities were defined as diseases which needed to be followed up and treated before RFA. Major complications were defined as those that, if left untreated, might threaten the patient's life, lead to substantial morbidity and disability or result in hospital admission or substantially lengthen the hospital stay after RFA, according to the previously described guidelines.20 All the other complications were defined as minor. We compared the complication rates per treatment in elderly patients with those in non-elderly patients.

Statistical methods

Comparisons of characteristics were made using the unpaired Student's t-test for continuous variables and the χ2-test for categorical variables. Recurrence rates and survival rates were calculated using the Kaplan–Meier method from the time of initial RFA and compared between groups using the log–rank test. Prognostic relevance of the 10 baseline variables to survival was analyzed by univariate and multivariate Cox proportional hazards regression models. Results of univariate or multivariate analyses are presented as relative risks with corresponding 95% confidence intervals (CI), with P-values from the Wald test. All significance tests were two-tailed and P < 0.05 was considered statistically significant.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

Patient characteristics

The clinical profiles of patients, divided into groups of elderly patients (age ≥75 years) and non-elderly patients (age <75 years), are shown in Table 1. In the elderly group, the proportion of women was significantly higher compared with that in the non-elderly group (47.1% vs 31.2%, respectively; P < 0.001). Concerning extrahepatic comorbidities before RFA, the prevalence of diabetes, hypertension, stroke history, cardiac dysfunction or arrhythmia were not significantly different between the two groups, however, chronic pulmonary diseases (such as chronic obstructive pulmonary disease and bronchial asthma) and renal dysfunction were more frequent in the elderly group compared with the non-elderly group. Patients with habitual alcohol consumption was greater in the non-elderly group compared with the elderly group (P < 0.001).

Table 1.  Clinical characteristics of the patients
 Elderly patientsNon-elderly patientsP-value
(n = 107)(n = 354)
  • Ab, antibody; AFP, α-fetoprotein; ALT, alanine aminotransferase; DCP, des-γ-carboxy prothrombin; HBsAg, hepatitis B surface antigen; HCV, hepatitis C virus; TACE, transcatheter arterial chemoembolization; γ-GTP, γ-glutamyl transpeptidase.

  • a

    Non-B non-C, patients negative for both HBsAg and HCV Ab.

  • b

    Serum AFP-L3 level was measured since April 2002.

Variables
Demography   
 Age (years) (range)78 (75–93)67 (38–74)
 Male, n (%)46 (52.9)218 (68.8)<0.001
Extrahepatic comorbidity   
 Diabetes, n (%)18 (16.8)76 (21.4)0.296
 Hypertension, n (%)32 (29.9)84 (23.7)0.197
 Stroke history, n (%)3 (2.8)11 (3.1)0.876
 Cardiac arrhythmia, n (%)7 (6.5)17 (4.8)0.478
 Cardiac dysfunction, n (%)14 (13.1)28 (7.9)0.103
 Chronic pulmonary disease, n (%)10 (9.3)12 (3.4)0.011
 Renal dysfunction, n (%)8 (7.5)11 (3.2)0.046
History of habitual alcohol consumption   
 (Excessive/habitual/none)9/33/6588/104/162<0.001
 Cause of liver dysfunction  0.026
 HBsAg positive, n (%)1 (1)24 (6.8) 
 HCV Ab positive, n (%)100 (93.4)293 (82.7) 
 HBsAg and HCV Ab positive, n (%)0 (0)7 (2) 
 Non-B/non-C-a6 (5.6)30 (8.5) 
Child–Pugh grade, n   
 A/B/C77/30/0278/76/00.157
Laboratory data, mean (range)   
 Platelet count (×104/µL)10.6 (3.4–29.8)10.0 (3.5–38)0.399
 Prothrombin activity (%)84.7 (57–110)82.1 (51–129)0.103
 Albumin (g/dL)3.6 (2.4–4.8)3.8 (2.0–5.0)0.616
 ALT (IU/L)41.0 (10–265)56.5 (11–363)<0.001
 Total bilirubin (mg/dL)0.9 (0.4–2.2)0.9 (0.2–2.8)0.325
 γ-GTP (IU/L)55 (10–293)64 (13–1445)0.008
Distribution of tumor markers, n (%)   
 Serum AFP (ng/mL)  0.278
  ≤2044 (41.1)180 (50.8) 
  21–10039 (36.4)105 (29.7) 
  101–40013 (12.2)44 (12.4) 
  ≥40111 (10.3)25 (7.1) 
 Serum DCP (mAU/mL)  0.378
  ≤4062 (57.9)218 (61.6) 
  41–10016 (15)66 (18.6) 
  101–40016 (15)42 (11.9) 
  ≥40113 (12.1)28 (7.9) 
 Serum AFP-L3 (%)-b  0.849
  <569 (85.2)240 (86) 
  ≤1512 (14.8)39 (14) 
Tumor characteristics   
 Tumor number, n (%)  0.250
  164 (59.8)226 (63.8) 
  231 (29)75 (21.2) 
  36 (5.6)35 (9.9) 
  ≥46 (5.6)18 (5.1) 
 Tumor size, n (%) (mm)   
  ≤2063 (58.8)220 (62.1) 
  21–3023 (21.5)80 (22.6) 
  31–5019 (17.8)47 (13.3) 
  ≥512 (1.9)7 (2) 
 TNM stage, n (%)  0.618
  I36 (33.6)140 (39.5) 
  II52 (48.6)162 (45.8) 
  IIIA19 (17.8)52 (14.8) 
Pre-treatment with TACE, n (%)23 (21.4)67 (18.9)0.957

Hepatitis C virus antibody positive patients were more frequent in the elderly group, compared with the non-elderly group (P = 0.026). Child–Pugh grade status was not different between the two groups. Serum alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (GGT) levels in the elderly group were significantly lower than those in the non-elderly group. There was no difference between the two groups in the distribution of tumor markers, tumor characteristics and executing rates of TACE before RFA.

Overall survival rates and recurrence rates after ablation

Cumulative overall survival rates after ablation in the elderly group were 82% after 3 years and 61% after 5 years, while those for the non-elderly group were 80% and 63%, respectively (Fig. 1). There was no significant difference in survival rates between the two groups (P = 0.824). With regard to the cause of death, eight patients (24.2% of deaths) in the elderly group and 31 patients (26.9% of deaths) in the non-elderly group died from causes other than hepatic diseases (tumor progression, hepatic failure, variceal rupture or other complications of cirrhosis), and there was no difference between the two groups (P = 0.755). In addition, we performed subgroup analysis of survival rates, excluding patients who died from causes other than hepatic diseases. As a result, the survival rates in the elderly and non-elderly groups were 88% and 88% after 3 years, and 66% and 68% after 5 years, respectively, and there was still no significant difference between the two groups (P = 0.949, data not shown in a figure).

image

Figure 1. Cumulative survival rates after radiofrequency ablation (RFA) treatment. Cumulative survival rates by the Kaplan–Meier method in the elderly (n = 107, thick line) and non-elderly groups (n = 354, thin line) are shown. There was no significant difference in survival rates between the two groups (P = 0.824, log–rank test).

Download figure to PowerPoint

The cumulative overall recurrence rates after RFA were similar in both groups; 49% after 3 years and 56% after 5 years (Fig. 2). The rates of local tumor progression were 6% after 1 year and 14% after 3 years in the elderly group, and 8% after 1 year and 12% after 3 years in the non-elderly group (Fig. 3), with no significant differences among the groups (P = 0.932). Even in patients who underwent RFA without preceding TACE, there were no differences in the survival rates (83.6% after 3 years and 66.8% after 5 years in the elderly; 82.9% after 3 years and 66.0% after 5 years in the non-elderly), the overall recurrence rates (47.3% after 3 years and 51.2% after 5 years in the elderly; 48.3% after 3 years and 58.5% after 5 years in the non-elderly) and the local tumor progression rates (10.1% after 3 years and 10.1% after 5 years in the elderly; 11.8% after 3 years and 13.2% after 5 years in the non-elderly) between the two groups.

image

Figure 2. Overall recurrence rates after radiofrequency ablation (RFA) treatment. Cumulative recurrence rates by the Kaplan–Meier method in the elderly (n = 107, thick line) and non-elderly groups (n = 354, thin line) are shown. There was no significant difference in recurrence rates between the two groups (P = 0.594, log–rank test).

Download figure to PowerPoint

image

Figure 3. Local recurrence rates after radiofrequency ablation (RFA) treatment. Cumulative local recurrence rates by the Kaplan–Meier method in elderly (n = 107, thick line) and non-elderly groups (n = 354, thin line) are shown. There was no significant difference in local recurrence rates between the two groups (P = 0.932, log–rank test).

Download figure to PowerPoint

Factors affecting survival

In multivariate analysis, the factors affecting survival in all patients, Child–Pugh grade, serum AFP levels and tumor size were independently selected (Table 2). In non-elderly patients, univariate and multivariate analysis showed that Child–Pugh grade B, a serum AFP level of over 20 ng/mL and a tumor size over 20 mm in diameter were independently associated with survival prognosis after RFA. Likewise, Child–Pugh grade B and a serum AFP level over 20 ng/mL were independently associated with survival in elderly patients (Table 3). Sex, the presence of comorbidity disease, excessive alcohol consumption, presence of viral marker, serum ALT level, serum DCP concentration and tumor number were not related to survival prognosis in either group.

Table 2.  Univariate and multivariate analyses of the relative risks for overall survival of patients
VariablesUnivariate analysisMultivariate analysis
Relative risk (95% CI)P-valueRelative risk (95% CI)P-value
  1. Ab, antibodies; ALT, alanine aminotransferase; AFP, α-fetoprotein; CI, confidence interval; DCP, des-γ-carboxy prothrombin; HCV, hepatitis C virus.

Age ≥75 years0.96 (0.653–1.416)0.8430.83 (0.555–1.248)0.374
Sex (male)0.96 (0.685–1.344)0.8121.07 (0.732–1.556)0.735
Comorbid disease (+)1.06 (0.764–1.459)0.7431.04 (0.746–1.543)0.825
Alcohol consumption (excessive)1.09 (0.746–1.593)0.6571.02 (0.669–1.543)0.942
HCV Ab (+)1.01 (0.629–1.615)0.9731.21 (0.242–6.071)0.655
Serum ALT (IU/L) >800.79 (0.545–1.149)0.2190.83 (0.555–1.228)0.343
Child–Pugh grade B2.41 (1.703–3.418)0.0012.15 (1.497–3.055)0.001
Serum AFP (ng/mL) >201.98 (1.416–2.777)0.0011.68 (1.183–2.384)0.004
Serum DCP (mAU/mL) >401.32 (0.950–1.827)0.0990.98 (0.671–1.423)0.904
Tumor number ≥21.19 (0.859–1.659)0.2931.14 (0.811–1.601)0.452
Tumor size (mm) >201.74 (1.256–2.398)0.0011.65 (1.135–2.393)0.009
Table 3.  Univariate and multivariate analyses of the relative risks for survival of elderly patients and non-elderly patients
VariablesUnivariate analysisMultivariate analysis
Relative risk (95% CI)P-valueRelative risk (95% CI)P-value
  1. Ab, antibodies; ALT, alanine aminotransferase; AFP, α-fetoprotein; CI, confidence interval; DCP, des-γ-carboxy prothrombin; HCV, hepatitis C virus.

Elderly patients    
 Sex (male)0.61 (0.300–1.220)0.1600.62 (0.279–1.432)0.272
 Comorbid disease (+)1.12 (0.565–2.233)0.7401.20 (0.574–2.499)0.631
 Alcohol consumption (excessive)0.93 (0.284–3.069)0.9090.87 (0.206–3.686)0.851
 HCV Ab (+)1.09 (0.260–4.555)0.9091.21 (0.242–6.071)0.815
 Serum ALT (IU/L) >800.56 (0.197–1.606)0.2831.36 (0.388–4.746)0.633
 Child–Pugh grade B2.71 (1.313–5.585)0.0072.59 (1.146–5.871)0.022
 Serum AFP (ng/mL) >204.19 (1.722–10.186)0.0023.72 (1.443–9.862)0.007
 Serum DCP (mAU/mL) >401.49 (0.752–2.952)0.2531.76 (0.618–5.000)0.291
 Tumor number ≥21.76 (0.888–3.483)0.1061.61 (0.782–3.324)0.196
 Tumor size (mm) >201.46 (0.735–2.844)0.2810.83 (0.278–2.476)0.737
Non-elderly patients    
 Sex (male)1.11 (0.739–1.661)0.6181.21 (0.777–1.883)0.400
 Comorbid disease (+)1.04 (0.717–1.496)0.8531.02 (0.699–1.484)0.923
 Alcohol consumption (excessive)1.11 (0.736–1.664)0.6281.04 (0.669–1.615)0.865
 HCV Ab (+)1.00 (0.606–1.659)0.9911.15 (0.675–1.953)0.610
 Serum ALT (IU/L) >800.83 (0.552–1.240)0.3580.79 (0.511–1.206)0.270
 Child–Pugh grade B2.37 (1.588–3.526)0.0012.12 (1.405–3.191)0.001
 Serum AFP (ng/mL) >201.69 (1.162–2.446)0.0061.48 (1.003–2.177)0.048
 Serum DCP (mAU/mL) >401.28 (0.879–1.858)0.1990.94 (0.619–1.425)0.768
 Tumor number ≥21.07 (0.730–1.560)0.7381.02 (0.687–1.505)0.932
 Tumor size (mm) >201.84 (1.271–2.652)0.0011.77 (1.174–2.663)0.006

Complications after RFA

In the elderly group, one major complication occurred in each of three cases (hepatic infarction, bile duct injury and pneumothorax) (Table 4). The cases with hepatic infarction and bile duct injury were managed conservatively, and the case with pneumothorax was treated with a thoracotomy tube. In the non-elderly group, 13 cases with major complications (two cases each of bile duct injury, hepatic abscess, burn injury, and one case each of infected biloma, hemobilia, intraperitoneal hemorrhage, duodenal perforation, pleural effusion, phrenic nerve paralysis, Takotsubo cardiomyopathy) occurred. The prevalence of major and minor complications caused by the RFA procedure was 2.8% and 1.9% in the elderly group and 3.7% and 2.0% in the non-elderly group, respectively. There was no statistical difference in the prevalence of major and minor complications between the two groups. No patient died from complications in either group. Distinctive complications in elderly patients did not occur.

Table 4.  Complications after radiofrequency ablation
ComplicationsNo. of complicationsPrevalence per treatment (%)
Elderly patients  
 Major  
  Hepatic infarction10.93
  Bile duct injury10.93
  Pneumothorax10.93
  Total32.80
 Minor  
  Subcutaneous hematoma10.93
  Asymptomatic biloma10.93
  Total21.86
Non-elderly patients  
 Major  
  Bile duct injury20.56
  Hepatic abscess20.56
  Burn injury20.56
  Infected biloma10.28
  Hemobilia10.28
  Intraperitoneal hemorrhage10.28
  Duodenal perforation10.28
  Pleural effusion10.28
  Phrenic nerve paralysis10.28
  Takotsubo cardiomyopathy10.28
  Total133.67
 Minor  
  Subcutaneous hematoma30.85
  Asymptomatic biloma41.13
  Total71.98

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

THE PRESENT STUDY showed that survival rates, curative effects, prognosis-related factors and complications of RFA treatment in patients over 75 years old with HCC were similar to those in patients under 75 years old. There have been many previous studies reporting the efficiency and safety of surgical treatment for HCC in elderly patients21–24 and most reports have shown similar survival rates and levels of safety when compared with non-elderly patients. However, there have been few reports investigating these points for RFA treatment of elderly patients. Tateishi et al. showed that there was no difference in a 3-year survival rate between patients aged over 68 years (76%) and under 68 years (79.2%) in 1000 patients treated with RFA.25 Their data was similar to our results in this study, but their definition of “elderly” was different to ours and detailed analyses were not performed. Our paper is the report, not only presenting survival rates, but also to precisely analyze the curativeness, survival-related factors, causes of death and complications of RFA in more elderly patients.

Regarding survival, the cumulative survival curve in the elderly group was identical with that in the non-elderly group, and aging was not associated with survival rates in multivariate analysis. But based on natural lifespan, long-term survival rates were expected to be lower in elderly patients than in non-elderly patients. It could be conceivable that this result was influenced by differences in baseline characteristics, including sex, alcohol habits, serum ALT levels and GGT levels, because these factors are associated with progression of hepatic fibrosis or carcinogenesis.26–30

As the background characteristics of both groups were different, as discussed above, we analyzed prognostic factors in each group. It was expected that the presence of comorbid diseases might be a poor prognostic factor in the elderly group, but this was not statistically associated with survival rates in either the elderly or the non-elderly groups.

These results suggest that RFA treatment should be addressed proactively even if the elderly HCC patient has a comorbid disease. However, there is a limitation to being able to generalize this result, because this study was retrospective and there was likely to be a bias for selecting patients with good liver function or without severe comorbid diseases when elderly patients were referred to our department. Hence, more investigations should be conducted in elderly patients to clarify the benefits of RFA treatment with respect to comorbid diseases. Another limitation of this study was that comparisons with other treatment methods, especially with hepatic resection, were not performed. It cannot therefore be suggested from this study which treatment methods should be recommended for elderly subjects. Several reports have shown that the cumulative survival rates of hepatic resection were almost 40–60% at 5 years in elderly subjects.21–24 Although simple comparisons should not be done, our RFA data was similar or superior to these results from hepatic resection. Because the complications from the RFA procedure were fewer, RFA treatment might be considered above hepatic resection for elderly patients.

We conclude that, even in over 75-year-olds, RFA treatment should be proactively employed to completely cure HCC, if liver function and tumor stage are acceptable.

ACKNOWLEDGMENTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

THE AUTHORS WOULD like to thank Dr Hirohisa Shigematsu at Kitakyushu Municipal Medical center, Ms Yukie Watanabe, Ms Chieko Ogawa and all the medical staff at Saga Medical School Hospital and Saga Prefectural Hospital for their assistance and excellent advice.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES