The American Journal of Surgery (2015) 209, 391-397
Clinical Science
Hepatectomy is a reasonable option for older patients with hepatocellular carcinoma Jong Man Kim, M.D., Ph.D.a, Bong Ick Cho, M.D.a, Choon Hyuck David Kwon, M.D., Ph.D.a, Jae-Won Joh, M.D., Ph.D.a,*, Jae Berm Park, M.D., Ph.D.a, Joon Hyeok Lee, M.D., Ph.D.b, Sung Joo Kim, M.D., Ph.D.a, Seung Woon Paik, M.D., Ph.D.b, Cheol Keun Park, M.D., Ph.D.c a
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-Dong Gangnam-Gu, Seoul 135-710, Korea; bDivision of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; cDepartment of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
KEYWORDS: Older; Hepatic resection; Hepatocellular carcinoma; Hepatitis B virus; Postoperative mortality; Pneumonia
Abstract BACKGROUND: Hepatic resection is the main treatment for patients with hepatocellular carcinoma. However, surgery is generally stressful for older patients. METHODS: Clinicopathologic data and outcomes after hepatic resection were retrospectively investigated for older patients with hepatocellular carcinoma. The younger group (n 5 219) included patients aged 60 to 69 years, and the older group (n 5 60) included patients .70 years of age. RESULTS: Hepatitis B virus was more common in the younger group than in the older group (64.5% vs 28.8%, P , .001). The occurrence of pneumonia was higher in older group than in the younger group (10.0% vs 2.3%, P 5 .015), but postoperative complications and mortality were not significantly different between the 2 groups. There was no statistically significant difference in disease-free survival rates between the 2 groups. CONCLUSIONS: Although the incidence of postoperative pneumonia was higher in the older group than in the younger group, hepatic resection was justified for hepatocellular carcinoma in selected patients .70 years of age. Crown Copyright Ó 2015 Published by Elsevier Inc. All rights reserved.
Hepatocellular carcinoma (HCC) is 1 of the most common cancers,1,2 with an estimated 500,000 cases annually worldwide. Although HCC is generally diagnosed in
Drs Jong Man Kim and Cho contributed equally to this work. The authors declare no conflicts of interest. * Corresponding author. Tel.: 182-2-3410-3466; fax: 182-2-34100040. E-mail address: [email protected] Manuscript received March 28, 2013; revised manuscript June 9, 2013
middle-aged and older people, the high prevalence of HCC and prolonged life expectancy have led to increased numbers of older patients’ being considered for treatment. The Korean population has 1 of the longest average life spans, and the size of the aged population is increasing rapidly. As a result, the prevalence of older patients with HCC has increased.3 Management of malignancy in older patients has become a global clinical issue because older patients have a high incidence of comorbid illnesses and are usually considered to be a high-risk group for major surgery.
0002-9610/$ - see front matter Crown Copyright Ó 2015 Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjsurg.2013.06.010
392 In general, older patients do not tolerate surgery well,4,5 and they can have poor parenchymal liver function.6 Therefore, surgery is thought to be unsuitable for older patients with HCC. Liver transplantation is probably the best treatment for selected patients, but the lack of donors limits its application in older patients. Liver resection remains the only potentially curative therapy for HCC in these patients. Many surgeons hesitate to choose hepatectomy for older cirrhotic patients with high operative risk because of a high incidence of comorbid illness in this population. In addition, HCC is frequently associated with cirrhosis, which is a cause of high mortality and morbidity after hepatectomy. Therefore, the issue of whether surgery is justified for older patients with HCC is important. The aim of this study was to identify the characteristics of older patients with HCC aged R70 years who underwent hepatectomy compared with younger patients with HCC (60 to 69 years old) and to identify risk factors for tumor recurrence after curative liver resection in patients aged R60 years.
Methods Patients From January 2006 to June 2010, 279 patients with HCC aged .60 years underwent curative resection, which was defined as macroscopic removal of all tumors, at Samsung Medical Center. Exclusion criteria were age ,60 years, pathologically proven mixed HCC and cholangiocarcinoma, or loss to follow-up after hepatectomy. The demographic, preoperative laboratory, and pathologic data of all patients were collected from electronic medical records for retrospective review. Liver function was evaluated using the Child-Pugh classification system. Patients were divided into 2 groups according to age at the time of surgery. The younger group (n 5 219) included patients aged 60 to 69 years, and the older group (n 5 60) included patients aged R70 years old. No patients in either group received postoperative adjuvant therapy before recurrence was detected.
The American Journal of Surgery, Vol 209, No 2, February 2015 comorbidity, and distant metastasis were contraindications for hepatectomy. Standard operative techniques for hepatectomy were used. Adequate mobilization was performed depending on the part of liver to be resected. Selective clamping of the portal vein and hepatic artery was performed when feasible; if not, the intermittent Pringle maneuver was performed. Parenchymal transection was performed using a Cavitron Ultrasonic Surgical Aspirator under low central venous pressure. Surgical procedures were classified according to the Brisbane terminology proposed by Strasberg and Phillips.7 Anatomic resection was defined as resection of the tumor with related portal vein branches and corresponding hepatic territory. Anatomic resection was classified as hemihepatectomy (resection of half the liver), extended hemihepatectomy (hemihepatectomy plus removal of additional contiguous segments), sectionectomy (resection of 2 Couinaud subsegments), or segmentectomy (resection of 1 Couinaud subsegment). Both peripheral tumors and central tumors were treated using nonanatomic resection. Peripheral tumors and tumors with extrahepatic growth were treated using partial hepatectomy, because this method is able to achieve sufficient surgical margins. Central tumors near the hepatic hilum or major vessels were treated by enucleation only, because removing enough of the liver to obtain adequate margins was too difficult or dangerous. Major hepatectomy was defined as resection of R3 Couinaud segments, and minor hepatectomy was defined as resection of ,3 segments. A single senior pathologist reviewed each specimen for histologic confirmation of the diagnosis. Postoperative histologic assessments and reporting included tumor diameter, cirrhosis, capsular invasion, portal vein invasion, bile duct invasion, microvascular invasion, and serosal involvement of HCC. Histologic grade was assessed according to the Edmonson-Steiner system8 as well differentiated (grade I), moderately differentiated (grade II), or poorly differentiated (grades III and IV). Hepatic fibrosis was assessed using the Ludwig-Batts scoring system and graded on a scale of F0 to F4 (F0 5 absent, F1 5 portal fibrosis, F2 5 periportal fibrosis, F3 5 bridging fibrosis, F4 5 cirrhosis). Cirrhosis was defined as stage 4 fibrosis.
Surgery and pathology Surveillance after surgical resection Before surgery, each patient underwent conventional liver function tests and measurement of the indocyanine green retention rate at 15 minutes. Preoperative evaluation of liver function included measurement of serum levels of bilirubin, transaminases, alkaline phosphatase, albumin, and prothrombin time. Hepatitis screening was done by measurement of hepatitis B surface antigen (HBsAg) and hepatitis C antibody. The levels of a-fetoprotein and protein induced by vitamin K absence/antagonism-II were measured in all patients. Selection criteria for liver resection were based on tumor location and extent, liver function, indocyanine green retention rate at 15 minutes, and future liver remnant volume. Child-Pugh class C, severe
Perioperative and postoperative complications and mortality were recorded to hepatectomy morbidity and mortality. Postoperative mortality was defined as death within 30 days of hepatectomy. After surgery, patients were followed up every 2 to 3 months. Follow-up included physical examination, serum a-fetoprotein, protein induced by vitamin K absence/antagonism-II, liver function test, and chest x-ray. Abdominal computed tomography was performed every 3 months or when recurrence was suspected. Magnetic resonance imaging and/or positron emission tomography was performed when computed tomography could not definitively determine evidence of suspected recurrence. Detailed
J.M. Kim et al.
Hepatectomy in older HCC patients
Table 1
Clinical characteristics
Variable
Younger group (n 5 219)
Older group (n 5 60)
168 (76.7%) 51 (23.3%) 63.6 6 2.8 30 (13.7%) 73 (33.3%)
46 (76.7%) 14 (23.3%) 73.2 6 2.8 15 (25.0%) 25 (41.7%)
140 17 7 49 4
17 11 3 27 1
Gender Male Female Age (y) Diabetes Hypertension Etiology HBV HCV Alcohol NBNC Others
393
P .994
(64.5%) (7.8%) (3.2%) (22.6%) (1.8%)
,.001 .047 .285 ,.001
(28.8%) (18.6%) (5.1%) (45.8%) (1.7%)
Data are expressed as number (percentage) or mean 6 SD. HBV 5 hepatitis B virus; HCV 5 hepatitis C virus; NBNC 5 non-B, non-C.
information was recorded for patients with recurrence. We treated recurrent HCC using repeat hepatic resection, local ablation therapy, and transarterial chemoembolization. Follow-up time was defined as time from surgery to last follow-up (December 1, 2011) or death. No patients were lost to follow-up and none died within 30 days after surgery; therefore, 279 patients were included in the survival analysis. Tumor recurrence and survival data were also recorded.
Statistical analysis All data were analyzed using SPSS version 19.0 (SPSS, Inc, Chicago, IL). Cutoff values for each variable were calculated using receiver operating characteristic curve analysis. Continuous variables were compared using Mann-Whitney U tests and are presented as mean 6 SD. Categorical variables were compared using Fisher’s exact tests, as appropriate. Disease-free survival rates were calculated using the Kaplan-Meier method and were compared using the log-rank test. Univariate analyses were performed to identify the predisposing factors for HCC recurrence using Cox regression models, and multivariate analysis was performed using a Cox proportional-hazards model for all variables that were associated with tumor recurrence on univariate analysis. P values ,.05 were considered statistically significant.
Results Preoperative characteristics All patients were in Child-Pugh class A. The characteristics of the patients in the 2 groups are given in Table 1. In the older group, 17 of the 60 patients (28.8%) had positive HBsAg results, whereas 140 of the 219 patients in the younger group (64.5%) had positive results. In the older
group, 27 patients (45.8%) did not have hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. In the younger group, 49 (22.6%) did not have either infection (P , .001). The proportion of patients with diabetes was higher in older group (n 5 15 [25.0%]) than in the younger group (n 5 30 [13.7%]) (P 5 .047). Preoperative laboratory tests showed no significant differences between the younger and the older groups (Table 2).
Perioperative parameters and pathologic findings The tumor characteristics and perioperative parameters for both groups are given in Table 3. Type of operation, extent of resection, blood loss during the operation, perioperative blood transfusion, and operative time were not significantly different between the 2 groups. In addition, no significant differences in pathologic findings were observed between the 2 groups.
Postoperative complications Operative mortality occurred in only a single patient in the younger group and was due to hepatic artery dissection during the Pringle maneuver. Mean hospitalization was 11 days for both groups. Six of the 60 patients in the older group (10%) developed pneumonia, whereas 5 of the 219 patients in the younger group (2.3%) developed pneumonia (P 5 .015). These patients were well controlled with antibiotics. Wound complications, atelectasis, pleural effusion, bile leakage, and ascites requiring diuretics between the 2 groups did not reach significant levels. Postoperative liver function tests such as total bilirubin, aspartate transaminase, alanine
Table 2
Preoperative laboratory results
Variable
Younger group (n 5 219)
Total protein (g/dL) Albumin (g/dL) Total bilirubin (mg/dL) AST (U/L) ALT (U/L) ALP (U/L) GGT (U/L) ICG-R15 (%) AFP (ng/mL) PIVKA-II (mAU/mL)
Older group (n 5 60)
P
7.1 6 .6
7.0 6 .5
.563
4.1 6 .4 .8 6 .5
4.1 6 .4 .8 6 .4
.590 .468
6 6 6 6 6 6 6
.947 .857 .894 .798 .087 .534 .149
41 41 87 81.1 12.8 3,392 288
6 6 6 6 6 6 6
28 29 34 98.0 7.6 19,934 385
40 42 84 85.1 14.1 1,006 306
23 31 30 120.2 7.1 3,985 333
Data are expressed as mean 6 SD. AFP 5 a-fetoprotein; ALP 5 alkaline phosphatase; ALT 5 alanine aminotransferase; AST 5 aspartate aminotransferase; GGT 5 gglutamyltransferase; ICG-R15 5 indocyanine green retention rate at 15 minutes; PIVKA-II 5 protein induced by vitamin K antagonism-II.
394
The American Journal of Surgery, Vol 209, No 2, February 2015
Table 3
.557
older group were 84.3% at 1 years, 64.6% at 2 years, and 51.5% at 3 years. Disease-free survival rates after hepatectomy in the younger group were 70.2% at 1 year, 61.0% at 2 years, and 56.3% at 3 years (P 5 .667). The disease-free survival rate was similar for both (Fig. 1).
.869
Risk factors for tumor recurrence
Perioperative parameters and pathologic findings Younger group Older group (n 5 219) (n 5 60) P
Variable Type of operation Anatomic Nonanatomic Extent of resection Major Minor Estimated blood loss (mL) Red blood cell transfusion Operation time (min) Tumor size (cm) Grade 1 and 2 3 and 4 Cirrhosis Capsular formation Microvascular invasion Portal vein invasion Bile duct invasion Serosal invasion Intrahepatic metastasis Multicentric occurrence Free resection margin (mm)
124 (56.6%) 95 (43.4%)
34 (56.7%) 26 (43.3%)
59 (26.9%) 160 (73.1%) 513 6 504 14 (6.4%) 293 6 93 4.9 6 3.6
15 (25.0%) 45 (75.0%) 569 6 675 6 (10.0%) 276 6 84 4.9 6 2.9
196 (90.7%) 20 (9.3%) 78 (35.6%) 199 (93.0%) 111 (50.7%) 9 (4.2%) 7 (3.3%) 3 (1.4%) 24 (11.2%) 14 (6.5%) 11 6 11
57 (95.0%) 3 (5.0%) 18 (30.0%) 57 (95.0%) 33 (55.0%) 1 (1.7%) 3 (5.0%) 1 (1.7%) 4 (6.7%) 4 (6.7%) 9.2 6 9.0
.880 .396 .151 .332 .429
.447 .771 .564 .696 .459 .873 .468 .966 .149
Data are expressed as number (percentage) or mean 6 SD.
By univariate analysis, the factors associated with the poorest disease-free survival for patients .60 years of age were protein induced by vitamin K absence/antagonism-II R200 mAU/mL; low hemoglobin and serum albumin levels; high serum aspartate transaminase, alanine transaminase, alkaline phosphatase, and international normalized ratio; increased tumor size; microvascular, portal vein, bile duct, or serosal invasion; and intrahepatic metastasis (Table 5). Multivariate analysis showed that serum albumin levels (odds ratio [OR], .366; 95% confidence interval [CI], .191 to .703; P 5 .003), tumor size (OR, 1.008; 95% CI, 1.002 to 1.014; P 5 .009), microvascular invasion (OR, 1.721; 95% CI, 1.050 to 2.822; P 5 .031), and intrahepatic metastasis (OR, 2.769; 95% CI, 1.561 to 4.914; P , .001) were closely associated with tumor recurrence in patients .60 years old.
Comments
transaminase, and international normalized ratio were not significantly different between the 2 groups (Table 4).
Outcomes
Age at diagnosis has a significant prognostic value in certain types of cancer. Worldwide, the age of patients diagnosed with HCC is increasing.2,9 Although the number of older patients with HCC is rising in Korea,3,10 the characteristics and prognosis of HCC in these patients are uncertain.
The mean follow-up period for all patients was 27 6 13 months. Disease-free survival rates after hepatectomy in the
Table 4
Postoperative characteristics
Variable Hospitalization (d) Wound complication Atelectasis Pneumonia Pleural effusion Bile leakage Ascites (diuretics) Peak total bilirubin (mg/dL) Peak AST (U/L) Peak ALT (U/L) Peak INR Follow-up (mo)
Younger group (n 5 219)
Older group (n 5 60)
P
11 6 8 20 (9.1%) 75 (34.2%) 5 (2.3%) 14 (6.4%) 21 (9.6%) 14 (6.4%) 2.9 6 4.8
11 6 4 6 (10.0%) 21 (35.0%) 6 (10.0%) 4 (6.7%) 4 (6.7%) 6 (10.0%) 2.6 6 2.8
.977 .838 .913 .015 .939 .615 .395 .707
297 6 270 291 6 280 1.47 6 .38 27 6 13
288 6 223 287 6 291 1.47 6 .28 27 6 14
.698 .650 .508 .791
Data are expressed as mean 6 SD or as number (percentage). ALT 5 alanine aminotransferase; AST 5 aspartate aminotransferase; INR 5 international normalized ratio.
Figure 1
Disease-free survival.
J.M. Kim et al. Table 5
Hepatectomy in older HCC patients
395
Risk factors for tumor recurrence in patients aged .60 years
Variable
OR
95% CI
P
Gender (female) Age Age (R70 years old) AFP R200 ng/mL PIVKA-II R200 mAU/mL White blood cell count Hemoglobin Platelet count INR Protein Albumin Total bilirubin AST ALT ALP Fasting blood glucose Creatinine Estimated GFR GGT ICG-R15 Type of operation (nonanatomic) Extent of operation (minor hepatectomy) Tumor size Cirrhosis Grade (3 and 4) Capsular formation Microvascular invasion Portal vein invasion Bile duct invasion Serosal invasion Intrahepatic metastasis Multicentric occurrence
.806 .970 .906 1.323 1.757 .982 .835 1.001 8.617 .912 .284 1.239 1.014 1.009 1.014 1.005 .798 .994 1.001 1.001 .874 .677 1.014 .946 1.762 1.464 2.338 3.053 2.198 3.636 2.982 1.001
.505–1.286 .931–1.012 .568–1.447 .861–2.032 1.197–2.578 .884–1.091 .750–.929 .998–1.003 1.162–63.932 .671–1.239 .185–.436 .822–1.867 1.009–1.018 1.004–1.014 1.009–1.019 1.001–1.008 .429–1.486 .981–1.007 1.000–1.003 .978–1.024 .599–1.277 .453–1.012 1.010–1.018 .633–1.413 1.004–3.090 .597–3.593 1.569–3.484 1.480–6.297 1.017–4.748 1.148–11.512 1.832–4.856 .465–2.153
.366 .163 .681 .202 .004 .735 .001 .532 .035 .556 ,.001 .306 ,.001 .001 ,.001 .004 .477 .334 .092 .934 .488 .057 ,.001 .787 .048 .405 ,.001 .003 .045 .028 ,.001 .998
AFP 5 a-fetoprotein; ALP 5 alkaline phosphatase; ALT 5 alanine aminotransferase; AST 5 aspartate aminotransferase; CI 5 confidence interval; GFR 5 glomerular filtration rate; GGT 5 g-glutamyltransferase; ICG-R15 5 indocyanine green retention rate at 15 minutes; INR 5 international normal ratio; OR 5 odds ratio; PIVKA-II 5 protein-induced by vitamin K antagonism-II.
In this study, we examined patients with HCC who were R70 years of age, identifying their clinicopathologic characteristics and comparing them with patients with HCC who were 60 to 69 years of age. The concept of ‘‘elderly’’ is becoming more difficult to define. The World Health Organization has not determined a standard age and has recently stated that persons aged .60 years could be considered an aged population.11 However, this criterion cannot be applied to all societies. Population aging has progressed more rapidly in South Korea than in any other country. According to a report by Statistics Korea in 2011, the proportion of older people is gradually increasing in Korea. The country is already an aging society, with 11% of the population aged .65 years and 15.7% of the population expected to be .65 years of age in 2020.12 For this reason, we used a cutoff value of 70 years to divide the study patients into younger and older groups to clarify the characteristics of HCC in patients aged .60 years. We believe that this allows for more
reasonable and meaningful comparisons with other previous studies.4,5,13,14 Other modalities of HCC management, such as percutaneous ethanol injection therapy, microwave coagulation therapy, or percutaneous radiofrequency ablation, can be acceptable alternatives to hepatic resection in older people, but the best treatment for older patients remains controversial. Generally, older patients received significant fewer surgical resections than younger patients.15 Liver transplantation has the advantage of removing the cirrhotic liver together with the tumor and restoring liver function. Nevertheless, patients .70 years of age are excluded from living donor liver transplantation programs because of the shortage of donors and cost-effectiveness. Whether hepatectomy affects the survival of older patients with HCC is somewhat controversial. Some studies found significantly higher morbidity and mortality rates in older people after hepatectomy for HCC.4,5 However, recent studies reported that liver resection is a relatively
396 safe procedure even in older patients because of improved surgical techniques, better perioperative assessment, and advances in anesthesia and medical care.14,16,17 Human organ function usually deteriorates with age, and older patients have a high incidence of comorbid illness. In addition, HCC is frequently associated with cirrhosis, which is itself a cause of high mortality and morbidity rates after hepatectomy. Therefore, older patients are considered at high risk for liver resection. In our series, mortality was extremely low, and only a single patient in the younger group died after hepatectomy. Our study showed a difference in etiology of HCC etiology between older and younger patients. The number of patients with a positive HBsAg test was significantly lower in the older group than in the younger group. The proportion of patients negative for HBsAg and anti-HCV antibody was clearly larger in the older than in the younger group. These findings are in agreement with the results of previous studies.10,18 Other reports showed that the average ages of diagnosis are approximately 55 years for HBVrelated HCC, 65 years for HCV-related HCC, and 70 years for non-B, non-C HCC.3,19 In Korea, HBV is predominantly transmitted during the prenatal period. Therefore, a large proportion of patients with cirrhosis and HCC from HBV die before reaching the age of 70 years because HBV is aggressive. Survived older patients have well-preserved hepatic function because HCC was caused by other etiologies. A recent study reported that patients with nonalcoholic steatohepatitis–related HCC are older at diagnosis than those with HCC related to HBV and HCV.20,21 These results suggest that some of cases of non-B, non-C HCC are nonalcoholic steatohepatitis–related HCC. Although our study was retrospective, we analyzed 2 groups of patients that were similar in terms of preoperative characteristics, surgical procedures, and pathologic features. The proportion of elderly patients with diabetes mellitus was higher than in the younger group, but there were no statistical differences in postoperative mortality and morbidity except pneumonia between the 2 groups. The incidence of pneumonia in the elderly group was higher than in the younger group. These patients were treated with antibiotics and lung care and recovered their health. The aggressive lung care after surgery must be needed in elderly patients. Our study found no significant difference in disease-free survival between older and younger patients with HCC. Thus, patient age was not an independent factor for tumor recurrence. These results suggested that preoperative evaluations of older patients with comorbid illnesses and patient selection were adequate in our program. Therefore, selected older patients should be able to tolerate even a major hepatectomy. With improved surgical techniques, better perioperative assessments, and advances in anesthesia and medical care, liver resection has become a safe procedure, even in aged patients.14 Recent improvements in results indicate that many older patients could benefit from surgical management.16,17 The high prevalence of HCC and prolonged life expectancy in the population has led to the
The American Journal of Surgery, Vol 209, No 2, February 2015 reconsideration of treatment strategies in older patients. Our study suggests that hepatectomy is a reasonable treatment option for older patients. This study included a relatively large number of hepatectomy patients. However, our study also had some limitations. First, a selection bias might have been present because data were collected from a single center. Indications for hepatectomy were similar in the older and younger patients in our program, and were according to tumor stage and hepatic functional reserve. However, bias might have resulted from selecting patients with good liver function among older patients referred to our surgical department. Second, we used a retrospective design. Third, patients of the same age can show individual differences in degree of physical aging. We could not collect enough data to evaluate the exact functional age of older patients.
Conclusions The outcomes of older patients with HCC were not different from those of younger patients. The results of this study suggest that the therapeutic strategy for older patients with HCC should be as aggressive as that for younger patients. Our results confirm that age by itself should no longer be considered a risk factor for liver surgery.
References 1. El-Serag HB, Mason AC. Risk factors for the rising rates of primary liver cancer in the United States. Arch Intern Med 2000; 160:3227–30. 2. Bosch FX, Ribes J, Diaz M, et al. Primary liver cancer: worldwide incidence and trends. Gastroenterology 2004;127:S5–16. 3. Song IH, Kim KS. Current status of liver diseases in Korea: hepatocellular carcinoma. Korean J Hepatol 2009;15(suppl):S50–9. 4. Yanaga K, Kanematsu T, Takenaka K, et al. Hepatic resection for hepatocellular carcinoma in elderly patients. Am J Surg 1988;155: 238–41. 5. Fortner JG, Lincer RM. Hepatic resection in the elderly. Ann Surg 1990;211:141–5. 6. Wakabayashi H, Nishiyama Y, Ushiyama T, et al. Evaluation of the effect of age on functioning hepatocyte mass and liver blood flow using liver scintigraphy in preoperative estimations for surgical patients: comparison with CT volumetry. J Surg Res 2002;106:246–53. 7. Strasberg SM, Phillips C. Use and dissemination of the brisbane 2000 nomenclature of liver anatomy and resections. Ann Surg 2013;257: 377–82. 8. Edmondson HA, Steiner PE. Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer 1954;7:462–503. 9. Deuffic S, Poynard T, Buffat L, et al. Trends in primary liver cancer. Lancet 1998;351:214–5. 10. Kim YJ, Jang BK, Kim ES, et al. Hepatocellular carcinoma in the elderly: clinical characteristics, treatment, survival analysis in Korean patients older than 70 years. J Korean Med Sci 2012;27:1147–54. 11. Brubaker TH, Powers EA. The stereotype of ‘‘old.’’ A review and alternative approach. J Gerontol 1976;31:441–7. 12. Statistics Korea. e-National Indicator. Available at: http://www.index. go.kr. Accessed January 10, 2012. 13. Falkson G, Cnaan A, Schutt AJ, et al. Prognostic factors for survival in hepatocellular carcinoma. Cancer Res 1988;48:7314–8.
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Hepatectomy in older HCC patients
14. Fong Y, Brennan MF, Cohen AM, et al. Liver resection in the elderly. Br J Surg 1997;84:1386–90. 15. Lee SH, Choi HC, Jeong SH, et al. Hepatocellular carcinoma in older adults: clinical features, treatments, and survival. J Am Geriatr Soc 2011;59:241–50. 16. Yamada S, Shimada M, Miyake H, et al. Outcome of hepatectomy in super-elderly patients with hepatocellular carcinoma. Hepatol Res 2012;42:454–8. 17. Kondo K, Chijiiwa K, Funagayama M, et al. Hepatic resection is justified for elderly patients with hepatocellular carcinoma. World J Surg 2008;32:2223–9.
397 18. Tsukioka G, Kakizaki S, Sohara N, et al. Hepatocellular carcinoma in extremely elderly patients: an analysis of clinical characteristics, prognosis and patient survival. World J Gastroenterol 2006;12:48–53. 19. Jeong SW, Jang JY, Chung RT. Hepatitis C virus and hepatocarcinogenesis. Clin Mol Hepatol 2012;18:347–56. 20. Ascha MS, Hanouneh IA, Lopez R, et al. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology 2010;51:1972–8. 21. Hashimoto E, Yatsuji S, Tobari M, et al. Hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. J Gastroenterol 2009;44 (suppl):89–95.
Clinical Science
Hepatectomy is a reasonable option for older patients with hepatocellular carcinoma Jong Man Kim, M.D., Ph.D.a, Bong Ick Cho, M.D.a, Choon Hyuck David Kwon, M.D., Ph.D.a, Jae-Won Joh, M.D., Ph.D.a,*, Jae Berm Park, M.D., Ph.D.a, Joon Hyeok Lee, M.D., Ph.D.b, Sung Joo Kim, M.D., Ph.D.a, Seung Woon Paik, M.D., Ph.D.b, Cheol Keun Park, M.D., Ph.D.c a
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-Dong Gangnam-Gu, Seoul 135-710, Korea; bDivision of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; cDepartment of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
KEYWORDS: Older; Hepatic resection; Hepatocellular carcinoma; Hepatitis B virus; Postoperative mortality; Pneumonia
Abstract BACKGROUND: Hepatic resection is the main treatment for patients with hepatocellular carcinoma. However, surgery is generally stressful for older patients. METHODS: Clinicopathologic data and outcomes after hepatic resection were retrospectively investigated for older patients with hepatocellular carcinoma. The younger group (n 5 219) included patients aged 60 to 69 years, and the older group (n 5 60) included patients .70 years of age. RESULTS: Hepatitis B virus was more common in the younger group than in the older group (64.5% vs 28.8%, P , .001). The occurrence of pneumonia was higher in older group than in the younger group (10.0% vs 2.3%, P 5 .015), but postoperative complications and mortality were not significantly different between the 2 groups. There was no statistically significant difference in disease-free survival rates between the 2 groups. CONCLUSIONS: Although the incidence of postoperative pneumonia was higher in the older group than in the younger group, hepatic resection was justified for hepatocellular carcinoma in selected patients .70 years of age. Crown Copyright Ó 2015 Published by Elsevier Inc. All rights reserved.
Hepatocellular carcinoma (HCC) is 1 of the most common cancers,1,2 with an estimated 500,000 cases annually worldwide. Although HCC is generally diagnosed in
Drs Jong Man Kim and Cho contributed equally to this work. The authors declare no conflicts of interest. * Corresponding author. Tel.: 182-2-3410-3466; fax: 182-2-34100040. E-mail address: [email protected] Manuscript received March 28, 2013; revised manuscript June 9, 2013
middle-aged and older people, the high prevalence of HCC and prolonged life expectancy have led to increased numbers of older patients’ being considered for treatment. The Korean population has 1 of the longest average life spans, and the size of the aged population is increasing rapidly. As a result, the prevalence of older patients with HCC has increased.3 Management of malignancy in older patients has become a global clinical issue because older patients have a high incidence of comorbid illnesses and are usually considered to be a high-risk group for major surgery.
0002-9610/$ - see front matter Crown Copyright Ó 2015 Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjsurg.2013.06.010
392 In general, older patients do not tolerate surgery well,4,5 and they can have poor parenchymal liver function.6 Therefore, surgery is thought to be unsuitable for older patients with HCC. Liver transplantation is probably the best treatment for selected patients, but the lack of donors limits its application in older patients. Liver resection remains the only potentially curative therapy for HCC in these patients. Many surgeons hesitate to choose hepatectomy for older cirrhotic patients with high operative risk because of a high incidence of comorbid illness in this population. In addition, HCC is frequently associated with cirrhosis, which is a cause of high mortality and morbidity after hepatectomy. Therefore, the issue of whether surgery is justified for older patients with HCC is important. The aim of this study was to identify the characteristics of older patients with HCC aged R70 years who underwent hepatectomy compared with younger patients with HCC (60 to 69 years old) and to identify risk factors for tumor recurrence after curative liver resection in patients aged R60 years.
Methods Patients From January 2006 to June 2010, 279 patients with HCC aged .60 years underwent curative resection, which was defined as macroscopic removal of all tumors, at Samsung Medical Center. Exclusion criteria were age ,60 years, pathologically proven mixed HCC and cholangiocarcinoma, or loss to follow-up after hepatectomy. The demographic, preoperative laboratory, and pathologic data of all patients were collected from electronic medical records for retrospective review. Liver function was evaluated using the Child-Pugh classification system. Patients were divided into 2 groups according to age at the time of surgery. The younger group (n 5 219) included patients aged 60 to 69 years, and the older group (n 5 60) included patients aged R70 years old. No patients in either group received postoperative adjuvant therapy before recurrence was detected.
The American Journal of Surgery, Vol 209, No 2, February 2015 comorbidity, and distant metastasis were contraindications for hepatectomy. Standard operative techniques for hepatectomy were used. Adequate mobilization was performed depending on the part of liver to be resected. Selective clamping of the portal vein and hepatic artery was performed when feasible; if not, the intermittent Pringle maneuver was performed. Parenchymal transection was performed using a Cavitron Ultrasonic Surgical Aspirator under low central venous pressure. Surgical procedures were classified according to the Brisbane terminology proposed by Strasberg and Phillips.7 Anatomic resection was defined as resection of the tumor with related portal vein branches and corresponding hepatic territory. Anatomic resection was classified as hemihepatectomy (resection of half the liver), extended hemihepatectomy (hemihepatectomy plus removal of additional contiguous segments), sectionectomy (resection of 2 Couinaud subsegments), or segmentectomy (resection of 1 Couinaud subsegment). Both peripheral tumors and central tumors were treated using nonanatomic resection. Peripheral tumors and tumors with extrahepatic growth were treated using partial hepatectomy, because this method is able to achieve sufficient surgical margins. Central tumors near the hepatic hilum or major vessels were treated by enucleation only, because removing enough of the liver to obtain adequate margins was too difficult or dangerous. Major hepatectomy was defined as resection of R3 Couinaud segments, and minor hepatectomy was defined as resection of ,3 segments. A single senior pathologist reviewed each specimen for histologic confirmation of the diagnosis. Postoperative histologic assessments and reporting included tumor diameter, cirrhosis, capsular invasion, portal vein invasion, bile duct invasion, microvascular invasion, and serosal involvement of HCC. Histologic grade was assessed according to the Edmonson-Steiner system8 as well differentiated (grade I), moderately differentiated (grade II), or poorly differentiated (grades III and IV). Hepatic fibrosis was assessed using the Ludwig-Batts scoring system and graded on a scale of F0 to F4 (F0 5 absent, F1 5 portal fibrosis, F2 5 periportal fibrosis, F3 5 bridging fibrosis, F4 5 cirrhosis). Cirrhosis was defined as stage 4 fibrosis.
Surgery and pathology Surveillance after surgical resection Before surgery, each patient underwent conventional liver function tests and measurement of the indocyanine green retention rate at 15 minutes. Preoperative evaluation of liver function included measurement of serum levels of bilirubin, transaminases, alkaline phosphatase, albumin, and prothrombin time. Hepatitis screening was done by measurement of hepatitis B surface antigen (HBsAg) and hepatitis C antibody. The levels of a-fetoprotein and protein induced by vitamin K absence/antagonism-II were measured in all patients. Selection criteria for liver resection were based on tumor location and extent, liver function, indocyanine green retention rate at 15 minutes, and future liver remnant volume. Child-Pugh class C, severe
Perioperative and postoperative complications and mortality were recorded to hepatectomy morbidity and mortality. Postoperative mortality was defined as death within 30 days of hepatectomy. After surgery, patients were followed up every 2 to 3 months. Follow-up included physical examination, serum a-fetoprotein, protein induced by vitamin K absence/antagonism-II, liver function test, and chest x-ray. Abdominal computed tomography was performed every 3 months or when recurrence was suspected. Magnetic resonance imaging and/or positron emission tomography was performed when computed tomography could not definitively determine evidence of suspected recurrence. Detailed
J.M. Kim et al.
Hepatectomy in older HCC patients
Table 1
Clinical characteristics
Variable
Younger group (n 5 219)
Older group (n 5 60)
168 (76.7%) 51 (23.3%) 63.6 6 2.8 30 (13.7%) 73 (33.3%)
46 (76.7%) 14 (23.3%) 73.2 6 2.8 15 (25.0%) 25 (41.7%)
140 17 7 49 4
17 11 3 27 1
Gender Male Female Age (y) Diabetes Hypertension Etiology HBV HCV Alcohol NBNC Others
393
P .994
(64.5%) (7.8%) (3.2%) (22.6%) (1.8%)
,.001 .047 .285 ,.001
(28.8%) (18.6%) (5.1%) (45.8%) (1.7%)
Data are expressed as number (percentage) or mean 6 SD. HBV 5 hepatitis B virus; HCV 5 hepatitis C virus; NBNC 5 non-B, non-C.
information was recorded for patients with recurrence. We treated recurrent HCC using repeat hepatic resection, local ablation therapy, and transarterial chemoembolization. Follow-up time was defined as time from surgery to last follow-up (December 1, 2011) or death. No patients were lost to follow-up and none died within 30 days after surgery; therefore, 279 patients were included in the survival analysis. Tumor recurrence and survival data were also recorded.
Statistical analysis All data were analyzed using SPSS version 19.0 (SPSS, Inc, Chicago, IL). Cutoff values for each variable were calculated using receiver operating characteristic curve analysis. Continuous variables were compared using Mann-Whitney U tests and are presented as mean 6 SD. Categorical variables were compared using Fisher’s exact tests, as appropriate. Disease-free survival rates were calculated using the Kaplan-Meier method and were compared using the log-rank test. Univariate analyses were performed to identify the predisposing factors for HCC recurrence using Cox regression models, and multivariate analysis was performed using a Cox proportional-hazards model for all variables that were associated with tumor recurrence on univariate analysis. P values ,.05 were considered statistically significant.
Results Preoperative characteristics All patients were in Child-Pugh class A. The characteristics of the patients in the 2 groups are given in Table 1. In the older group, 17 of the 60 patients (28.8%) had positive HBsAg results, whereas 140 of the 219 patients in the younger group (64.5%) had positive results. In the older
group, 27 patients (45.8%) did not have hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. In the younger group, 49 (22.6%) did not have either infection (P , .001). The proportion of patients with diabetes was higher in older group (n 5 15 [25.0%]) than in the younger group (n 5 30 [13.7%]) (P 5 .047). Preoperative laboratory tests showed no significant differences between the younger and the older groups (Table 2).
Perioperative parameters and pathologic findings The tumor characteristics and perioperative parameters for both groups are given in Table 3. Type of operation, extent of resection, blood loss during the operation, perioperative blood transfusion, and operative time were not significantly different between the 2 groups. In addition, no significant differences in pathologic findings were observed between the 2 groups.
Postoperative complications Operative mortality occurred in only a single patient in the younger group and was due to hepatic artery dissection during the Pringle maneuver. Mean hospitalization was 11 days for both groups. Six of the 60 patients in the older group (10%) developed pneumonia, whereas 5 of the 219 patients in the younger group (2.3%) developed pneumonia (P 5 .015). These patients were well controlled with antibiotics. Wound complications, atelectasis, pleural effusion, bile leakage, and ascites requiring diuretics between the 2 groups did not reach significant levels. Postoperative liver function tests such as total bilirubin, aspartate transaminase, alanine
Table 2
Preoperative laboratory results
Variable
Younger group (n 5 219)
Total protein (g/dL) Albumin (g/dL) Total bilirubin (mg/dL) AST (U/L) ALT (U/L) ALP (U/L) GGT (U/L) ICG-R15 (%) AFP (ng/mL) PIVKA-II (mAU/mL)
Older group (n 5 60)
P
7.1 6 .6
7.0 6 .5
.563
4.1 6 .4 .8 6 .5
4.1 6 .4 .8 6 .4
.590 .468
6 6 6 6 6 6 6
.947 .857 .894 .798 .087 .534 .149
41 41 87 81.1 12.8 3,392 288
6 6 6 6 6 6 6
28 29 34 98.0 7.6 19,934 385
40 42 84 85.1 14.1 1,006 306
23 31 30 120.2 7.1 3,985 333
Data are expressed as mean 6 SD. AFP 5 a-fetoprotein; ALP 5 alkaline phosphatase; ALT 5 alanine aminotransferase; AST 5 aspartate aminotransferase; GGT 5 gglutamyltransferase; ICG-R15 5 indocyanine green retention rate at 15 minutes; PIVKA-II 5 protein induced by vitamin K antagonism-II.
394
The American Journal of Surgery, Vol 209, No 2, February 2015
Table 3
.557
older group were 84.3% at 1 years, 64.6% at 2 years, and 51.5% at 3 years. Disease-free survival rates after hepatectomy in the younger group were 70.2% at 1 year, 61.0% at 2 years, and 56.3% at 3 years (P 5 .667). The disease-free survival rate was similar for both (Fig. 1).
.869
Risk factors for tumor recurrence
Perioperative parameters and pathologic findings Younger group Older group (n 5 219) (n 5 60) P
Variable Type of operation Anatomic Nonanatomic Extent of resection Major Minor Estimated blood loss (mL) Red blood cell transfusion Operation time (min) Tumor size (cm) Grade 1 and 2 3 and 4 Cirrhosis Capsular formation Microvascular invasion Portal vein invasion Bile duct invasion Serosal invasion Intrahepatic metastasis Multicentric occurrence Free resection margin (mm)
124 (56.6%) 95 (43.4%)
34 (56.7%) 26 (43.3%)
59 (26.9%) 160 (73.1%) 513 6 504 14 (6.4%) 293 6 93 4.9 6 3.6
15 (25.0%) 45 (75.0%) 569 6 675 6 (10.0%) 276 6 84 4.9 6 2.9
196 (90.7%) 20 (9.3%) 78 (35.6%) 199 (93.0%) 111 (50.7%) 9 (4.2%) 7 (3.3%) 3 (1.4%) 24 (11.2%) 14 (6.5%) 11 6 11
57 (95.0%) 3 (5.0%) 18 (30.0%) 57 (95.0%) 33 (55.0%) 1 (1.7%) 3 (5.0%) 1 (1.7%) 4 (6.7%) 4 (6.7%) 9.2 6 9.0
.880 .396 .151 .332 .429
.447 .771 .564 .696 .459 .873 .468 .966 .149
Data are expressed as number (percentage) or mean 6 SD.
By univariate analysis, the factors associated with the poorest disease-free survival for patients .60 years of age were protein induced by vitamin K absence/antagonism-II R200 mAU/mL; low hemoglobin and serum albumin levels; high serum aspartate transaminase, alanine transaminase, alkaline phosphatase, and international normalized ratio; increased tumor size; microvascular, portal vein, bile duct, or serosal invasion; and intrahepatic metastasis (Table 5). Multivariate analysis showed that serum albumin levels (odds ratio [OR], .366; 95% confidence interval [CI], .191 to .703; P 5 .003), tumor size (OR, 1.008; 95% CI, 1.002 to 1.014; P 5 .009), microvascular invasion (OR, 1.721; 95% CI, 1.050 to 2.822; P 5 .031), and intrahepatic metastasis (OR, 2.769; 95% CI, 1.561 to 4.914; P , .001) were closely associated with tumor recurrence in patients .60 years old.
Comments
transaminase, and international normalized ratio were not significantly different between the 2 groups (Table 4).
Outcomes
Age at diagnosis has a significant prognostic value in certain types of cancer. Worldwide, the age of patients diagnosed with HCC is increasing.2,9 Although the number of older patients with HCC is rising in Korea,3,10 the characteristics and prognosis of HCC in these patients are uncertain.
The mean follow-up period for all patients was 27 6 13 months. Disease-free survival rates after hepatectomy in the
Table 4
Postoperative characteristics
Variable Hospitalization (d) Wound complication Atelectasis Pneumonia Pleural effusion Bile leakage Ascites (diuretics) Peak total bilirubin (mg/dL) Peak AST (U/L) Peak ALT (U/L) Peak INR Follow-up (mo)
Younger group (n 5 219)
Older group (n 5 60)
P
11 6 8 20 (9.1%) 75 (34.2%) 5 (2.3%) 14 (6.4%) 21 (9.6%) 14 (6.4%) 2.9 6 4.8
11 6 4 6 (10.0%) 21 (35.0%) 6 (10.0%) 4 (6.7%) 4 (6.7%) 6 (10.0%) 2.6 6 2.8
.977 .838 .913 .015 .939 .615 .395 .707
297 6 270 291 6 280 1.47 6 .38 27 6 13
288 6 223 287 6 291 1.47 6 .28 27 6 14
.698 .650 .508 .791
Data are expressed as mean 6 SD or as number (percentage). ALT 5 alanine aminotransferase; AST 5 aspartate aminotransferase; INR 5 international normalized ratio.
Figure 1
Disease-free survival.
J.M. Kim et al. Table 5
Hepatectomy in older HCC patients
395
Risk factors for tumor recurrence in patients aged .60 years
Variable
OR
95% CI
P
Gender (female) Age Age (R70 years old) AFP R200 ng/mL PIVKA-II R200 mAU/mL White blood cell count Hemoglobin Platelet count INR Protein Albumin Total bilirubin AST ALT ALP Fasting blood glucose Creatinine Estimated GFR GGT ICG-R15 Type of operation (nonanatomic) Extent of operation (minor hepatectomy) Tumor size Cirrhosis Grade (3 and 4) Capsular formation Microvascular invasion Portal vein invasion Bile duct invasion Serosal invasion Intrahepatic metastasis Multicentric occurrence
.806 .970 .906 1.323 1.757 .982 .835 1.001 8.617 .912 .284 1.239 1.014 1.009 1.014 1.005 .798 .994 1.001 1.001 .874 .677 1.014 .946 1.762 1.464 2.338 3.053 2.198 3.636 2.982 1.001
.505–1.286 .931–1.012 .568–1.447 .861–2.032 1.197–2.578 .884–1.091 .750–.929 .998–1.003 1.162–63.932 .671–1.239 .185–.436 .822–1.867 1.009–1.018 1.004–1.014 1.009–1.019 1.001–1.008 .429–1.486 .981–1.007 1.000–1.003 .978–1.024 .599–1.277 .453–1.012 1.010–1.018 .633–1.413 1.004–3.090 .597–3.593 1.569–3.484 1.480–6.297 1.017–4.748 1.148–11.512 1.832–4.856 .465–2.153
.366 .163 .681 .202 .004 .735 .001 .532 .035 .556 ,.001 .306 ,.001 .001 ,.001 .004 .477 .334 .092 .934 .488 .057 ,.001 .787 .048 .405 ,.001 .003 .045 .028 ,.001 .998
AFP 5 a-fetoprotein; ALP 5 alkaline phosphatase; ALT 5 alanine aminotransferase; AST 5 aspartate aminotransferase; CI 5 confidence interval; GFR 5 glomerular filtration rate; GGT 5 g-glutamyltransferase; ICG-R15 5 indocyanine green retention rate at 15 minutes; INR 5 international normal ratio; OR 5 odds ratio; PIVKA-II 5 protein-induced by vitamin K antagonism-II.
In this study, we examined patients with HCC who were R70 years of age, identifying their clinicopathologic characteristics and comparing them with patients with HCC who were 60 to 69 years of age. The concept of ‘‘elderly’’ is becoming more difficult to define. The World Health Organization has not determined a standard age and has recently stated that persons aged .60 years could be considered an aged population.11 However, this criterion cannot be applied to all societies. Population aging has progressed more rapidly in South Korea than in any other country. According to a report by Statistics Korea in 2011, the proportion of older people is gradually increasing in Korea. The country is already an aging society, with 11% of the population aged .65 years and 15.7% of the population expected to be .65 years of age in 2020.12 For this reason, we used a cutoff value of 70 years to divide the study patients into younger and older groups to clarify the characteristics of HCC in patients aged .60 years. We believe that this allows for more
reasonable and meaningful comparisons with other previous studies.4,5,13,14 Other modalities of HCC management, such as percutaneous ethanol injection therapy, microwave coagulation therapy, or percutaneous radiofrequency ablation, can be acceptable alternatives to hepatic resection in older people, but the best treatment for older patients remains controversial. Generally, older patients received significant fewer surgical resections than younger patients.15 Liver transplantation has the advantage of removing the cirrhotic liver together with the tumor and restoring liver function. Nevertheless, patients .70 years of age are excluded from living donor liver transplantation programs because of the shortage of donors and cost-effectiveness. Whether hepatectomy affects the survival of older patients with HCC is somewhat controversial. Some studies found significantly higher morbidity and mortality rates in older people after hepatectomy for HCC.4,5 However, recent studies reported that liver resection is a relatively
396 safe procedure even in older patients because of improved surgical techniques, better perioperative assessment, and advances in anesthesia and medical care.14,16,17 Human organ function usually deteriorates with age, and older patients have a high incidence of comorbid illness. In addition, HCC is frequently associated with cirrhosis, which is itself a cause of high mortality and morbidity rates after hepatectomy. Therefore, older patients are considered at high risk for liver resection. In our series, mortality was extremely low, and only a single patient in the younger group died after hepatectomy. Our study showed a difference in etiology of HCC etiology between older and younger patients. The number of patients with a positive HBsAg test was significantly lower in the older group than in the younger group. The proportion of patients negative for HBsAg and anti-HCV antibody was clearly larger in the older than in the younger group. These findings are in agreement with the results of previous studies.10,18 Other reports showed that the average ages of diagnosis are approximately 55 years for HBVrelated HCC, 65 years for HCV-related HCC, and 70 years for non-B, non-C HCC.3,19 In Korea, HBV is predominantly transmitted during the prenatal period. Therefore, a large proportion of patients with cirrhosis and HCC from HBV die before reaching the age of 70 years because HBV is aggressive. Survived older patients have well-preserved hepatic function because HCC was caused by other etiologies. A recent study reported that patients with nonalcoholic steatohepatitis–related HCC are older at diagnosis than those with HCC related to HBV and HCV.20,21 These results suggest that some of cases of non-B, non-C HCC are nonalcoholic steatohepatitis–related HCC. Although our study was retrospective, we analyzed 2 groups of patients that were similar in terms of preoperative characteristics, surgical procedures, and pathologic features. The proportion of elderly patients with diabetes mellitus was higher than in the younger group, but there were no statistical differences in postoperative mortality and morbidity except pneumonia between the 2 groups. The incidence of pneumonia in the elderly group was higher than in the younger group. These patients were treated with antibiotics and lung care and recovered their health. The aggressive lung care after surgery must be needed in elderly patients. Our study found no significant difference in disease-free survival between older and younger patients with HCC. Thus, patient age was not an independent factor for tumor recurrence. These results suggested that preoperative evaluations of older patients with comorbid illnesses and patient selection were adequate in our program. Therefore, selected older patients should be able to tolerate even a major hepatectomy. With improved surgical techniques, better perioperative assessments, and advances in anesthesia and medical care, liver resection has become a safe procedure, even in aged patients.14 Recent improvements in results indicate that many older patients could benefit from surgical management.16,17 The high prevalence of HCC and prolonged life expectancy in the population has led to the
The American Journal of Surgery, Vol 209, No 2, February 2015 reconsideration of treatment strategies in older patients. Our study suggests that hepatectomy is a reasonable treatment option for older patients. This study included a relatively large number of hepatectomy patients. However, our study also had some limitations. First, a selection bias might have been present because data were collected from a single center. Indications for hepatectomy were similar in the older and younger patients in our program, and were according to tumor stage and hepatic functional reserve. However, bias might have resulted from selecting patients with good liver function among older patients referred to our surgical department. Second, we used a retrospective design. Third, patients of the same age can show individual differences in degree of physical aging. We could not collect enough data to evaluate the exact functional age of older patients.
Conclusions The outcomes of older patients with HCC were not different from those of younger patients. The results of this study suggest that the therapeutic strategy for older patients with HCC should be as aggressive as that for younger patients. Our results confirm that age by itself should no longer be considered a risk factor for liver surgery.
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Hepatectomy in older HCC patients
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