Introduction

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide [1] and the fourth most common cancer in Japan [2]. In recent years, the prognosis of HCC patients has improved because of new developments in surgical techniques and perioperative management. Japan has the highest national life expectancy in the world, with life expectancies at birth of 79.55 years for males and 86.30 years for females [3]. Therefore, the rates of hepatic resection for HCC are increasing in elderly patients aged ≥70 years. Recently, and particularly in the 21st century, liver resection has been performed at increasing rates to treat HCC in Japanese patients aged ≥80 years.

Many reports on the outcomes of hepatic resection in elderly HCC patients have been published [4–25, 27]. Previous reports from the 1980 s defined elderly patients as those aged ≥65 years [4–6], whereas reports from 1990 to 2009 defined this group as patients aged ≥70 years and >75 years [12–27]. In the present study with a follow-up period during the most recent decade (2000–2010), the age distribution of HCC patients was as follows: ~40 % were elderly patients aged >70 years and ~5 % were octogenarian patients. Therefore, at our institution, hepatic resection was commonly performed on elderly HCC patients, and hepatectomy had also become relatively common for octogenarian patients with HCC.

The proportion of octogenarian HCC patients is expected to increase further in the near future. In a search of the PubMed database, only a few reports were found that described the outcomes of hepatic resection in HCC patients aged ≥80 years [7–11]. Wu et al. [9] initially reported the surgical outcomes of octogenarian patients with HCC in Taiwan. In Japan, Sirabe et al. [10], Yamada et al. [7] and Tsujita et al. [8] reported on hepatic resection for HCC in patients aged ≥80 years. Nanashima et al. [11] reported that the number of patients in the >80-year age group had increased during the period from 2000 to 2009, and significant differences were not observed among the age groups with regard to long-term prognosis.

In the present study, we evaluated the preoperative and postoperative characteristics and prognosis of super-elderly patients (aged ≥80 years) with HCC to evaluate whether liver resection is appropriate for octogenarian patients.

Methods

The study subjects were 431 patients who underwent initial hepatic resection for HCC between January 2000 and December 2010. The patients were classified into three groups according to their age at the time of surgery: a super-elderly group (n = 20), ≥80 years old; an elderly group (n = 172), 70–80 years old and a younger group (n = 239), <70 years. We compared the patient’s clinical characteristics (background factors, hepatitis viral infection status, preoperative comorbidity and liver function data), surgical factors (hepatic resection type, length of operation, blood loss and blood transfusion status), pathological factors, postoperative complications (including delirium [28]), hospital stay and prognosis among the three groups to evaluate whether liver resection is appropriate for super-elderly patients.

At our institution, the general condition of super-elderly patients is evaluated to determine their ability to tolerate surgery. Most of the patients in the super-elderly group consulted with a specialist who assessed the adequacy of their preoperative cardiovascular and pulmonary condition through electrocardiography, echocardiography, myocardial scintigraphy, respiratory function testing and chest computed tomography. Furthermore, the super-elderly patients also consulted with a psychiatrist who assessed their psychological condition (including the risk of postoperative delirium). Super-elderly patients concerned about postoperative delirium were prescribed antipsychotic treatments by a psychiatrist.

The terminology for the hepatic anatomy and type of liver resection were classified according to the Brisbane 2000 Terminology of Liver Anatomy and Resections [29]. Liver resection was performed according to the criteria proposed by Makuuchi et al. [30]. In the super-elderly group, if more than one type of liver resection was allowed, the less invasive method (shorter operation and less tissue removal) was selected.

The postoperative complications analyzed were those that corresponded to a Clavien-Dindo grade above IIIa. Postoperative delirium was diagnosed by consulting with a psychiatrist. In addition, professional psychiatric treatment was recommended for patients with a Clavien–Dindo grade above II [31]. Postoperative bile leakage [32] and postoperative liver failure [33] were defined and graded according to the guidelines of the International Study Group of Liver Surgery (ISGLS).

This study was conducted in accordance with the declaration of Helsinki and the guidelines of the ethics committee of our institution. Written informed consent was obtained from each patient.

Statistical analysis

The data are presented as medians with the 10th and 90th percentiles. The Tukey–Kramer honest significant difference test or χ 2 test was used to compare clinicopathological variables among the three groups. The survival rates were estimated according to the Kaplan–Meier method, and differences in the survival rates among the groups were compared using the log-rank test. All statistical analyses were performed using a statistical software program (JMP 9.0.0.; SAS, Cary, NC, USA). A p value <0.05 was considered to be significant.

Results

Clinical characteristics of the three groups (Table 1)

The super-elderly group comprised 14 males and six females, with a mean age of 81.5 ± 1.5 years. The elderly group comprised 125 males and 47 females, with a mean age of 73.9 ± 2.6 years. The younger group comprised 199 males and 43 females, with a mean age of 61.6 ± 7.0 years. The percentage of patients positive for the hepatitis B surface antigen (HBs Ag) was higher in the younger group. The percentage of patients positive for the hepatitis C virus antibody (HCV Ab) was higher in the elderly group and the percentage of patients negative for both HBs Ag and HCV Ab (non-B non-C HCC) was higher in the super-elderly group. There were no significant differences among the three groups with regard to alcohol abuse or body mass index. The prevalence of diabetes was lower in the super-elderly group than in the other groups, but the prevalence of hypertension was higher in the super-elderly group compared to the other groups.

Table 1 The preoperative patient characteristics according to age
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The percentages of patients with histories of preoperative cardiac disorders and pulmonary disorders were higher in the super-elderly group than in the other groups, but there were no significant differences in the preoperative complications in other organs among the three groups. All three groups had similar American Society of Anesthesiologist (ASA) scores. The percentage of patients with a history of cancer in other organs and abdominal surgery increased with age. There were no significant differences in the liver function among the three groups, with the exception of the alanine aminotransferase level. No differences were found in the Child-Pugh classifications, alpha-fetoprotein levels or levels of protein induced by vitamin K absence or antagonists-II among the three groups. No differences in the oncological aspects of the disease were found among the three groups.

Intraoperative and postoperative factors of the three groups (Table 2)

Anatomical resection was performed for nine patients in the super-elderly group. However, segmentectomy was selected more often in the super-elderly group than in the other groups. Right lobectomy and trisectionectomy were not performed in the super-elderly group.

Table 2 The postoperative patient characteristics according to age
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The super-elderly group had shorter operations and reduced hemorrhage rates compared to the other groups. Intraoperative transfusions, thoracotomy and laparoscopic hepatectomy were performed at equivalent rates among the three groups. The pathological factors were not significantly different among the three groups. The percentage of patients with a solitary tumor was higher in the super-elderly group.

The percentages of patients with postoperative cardiac disorders and delirium were higher in the super-elderly group than in the other groups, but there were no differences in the postoperative complications associated with other organs among the three groups. The median postoperative hospital stay was 11 days in the super-elderly group, 15 days in the elderly group and 17 days in the younger group.

The long-term prognosis in the three groups

The overall survival rates of the three groups are shown in Fig. 1, and the tumor-free survival rates are shown in Fig. 2. There were no significant differences in the overall survival and tumor-free survival rates among the three groups. The 5-year overall survival rates in the super-elderly, elderly and younger groups were 66.9, 59.5 and 65.3 %, respectively (p = 0.44). The 3-year tumor-free survival rates in the super-elderly, elderly and younger groups were 33.7, 41.2 and 46.4 %, respectively (p = 0.78). The super-elderly group had a lower rate of liver or HCC-related deaths, and a higher rate of death due to other causes (pneumonia, cardiovascular disease, cerebrovascular disease and other malignancy excluding HCC) than the other groups (Table 2).

Fig. 1
figure 1

A comparison of the overall survival curves after primary hepatectomy for the 1 super-elderly (≥80 years), elderly (≥70 years and <80 years) and younger (<70 years) two groups. Thin line is elderly group, dotted line is younger group, and thick line is three super-elderly group

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Fig. 2
figure 2

A comparison of the tumor-free survival curves after primary hepatectomy for the super-elderly (≥80 years), elderly (≥70 years and <80 years) and younger (<70 years) groups. Thin line is elderly group, dotted line is younger group, and thick line is three super-elderly group

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Discussion

There have been many reports about the outcomes of hepatic resection in elderly HCC patients. Over the past few decades, the definition of “elderly patients” has changed. In the 1980s [4–6], elderly patients were defined as those aged ≥65 years, whereas the same term was used for those aged ≥70 years or those >75 years during the period from 1990 to 2009 [12–27]. In the present study, the follow-up period was during the most recent decade (2000–2010), and ~40 % of the elderly HCC patients were aged >70 years. Therefore, hepatic resection for HCC was commonly performed on elderly HCC patients at our institution, and liver resection for octogenarian HCC patients has become relatively common. The proportion of octogenarian patients with HCC is expected to increase in the near future.

Wu [9] stated that octogenarians had a lower incidence of HBs Ag positivity. In the present study, no patient in the super-elderly group was positive for HBs Ag, and only a small proportion of patients were positive for HCV Ab in the elderly group. The proportion of patients negative for both HBs Ag and HCV Ab was higher in the super-elderly group than in the other groups. One reason for this may be that, in Japan, recent HCC screenings for viral hepatitis patients have led to the early detection and rapid treatment of HCC. Additionally, the HBs Ab titers might decrease with age, which may explain why few elderly patients in this study were positive for HBs Ag. In fact, at least three patients in the super-elderly group were positive for the HBs Ab and/or hepatitis B core antibody (data not shown). Some authors have reported that a higher proportion of elderly HCC patients had HCV Ab positivity [15–17]. Therefore, the number of HCV patients aged ≥80 years might increase in the future.

The incidence of preoperative comorbidities among elderly patients is controversial [7–12, 16, 19, 23, 25, 27]. In this study, there were no significant differences among the three groups with respect to the incidence of preoperative systemic complications, with the exception of cardiovascular and respiratory complications and hypertension, which were more common in the super-elderly patients. Kaibori et al. [12] reported that elderly HCC patients were more likely to have a history of alcohol abuse. However, in our study, the super-elderly patients did not have any remarkable history of alcohol consumption. The ASA scores were similar in the three groups in our study. However, most patients in the super-elderly group consulted with specialists, who confirmed the adequacy of their preoperative cardiovascular, pulmonary and psychological condition, including a favorable risk for postoperative delirium. Therefore, in the super-elderly group, the patients had already been pre-selected so that they had a good physical status before they would be considered as candidates for liver resection.

The mean tumor size tended to be larger in the super-elderly group than in the other groups. This might be because of the higher incidence of non-B non-C HCC in this group; as such patients might not have been followed up or screened until the diagnosis of HCC. Although anatomical resection was selected more often for the super-elderly group than for the elderly group, the super-elderly patients tended to undergo less invasive resections (i.e., segmentectomy) than the other groups. Therefore, although the liver resection volume was similar among the three groups, the length of the operation and intraoperative hemorrhage rates were lower in the super-elderly group than in the other groups. Furthermore, the postoperative complication rates did not differ among the three groups. Although the prevalence of cardiovascular disease was higher in the super-elderly group than in the other groups, this difference was not significant.

Delirium is a major complication in elderly patients undergoing liver resection [28]. In the present study, elderly patients, particularly the super-elderly patients, consulted with a psychiatrist to evaluate their preoperative psychiatric condition. The psychiatrist provided advice or premedication for the patients. Therefore, the postoperative delirium rate was relatively low in our patients. Nevertheless, in the present study, the incidence of postoperative delirium was higher in the super-elderly group than in the other groups. Therefore, postoperative delirium needs to be appropriately managed, and meticulous nursing care should be provided to super-elderly patients, especially those who exhibit risk factors for delirium, such as hypoalbuminemia and lengthy operations [28].

The postoperative hospital stay tended to be shorter in the super-elderly group than in the other groups. This was likely because we tended to perform less invasive surgeries on super-elderly patients. The increasing use of laparoscopic surgery has permitted super-elderly HCC patients to undergo less invasive surgeries. Furthermore, the shorter postoperative hospital stays might have led to a reduced risk of delirium in the super-elderly patients. After selection, the outcome of hepatic resection for HCC was not significantly different between the super-elderly group and the other groups.

Nearly all of the previous studies have reported a lack of significant differences between younger and elderly patients with regard to the resection type, length of operation and hemorrhage. Yamamoto et al. [25] reported that, in elderly patients (>70 years), right hepatic lobectomy was associated with an increased risk of postoperative hepatic failure and in-hospital death. They also reported that the regeneration rate of the residual left lobe at 1-month after a right hepatectomy tended to be lower in the elderly group than in the younger groups. Kaibori et al. [12] reported that the liver weight and hepatic blood flow were decreased in elderly patients, whereas Schmucker [26] noted that aging led to decreased hepatic regeneration. In our study, right lobectomy was not performed in the super-elderly group, and therefore, we cannot discuss the outcome of more invasive hepatectomies in super-elderly HCC patients.

In conclusion, super-elderly HCC patients (≥80 years) might have favorable prognoses after hepatic resection if they are appropriately selected and evaluated not only according to their risk of liver function-related complications, but also according to their general condition, including their cardiovascular and pulmonary condition and psychological state.