World J Surg (2014) 38:958–967 DOI 10.1007/s00268-013-2342-9
Impact of Surgery on Quality of Life in Patients with Hepatocellular Carcinoma Yoshihiro Mise • Shouichi Satou • Takeaki Ishizawa • Junichi Kaneko • Taku Aoki • Kiyoshi Hasegawa • Yasuhiko Sugawara • Masatoshi Makuuchi • Norihiro Kokudo
Published online: 5 December 2013 Ó Socie´te´ Internationale de Chirurgie 2013
Abstract Background Liver resection is the mainstay of curative treatment for localized hepatocellular carcinoma (HCC). However, the impact of surgery for HCC on quality of life (QOL) has not been well assessed. Methods Health-related QOL was assessed using the Short Form-36 questionnaire in 108 patients who underwent a liver resection for HCC between January 2004 and January 2008. The QOL assessment was scheduled before and every 3 months after the operation. Patients were divided into two groups based on patient-, tumor-, and surgery-related variables. The physical component summary (PCS) and mental component summary (MCS) were compared between the two groups. Results Altogether, 69 patients (64 %) completed the consecutive QOL assessments until 6 months after surgery. At 3 months, the PCS scores were significantly lower for women and for patients who had undergone thoracotomy than among men (p = 0.010) and patients who had not undergone thoracotomy (p = 0.048), respectively. No significant differences in any of the PCS scores were observed at 6 months. No significant differences in the MCS scores were observed between the groups throughout the investigation, and improvement relative to the preoperative status was observed at 6 months.
Y. Mise S. Satou T. Ishizawa J. Kaneko T. Aoki K. Hasegawa Y. Sugawara N. Kokudo (&) Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan e-mail: [email protected] M. Makuuchi Department of Hepato-Biliary-Pancreatic Surgery, Japanese Red Cross Medical Center, Tokyo, Japan
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Conclusions Physical impairments in the QOL after surgery had returned to the baseline at 6 months, and the postoperative mental QOL improved relative to the preoperative state. The surgical candidates were expected to have a satisfactory QOL regardless of the preoperative status and surgical outcomes. A thoracoabdominal approach had a transient negative impact on the physical health status.
Introduction Liver resection represents the mainstay of curative treatment for localized hepatocellular carcinoma (HCC), providing better prognostic outcomes than other treatments such as percutaneous radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) [1–3]. However, the physical invasiveness of surgical procedures is apparent compared with that of RFA or TACE treatment. Some patients hesitate to undergo liver resection for fear of a prolonged recovery period after the treatment, even when they are good candidates for a curative operation. From the 1990s onward, there has been a growing emphasis on the assessment of quality of life (QOL) in patients with cancer [4–7]. Health-related QOL has become a considerable factor when selecting the optimal treatment. Several studies have evaluated the effects of treatment modalities on health-related QOL in patients with HCC [8– 18]. However, only two reports evaluated the changes in QOL before and after surgical treatment for HCC [19, 20]. Poon et al. [20] first reported that the QOL at 3 months postoperatively was significantly better than the preoperative state. On the other hand, Toro et al. [19] demonstrated that it took more than 12 months to recover to the preoperative baseline in terms of the physical and mental QOL.
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Thus, the time to return to the preoperative baseline QOL after surgery widely varied between the two studies. Several reports have discussed the impact of liver resection on postoperative QOL, reporting a time-to-returnto-baseline of 1.5–12.0 months [21–26]. However, these studies were not disease-specific, and patients with HCC accounted for only around 10 % of the study population. Considering the possible background of cirrhosis, coagulation abnormalities, and, above all, the liver function impairment induced by the surgical procedure itself, the invasiveness of liver resection in patients with HCC has not been adequately evaluated. In this study, a prospective QOL assessment was conducted in patients who underwent liver resection for HCC according to patient-, tumor-, and surgery-related variables. The aim of this study was to assess the impact of surgical invasiveness on the QOL in HCC patients and to identify perioperative factors affecting changes in the QOL.
Methods Patients Between January 2004 and January 2008, a total of 201 patients underwent liver resection for the treatment of HCC at The University of Tokyo Hospital. Informed consent and eligible responses to the QOL questionnaires described below were obtained from 108 of the 201 patients (53 %). Surgical procedures Consistent criteria for surgical treatment were applied in this study. The extent of liver resection was based on the
Table 1 Characteristics of 69 patinets who completed the consecutive QOL assessment until 6 months after surgery
serum total bilirubin level and liver function, as estimated using the indocyanine green retention rate at 15 min (ICGR15) [27]. The standard procedures for liver resection used in this study have been described elsewhere [28, 29]. The use of a thoracoabdominal approach to obtain a better surgical field was left to the discretion of the surgeons in cases where the tumors were located on the right side of the liver. Perioperative morbidity and mortality were monitored and stratified according to the Clavien-Dindo classification of surgical complications [30].
Study protocols This endeavor was conducted as an observational study of patient QOL before surgery and at every 3 months after surgery. No study-specific treatment was provided to the patients as part of this assessment. Upon enrollment, the study coordinator or research assistant completed the treatment history and demographics. QOL questionnaires were assessed at the scheduled followup appointments and did not burden the patients. If the patients missed the appointments or continued the follow-up at another hospital, the questionnaires were mailed to the patients. Clinical events were reviewed based on the medical records. Patients were divided into two groups based on the following variables (Table 1): patient-related variables (age, sex, ICGR15), tumor-related variables (maximum size, number of tumors, pTMN stage), and surgery-related variables (operation time, blood loss, blood transfusion, extent of liver resection, history of previous liver resection, thoracoabdominal approach, morbidity).
Patient-related Age (year)
69
\70/C70
37/32
Male/female
55/14
(4.8–52.3)
\10/C10
19/50
(35–90)
Sex ICGR15 (%)
11.9
Tumor-related Maximum size (cm)
4.0
(1.1–14.5)
\5/C5
37/32
Number of tumors
1
(1–6)
Solitary/multiple
50/19
I:II/III:IV
11:25/28:5
pTNM stage Surgery-related Operation time (h)
5.8
(1.3–10.7)
\6/C6
39/30
Blood loss (ml)
740
(0–3,390)
\1,000/C1,000
48/21
Red blood cell transfusion Extent of liver resection
No/yes \2 segments/C2 segments
62/7 49/20
Data were expressed as the median (range)
History of liver resection
Initial/repeated
61/8
Thoracoabdominal approach
No/yes
30/39
ICGR15 indocyanine green retention rate at 15 minutes
Morbidity
No/yes
44/25
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Instrument for QOL assessment The health-related QOL of the patients was assessed using the Short-Form 36 (SF-36) health status survey version 1.2, which is one of the most widely used instruments for assessing QOL in patients with cancer [31–35]. The SF-36 assesses eight health concepts: (1) limitations in physical activities because of health problems (physical function); (2) limitations in usual role activities because of physical health problems (role-physical); (3) physical pain (bodily pain); (4) perception of general health (general health); (5) vitality, energy, and fatigue (vitality); (6) limitations in social activities because of physical or emotional problems (social function); (7) limitations in usual role activities because of emotional problems (role-emotional); (8) general mental health, psychological distress, and well-being (mental health).The raw scale scores were transformed to norm-based scores for all eight subsets. The physical component summary (PCS) and the mental component summary (MCS) were calculated from the scores to simplify the interpretation of the results. The PCS, mainly derived from physical function, role-physical, bodily pain, and general health, reflects the patient’s overall physical health status. The MCS is derived mainly from vitality, social function, role-emotional, and mental health, reflecting the overall mental health status. The derived scores were standardized to the general Japanese population (mean score 50; standard deviation 10). Scoring of the SF-36 was performed according to the methods described by Ware [34] and Ware and Gandek [35]. Statistical analysis Clinical data were analyzed using the statistical software JMP (SAS Institute Japan, Tokyo, Japan). Continuous variables were compared using the Mann–Whitney U test, and categoric variables were compared with v2 tests. A value of p \ 0.050 was considered statistically significant. All analyses were performed in accordance with the ethical guidelines for clinical studies at The University of Tokyo Hospital.
Results Patient population Of the 108 patients, 69 (64 %) completed the consecutive QOL assessment before surgery and up to 6 months after surgery. Overall, 23 patients (21 %) completed the assessment up to 12 months after surgery. Table 1 shows the demographics of the 69 patients and the subgroups classified according to patient-, tumor-, and surgery-related variables.
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Fig. 1 Changes in quality of life (QOL) over 12 months after surgery in 23 patients. Mean scores of the physical component summary (PCS) and the mental component summary (MCS) are shown. The MCS scores at 9 and 12 months were significantly higher than the preoperative scores (p = 0.011 and 0.028, respectively)
Surgical outcomes No hospital mortalities occurred among the 69 patients. Postoperative morbidity occurred in 25 patients (38 %), with wound infection occurring in 2 patients (grade I), viral colitis in 1 (grade I), ascites in 6 (grade I), pleural effusion in 9 (grade I), bile leakage in 8 (7 with grade I and 1 with grade IIIb), and postoperative bleeding in 1 (grade II). The median hospital stay after surgery was 15 days (range 8–44 days). Changes in QOL over 12 months after surgery Figure 1 shows the longitudinal changes in the mean QOL scores in the 23 patients who completed the consecutive questionnaires until 12 months after surgery. The physical health status was temporarily impaired after surgery, whereas the mental health status improved immediately after surgery and reached the Japanese national norm within 9 months, demonstrating a significant difference compared with the preoperative status (p = 0.011). QOL changes over 6 months stratified according to variables Time series changes within subgroups Figures 2, 3, and 4 show the QOL changes over 6 months of two subgroups classified according to patient-, tumor-, and surgery-related variables, respectively. Compared with the preoperative state, the PCS at 3 months was significantly lower in patients who were \70 years (p = 0.028), patients with an ICGR15 \ 10 % (p = 0.034), patients with a tumor size of \5 cm (p = 0.031), and patients who underwent thoracotomy (p = 0.026). No significant difference was observed in the MCS scores at 3 or 6 months compared with the preoperative scores for any of the variables. The mean MCS scores at 6 months were higher
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Fig. 2 Changes in QOL over 6 months stratified according to patient-related variables. In patients \ 70 years of age and patients with ICGR15 \ 10 %, the PCS scores at 3 months were significantly lower than the preoperative scores (p = 0.028, and 0.034, respectively, dotted line). In comparisons with each subgroup, the PCS scores at 3 months after surgery were significantly lower in women than in men (p = 0.010, line with asterisk). ICGR15: indocyanine green retention rate at 15 min
than the preoperative score except in patients who were 70 years and patients with multiple tumors. Comparison between the subgroups In comparison with each subgroup, the PCS scores at 3 months after surgery were significantly lower in women than in men (p = 0.010). The PCS scores at 6 months and the MCS scores throughout the study period showed no significant difference between the subgroups for any of the variables. The MCS of patients with repeated resection was relatively high (close to that of the general population) throughout the observation period, compared with that of patients who underwent an initial liver resection. As for surgery-related variables, the physical health status at 3 months was significantly impaired in patients treated with a thoracoabdominal approach (p = 0.048). Figure 5 shows the QOL scores on the eight subsets at 3
and 6 months for patients treated with and those treated without a thoracoabdominal approach. Only the bodily pain score at 3 months was significantly lower in the patients who had undergone thoracotomy (p = 0.014). However, no significant differences were observed at 6 months.
Discussion In this study, QOL changes in patients who had undergone liver resection for HCC were assessed according to variables related to the patients, tumors, and surgical procedures. The results provided the following conclusions. First, the physical impairment of QOL following surgical treatment returned to baseline within 6 months, whereas the mental QOL improved, relative to the preoperative state, immediately after the operation. Second, the selected candidates for surgery were expected to have a satisfactory
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Fig. 3 Changes in QOL over 6 months stratified according to tumor-related variables. In patients with a tumor \ 5 cm, the PCS scores at 3 months were significantly lower than the preoperative scores (p = 0.031, dotted line)
QOL regardless of the preoperative status and surgical outcomes. Finally, a thoracoabdominal approach impaired the physical QOL for 3 months, especially in terms of bodily pain, although the deteriorated physical QOL had recovered at 6 months. Surgical treatment for HCC impaired the physical QOL temporarily. However, surgical removal of the tumors improved the mental QOL steadily over the national average. The results of longitudinal QOL scores demonstrated that physical QOL was significantly worse at 3 months in several subgroups, although it had returned to the preoperative baseline at 6 months for all of the variables. Interestingly, a significant deterioration in the physical QOL at 3 months, compared with the preoperative state, was observed in patients with good preoperative status (i.e., an age \ 70 years, an ICGR15 \ 10 %, and maximum tumor size \5 cm. However, a comparison between the physical QOL at 3 months with that of patients
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who had a worse preoperative status showed no significant difference between the subgroups. This finding suggests that patients in a good preoperative state are susceptible to physical invasiveness even though the impact of the surgical invasiveness on the physical QOL does not differ, regardless of the preoperative state. Mental QOL was not impaired after the operation. Moreover, the MCS at 6 months was higher than the preoperative score for most of the variables. The consecutive analysis at 12 months demonstrated steady improvement in the MCS scores, reaching the national average. The benefit of surgical removal of HCCs to the mental QOL has been reported in previous prospective studies. Poon et al. [20] demonstrated that the physical and mental QOL scores at 3 months after surgery for HCC were significantly better than the preoperative scores. They noted that removal of the tumors not only improved physical well-being but enhanced the social and emotional health status. In a
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Fig. 4 Changes in QOL over 6 months stratified according to surgery-related variables. In patients treated with a thoracotomy, the PCS scores at 3 months were significantly lower than the preoperative scores (p = 0.026, dotted line). The PCS at 3 months was also impaired in these thoracotomytreated patients when compared with those without a thoracotomy (p = 0.048, line with asterisk)
comparative study of treatments for HCC [19], sustainable improvement in the mental and physical QOL was observed after liver resection until 24 months. In contrast, a steady decline in the QOL over the follow-up period was demonstrated in patients with RFA and TACE. The anxiety resulting from the tumor remnant even after treatment was thought to have caused the decline in the mental QOL after RFA and TACE. Further investigation of the impact on QOL following not only surgery but also RFA or TACE
would help with selecting the optimal treatment for HCC from the viewpoints of the patient’s QOL and prognosis. The surgical procedures and outcomes did not affect the QOL scores, which confirmed the safety of liver resection for HCC from the aspect of health-related QOL. Candidates for surgical treatment of HCC are highly selected in terms of their liver function and tumor status. The strict selection criteria have contributed to recent refinements in the safety of liver surgery. Among these highly selected
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Fig. 4 continued
patients, our survey showed that the postoperative QOL was not impaired regardless of the preoperative status or the surgical outcomes. Previous studies have reported positive correlations between liver function and healthrelated QOL in patients with chronic liver disease [12, 15]. However, in the present survey, no differences in the QOL scores were observed between subgroups stratified according to their ICGR15 values. This result implies that the candidates selected for surgery were expected to have comparable QOL outcomes, regardless of liver function. As for surgery-related factors, the result that the extent of the liver resection did not affect the postoperative QOL agrees with the results of previous reports [20, 23], providing further justification for an aggressive surgical approach, as needed. Postoperative complications did not have a significant impact on the QOL, which is also compatible with the results of previous reports [20, 23] The low rate of severe complications requiring intervention (1 %) contributed to the result that postoperative morbidity did not have a lasting adverse effect on the QOL.
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To our knowledge, this study was the first attempt to estimate the invasiveness of the thoracoabdominal approach quantitatively in terms of health-related QOL scores. During right-sided liver resections, the thoracoabdominal approach provides a wider surgical field, easier access to the zone around the inferior vena cava, and a quicker response to unexpected bleeding from the hepatic veins, compared with the conventional abdominal approach. The benefit and the safety of the thoracoabdominal approach have been discussed previously. Some reports demonstrated shorter operative times and less blood loss using the thoracoabdominal approach [36–38], whereas others have reported increased invasiveness and morbidity [36, 39–43]. In the present study, the thoracoabdominal approach was the only surgery-related variable that affected the physical QOL in terms of bodily pain at 3 months. However, impaired physical health status had recovered at 6 months. The result implies that the temporary physical impairment caused by thoracotomy might be justified in cases where a good surgical view, which is a
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women were consistently low, resulting in a significant difference between the sexes at 3 months. Female sex is reportedly associated with an impaired health-related QOL for several diseases including chronic hepatitis [12, 15, 50– 54]. Some investigators have suggested that sex differences in health-related QOL are due to the differences in the expression of somatic complaints and psychological illnesses [54, 55]. Others have speculated that female patients are more sensitive to impaired physical activity while performing daily housework [12]. No convincing explanation has been made. However, the consistently reported impairment of QOL in women must be kept in mind during daily clinical practice. The results of this prospective survey should be interpreted with caution because the dropout patients (39/108) might have resulted in an overestimation of the actual health-related QOL. Only healthy individuals or those who were satisfied with their surgical results might have responded to the questionnaires at all time points.
Conclusions
Fig. 5 Mean scores for eight health concepts in patients with or without a thoracotomy. a Scores at 3 months. The pain score was significantly lower in patients with thoracotomy than in those who did not undergo thoracotomy (p = 0.014, line with asterisk). b Scores at 6 months. No significant differences were observed
basic requirement for safe liver resection, is difficult to obtain. A previous liver resection mentally indurates patients for repeated surgical treatment. Repeated resection is the treatment of choice for the recurrence of HCC, offering acceptable prognostic outcomes [44–49]. We performed aggressive repeated resection according to the same indication criteria as those used for the initial hepatectomy for HCC [49]. In this study, the MCS of patients with repeated resection was relatively high, close to that of the general population, throughout the observation period including the preoperative state, compared with that of patients who underwent an initial surgical treatment, although no significant difference was observed. This result supports the efficacy of repeated resection for recurrent HCC from a mental viewpoint as well. A history of initial hepatectomy reduces patients’ anxiety regarding surgical treatment, and the relief that a repeated resection is available for the treatment of a recurrence might also sustain patients with recurrent HCC. The impaired physical QOL of female patients requires special consideration when determining strategies for postoperative management. Physical QOL scores in
Liver resection for HCC provides a satisfactory postoperative QOL regardless of the preoperative status and surgical outcomes. However, the thoracoabdominal approach can temporarily impair physical QOL. Acknowledgments This study was supported by a grant-in-aid for Scientific Research from the Ministry of Health, Labor, and Welfare of Japan.
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Impact of Surgery on Quality of Life in Patients with Hepatocellular Carcinoma Yoshihiro Mise • Shouichi Satou • Takeaki Ishizawa • Junichi Kaneko • Taku Aoki • Kiyoshi Hasegawa • Yasuhiko Sugawara • Masatoshi Makuuchi • Norihiro Kokudo
Published online: 5 December 2013 Ó Socie´te´ Internationale de Chirurgie 2013
Abstract Background Liver resection is the mainstay of curative treatment for localized hepatocellular carcinoma (HCC). However, the impact of surgery for HCC on quality of life (QOL) has not been well assessed. Methods Health-related QOL was assessed using the Short Form-36 questionnaire in 108 patients who underwent a liver resection for HCC between January 2004 and January 2008. The QOL assessment was scheduled before and every 3 months after the operation. Patients were divided into two groups based on patient-, tumor-, and surgery-related variables. The physical component summary (PCS) and mental component summary (MCS) were compared between the two groups. Results Altogether, 69 patients (64 %) completed the consecutive QOL assessments until 6 months after surgery. At 3 months, the PCS scores were significantly lower for women and for patients who had undergone thoracotomy than among men (p = 0.010) and patients who had not undergone thoracotomy (p = 0.048), respectively. No significant differences in any of the PCS scores were observed at 6 months. No significant differences in the MCS scores were observed between the groups throughout the investigation, and improvement relative to the preoperative status was observed at 6 months.
Y. Mise S. Satou T. Ishizawa J. Kaneko T. Aoki K. Hasegawa Y. Sugawara N. Kokudo (&) Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan e-mail: [email protected] M. Makuuchi Department of Hepato-Biliary-Pancreatic Surgery, Japanese Red Cross Medical Center, Tokyo, Japan
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Conclusions Physical impairments in the QOL after surgery had returned to the baseline at 6 months, and the postoperative mental QOL improved relative to the preoperative state. The surgical candidates were expected to have a satisfactory QOL regardless of the preoperative status and surgical outcomes. A thoracoabdominal approach had a transient negative impact on the physical health status.
Introduction Liver resection represents the mainstay of curative treatment for localized hepatocellular carcinoma (HCC), providing better prognostic outcomes than other treatments such as percutaneous radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) [1–3]. However, the physical invasiveness of surgical procedures is apparent compared with that of RFA or TACE treatment. Some patients hesitate to undergo liver resection for fear of a prolonged recovery period after the treatment, even when they are good candidates for a curative operation. From the 1990s onward, there has been a growing emphasis on the assessment of quality of life (QOL) in patients with cancer [4–7]. Health-related QOL has become a considerable factor when selecting the optimal treatment. Several studies have evaluated the effects of treatment modalities on health-related QOL in patients with HCC [8– 18]. However, only two reports evaluated the changes in QOL before and after surgical treatment for HCC [19, 20]. Poon et al. [20] first reported that the QOL at 3 months postoperatively was significantly better than the preoperative state. On the other hand, Toro et al. [19] demonstrated that it took more than 12 months to recover to the preoperative baseline in terms of the physical and mental QOL.
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Thus, the time to return to the preoperative baseline QOL after surgery widely varied between the two studies. Several reports have discussed the impact of liver resection on postoperative QOL, reporting a time-to-returnto-baseline of 1.5–12.0 months [21–26]. However, these studies were not disease-specific, and patients with HCC accounted for only around 10 % of the study population. Considering the possible background of cirrhosis, coagulation abnormalities, and, above all, the liver function impairment induced by the surgical procedure itself, the invasiveness of liver resection in patients with HCC has not been adequately evaluated. In this study, a prospective QOL assessment was conducted in patients who underwent liver resection for HCC according to patient-, tumor-, and surgery-related variables. The aim of this study was to assess the impact of surgical invasiveness on the QOL in HCC patients and to identify perioperative factors affecting changes in the QOL.
Methods Patients Between January 2004 and January 2008, a total of 201 patients underwent liver resection for the treatment of HCC at The University of Tokyo Hospital. Informed consent and eligible responses to the QOL questionnaires described below were obtained from 108 of the 201 patients (53 %). Surgical procedures Consistent criteria for surgical treatment were applied in this study. The extent of liver resection was based on the
Table 1 Characteristics of 69 patinets who completed the consecutive QOL assessment until 6 months after surgery
serum total bilirubin level and liver function, as estimated using the indocyanine green retention rate at 15 min (ICGR15) [27]. The standard procedures for liver resection used in this study have been described elsewhere [28, 29]. The use of a thoracoabdominal approach to obtain a better surgical field was left to the discretion of the surgeons in cases where the tumors were located on the right side of the liver. Perioperative morbidity and mortality were monitored and stratified according to the Clavien-Dindo classification of surgical complications [30].
Study protocols This endeavor was conducted as an observational study of patient QOL before surgery and at every 3 months after surgery. No study-specific treatment was provided to the patients as part of this assessment. Upon enrollment, the study coordinator or research assistant completed the treatment history and demographics. QOL questionnaires were assessed at the scheduled followup appointments and did not burden the patients. If the patients missed the appointments or continued the follow-up at another hospital, the questionnaires were mailed to the patients. Clinical events were reviewed based on the medical records. Patients were divided into two groups based on the following variables (Table 1): patient-related variables (age, sex, ICGR15), tumor-related variables (maximum size, number of tumors, pTMN stage), and surgery-related variables (operation time, blood loss, blood transfusion, extent of liver resection, history of previous liver resection, thoracoabdominal approach, morbidity).
Patient-related Age (year)
69
\70/C70
37/32
Male/female
55/14
(4.8–52.3)
\10/C10
19/50
(35–90)
Sex ICGR15 (%)
11.9
Tumor-related Maximum size (cm)
4.0
(1.1–14.5)
\5/C5
37/32
Number of tumors
1
(1–6)
Solitary/multiple
50/19
I:II/III:IV
11:25/28:5
pTNM stage Surgery-related Operation time (h)
5.8
(1.3–10.7)
\6/C6
39/30
Blood loss (ml)
740
(0–3,390)
\1,000/C1,000
48/21
Red blood cell transfusion Extent of liver resection
No/yes \2 segments/C2 segments
62/7 49/20
Data were expressed as the median (range)
History of liver resection
Initial/repeated
61/8
Thoracoabdominal approach
No/yes
30/39
ICGR15 indocyanine green retention rate at 15 minutes
Morbidity
No/yes
44/25
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Instrument for QOL assessment The health-related QOL of the patients was assessed using the Short-Form 36 (SF-36) health status survey version 1.2, which is one of the most widely used instruments for assessing QOL in patients with cancer [31–35]. The SF-36 assesses eight health concepts: (1) limitations in physical activities because of health problems (physical function); (2) limitations in usual role activities because of physical health problems (role-physical); (3) physical pain (bodily pain); (4) perception of general health (general health); (5) vitality, energy, and fatigue (vitality); (6) limitations in social activities because of physical or emotional problems (social function); (7) limitations in usual role activities because of emotional problems (role-emotional); (8) general mental health, psychological distress, and well-being (mental health).The raw scale scores were transformed to norm-based scores for all eight subsets. The physical component summary (PCS) and the mental component summary (MCS) were calculated from the scores to simplify the interpretation of the results. The PCS, mainly derived from physical function, role-physical, bodily pain, and general health, reflects the patient’s overall physical health status. The MCS is derived mainly from vitality, social function, role-emotional, and mental health, reflecting the overall mental health status. The derived scores were standardized to the general Japanese population (mean score 50; standard deviation 10). Scoring of the SF-36 was performed according to the methods described by Ware [34] and Ware and Gandek [35]. Statistical analysis Clinical data were analyzed using the statistical software JMP (SAS Institute Japan, Tokyo, Japan). Continuous variables were compared using the Mann–Whitney U test, and categoric variables were compared with v2 tests. A value of p \ 0.050 was considered statistically significant. All analyses were performed in accordance with the ethical guidelines for clinical studies at The University of Tokyo Hospital.
Results Patient population Of the 108 patients, 69 (64 %) completed the consecutive QOL assessment before surgery and up to 6 months after surgery. Overall, 23 patients (21 %) completed the assessment up to 12 months after surgery. Table 1 shows the demographics of the 69 patients and the subgroups classified according to patient-, tumor-, and surgery-related variables.
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Fig. 1 Changes in quality of life (QOL) over 12 months after surgery in 23 patients. Mean scores of the physical component summary (PCS) and the mental component summary (MCS) are shown. The MCS scores at 9 and 12 months were significantly higher than the preoperative scores (p = 0.011 and 0.028, respectively)
Surgical outcomes No hospital mortalities occurred among the 69 patients. Postoperative morbidity occurred in 25 patients (38 %), with wound infection occurring in 2 patients (grade I), viral colitis in 1 (grade I), ascites in 6 (grade I), pleural effusion in 9 (grade I), bile leakage in 8 (7 with grade I and 1 with grade IIIb), and postoperative bleeding in 1 (grade II). The median hospital stay after surgery was 15 days (range 8–44 days). Changes in QOL over 12 months after surgery Figure 1 shows the longitudinal changes in the mean QOL scores in the 23 patients who completed the consecutive questionnaires until 12 months after surgery. The physical health status was temporarily impaired after surgery, whereas the mental health status improved immediately after surgery and reached the Japanese national norm within 9 months, demonstrating a significant difference compared with the preoperative status (p = 0.011). QOL changes over 6 months stratified according to variables Time series changes within subgroups Figures 2, 3, and 4 show the QOL changes over 6 months of two subgroups classified according to patient-, tumor-, and surgery-related variables, respectively. Compared with the preoperative state, the PCS at 3 months was significantly lower in patients who were \70 years (p = 0.028), patients with an ICGR15 \ 10 % (p = 0.034), patients with a tumor size of \5 cm (p = 0.031), and patients who underwent thoracotomy (p = 0.026). No significant difference was observed in the MCS scores at 3 or 6 months compared with the preoperative scores for any of the variables. The mean MCS scores at 6 months were higher
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Fig. 2 Changes in QOL over 6 months stratified according to patient-related variables. In patients \ 70 years of age and patients with ICGR15 \ 10 %, the PCS scores at 3 months were significantly lower than the preoperative scores (p = 0.028, and 0.034, respectively, dotted line). In comparisons with each subgroup, the PCS scores at 3 months after surgery were significantly lower in women than in men (p = 0.010, line with asterisk). ICGR15: indocyanine green retention rate at 15 min
than the preoperative score except in patients who were 70 years and patients with multiple tumors. Comparison between the subgroups In comparison with each subgroup, the PCS scores at 3 months after surgery were significantly lower in women than in men (p = 0.010). The PCS scores at 6 months and the MCS scores throughout the study period showed no significant difference between the subgroups for any of the variables. The MCS of patients with repeated resection was relatively high (close to that of the general population) throughout the observation period, compared with that of patients who underwent an initial liver resection. As for surgery-related variables, the physical health status at 3 months was significantly impaired in patients treated with a thoracoabdominal approach (p = 0.048). Figure 5 shows the QOL scores on the eight subsets at 3
and 6 months for patients treated with and those treated without a thoracoabdominal approach. Only the bodily pain score at 3 months was significantly lower in the patients who had undergone thoracotomy (p = 0.014). However, no significant differences were observed at 6 months.
Discussion In this study, QOL changes in patients who had undergone liver resection for HCC were assessed according to variables related to the patients, tumors, and surgical procedures. The results provided the following conclusions. First, the physical impairment of QOL following surgical treatment returned to baseline within 6 months, whereas the mental QOL improved, relative to the preoperative state, immediately after the operation. Second, the selected candidates for surgery were expected to have a satisfactory
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Fig. 3 Changes in QOL over 6 months stratified according to tumor-related variables. In patients with a tumor \ 5 cm, the PCS scores at 3 months were significantly lower than the preoperative scores (p = 0.031, dotted line)
QOL regardless of the preoperative status and surgical outcomes. Finally, a thoracoabdominal approach impaired the physical QOL for 3 months, especially in terms of bodily pain, although the deteriorated physical QOL had recovered at 6 months. Surgical treatment for HCC impaired the physical QOL temporarily. However, surgical removal of the tumors improved the mental QOL steadily over the national average. The results of longitudinal QOL scores demonstrated that physical QOL was significantly worse at 3 months in several subgroups, although it had returned to the preoperative baseline at 6 months for all of the variables. Interestingly, a significant deterioration in the physical QOL at 3 months, compared with the preoperative state, was observed in patients with good preoperative status (i.e., an age \ 70 years, an ICGR15 \ 10 %, and maximum tumor size \5 cm. However, a comparison between the physical QOL at 3 months with that of patients
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who had a worse preoperative status showed no significant difference between the subgroups. This finding suggests that patients in a good preoperative state are susceptible to physical invasiveness even though the impact of the surgical invasiveness on the physical QOL does not differ, regardless of the preoperative state. Mental QOL was not impaired after the operation. Moreover, the MCS at 6 months was higher than the preoperative score for most of the variables. The consecutive analysis at 12 months demonstrated steady improvement in the MCS scores, reaching the national average. The benefit of surgical removal of HCCs to the mental QOL has been reported in previous prospective studies. Poon et al. [20] demonstrated that the physical and mental QOL scores at 3 months after surgery for HCC were significantly better than the preoperative scores. They noted that removal of the tumors not only improved physical well-being but enhanced the social and emotional health status. In a
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Fig. 4 Changes in QOL over 6 months stratified according to surgery-related variables. In patients treated with a thoracotomy, the PCS scores at 3 months were significantly lower than the preoperative scores (p = 0.026, dotted line). The PCS at 3 months was also impaired in these thoracotomytreated patients when compared with those without a thoracotomy (p = 0.048, line with asterisk)
comparative study of treatments for HCC [19], sustainable improvement in the mental and physical QOL was observed after liver resection until 24 months. In contrast, a steady decline in the QOL over the follow-up period was demonstrated in patients with RFA and TACE. The anxiety resulting from the tumor remnant even after treatment was thought to have caused the decline in the mental QOL after RFA and TACE. Further investigation of the impact on QOL following not only surgery but also RFA or TACE
would help with selecting the optimal treatment for HCC from the viewpoints of the patient’s QOL and prognosis. The surgical procedures and outcomes did not affect the QOL scores, which confirmed the safety of liver resection for HCC from the aspect of health-related QOL. Candidates for surgical treatment of HCC are highly selected in terms of their liver function and tumor status. The strict selection criteria have contributed to recent refinements in the safety of liver surgery. Among these highly selected
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Fig. 4 continued
patients, our survey showed that the postoperative QOL was not impaired regardless of the preoperative status or the surgical outcomes. Previous studies have reported positive correlations between liver function and healthrelated QOL in patients with chronic liver disease [12, 15]. However, in the present survey, no differences in the QOL scores were observed between subgroups stratified according to their ICGR15 values. This result implies that the candidates selected for surgery were expected to have comparable QOL outcomes, regardless of liver function. As for surgery-related factors, the result that the extent of the liver resection did not affect the postoperative QOL agrees with the results of previous reports [20, 23], providing further justification for an aggressive surgical approach, as needed. Postoperative complications did not have a significant impact on the QOL, which is also compatible with the results of previous reports [20, 23] The low rate of severe complications requiring intervention (1 %) contributed to the result that postoperative morbidity did not have a lasting adverse effect on the QOL.
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To our knowledge, this study was the first attempt to estimate the invasiveness of the thoracoabdominal approach quantitatively in terms of health-related QOL scores. During right-sided liver resections, the thoracoabdominal approach provides a wider surgical field, easier access to the zone around the inferior vena cava, and a quicker response to unexpected bleeding from the hepatic veins, compared with the conventional abdominal approach. The benefit and the safety of the thoracoabdominal approach have been discussed previously. Some reports demonstrated shorter operative times and less blood loss using the thoracoabdominal approach [36–38], whereas others have reported increased invasiveness and morbidity [36, 39–43]. In the present study, the thoracoabdominal approach was the only surgery-related variable that affected the physical QOL in terms of bodily pain at 3 months. However, impaired physical health status had recovered at 6 months. The result implies that the temporary physical impairment caused by thoracotomy might be justified in cases where a good surgical view, which is a
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women were consistently low, resulting in a significant difference between the sexes at 3 months. Female sex is reportedly associated with an impaired health-related QOL for several diseases including chronic hepatitis [12, 15, 50– 54]. Some investigators have suggested that sex differences in health-related QOL are due to the differences in the expression of somatic complaints and psychological illnesses [54, 55]. Others have speculated that female patients are more sensitive to impaired physical activity while performing daily housework [12]. No convincing explanation has been made. However, the consistently reported impairment of QOL in women must be kept in mind during daily clinical practice. The results of this prospective survey should be interpreted with caution because the dropout patients (39/108) might have resulted in an overestimation of the actual health-related QOL. Only healthy individuals or those who were satisfied with their surgical results might have responded to the questionnaires at all time points.
Conclusions
Fig. 5 Mean scores for eight health concepts in patients with or without a thoracotomy. a Scores at 3 months. The pain score was significantly lower in patients with thoracotomy than in those who did not undergo thoracotomy (p = 0.014, line with asterisk). b Scores at 6 months. No significant differences were observed
basic requirement for safe liver resection, is difficult to obtain. A previous liver resection mentally indurates patients for repeated surgical treatment. Repeated resection is the treatment of choice for the recurrence of HCC, offering acceptable prognostic outcomes [44–49]. We performed aggressive repeated resection according to the same indication criteria as those used for the initial hepatectomy for HCC [49]. In this study, the MCS of patients with repeated resection was relatively high, close to that of the general population, throughout the observation period including the preoperative state, compared with that of patients who underwent an initial surgical treatment, although no significant difference was observed. This result supports the efficacy of repeated resection for recurrent HCC from a mental viewpoint as well. A history of initial hepatectomy reduces patients’ anxiety regarding surgical treatment, and the relief that a repeated resection is available for the treatment of a recurrence might also sustain patients with recurrent HCC. The impaired physical QOL of female patients requires special consideration when determining strategies for postoperative management. Physical QOL scores in
Liver resection for HCC provides a satisfactory postoperative QOL regardless of the preoperative status and surgical outcomes. However, the thoracoabdominal approach can temporarily impair physical QOL. Acknowledgments This study was supported by a grant-in-aid for Scientific Research from the Ministry of Health, Labor, and Welfare of Japan.
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