Abstract
[Purpose] The purpose of this study was to investigate the relationship among aging factors using the new Japanese elderly standard, early postoperative physical function, and health-related quality of life (HRQOL) in patients with gastrointestinal cancer. [Participants and Methods] We studied 94 patients scheduled for elective surgery of gastrointestinal cancer: 53 males and 41 females aged 62.0 ± 12.1 years (mean ± SD). Patients were divided into three groups based on age at baseline: young (<65 years), pre-old (65–74 years), and old (≥75 years) groups. We measured body mass index, isometric knee extension force (IKEF), 6-minute walk test (6MWT), and Short-Form 36-Item Health Survey version 2 (SF-36) at baseline and 4 weeks after surgery. [Results] Patients 75 years or older had significantly lower IKEF and 6MWT compared to the other groups. Patients younger than 65 years had significantly greater scores on the mental health SF36 subscale 4 weeks after surgery compared to baseline. Comparatively, patients older than 75 years had significantly decreased mental health scores 4 weeks after surgery. [Conclusion] Based on the new Japanese elderly standard, advanced age appears to worsen the postoperative change of HRQOL in patients with gastrointestinal cancer.
Key words: Elderly, Gastrointestinal cancer, Postoperative quality of life
INTRODUCTION
Previous work around the world has shown that aging of patients with gastrointestinal cancer increases perioperative risk factors, such as onset of postoperative complications1, 2), reduces postoperative health-related quality of life (HRQOL)3) and also reduced physical function after surgery4). The International Society of Geriatric Oncology and National Comprehensive Cancer Network recommend the incorporation of geriatric assessment in treatment planning5,6,7). Thus, the utility of geriatric assessment is being recognized increasingly in oncology.
The classification of “older” in Japan was previously defined as 65 years of age or higher, the same as other countries8). Additionally, Japanese “older” was sub-classified two groups: the young-old, 65 to 74 years old, and the old-old, 75 years of age or older. However, medical advances and improved educational standards have prompted a revision of these standards. In particular, the physical function in older of 65 years of age of higher at 2006 were significantly increased compared with older at 1997. From these things, the Japan Geriatrics society proposed changing the definition of older to 75 years of age or older8). Consequently, Japanese medical research needs to be reevaluated based on how this new Japanese elderly standard influences treatment progress of various diseases. As mentioned previously, important clinical outcome such as physical function and HRQOL in patients with gastrointestinal cancer should be investigate how new Japanese elderly standard influences.
The purpose of this study was to investigate how this new Japanese elderly standard influences postoperative course such as physical function and HRQOL in surgical patients with gastrointestinal cancer at a single center.
PARTICIPANTS AND METHODS
This study was approved by the Research Ethics Board of the International University Health and Welfare Mita Hospital, Minato-ku, Tokyo, Japan. All study procedures were carried out in accordance with ethical standards (registration: 5-15-1). In addition, all participants received an explanation of the research and agreed to participate based on the Declaration of Helsinki. Participants were scheduled for elective surgery for gastrointestinal cancer or suspected gastrointestinal cancer at the International University Health and Welfare Mita Hospital between April 1, 2012, and December 31, 2017. Patients were excluded if the surgery was performed emergently, if the non-malignancy tumor was diagnosed after surgery, if it corresponded with a heavy impact postoperative course such as under the Dindo-Clavien classification9) grade III or higher, or if the home discharge was difficult at the investigation period.
The following clinical data were collected prospectively: age at baseline, gender, clinical stage of cancer after surgery, comorbidities (hypertension, hyperlipidemia, diabetes mellitus, cardiac diseases, respiratory diseases, orthopedic diseases, and cerebrovascular diseases), diagnosis, received neoadjuvant therapy, type of surgical (laparoscopic or open surgery), surgery duration, blood loss, blood transfusion (red cell concentrates and fresh frozen plasma), baseline laboratory data (serum-albumin and C-reactive protein), C-reactive protein at 3 days after surgery, and length of hospital stay.
This was a prospective observational study at a single clinical center. Patients were evaluated for physical function and HRQOL at baseline (1–2 days prior to surgery) and 4 weeks after surgery. Perioperative care for all participants was managed by gastrointestinal surgeons based on the clinical course for resection of gastrointestinal cancer of International University Health and Welfare Mita Hospital. Study patients were divided into three age groups based on based on the new Japanese elderly standard8): the young group, under 65 years, the pre-old group, 65 to 74 years, and the old group, 75 years or older.
The following parameters were measured at baseline and 4 weeks after surgery: body mass index, isometric knee extension force (IKEF), exercise capacity, and HRQOL.
BMI was calculated by weight in kilograms measured while wearing clothes, and height in meters.
IKEF was evaluated using an isometric test device (HUR® 5530 leg extension/curl rehab machine, HUR Ltd, Kokkola, Finland). Patients performed a 5 second maximal effort of right knee extension twice in the sitting position on HUR manual. The evaluation value normalized the joint torque calculated from maximum value and distance from the knee joint space to the pad center by body mass.
Exercise capacity was evaluated using a 6-minute walk test (6MWT) based on the guidelines set forth by the American Thoracic Society10). Patients were instructed to walk back and forth along a 50-meter stretch of hallway for 6 minutes at pace representing maximal effort by the end of the walk. The total distance covered in 6 min was recorded in meters only once at each evaluation period.
HRQOL was evaluated using the 36-Item Short-Form Health Survey version 2 Acute, Japan (SF-36) based on previous studies11, 12). SF36 is a self-administered questionnaire which includes eight subscales: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. Eight subscale scores were calculated using a scoring program as recommended by iHope International13). In this study, each subscale was scored from 0 to 100 points, with higher scores indicating higher HRQOL.
Clinical characteristics at baseline (i.e., age, surgical duration, blood loss and laboratory data) among the three groups (the young group, pre-old group and old group) were compared at baseline and post-surgery using the one-way analysis of variance for continuous variables. Categorical variables at baseline (i.e., gender, clinical stage of cancer, comorbidities and diagnosis) were compared using the χ2 test.
The perioperative changes in the parameters such as BMI, IKEF, 6MWT, and SF-36 subscales among the three groups were analyzed with two-way analysis of variance for continuous variables. Additionally, parameters with significant interaction effects were compared using the simple main effect test. All statistical analyses were performed using SPSS version 24.0 (SPSS Inc, Chicago, IL, USA). A p-value of less than 0.05 was considered significant.
RESULTS
A total of 696 patients were approached for consent; of these, 399 declined consent (57%), 203 were excluded as per the exclusion criteria (29%), and 94 patients (14%) were included in the study (Fig. 1). Of the 94 patients 55 were assigned to the young group (8%), 25 to the pre-old group (4%), and 14 to the old group (2%) based on age at baseline. The baseline clinical characteristics of the three groups are shown in Table 1. The mean values of serum-albumin in the young group at baseline were significantly higher than the pre-old and old groups. The old group had a significantly higher ratio of patients on hypertension and open surgery compared to the young group.
Fig. 1.
Diagram for the study.
Table 1. Clinical characteristics.
| Young groupn=55 | Pre-old groupn=25 | Old groupn=14 | ||
| Age (years) | 54.1 ± 8.6 | 69.4 ± 2.6* | 79.9 ± 3.6* ** | |
| Gender | Female | 24 (44) | 10 (40) | 7 (50) |
| Male | 31 (56) | 15 (60) | 7 (50) | |
| Clinical stage of the cancer | I | 19 (35) | 9 (36) | 4 (29) |
| II | 11 (20) | 7 (28) | 2 (14) | |
| III | 20 (36) | 7 (28) | 5 (36) | |
| IV | 5 (9) | 2 (8) | 3 (21) | |
| Comorbidities | Hypertension | 7 (13) | 9 (36) | 7 (50†) |
| Hyperlipidemia | 3 (5) | 1 (4) | 1 (7) | |
| Diabetes mellitus | 4 (7) | 4 (16) | 1 (7) | |
| Cardiac diseases | 2 (4) | 2 (8) | 1 (7) | |
| Respiratory diseases | 3 (5) | 2 (8) | 1 (7) | |
| Orthopedic diseases | 2 (4) | 1 (4) | 1 (7) | |
| Cerebrovascular diseases | 0 (0) | 2 (8) | 2 (14) | |
| Diagnosis | Esophagus cancer | 2 (4) | 1 (4) | 1 (7) |
| Gastric cancer | 1 (2) | 4 (16) | 0 (0) | |
| Liver cancer | 3 (5) | 1 (4) | 3 (21) | |
| Gallbladder cancer | 0 (0) | 2 (8) | 0 (0) | |
| Bile duct cancer | 0 (0) | 0 (0) | 1 (7) | |
| Pancreatic cancer | 5 (9) | 4 (16) | 1 (7) | |
| Colon cancer | 23 (42) | 8 (32) | 5 (36) | |
| Rectal cancer | 21 (38) | 5 (20) | 3 (21) | |
| Received neoadjuvant therapy | 5 (9) | 1 (4) | 0 (0) | |
| Type of surgery | Open surgery | 9 (16) | 10 (40) | 7 (50†) |
| Laparoscopic surgery | 46 (84) | 15 (60) | 7 (50) | |
| Surgery duration (min) | 275.4 ± 104.9 | 287.4 ± 95.2 | 247.8 ± 101.4 | |
| Blood loss (mL) | 275.9 ± 626.0 | 243.4 ± 359.8 | 268.1 ± 419.8 | |
| Blood transfusion (mL) | Red cell concentrates | 157.8 ± 637.0 | 134.4 ± 334.4 | 80.0 ± 299.3 |
| Fresh frozen plasma | 50.2 ± 273.0 | 28.8 ± 144.0 | 68.6 ± 256.6 | |
| Laboratory data | Serum-albumin (mg/dL) | 4.5 ± 0.3 | 4.2 ± 0.5* | 4.2 ± 0.4* |
| C-reactive protein (mg/dL) | 0.20 ± 0.38 | 1.00 ± 3.14 | 0.18 ± 0.21 | |
| C-reactive protein at 3 days after surgery (mg/dL) | 8.83 ± 6.23 | 11.65 ± 6.46 | 12.31 ± 8.37 | |
| Length of hospital stay (days) | 16.5 ± 8.2 | 21.3 ± 12.5 | 21.2 ± 8.9 | |
Values are numbers (%) or mean ± standard deviation.
*Significant difference from young group (Bonferroni), **Significant difference from pre-old group (Bonferroni).
†Significant difference from young group (χ2 test).
Perioperative changes in BMI, IKEF, and 6MWT are shown in Table 2. The BMI was significantly decreased 4 weeks after surgery compared to baseline in all groups. However, IKEF and 6MWT was not different between baseline and 4 weeks post-surgery. The mean values of IKEF and 6MWT in the old group were significantly decreased compared to the other two groups.
Table 2. Perioperative changes of each parameter at baseline to 4 weeks after surgery.
| Baseline | 4 weeks after surgery | |||
| Body mass index | Young group | 23.3 ± 5.0 | 22.3 ± 4.4* | |
| Pre-old group | 23.6 ± 3.4 | 22.2 ± 3.6 | ||
| Old group | 22.8 ± 2.5 | 22.0 ± 2.6 | ||
| Isometric knee extension force | Young group | 4.87 ± 1.59 | 4.82 ± 1.48 | |
| Pre-old group | 4.36 ± 1.64 | 4.12 ± 1.26 | ||
| Old group ** † | 3.01 ± 1.06 | 3.03 ± 0.94 | ||
| 6-minute walk test | Young group | 556.0 ± 76.8 | 556.3 ± 94.1 | |
| Pre-old group ** | 509.1 ± 68.2 | 498.3 ± 74.9 | ||
| Old group ** † | 442.7 ± 86.2 | 416.4 ± 83.7 | ||
| SF-36 subscales | Physical functioning | Young group | 91.6 ± 9.1 | 84.6 ± 13.2* |
| Pre-old group ** | 84.8 ± 14.5 | 76.2 ± 18.4 | ||
| Old group ** † | 74.3 ± 21.1 | 64.3 ± 21.0 | ||
| Role physical | Young group | 85.8 ± 24.2 | 63.7 ± 27.7* | |
| Pre-old group | 79.0 ± 19.3 | 55.0 ± 29.1 | ||
| Old group | 67.4 ± 29.9 | 58.9 ± 25.1 | ||
| Bodily pain | Young group | 83.4 ± 18.8 | 65.3 ± 22.1* | |
| Pre-old group | 77.3 ± 19.8 | 65.9 ± 19.7 | ||
| Old group | 69.7 ± 33.2 | 68.9 ± 26.1 | ||
| General health | Young group | 60.4 ± 14.4 | 62.6 ± 14.1 | |
| Pre-old group | 55.1 ± 14.3 | 56.6 ± 16.0 | ||
| Old group | 56.5 ± 16.4 | 53.6 ± 16.1 | ||
| Vitality | Young group | 66.3 ± 15.6 | 63.9 ± 15.3* | |
| Pre-old group | 63.3 ± 17.4 | 58.5 ± 17.3 | ||
| Old group | 67.9 ± 20.9 | 55.4 ± 21.8 | ||
| Social functioning | Young group | 79.8 ± 20.9 | 69.5 ± 26.8 | |
| Pre-old group | 76.5 ± 24.0 | 63.0 ± 31.6 | ||
| Old group | 77.7 ± 24.1 | 65.2 ± 31.5 | ||
| Role emotional | Young group | 86.3 ± 18.3 | 74.7 ± 26.6* | |
| Pre-old group | 74.7 ± 22.2 | 62.7 ± 29.1 | ||
| Old group | 72.0 ± 33.1 | 70.8 ± 32.8 | ||
| Mental health ‡ | Young group | 69.7 ± 17.8 | 75.9 ± 13.71) | |
| Pre-old group | 66.6 ± 23.4 | 71.0 ± 18.3 | ||
| Old group | 71.4 ± 23.7 | 62.9 ± 22.22) | ||
Values are mean ± standard deviation. SF-36: Short-Form 36-Item Health Survey; ANOVA: analysis of variance.
*Significant difference from baseline (two-way analysis of variance), **Significant difference from young group (Bonferroni), †Significant difference from pre-old group (Bonferroni), ‡Significant interaction effect (two-way analysis of variance).
1) Significant increase for simple main effect test (Bonferroni) when compared with the young group at baseline.
2) Significant decrease for simple main effect test (Bonferroni) when compared with the young group at 4 weeks after surgery.
The perioperative changes in SF-36 subscales are shown in Table 2. Physical functioning, role physical, bodily pain, vitality, social functioning, and role emotional at 4 weeks after surgery were significantly decreased compared to baseline. There was no significant difference in general health and mental health between baseline and post-surgery. Physical functioning was significantly different among the three groups. The effect of surgery on mental health depended on age: the young group had significantly increased mental health from baseline to 4 weeks after surgery, but the old group had significantly decreased mental health (Table 2).
DISCUSSION
With regard to physical measures, only BMI was reduced after surgery in patients with gastrointestinal cancer (Table 2). This is consistent with previous studies, which showed that reduced BMI delayed improvements in physical function at after surgery in gastrointestinal patients14). In the HRQOL of patients with gastrointestinal cancer, SF-36 subscaled after surgery compared to before surgery; the general and mental health were significantly decreased (Table 2). A previous study of HRQOL pre-surgery and 6 weeks after discharge in patients with gastrointestinal cancer reported that only psychological function relating to depression was significantly decreased3). Our study is a relatively shorter follow up period than this previous work but is consistent with HRQOL pathognomonic changes early after surgery.
We observed exercise capacity and physical functioning reduced post-surgery (Table 2), with significant differences between the new Japanese elderly standard age groups. This is consistent with previous studies linking this to an age effect3, 4, 11, 12). This suggests that this new Japanese elderly standard captures the age-related reduction in exercise capacity in patients with gastrointestinal cancer. This is likely related to the reduction in muscle strength we observed in the older group (Table 2). This new Japanese elderly standard may also stratify differences in muscle weakness in elderly patients with gastrointestinal cancer. Additionally, the pre-old group, which corresponds to the formerly elderly group was not significantly different than the young group (Table 2). Thus, this may validate the new Japanese elderly standard of 75 years or older. In this study IKEF, which is a typical value of motor function in the elderly, could not be classified like 6MWT and HRQOL. Elderly patients with gastrointestinal cancer may be influenced by other factors such as additional comorbidities and type of surgery.
The young group significantly increased their mean value of mental health of SF-36 subscale from before to post-surgery, while the old group decreased mental health (Table 2). Based on these results, aging may affect the change in HRQOL in the early post-surgery period. The mental health SF-36 subscale is influenced by factors such as spiritual fatigue and stress13). Previous studies stress that mental health, such as depression and fatigue, should be prevented and treated in elderly cancer patients15, 16). In addition, cancer-related chronic fatigue is present in 70%–100% of cancer patients, especially during active treatment17). The biological mechanisms are currently unclear, although several proposed mechanisms include serotonin dysregulation, endocrine dysfunction, circadian rhythm disruption, and cytokine dysregulation; multiple mechanisms may be at play15,16,17). Elderly patients with gastrointestinal cancer as classified by new Japanese elderly standard may need to address the decrements in HRQOL at after surgery, perhaps with comprehensive intervention such as adjustments circadian rhythm in hospital and counseling by clinical psychologists.
In conclusion, based on the new Japanese elderly standard, elderly patients with gastrointestinal cancer appear to have reduced physical and HRQOL before and after surgery, and also early postoperative changes in HRQOL.
There are some limitations of this study. First, the generalizability of the results of this study is limited due to the relatively small number of patients with gastrointestinal cancer at a single institute. Future studies should repeat this study with a larger number of patients from multiple institutions. Second, some other factors which were different between the young and old group were not examined in this study. Ideally, the relationship between elderly patients with gastrointestinal cancer and hypertension comorbidity or receiving open surgery should re-investigated in detail. Finally, physical activity from discharge to 4 weeks after surgery were not reported, and thus might be confounders to the follow up measures. Future studies should monitor and consider the physical activity at discharge.
Funding
This study was funded by The Grants-in-Aid for Scientific Research (grant number: 19K19880) from the Japan Society for the Promotion of Science.
Conflict of interest
None.
Acknowledgments
We thank the rehabilitation staff at the International University Health and Welfare Mita Hospital for their help with the data collection.
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