423

ORIGINAL
Prognostic impact of frailty after gastrectomy in elderly gastriccancer patients
Masaaki Nishi, Yuma Wada, Kozo Yoshikawa, Chie Takasu, Takuya Tokunaga, Toshihiro Nakao, Hideya Kashihara,
Shinichiro Yamada, Toshiaki Yoshimoto, and Mitsuo Shimada
Department of Surgery, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan

Abstract : Background : Frailty plays a crucial role in cancer patients who have received surgery in this recent
aging society. We aimed to investigate frailty as a prognostic factor in elderly gastric cancer (GC) patients who
underwent curative gastrectomy. Methods : We analyzed 86 elderly (over 75 years old) GC patients who underwent curative gastrectomy. Patients were assigned to two groups ; frailty group (n = 29) and no-frailty group(n = 57). Clinicopathological values were compared between the two groups. Results : The OS rate of the frailty
group was significantly poorer than that of the no-frailty group (5-yr OS rate ; frailty group 52.49% vs. no-frailty
group 74.87%, p < 0.05). Multivariate analysis of the OS showed that frailty tended to be significant prognostic
factor (p = 0.09). The DFS rate of the frailty group was significantly poorer than that of the no-frailty group (5-yr
DFS rate ; frailty group 42.30% vs. no-frailty group 71.55%, p < 0.05). Multivariate analysis of the DFS showed thatfrailty tended to be significant prognostic factor (p = 0.14). Conclusion : We identified the clinical impact of frailty
prognostic factor for elderly GC patients who underwent gastrectomy. J. Med. Invest. 70 : 423-429, August, 2023
Keywords : Gastric cancer, Frailty, Elderly patientsINTRODUCTION
With the recent increasing aging of society in many countries,
the average life expectancy of the elderly has been rising. Major
social, medical, and economic consequences result from an aging
population (1). With elevated numbers of the elderly cancer patients, the frequency of surgical cases for malignant disease has
been increasing (2).
Gastric cancer (GC) is one of the most common malignancies,
particularly in East Asia. It results in 44,000 mortalities annually in Japan (3). Although the total number of GC deaths has
been decreasing in Japan, those among the elderly has increased(3). Surgical intervention for GC is the only curative treatment
and is well standardized. GC surgery can lead to body weight
loss, appetite loss, malnutrition anemia, and osteoporosis after
surgery despite the curative effect of such a resection (4, 5).
Frailty is a multidimensional and heterogeneous syndrome
associated with instability (6-10). It has been gaining attention
in surgery with respect to the recently increasingly aged society.
We previously reported the significance of frailty in elderly hepatocellular carcinoma patients after hepatectomy and in pancreatic ductal adenocarcinoma patients following pancreatectomy(9, 10). By contrast, little is known about the clinical impact offrailty in GC (11-13).
In the present study, we investigated the clinical impact offrailty in elderly GC patients.

Received for publication December 27, 2022 ; accepted June 21, 2023.
Address correspondence and reprint requests to Masaaki Nishi, MD,
PhD, FACS, Department of Surgery, Institute of Biomedical Sciences,
Tokushima University, 3-18-15 Kuramoto-cho, Tokushima 7708503, Japan and Fax : +81-88-631-9698. E-mail : nishi.masaaki@
tokushima-u.ac.jp

METHODS
Patients

A total of 86 elderly GC patients who underwent standard
curative gastrectomy with regional lymphadenectomy at theTokushima University Hospital from 2011 to 2015 were enrolled
in this study. Patient selection was based on the following inclusion criteria : (1) over 75 years old, (2) without any neoadjuvant
chemotherapy, and (3) with pathologically confirmed gastric adenocarcinoma. Patients who received neoadjuvant chemotherapy,
palliative surgery, or combined resection (hepatectomy, colectomy) or had a non-adenocarcinoma condition were excluded. All
patients signed a written informed consent form for the surgery
after detailed explanation of the procedure and the surgical risk.
Patient background and disease baseline characteristics wereobtained from medical records. The classification of lymph nodestation was according to the Japanese Classification of Gastric
Carcinoma (The 15th edition) (14). The surgical indications followed the Japanese Gastric Cancer Treatment Guidelines 2018(ver. 5) (15). The median follow-up period was 4.7 years (0.1–9.7
years). Frailty was defined as a clinical frailty scale score of ≥ 4(9). The immune-nutritional prognostic factors were also assessed using the total lymphocyte count (TLC), lymphocyte
c-reactive protein (CRP) ratio (LCR) (16), neutrophil lymphocyte
ratio (NLR) (17), modified Glasgow prognostic score (mGPS)(18), and prognostic nutritional index (PNI) (19). The definitionof sarcopenia and osteopenia was described previously (20). The
frailty assessment was described previously (8, 9). This study
was authorized in advance by The Ethics Committee of Tokushima
University Hospital (TOCMS : 3215-1). Limited lymph node dissection was defined as lymph node dissected that did not reach
recommended lymph node dissection from the Japanese gastriccancer guideline (21).

Definition of comorbidity
Comorbidities in each patient were defined as follows ; renal
failure : dialysis or serum creatinine level ≥ 2 mg / dl, livercirrhosis : preoperative indocyanine green R15 ≥ 15%, cardiac

The Journal of Medical Investigation Vol. 70 2023

424

M. Nishi, et al. Impact of frailty in elderly GC patients

disease : previous history of myocardial infarction, percutaneous coronary intervention, coronary artery bypass grafting,or heart failure, pulmonary disease : % vital capacity or forced
expiratory volume 1.0 ≤ 50%, diabetes mellitus : insulin use,leanness : body mass index (BMI) ≤ 18.5%.

Statistical analysis
Values are shown as the mean ± standard deviation. All
statistical analyses were performed using statistical software(JMP 8.0.1. ; SAS Institute, Cary, NC, USA). Chi square test or
Mann–Whitney U test were used to compare clinicopathologicalfactors. Overall survival (OS) and disease-free survival (DFS)
curves were generated using the Kaplan–Meier method using
the log-rank test. Cox proportional hazard regression model wasused in multivariate analysis. The variables with a p value < 0.2
on univariate analyses included in the multivariate Cox model.
For all statistical analyses, p value < 0.05 was considered to indicate statistical significance.

RESULTS
According to the clinical frailty score, patients were divided totwo groups ; frailty group (n = 29) and no-frailty group (n = 57).
The distribution of clinical frailty scale scores was shown in
Fig. 1. The patients’ characteristics in the frailty and no-frailty
groups are summarized in Table 1. There were no significant
differences in age, sex, BMI, white blood cell count, TLC, serum
albumin level, CRP level, tumor markers and comorbidity between the two groups. In terms of the immuno-nutrition status,
the respective prognostic scores, including the NLR, PNI, LCR,mGPS, sarcopenia and osteopenia displayed no significant differences between the two groups. Regarding the perioperative
factors, there were no significant differences in tumor or surgicalfactors, including surgical procedure, blood loss, lymph node dissection, and limited lymph node dissection. Respective complications (Clavien–Dindo classification II ≤), including pancreatic
fistula, anastomotic leakage, stasis, and pneumonia, showed nosignificant differences between the two groups (Table 2).
Regarding long-term outcomes, the OS rate of the frailty
group was significantly poorer than that of the no-frailty group(5-yr OS rate ; frailty group 52.49% vs. no-frailty group 74.87%,
p < 0.05) (Fig. 2a). Univariate analysis of the OS showed that
Figure.1
frailty was a significant prognostic factor (p < 0.05) (Table 3).
Multivariate analysis revealed that frailty was tended to be an
independent prognostic factor (p = 0.09) (Table 3). Furthermore,

the DFS rate of the frailty group was significantly poorer thanthat of the no-frailty group (5-yr DFS rate ; frailty group 42.30%
vs. no-frailty group 71.55%, p < 0.05) (Fig. 2b). Univariate analysis of the DFS showed that frailty and CA19-9 were significant
prognostic factors (p < 0.05) (Table 4). Multivariate analysis
revealed that frailty was tended to be an independent prognostic
factor (p = 0.14) (Table 4).

DISCUSSION
In the current study, we identified frailty as a significant prognostic factor in elderly GC patients and a relationship between
frailty and clinicopathological factors, including comorbidity andthe immune-nutritional status.
Elderly patients have multiple physiological and social problems. Major abdominal surgery for malignancy is generally
considered to be associated with a high risk for peri-operativecomplications in elderly patients. These complications are associated with cardiac, pulmonary, liver, renal, neurological, or
metabolic comorbidities. A retrospective cohort study demonstrated that the surgical outcome of GC surgery was comparable
between young and elderly patients (22). By contrast, anotherstudy suggested that elderly GC patients experienced a higher
incidence of postoperative morbidity than non-elderly patients(23). Furthermore, the survival benefit in elderly GC patientswere poor because of the high incidence of non-cancer related
mortality (23). For some elderly GC patients, it may be appropriate to reconsider the treatment strategy regarding the balance
between the invasiveness of the surgery and the patient’s prognosis (24).
Frailty is a useful evaluative tool for an individual’s functional
physiologic reserve and ability rather than chronological age.
The frailty prevalence in elderly patients ranged over 4.6–27.3%
based on previous reports (25-27). It can predict the patient’s
response after surgery. In GC, frailty was associated with boththe short- and long-term outcomes (11-13). Tanaka et al. reported
that frailty increased systemic postoperative complications, andfrailty and leanness were significant prognostic factors (13).
Several prognostic scores, including the NLR, LCR, PNI, andmGPS, which are the surrogate markers of systemic or local
inflammation in the tumor microenvironment, immune-nutritional status, and host-tumor interaction, were recognized asvital biomarkers for several malignancy types (16-19). These
scoring systems are readily measurable from routine blood examination and reflects host-immunity, nutritional status and

CFS: 1(n=3)
CFS: 6<(n=6)
CFS: 5(n=8)

n=29

Frailty

CFS: 4(n=15)

CFS: 3(n=33)

n=57

No frailty

Fig 1. The distribution of clinical frailty scale scores

CFS: 2(n=21)

425

The Journal of Medical Investigation Vol. 70 August 2023
Table 1. Patients’ characteristics in the no-frailty and frailty groups
Variables

No frailty(n = 57)

Frailty(n = 29)

p value

0.10

Patients’ factors
Age80.33 ± 4.16

81.79 ± 4.47

Male / Female

38 / 19

21 / 80.58

BMI (kg / m2)

22.52 ± 3.49

22.28 ± 3.84

0.44

WBC ( / µl)

5724 ± 1509

5817 ± 1585

0.77

TLC ( / µl)1408 ± 549

1379 ± 718

0.53

PLT (*104 / µl)23.49 ± 10.15

26.18 ± 10.71

0.15

ALB (g / dl)

3.60 ± 0.70

3.50 ± 0.63

0.41

CRP (mg / dl)

0.67 ±1.35

0.25 ± 0.23

0.74

CEA (<5 / ≥5 ng / ml)

52 / 524 / 5

0.26

CA19-9 (<37 / ≥37 IU / ml)

53 / 424 / 5

0.15

Renal failure (No / Yes)

55 / 226 / 30.22

Liver cirrhosis (No / Yes)

53 / 427 / 20.98

Cardiac disease (No / Yes)

54 / 327 / 2

0.76

Pulmonary disease (No / Yes)

54 / 326 / 30.39

Diabetes mellitus (No / Yes)

55 / 228 / 1

0.99

Leanness (No / Yes)

54 / 326 / 3

0.39

Comorbidity

Tumor factors
Differentiation (dif. / undif.)

39 / 18

19 / 100.77

Tumor diameter (mm)43.79 ± 26.99

43.09 ± 29.30

0.85

fT 1 / 2 / 3 / 4

18 / 15 / 16 / 2

11 / 6 / 8 / 4

0.42

fN (−/ +)29 / 28

15 / 140.94

36 / 2116 / 13

0.48

Surgical factors
DG / TG
LN dissection (D0 / D1 / D1+ / D2)

1 / 5 / 25 / 26

0 / 5 / 9 / 15

0.40

Operation time (min)303.79 ± 68.61

297.69 ± 73.75

0.59

Bleeding (ml)121.14 ± 107.06

147.48 ± 134.19

0.64

10 / 47

6 / 230.22

NLR

4.65 ± 2.27

16.35 ± 63.19

0.41

PNI

42.89 ± 8.57

41.93 ± 8.04

0.49

LCR

16038 ± 12733

12666 ± 12733

0.46

37 / 20

17 / 120.57

Limited LN dissection (Yes / No)
Immuno-nutrition statusmGPS (0 / 1, 2)
Sarcopenia (No / Yes)

50 / 724 / 50.54

Osteopenia (No / Yes)

28 / 29

17 / 120.40

BMI body mass index, WBC white blood cell, TLC total lymphocyte count, PLT platelet, ALB white albumin, CRP
C reactive protein, CEA, carcinoembryonic antigen, CA19-9 carbohydrate antigen 19-9, DG distal gastrectomy,
TG total gastrectomy, LN lymph node, NLR, neutrophil lymphocyte ratio, PNI prognostic nutritional index, LCR
lymphocyte-to CRP ratio, mGPS modified Glasgow Prognostic Score. Values are shown as the mean ± standard
deviation.

Table 2. Postoperative morbidity in the no-frailty and frailty groups
Variables
Pancreatic fistula

No frailty(n = 57)

Frailty(n = 29)

4 (7.0%)0 (0%)

Anastomotic leakage

1 (1.8%)2 (6.9%)

Stasis1 (1.8%)2 (6.9%)Pneumonia

1 (1.8%)2 (6.9%)Total

7 (12.3%)

6 (20.7%)

p value

0.31

M. Nishi, et al. Impact of frailty in elderly GC patients426

Fig 2. Comparison of overall survival (OS) (a) and disease-free survival (DFS) (b) rates of elderly gastric cancer patients
after gastrectomy between the frailty and no-frailty groups. The OS and DFS were estimated using the Kaplan-Meier method

Table 3. Univariate and multivariate Cox proportional hazard regression analyses of overall survival
Variables

Univariate analysis

Multivariate analysis

5-year OS (%)

p valueHR

95% CI

p valueAge (< 85 / ≥ 85)

72.39 / 56.25

0.13

2.20

0.95 -5.11

0.07

Sex (M / F)65.85 / 71.77

0.68

Differentiation

65.58 / 72.75

0.31

pT factor (T1,2 / 3.4)

68.89 / 73.97

0.58

pN (−  /  +)

72.54 / 63.35

0.20

1.25

0.71-2.21

0.42

CEA (< 5 / ≥ 5 ng / ml)

67.82 / 46.67

0.20

2.13

0.77-5.29

0.16

CA19-9 (< 37 / ≥ 37 IU / ml)69.55 / 50.79

0.31
1.23

0.67-2.30

0.50

1.81

0.92-3.53

0.09

1.06

0.61-1.84

0.83

Patients and tumor factors(dif. / undif.)

DG / TG

74.26 / 58.44

0.12

LN dissection

70.35 / 64.76

0.70

71.94 / 58.64

0.55(D0, D1, D1+ / D2)
Limited LN dissection (Yes / No)
Comorbidity
Renal failure (No / Yes)

68.16 / 100

0.26

Liver cirrhosis (No / Yes)

68.42 / 62.50

0.76

Cardiac disease (No / Yes)

68.76 / 60.00

0.83

Pulmonary disease (No / Yes)

68.34 / 50.00

0.84

Diabetes mellitus (No / Yes)

67.47 / 75.00

0.49

Leanness (No / Yes)

70.11 / 55.56

0.49

Immuno-nutritional factor
Frailty (No / Yes)

74.87 / 52.49<0.05

NLR (< 4 / ≥ 4)

66.06 / 78.67

0.23

PNI (< 40 / ≥ 40)

60.35 / 71.61

0.91

LCR (< 6000 / ≥ 6000)

79.34 / 59.14

0.11

mGPS (0 / 1, 2)

73.55 / 59.35

0.40

Sarcopenia (No / Yes)

69.68 / 68.57

0.68

Osteopenia (No / Yes)

63.26 / 72.63

0.27

CI confidence interval, CEA carcinoembryonic antigen, CA19-9 carbohydrate antigen 19-9, DG distal gastrectomy, HR hazard
ratio, OS overall survival, TG total gastrectomy, LN lymph node, NLR, neutrophil lymphocyte ratio, PNI prognostic nutritional index, LCR lymphocyte-to CRP ratio, mGPS modified Glasgow Prognostic Score.

427

The Journal of Medical Investigation Vol. 70 August 2023
Table 4. Univariate and multivariate Cox proportional hazard regression analyses of disease-free survival
Variables

Univariate analysis
5-year DFS (%)

p valueAge (< 85 / ≥ 85)

66.01 / 50.51

0.26

Sex (M / F)

63.72 / 65.27

0.99

Differentiation

63.53 / 65.38

0.30

pT factor (T1,2 / 3.4)

65.55 / 57.93

0.84

pN (−  /  +)

71.44 / 56.98

0.12

CEA (< 5 / ≥ 5 ng / ml)

64.07 / 32.81

0.85

68.63 / 0

< 0.001

DG / TG

69.63 / 57.78

0.19

LN dissection

71.22 / 56.33

0.24

53.20 / 66.19

0.93

Renal failure (No / Yes)

62.59 / 100

0.23

Liver cirrhosis (No / Yes)

64.50 / 62.50

0.81

Cardiac disease (No / Yes)

69.28 / 53.33

0.67

Pulmonary disease (No / Yes)

64.61 / 0

0.97

Diabetes mellitus (No / Yes)

61.10 / 66.67

0.44

Leanness (No / Yes)

66.38 / 50.79

0.49

Frailty (No / Yes)

71.55 / 42.30< 0.05NLR (< 4 / ≥ 4)

62.79 / 70.62

0.43

PNI (< 40 / ≥ 40)

57.84 / 63.49

0.87

LCR (< 6000 / ≥ 6000)

74.87 / 58.29

0.20

mGPS (0 / 1, 2)

66.32 / 57.31

0.57

Sarcopenia (No / Yes)

63.31 / 68.57

0.91

Osteopenia (No / Yes)

58.09 / 70.95

0.29

Multivariate analysis
HR

95% CI

p value

1.40

0.61-3.23

0.43

5.38

18.00

< 0.05

1.54

0.68-3.53

0.30

1.89

0.81-4.42

0.14

1.83

0.79-4.24

0.15

Patients and tumor factors(dif. / undif.)CA19-9 (< 37 / ≥ 37 IU / ml)(D0, D1, D1+ / D2)
Limited LN dissection (Yes / No)
Comorbidity

Immuno-nutritional factor

CI confidence interval, CEA carcinoembryonic antigen, CA19-9 carbohydrate antigen 19-9, DFS : disease free survival, DG
distal gastrectomy, HR hazard ratio, TG total gastrectomy, LN lymph node, NLR, neutrophil lymphocyte ratio, PNI prognostic
nutritional index, LCR lymphocyte-to CRP ratio, mGPS modified Glasgow Prognostic Score.

the inflammatory condition.
To prevent postoperative morbidity, prolong the patients’survival, and avoid the detrimental physical and psychologicalimpacts of frailty, perioperative rehabilitation is adapted for thefrail patients (28, 29). Rehabilitation for frail patients may be an
appropriate process through which the operative risk can be decreased (28, 29). In our department, perioperative nutrition andexercise intervention was adapted for elderly and frail patientsand improved the surgical outcomes (30).
The current study has several potential limitations. This wasa retrospective cohort study at a single center, the number ofcases was relatively limited, and there may have been potential
selection bias. A further prospective study with larger sample
size is warranted to confirm the present results.
In conclusion, we identified the clinical impact of frailty a
prognostic factor for elderly GC patients who underwent curative
gastrectomy. These findings highlight optimizing treatment
strategies and improving patient selection and management for
elderly GC patients.

ETHICS APPROVAL
The protocol for this research project was approved by the Ethics Committee of Tokushima University, Approval No. 3215-1.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation(institutional and national) and with the Helsinki Declaration of1964 and later versions.

DISCLOSUREETHICS APPROVAL AND CONSENT TO PARTICIPATE / CONSENT FOR PUBLICATION
The protocol for this research project was approved by the Ethics Committee of Tokushima University, Approval No. 3215-1.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation(institutional and national) and with the Helsinki Declaration

428

M. Nishi, et al. Impact of frailty in elderly GC patientsof 1964 and later versions and all patients signed a written informed consent form for the surgery after a detailed explanationof the procedure and the surgical risk.

FUNDINGNo funding.

AUTHORS’ CONTRIBUTIONS
M Nishi, and M Shimada designed the study. M Nishi, K
Yoshikawa, C Takasu, T Tokunaga and T Nakao performed
the data analyses. M Nishi, Y Wada drafted the manuscript. M
Nishi, Y Wada , H Kashihara, T Yoshimoto prepared the table
and Figure. All authors read and approved the final manuscript.

CONFLICT OF INTEREST
Masaaki Nishi, Yuma Wada, Kozo Yoshikawa, Chie Takasu,
Takuya Tokunaga, Toshihiro Nakao, Hideya Kashihara,
Shinichiro Yamada, Toshiaki Yoshimoto, and Mitsuo Shimada,
have no conflicts of interest or financial ties to disclose.

ACKNOWLEDGMENT
We thank Robert Blakytny, DPhil, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

REFERENCES
1.

2.

3.

4.

5.

6.

7.

Nomura K, Koizumi A : Strategy against aging society withdeclining birthrate in Japan. Ind Health 54(6) : 477-479,
2016. doi : 10.2486/indhealth.54-477. PMID : 27928131 ;PMCID : PMC5136603
Hasegawa H, Takahashi A, Kakeji Y, Ueno H, Eguchi S,
Endo I, Sasaki A, Takiguchi S, Takeuchi H, Hashimoto M,
Horiguchi A, Masaki T, Marubashi S, Yoshida K, Konno
H, Gotoh M, Miyata H, Seto Y : Surgical outcomes of gastroenterological surgery in Japan : Report of the National
Clinical Database 2011-2017. Ann Gastroenterol Surg
3(4) : 426-450, 2019
Asaka M, Kobayashi M, Kudo T, Akino K, Asaka Y,
Fujimori K, Kikuchi S, Kawai S, Kato M ; Gastric cancer
deaths by age group in Japan : Gastric cancer deaths by age
group in Japan : Outlook on preventive measures for elderly
adults. Cancer Sci 111(10) : 3845-3853, 2020
Lim HS, Lee B, Cho I, Cho GS : Nutritional and clinicalfactors affecting weight and fat-free mass loss after gastrectomy in patients with gastric cancer. Nutrients 12(7) : 1905,
2020
Yoo SH, Lee JA, Kang SY, Kim YS, Sunwoo S, Kim BS,
Yook JH : Risk of osteoporosis after gastrectomy in longterm gastric cancer survivors. Gastric Cancer 21(4) : 720727, 2018Fried LP, Tangen CM, Walston J, Newman AB, Hirsch
C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G,
McBurnie MA : Cardiovascular Health Study Collaborative
Research Group. Frailty in older adults : evidence for aphenotype. J Gerontol A Biol Sci Med Sci 56(3) : M146-156,
2001
Hogan DB, MacKnight C, Bergman H ; Steering Committee,

Canadian Initiative on Frailty and Aging : Models, definitions, and criteria of frailty. Aging Clin Exp Res 15(3Suppl.) : 1-29, 2003
8. Rockwood K, Song X, MacKnight C, Bergman H, Hogan
DB, McDowell I, Mitnitski A : A global clinical measure offitness and frailty in elderly people. CMAJ 173(5) : 489-495,
2005
9. Yamada S, Shimada M, Morine Y, Imura S, Ikemoto T,
Arakawa Y, Saito Y, Yoshikawa M, Miyazaki K : Significance of frailty in prognosis after hepatectomy for elderly
patients with hepatocellular carcinoma. Ann Surg Oncol
28(1) : 439-446, 2021
10. Yamada S, Shimada M, Morine Y, Imura S, Ikemoto T,
Saito Y, Miyazaki K, Tokunaga T, Nishi M : Significance offrailty in prognosis after surgery in patients with pancreatic
ductal adenocarcinoma. World J Surg Oncol 19(1) : 94, 2021
11. Shen Y, Hao Q, Zhou J, Dong B : The impact of frailty andsarcopenia on postoperative outcomes in older patients
undergoing gastrectomy surgery : a systematic review andmeta-analysis. BMC Geriatr 17(1) : 188, 2017
12. Kim G, Min SH, Won Y, Lee K, Youn SI, Tan BC, Park YS,
Ahn SH, Park DJ, Kim HH : Frailty in elderly gastric cancer patients undergoing gastrectomy. Dig Surg 8 : 1-7, 2020
13. Tanaka T, Suda K, Inaba K, Umeki Y, Gotoh A, Ishida Y,
Uyama I : Impact of frailty on postoperative outcomes forlaparoscopic gastrectomy in patients older than 80 years.
Ann Surg Oncol 26(12) : 4016-4026, 201914. Japanese Gastric Cancer Association, Japanese Classification of Gastric Carcinoma (The 15th Edition)
15. Japanese Gastric Cancer Association : Japanese classification of gastric carcinoma : (The 6th Edition) Japanese
Gastric Cancer Association, 2021
16. Ishikawa D, Nishi M, Takasu C, Kashihara H, Tokunaga T,
Higashijima J, Yoshikawa K, Shimada M : The role of neutrophil-to-lymphocyte ratio on the effect of CRT for patientswith rectal cancer. In Vivo 34(2) : 863-868, 2020
17. Nishi M, Shimada M, Tokunaga T, Higashijima J,
Yoshikawa K, Kashihara H, Takasu C, Ishikawa D, Wada
Y, Eto S, Yoshimoto T : Lymphocyte to C-reactive protein
ratio predicts long-term outcomes for patients with lower
rectal cancer. World J Surg Oncol 19(1) : 201, 2021
18. Hirashima K, Watanabe M, Shigaki H, Imamura Y, Ida S,
Iwatsuki M, Ishimoto T, Iwagami S, Baba Y, Baba H : Prognostic significance of the modified Glasgow prognostic scorein elderly patients with gastric cancer. J Gastroenterol
49(6) : 1040-1046, 201419. Saito Y, Imura S, Morine Y, Ikemoto T, Yamada S, Shimada
M : Preoperative prognostic nutritional index predicts shortand long-term outcomes after liver resection in patientswith hepatocellular carcinoma. Oncol Lett 21(2) : 153, 2021
20. Abe K, Furukawa K, Okamoto T, Matsumoto M, Futagawa
Y, Haruki K, Shirai Y, Ikegami T : Impact of osteopenia on
surgical and oncological outcomes in patients with pancreatic cancer. Impact of osteopenia on surgical and oncologicaloutcomes in patients with pancreatic cancer. Int J Clin
Oncol 26(10) : 1929-1937, 2021
21. Yoshikawa K, Shimada M, Higashijima J, Nakao T, Nishi
M, Kashihara H, Takasu C : Limited lymph node dissection
in elderly patients with gastric cancer. J Med Invest 63(12) : 91-5, 201622. Saidi RF, Bell JL, Dudrick PS : Surgical resection for
gastric cancer in elderly patients : is there a difference inoutcome? J Surg Res 118(1) : 15-20, 2004
23. Hashimoto T, Kurokawa Y, Mikami J, Takahashi T,
Miyazaki Y, Tanaka K, Makino T, Yamasaki M, Motoori
M, Kimura Y, Nakajima K, Mori M, Doki Y : Postoperative

The Journal of Medical Investigation Vol. 70 August 2023
long-term outcomes in elderly patients with gastric cancer
and risk factors for death from other diseases. World J Surg
43(11) : 2885-2893, 201924. Nunobe S, Oda I, Ishikawa T, Akazawa K, Katai H, Isobe
Y, Miyashiro I, Tsujitani S, Ono H, Tanabe S, Fukagawa T,
Suzuki S, Kakeji Y ; Registration Committee of the Japanese Gastric Cancer : Surgical outcomes of elderly patientswith Stage I gastric cancer from the nationwide registry of
the Japanese Gastric Cancer Association. Gastric Cancer
23(2) : 328-338, 2020
25. Collard RM, Boter H, Schoevers RA, Oude Voshaar RC : Prevalence of frailty in community-dwelling older persons : asystematic review. J Am Geriatr Soc 60(8) : 1487-1492, 2012
26. Choi J, Ahn A, Kim S, Won CW : Global prevalence ofphysical frailty by Fried’s criteria in community-dwellingelderly with national population-based surveys. J Am Med
Dir Assoc 16(7) : 548-550, 2015

429

27. Kojima G, Iliffe S, Taniguchi Y, Shimada H, Rakugi H,
Walters K : Prevalence of frailty in Japan : A systematic
review and meta-analysis. J Epidemiol 27(8) : 347-353, 201728. Minnella EM, Awasthi R, Loiselle SE, Agnihotram RV,
Ferri LE, Carli F : Effect of exercise and nutrition prehabilitation on functional capacity in esophagogastriccancer surgery : A randomized clinical trial. JAMA Surg
153(12) : 1081-1089 , 201829. Baimas-George M, Watson M, Elhage S, Parala-Metz A,
Vrochides D, Davis BR : Prehabilitation in frail surgicalpatients : A systematic review. World J Surg 44(11) : 36683678, 2020
30. Wada Y, Nishi M, Yoshikawa K, Takasu C, Tokunaga T,
Nakao T, Kashihara H, Yoshimoto T, Shimada M : Preoperative nutrition and exercise intervention in frailty patientswith gastric cancer undergoing gastrectomy. Int J Clin
Oncol 27(9) : 1421-1427, 2022