Study design and participants
This was a cross-sectional study to assess the prevalence of frailty and its risk factors in patients with gastrointestinal cancer. The patients who successfully underwent surgery participated in this study. They were all recruited from the First Affiliated Hospital of Anhui Medical University from Mar. 2020 to Nov. 2020. The inclusion criteria were as follows: (1) with diagnosed gastric or colorectal cancer; (2) ≥ 60 years old; (3) had normal function of limb movement; (4) signed informed consent. The exclusion criteria were as follows: (1) postoperative histopathology confirmed the diagnosis of precancerous or mesothelioma or benign lesions; (2) with recurrent gastric or colorectal cancer; (3) admitted to hospital with acute intestinal obstruction or massive alimentary tract bleeding; (4) had severely diseased heart, liver, kidney, brain, etc.; (5) had a severe infection or inflammatory disease within 1 month.
Ethical approval was granted from the Clinical Medical Research Ethics Committee of the First Affiliated Hospital of Anhui Medical University (PJ2020-03-29). This study conformed to the standards of the Declaration of Helsinki and was registered with Chinese Clinical Trial Registry (ChiCTR2000031250).
After a 12-h overnight fast, all patients’ venous blood samples, including blood routine (white blood cell, WBC; red blood cell, RBC; hemoglobin, HGB; reticulocyte, RET; lymphocyte, LYMPH), plasma protein (prealbumin, PA; albumin, ALB; globulin, GLO; total protein, TP), and tumor markers (alpha-fetoprotein, AFP; carcino-embryonic antigen, CEA; carbohydrate antigen 125, CA125; carbohydrate antigen 19-9, CA19-9; carbohydrate antigen 72-4, CA72-4), were collected together in the morning. Blood routine, plasma protein, and tumor markers were detected with an automatic blood analyzer (XN-9000, Sysmex, Japan), an automatic chemistry analyzer (Cobas 8000, Roche, Germany), and an automatic electrochemiluminescence immunoassay analyzer (Cobas 6000, Roche, Germany), respectively. Tumor area, stage, and histological grade were collected as well after surgery.
Demographic and clinical characteristics
A self-designed questionnaire that included detailed information such as age, sex, body mass index (BMI), educational background, marital status, smoking history, drinking history, past medical history, have regular exercise habit or not, cancer type, preoperative chemoradiotherapy, and blood transfusion before or after surgery, was used to collect patients’ general demographic and clinical data. Smoking/Drinking history is defined as the patients who are currently smoking/drinking, or they used to smoke/drink, but now they do not smoke/drink.
Frailty was measured with the self-report version of GFI that has been revised by Peters et al, and it contains 15 items on physical, cognitive, social, and psychological domains. The answer to each item has the score of either 0 or 1, with 1 indicating a dependent problem. The total score of GFI ranges from 0 to 15, with higher scores indicating greater frailty. The cut-off value of GFI ≥3 was considered frail in geriatric oncology. Two studies[23, 27] have proved moderate internal consistency of the GFI (Cronbach’s α ranged from 0.68 to 0.712). All patients filled out the GFI questionnaires within three days of their hospital admission.
Short-Form Mini-Nutritional Assessment (MNA-SF) questionnaire
The MNA-SF, revised by Rubenstein et al based on the Mini-Nutritional Assessment, is a validated tool to screen malnourished hospitalized patients. The sensitivity, specificity, and diagnostic accuracy of MNA-SF for the prediction of malnutrition were 97.9%, 100%, and 98.7%, respectively. It contains 6 items, namely, weight loss, body mass index, stress or illness, mobility, dementia or depression, and loss of appetite. The total score of MNA-SF ranges from 0 to 14, with the score >11 (£11) being well-nourished (at risk of malnutrition or malnourished). Trained researchers routinely obtained patients’ MNA-SF scores within three days of their hospital admission.
Handgrip strength was measured in kilograms (Kg) with a handheld dynamometer based on the digital strain gauge sensors (Jamar® Plus+, Performance Health Supply, Inc., Cedarburg, WI, USA). Before performing tests, researchers explained the detailed methods to the patients. Measurements were conducted with the patient seated, shoulders adducted and neutrally rotated, elbow in 90° flexion, and the forearm and twist in neutral position. All patients were asked to squeeze the dynamometer as much as possible with the dominant hand. Two tests were performed with a rest interval of at least 30 seconds, and the maximum value of the two tests was recorded. If the two results differed over 10%, a third test would be carried out. Low handgrip strength is defined as <26 kg for male and <18 kg for female.
4-Meter Walk Test
Walking speed was performed through a 4-meter walk test, with an additional two meters being added at the beginning and the end of the walkway that was provided for accelerating or decelerating. Patients in standing still position were asked to walk at their usual pace (normal gait speed) with or without using auxiliary aids (e.g., canes, walkers). Walking time was measured by a trained researcher with a digital stopwatch (PS-60, China) from the moment that the patient’s first foot crossed the 2-m line until the moment that the patient’s first foot completely crossed the 6-m line. The test was performed twice, and the shortest time was applied for analysis. Slow gait speed is defined as £0.8 m/s.
Mid-upper arm circumference (MUAC) and calf circumference (CC)
MUAC and CC were measured to the nearest 0.1 cm with a non-elastic tape (Deli, China) without compressing the subcutaneous tissue. MUAC was measured at the mid-point around the arm between the acromion and the ulnar olecranon, with the patient’s upper limb in a state of natural hanging. CC was measured around the widest part of the calf, while subjects stood with their legs shoulder-width apart.
The Kolmogorov-Smirnov test was conducted to verify the normal distribution of continuous variables. All data were expressed as mean ± standard deviation, or median and inter-quartile range, or frequency and percentiles. Differences in demographic and clinical characteristics and biochemical laboratory parameters data between frail and non-frail patients were tested using two independent-samples t test or non-parametric test or chi-square test. To determine risk factors that were associated with frailty and estimate their 95% confidence intervals (CI), independent variables with a P value<0.05 (was set at a stringent level) on univariate analysis as described above were entered into a multivariate logistic regression model analysis by adopting the Forward LR method. Data analyses were performed with SPSS 23.0 software package (IBM, Armonk, NY, USA). A P value<0.05 was considered statistically significant.