Clinical Impact of a Perioperative Exercise Program for Sarcopenia and Overweight/Obesity Gastric Cancer

Clinical Impact of Perioperative Sarcopenia on Gastric Cancer Outcomes

Sarcopenia is a condition characterized by the loss of the skeletal muscle mass and function. Recent studies have shown that perioperative sarcopenia affects short-term outcomes in gastric cancer patients (17-19). Ma et al. evaluated the clinical influence of sarcopenia on postoperative surgical complications in 545 gastric cancer patients who received curative resection (17), where sarcopenia was defined as a low muscle mass plus a low muscle strength or low physical performance based on the European Working Group on Sarcopenia in Older People criteria. Among these 545 patents, 40 (7.3%) were diagnosed with sarcopenia. The authors reported that the incidence of postoperative complications was significantly higher in patients with sarcopenia than in those without sarcopenia (21.1% vs. 7.3%). In addition, sarcopenia was an independent risk factor for postoperative surgical complications [hazard ratio (HR)=2.330, 95% confidence interval (CI)=1.132-4.796, p=0.022]. Similar results have been observed in other reports (18, 19).

In addition to its influence on short-term outcomes, however, preoperative sarcopenia was also reported to affect the long-term oncological outcomes in gastric cancer (20-22). Kawamura et al. evaluated whether or not preoperative sarcopenia affected the long-term outcomes of 951 gastric cancer patients ≥65 years old who received curative gastrectomy (20), with sarcopenia defined as a decreased arm muscle area of <38.05 cm² in men and <27.87 cm² in women. Among their 951 patients, 111 (11.7%) were diagnosed with sarcopenia. Both the overall survival (OS) and cancer-specific survival (CSS) were significantly lower in patients with sarcopenia compared to those without sarcopenia. In addition, sarcopenia was an independent prognostic factor for both the OS and CSS [HR (95%CI) for the OS: 1.82 (1.32-2.47), p<0.001; HR (95%CI) for the CCS: 1.73 (1.02-2.80), p=0.043]. Similar results have also been reported in other studies (21, 22).

Given these previous findings, preoperative sarcopenia appears to affect both the short- and long-term oncological outcomes in gastric cancer patients.

Clinical Impact of a Perioperative Exercise Program in Sarcopenic Gastric Cancer Patients

Yamamoto et al. evaluated the effects of a preoperative exercise program and nutritional support program in 22 sarcopenia gastric cancer patients who were ≥65 years old (23). The preoperative exercise program involved handgrip training, walking, and resistance training. The resistance training was performed in two patterns: one is squats, push-ups, and twisting sits-up; another is straight sits-ups, standing on tiptoes, and one arm and the opposite side leg lifted up. These were performed at home until admission for surgery. In that study, the median period of exercise program was 16 days. The authors found that the handgrip strength was 20.0 kg before exercise and 21.2 kg after exercise (p=0.022). In addition, four patients became non-sarcopenic after the exercise program. However, the working speed and skeletal muscle mass index were similar before and after exercise. They concluded that nutritional support programs and preoperative exercise might reduce sarcopenia in elderly sarcopenia gastric cancer patients.

Cho et al. evaluated the safety and feasibility of a postoperative recovery exercise program developed specifically for gastric cancer patients (PREP-GC) in 24 patients who underwent laparoscopic or robot-assisted gastrectomy for gastric cancer (24). The exercise program had three phases: in-hospital exercise (one week), home exercise (one week), and fitness improvement exercise (eight weeks). In the hospital phase, exercise was selected to increase the range of motion after gastrectomy. All exercises were under the supervision of an exercise specialist. Walking was also encouraged whenever possible. In the home exercise phase, the exercise program was designed to improve the range of motion after discharge from the hospital. A handout illustrating the home exercise regimen was provided to the patients. They were recommended to perform the bed and home exercise regimens at least twice a day and to report their daily activity. In the fitness exercise phase, the program was designed to improve the function and reduction in muscle volume after surgery. Patients performed exercise three times a week. The eight weeks of resistance exercise were divided into four periods. Among the 24 patients enrolled in this study, 20 completed the PREP-GC. There were no adverse events related to the exercise program. The adherence rate was 79.4% and the compliance rate was 99.4% in this study. After completing the PREP-GC, patients showed improvement in muscular strength, cardiopulmonary function, emotional functioning, and global health status. The authors concluded that a systematic exercise intervention program might have some clinical benefit for patients undergoing gastrectomy for gastric cancer.

Given the above findings, perioperative exercise programs might be safe and feasible, and have some clinical influence on the outcomes of patients undergoing gastrectomy for gastric cancer. However, the clinical benefits of such exercise intervention for patients after gastrectomy during the perioperative period should be clarified in a randomized trial.

Clinical Impact of a Perioperative Overweight or Obese Status on Gastric Cancer Outcomes

Overweight and obesity are defined as an abnormal or excessive fat accumulation that presents a risk to one’s health. A body mass index (BMI) over 25 is considered overweight, while that over 30 is considered obese (25). Recent studies have shown that perioperative overweight and obesity affect both the short- and long-term outcomes of gastric cancer patients (26, 27).

Kambara et al. evaluated the clinical impact of the preoperative BMI in 460 patients with locally advanced gastric cancer who received curative resection (26). The patients were classified into groups with BMI <18.5 kg/m², 18.5-25 kg/m², and ≥25 kg/m². Upon comparing the patients’ characteristics, those with a BMI ≥25 kg/m² had a longer operation (239 vs. 206 and 229, p=0.0610), more blood loss (420 vs. 222 and 300, p=0.0200), and more frequent intra-abdominal abscess (16% vs. 3% and 4%, p=0.0012) than those with a BMI of <18.5 and 18.5-25 kg/m². The 5-year relapse-free survival rate was 47.6% in the BMI <18.5 kg/m² group, 54.3% in the BMI 18.5-25 kg/m² group, and 40.0% in the BMI >25 kg/m² group, respectively (p=0.0614), while the 5-year overall survival rate was 50.1% in the BMI <18.5 kg/m² group, 62.5% in the BMI 18.5-25 kg/m² group, and 53.8% in the BMI >25 kg/m² group (p=0.0413). The authors found that the BMI was a significant risk factor for both short- and long-term oncological outcomes in locally advanced gastric cancer patients. They concluded that a greater surgical stress, fewer dissected lymph nodes, and a higher rate of postoperative infective complications might contribute to the unfavorable prognosis of patients with a BMI ≥25 kg/m².

We et al. evaluated the clinical influence of overweight (BMI ≥25 kg/m²) in gastric cancer patients who received gastrectomy using a meta-analysis (27). This meta-analysis included 23 studies with 20,678 gastric cancer patients (4897 with BMI ≥25 kg/m² and 15781 with BMI <25 kg/m²). Overweight patients had significantly longer operation times (p<0.00001) and more blood loss (p=0.001) than those with a BMI <25 kg/m². The incidence of anastomosis leakage (p=0.002) and pancreatic fistula was significantly higher in patients with a BMI >25 kg/m² than in those with a BMI <25 kg/m² (p=0.002 and p<0.00001, respectively). In addition, patients with a BMI ≥25 kg/m² showed a significantly poorer survival than those with a BMI <25 kg/m² (relative risk: 1.14; 95%CI=1.07-1.20, p<0.0001). However, the mortality rate and length of hospital stay were similar between the two groups.

Notably, the “obesity paradox” has been proposed for various malignancies (28-30). In gastric cancer, Tokunaga et al. evaluated the relationships between the BMI and long-term oncological outcomes in 7,925 gastric cancer patients who underwent gastrectomy (31). The patients were divided into those with a BMI <25 kg/m² (n=6799, N-BMI) and those with a BMI ≥25 kg/m² (n=1126, H-BMI). They found that the 5-year overall survival was significantly better in the H-BMI group than in the N-BMI group (81.5% vs. 74.1%, respectively; p<0.001). Similar results have also been observed in other studies (32, 33). Given these previous findings, although overweight and obesity do have negative effects on the short-term oncological outcomes, the clinical impact of overweight and obesity on the long-term oncological outcomes in gastric cancer must be further evaluated.

Clinical Impact of a Perioperative Exercise Program on Obese Gastric Cancer Patients

Overweight and obesity are risk factors for the perioperative management and postoperative surgical complications after gastrectomy for gastric cancer. Some studies have evaluated the efficacy of perioperative exercise programs in reducing postoperative surgical complications in gastric cancer patients with overweight or obesity. Cho et al. evaluated whether or not a preoperative exercise program would be safe and effective for obese gastric cancer patients (34). The training program included stretching exercise, aerobic exercise, and resistance training. The aerobic exercise involved using swimming, bicycle ergometer, dancing, or jogging. These exercises were performed at least three days per week. In this study, 30 kcal/kg/week was expected to be the energy expenditure of the exercise. Resistance training was carried out at least one time per week. The exercise program continued for four weeks. In this study, 18 patients were enrolled in the exercise group, and 54 patients enrolled in the control group were matched to the exercise group patients. After the exercise program, body weight, abdominal circumference, and the BMI were significantly lower after the exercise than before the exercise, following the four-week program. When comparing the surgical results between the exercise group and control group, the median blood loss was slightly lower in the exercise group than in the control group (105 ml vs. 130 ml, p=0.692). In addition, the incidence of abdominal postoperative surgical abscess (0% vs. 18.5%, p=0.089) and anastomotic leakage (0% vs. 16.7%, p=0.125) tended to be lower in the exercise group than in the control group. The authors concluded that preoperative exercise was safe and had clinical benefit in reducing postoperative surgical complications.

Future Perspective and Ongoing Trial

Since 2010, several ongoing studies have been examining perioperative exercise program for gastric cancer patients. A Taiwanese group is conducting a randomized control trial comparing the efficacy of a rehabilitation exercise program with the usual care, in 160 gastric cancer patients who received gastrectomy (ClinicalTrials.gov Identifier: NCT04593134). Their exercise group performed a 12-week regimen of home-based walking exercise comprising walking at a moderate intensity for 40 min, 3 times a week. The primary endpoint is the quality of life using EORTC QLQ-C30 and STO-22, and the secondary endpoints are fatigue, emotional distress, sleep quality, and circadian rhythms.

A UK group is conducting a randomized control trial comparing the efficacy of multimodal pre-operative rehabilitation program with the usual care during neo-adjuvant therapy in 50 esophago-gastric cancer patients (ClinicalTrials.gov Identifier: NCT02950324). The patients in the rehabilitation group performed 15 weeks of exercise and received nutritional support and psychological rehabilitation in the form of ‘Medical Coaching’. The primary endpoint is the cardiopulmonary exercise performance, and the secondary endpoints are changes in insulin resistance, quality of life, and grip-strength.

A Chinese group is conducting a randomized control trial comparing efficacy of a pre-operative rehabilitation program with the usual care during neo-adjuvant therapy in 82 gastric cancer patients with metabolic syndrome (ClinicalTrials.gov Identifier: NCT02649348). The patients in the rehabilitation group climbed 6 flights of stairs (approximately 20 meters in height) at least 6 times as a daily routine and performed adaptive simulated training of restrictive ventilation dysfunction following abdominal surgery using a full elastic breathable abdominal bandage. The primary endpoint is the incidence of postoperative surgical complications.

Bausys et al. evaluated whether or not home-based rehabilitation can reduce postoperative morbidity in patients who received gastrectomy for gastric cancer (ClinicalTrials.gov Identifier: NCT04223401). They conducted a multi-center, open-label randomized control trial comparing the incidence of 90-day postoperative morbidity after gastrectomy for gastric cancer between patients with and without rehabilitation. In their trial, 128 patients were enrolled into either the intervention or control group. The secondary outcomes of the study were the physical and nutritional status, anxiety and depression level, quality of life, postoperative mortality rates, and full completion of the oncological treatment.

Although perioperative exercise programs have been shown to have clinical influence on the outcomes of various malignancies, several points need to be clarified to optimize the perioperative exercise program for gastric cancer patients. First, the definition and evaluation methods of sarcopenia were unclear in the reviewed studies. Second, the optimal duration and methods of perioperative exercise were unclear. Third, the clinical benefits of the perioperative exercise on the long-term oncological outcomes were unclear. If these points could be clarified, an effective program might be able to be established for gastric cancer patients.