Prehabilitation on Fitness, Surgical Outcomes and Mitochondria Functionality in Patients With Esophageal Cancer

The most often reported complications of patients with resectable esophageal malignancies are pulmonary (25\~57%), which may cause increased intensive care unit utilization, prolonged length of hospital stay, increased mortality and medical expense. Also, neoadjuvant chemotherapy has a deleterious effect on patients' cardiopulmonary capacity, strength and muscle mass. Prehabilitation includes preoperative exercise training and nutrition management. The reporting outcome regarding whether it improves surgical outcomes is inconsistent. One of the reasons is that pulmonary complication tends to occur in patients with low cardiopulmonary fitness, but all studies included patients with all level of fitness. Most of the chemotherapy interferes with cell division to inhibit tumor growth but is also harmful to mitochondria functionality. For example, Cisplatin and Paclitaxel, commonly used in esophageal cancer, alter mitochondria function, caused by disruption of respiratory chain function and increased production of reactive oxygen species. However, it remains unclear their negative effects on the oxidative phosphorylation capacity of mitochondria (OXPHOS). Furthermore, whether prehabilitation reverses this negative effect is scarcely explored. Patients will be inquired to participate and randomized into prehabilitation or control group. The latter will undergo conventional therapy only, while the former will receive additional prehabilitation program. The prehabilitation program encompasses supervised and home-based aerobic, resistance training (large and inspiratory muscle) and nutrition management. The supervised exercise training will be performed right before or after the radiotherapy. Outcome variables are fitness-related testing \[the 1st year\], quality of life and surgical outcomes \[the 2nd year\] and mitochondria functionality (OXPHOS, membrane potential, matrix oxidant burden) \[the 3rd year\]. Evaluation is performed 3 times at baseline, before surgery and 4