Effects of Fasting Strategies on Postoperative Recovery and Long-term Prognosis in Patients With Colorectal Cancer

Effects of Different Fasting Strategies in Perioperative Period on Postoperative Recovery, Immune Function, and Long-term Prognosis in Patients With Radical Resection of Colorectal Cancer

In 2018, colorectal cancer is the third most common malignant tumor in terms of morbidity and second mortality in the world. Surgical resection is still the main treatment for colorectal cancer.With the introduction of the ERAS, the latest international and domestic guidelines for fasting before surgery all advocate shortening the fasting time. For example, 2 hours before surgery, oral take cleared fluids, including water, sugar water, fruit juice, tea and black coffee (without milk) is allowed.Solid food can be consumed 4 hours before surgery, and oral diet should be resumed as soon as possible after surgery. Changes in diet, nutritional status, and physical activity are closely related to the incidence of colorectal cancer. Therefore, we believe that the intestine may be very sensitive to different fasting times during the perioperative period. Prolonging the fasting time may improve the prognosis by improving postoperative insulin resistance, reducing inflammation and protecting anti-tumor immune function in patients with colorectal cancer.Prolonged fasting time seems to be contrary to the results of some studies, and whether it is applicable to patients with tumor surgery is unclear. Therefore, there is an urgent need to conduct large-scale, prospective, randomized controlled clinical studies to clarify the most suitable perioperative fasting strategy (including composition, interval, and amount) for cancer patients, which can not only reduce surgical stress and speed up postoperative rehabilitation,reduce postoperative metastasis and recurrence and improve mid- and long-term prognosis.

As early as a century ago, Investigators proved that diet restriction can prevent the occurrence of transplanted tumors in mice. Following this milestone, many animal studies (from mice to primates) have confirmed that diet restriction can slow the development of spontaneous tumors and transplanted tumors. A study of macaque monkeys for more than 20 years revealed that restricting diet by 30% can reduce the incidence of tumors by 50%, which makes people see the potential value of restricting diet to humans. However, whether diet restriction can also reduce the incidence of human tumors is not entirely clear. The growth of tumor cells requires a nutrient-rich environment, and the lack of glucose and amino acids caused by diet restrictions is very detrimental to tumor cells. Unlike normal cells, tumor cells mainly rely on glycolysis (Warburg effect) rather than energy and biosynthetic precursors provided by oxidative phosphorylation for proliferation. These characteristics make tumor cells extremely sensitive to changes in the surrounding environment, which is called differential stress sensitization (DSS).Investigators found that the use of low sugar and low serum in a cell model to simulate periodic fasting can enhance the sensitivity of human or animal tumor cells to doxorubicin and cyclophosphamide, and also found that they were transplanted subcutaneously in mice Melanoma or breast cancer, diet combined with chemotherapy is better than chemotherapy alone; in the mouse metastatic neuroblastoma model, fasting before high-dose chemotherapy can successfully reduce the toxic side effects of chemotherapy drugs and reduce metastasis and prolong the tumor-free survival. Surgery and stress are twin brothers. Surgical resection, blood flow blockage, ischemia-reperfusion injury, tissue damage, local inflammatory factor release, and changes in systemic neuroendocrine and metabolism all affect blood flow, blood coagulation, and immune function. Investgators found restricted diet can reduce the inflammatory response after myocardial ischemia-reperfusion injury in mice. Many animal experiments have confirmed that perioperative fasting can effectively protect the liver, kidneys, and brain from organ damage. The specific mechanism may be related to fasting increasing antioxidant enzyme activity, reducing insulin-like growth factor-1 (IGF-1), and activating the autophagy pathway. Similar to chemotherapy, there is currently no randomized clinical controlled study to evaluate the impact of individualized perioperative dietary regimens (such as restricted diet) on the prognosis of tumor surgery.

In 2018, colorectal cancer is the third most common malignant tumor in terms of morbidity and second mortality in the world. Surgical resection is still the main treatment for colorectal cancer.With the introduction of the ERAS, the latest international and domestic guidelines for fasting before surgery all advocate shortening the fasting time. For example, 2 hours before surgery, oral take cleared fluids, including water, sugar water, fruit juice, tea and black coffee (without milk) is allowed.Solid food can be consumed 6 hours before surgery, and oral diet should be resumed as soon as possible after surgery. Changes in diet, nutritional status, and physical activity are closely related to the incidence of colorectal cancer. Therefore, we believe that the intestine may be very sensitive to different fasting times during the perioperative period. Prolonging the fasting time may improve the prognosis by improving postoperative insulin resistance, reducing inflammation and protecting anti-tumor immune function in patients with colorectal cancer.Prolonged fasting time seems to be contrary to the results of some studies, and whether it is applicable to patients with tumor surgery is unclear. Therefore, there is an urgent need to conduct large-scale, prospective, randomized controlled clinical studies to clarify the most suitable perioperative fasting strategy (including composition, interval, and amount) for cancer patients, which can not only reduce surgical stress and speed up postoperative rehabilitation,reduce postoperative metastasis and recurrence and improve mid- and long-term prognosis.

Inclusion Criteria:

1. Age 20 ~ 70 years old
2. With BMI 20.5-25.0 kg/m2
3. Without any Endocrine and metabolic diseases
4. A stable body weight (±3 kg) for at least 6 months
5. Those diagnosed with colorectal cancer by preoperative pathology or enteroscopy
6. Patients undergoing laparoscopic radical colorectal cancer resection
7. ASA grade I-III grade
8. Initial patients have not received any treatment for bowel cancer except neoadjuvant chemotherapy
9. Patients with confirmed and feasible radical resection of colorectal cancer
10. No evidence of distant metastasis before surgery
11. Willing to participate in the research of the subject and agree to follow up regularly

Exclusion Criteria:

1. Patients with relapsed colorectal cancer who are going to undergo surgery and re-excision
2. accompanied by other malignant tumors
3. Severe malnourished patients
4. History of systemic metabolism such as diabetes
5. Before surgery, have received other treatments for colorectal cancer (such as local excision, etc.) in addition to neoadjuvant chemotherapy
6. Have a history of immunotherapy before surgery
7. Combined with basic diseases of serious heart, lung, brain, kidney and other important organs
8. Combined with severe primary diseases such as severe immune system or hematopoietic system
9. The tumor burden cannot be cured, and there is distant metastasis. Those who intend to undergo palliative surgery
10. People with gastroesophageal reflux disease, difficulty swallowing, intestinal obstruction, or difficulty in airway management
11. People who refuse to participate in the study or cannot receive long-term follow-up