Programmed death-1 (PD-1) and its ligand PD-L1 are the major members of inhibitory costimulatory molecules and express high in a variety of tumor cells and their associated cells surface,while the proportion of regulatory T cells (Tregs) are abnormally elevated in tumor infiltrating T lymphocytes cells.PD-L1 combined with PD-1 and Treg help tumors evade immune clearance,weaken immune responses and induce immune tolerance.New researches find that PD-L1 plays an important role in the development and function maintenance of inducible Treg (iTreg),and PD-L1 signal can change initial CD4 + CD25-T cells into iTreg to play a role of immunosuppression.Research on PD-1 signaling pathway can provide a new theoretical basis for the inhibition of tumor immune escape in clinical application of immunotherapy and better treatments.

Programmed death-1 (PD-1) and its ligand 1 (PD-L1) play critical roles in the identification and elimination of tumor cells evading the host's immune system.Tumor model in mice which is given anti-PD-L1 monoclonal antibody shows obviously host anti-tumor response.Currently,immunotherapy drugs of PD-1/PD-L1 signaling pathways receive good effects in a variety of tumors failure of the traditional method,and with less adverse reaction,which provide valuable clinical experiences in advanced tumor immunotherapy.

Objective:To evaluate the safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy.Methods:This prospective, multi-center, single-arm study was initiated by the Affiliated Cancer Hospital of Zhengzhou University in June 2021 (CRAFT Study, NCT05282563). Participating institutions included Nanyang Central Hospital, Zhumadian Central Hospital, Luoyang Central Hospital, First Affiliated Hospital of Henan Polytechnic University, First Affiliated Hospital of Henan University, Luohe Central Hospital, the People's Hospital of Hebi, First People's Hospital of Shangqiu, Anyang Tumor Hospital, First People's Hospital of Pingdingshan, and Zhengzhou Central Hospital Affiliated to Zhengzhou University. Inclusion criteria were as follows: (1) gastric adenocarcinoma confirmed by preoperative gastroscopy;(2) preoperative imaging assessment indicated that R0 resection was feasible; (3) preoperative assessment showed no contraindications to surgery;(4) esophagojejunostomy planned during the procedure; (5) patients volunteered to participate in this study and gave their written informed consent; (6) ECOG score 0–1; and (7) ASA score I–III. Exclusion criteria were as follows: (1) history of upper abdominal surgery (except laparoscopic cholecystectomy);(2) history of gastric surgery (except endoscopic submucosal dissection and endoscopic mucosal resection); (3) pregnancy or lactation;(4) emergency surgery for gastric cancer-related complications (perforation, hemorrhage, obstruction); (5) other malignant tumors within 5 years or coexisting malignant tumors;(6) arterial embolism within 6 months, such as angina pectoris, myocardial infarction, and cerebrovascular accident; and (7) comorbidities or mental health abnormalities that could affect patients' participation in the study. Patients were eliminated from the study if: (1) radical gastrectomy could not be completed; (2) end-to-side esophagojejunal anastomosis was not performed during the procedure; or (3) esophagojejunal anastomosis reinforcement was not possible. Double and a half layered esophagojejunal anastomosis was performed as follows: (1) Open surgery: the full thickness of the anastomosis is continuously sutured, followed by embedding the seromuscular layer with barbed or 3-0 absorbable sutures. The anastomosis is sutured with an average of six to eight stitches. (2) Laparoscopic surgery: the anastomosis is strengthened by counterclockwise full-layer sutures. Once the anastomosis has been sutured to the right posterior aspect of the anastomosis, the jejunum stump is pulled to the right and the anastomosis turned over to continue to complete reinforcement of the posterior wall. The suture interval is approximately 5 mm. After completing the full-thickness suture, the anastomosis is embedded in the seromuscular layer. Relevant data of patients who had undergone radical gastrectomy in the above 12 centers from June 2021 were collected and analyzed. The primary outcome was safety (e.g., postoperative complications, and treatment). Other studied variables included details of surgery (e.g., surgery time, intraoperative bleeding), postoperative recovery (postoperative time to passing flatus and oral intake, length of hospital stay), and follow-up conditions (quality of life as assessed by Visick scores).Result:[1] From June 2021 to September 2022,457 patients were enrolled, including 355 men and 102 women of median age 60.8±10.1 years and BMI 23.7±3.2 kg/m2. The tumors were located in the upper stomach in 294 patients, mid stomach in 139; and lower stomach in 24. The surgical procedures comprised 48 proximal gastrectomies and 409 total gastrectomies. Neoadjuvant chemotherapy was administered to 85 patients. Other organs were resected in 85 patients. The maximum tumor diameter was 4.3±2.2 cm, number of excised lymph nodes 28.3±15.2, and number of positive lymph nodes five (range one to four. As to pathological stage,83 patients had Stage I disease, 128 Stage II, 237 Stage III, and nine Stage IV. [2] The studied surgery-related variables were as follows: The operation was successfully completed in all patients, 352 via a transabdominal approach, 25 via a transhiatus approach, and 80 via a transthoracoabdominal approach. The whole procedure was performed laparoscopically in 53 patients (11.6%), 189 (41.4%) underwent laparoscopic-assisted surgery, and 215 (47.0%) underwent open surgery. The median intraoperative blood loss was 200 (range, 10–1 350) mL, and the operating time 215.6±66.7 minutes. The anastomotic reinforcement time was 2 (7.3±3.9) minutes for laparoscopic-assisted surgery, 17.6±1.7 minutes for total laparoscopy, and 6.0±1.2 minutes for open surgery. [3] The studied postoperative variables were as follows: The median time to postoperative passage of flatus was 3.1±1.1 days and the postoperative gastrointestinal angiography time 6 (range, 4–13) days. The median time to postoperative oral intake was 7 (range, 2–14) days, and the postoperative hospitalization time 15.8±6.7 days. [4] The safety-related variables were as follows: In total, there were 184 (40.3%) postoperative complications. These comprised esophagojejunal anastomosis complications in 10 patients (2.2%), four (0.9%) being anastomotic leakage (including two cases of subclinical leakage and two of clinical leakage; all resolved with conservative treatment); and six patients (1.3%) with anastomotic stenosis (two who underwent endoscopic balloon dilation 21 and 46 days after surgery, the others improved after a change in diet). There was no anastomotic bleeding. Non-anastomotic complications occurred in 174 patients (38.1%). All patients attended for follow-up at least once, the median follow-up time being 10 (3–18) months. Visick grades were as follows: Class I, 89.1% (407/457); Class II, 7.9% (36/457); Class III, 2.6% (12/457); and Class IV 0.4% (2/457).Conclusion:Double and a half layered esophagojejunal anastomosis in radical gastrectomy is safe and feasible.

Objective:To evaluate the safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy.Methods:This prospective, multi-center, single-arm study was initiated by the Affiliated Cancer Hospital of Zhengzhou University in June 2021 (CRAFT Study, NCT05282563). Participating institutions included Nanyang Central Hospital, Zhumadian Central Hospital, Luoyang Central Hospital, First Affiliated Hospital of Henan Polytechnic University, First Affiliated Hospital of Henan University, Luohe Central Hospital, the People's Hospital of Hebi, First People's Hospital of Shangqiu, Anyang Tumor Hospital, First People's Hospital of Pingdingshan, and Zhengzhou Central Hospital Affiliated to Zhengzhou University. Inclusion criteria were as follows: (1) gastric adenocarcinoma confirmed by preoperative gastroscopy;(2) preoperative imaging assessment indicated that R0 resection was feasible; (3) preoperative assessment showed no contraindications to surgery;(4) esophagojejunostomy planned during the procedure; (5) patients volunteered to participate in this study and gave their written informed consent; (6) ECOG score 0–1; and (7) ASA score I–III. Exclusion criteria were as follows: (1) history of upper abdominal surgery (except laparoscopic cholecystectomy);(2) history of gastric surgery (except endoscopic submucosal dissection and endoscopic mucosal resection); (3) pregnancy or lactation;(4) emergency surgery for gastric cancer-related complications (perforation, hemorrhage, obstruction); (5) other malignant tumors within 5 years or coexisting malignant tumors;(6) arterial embolism within 6 months, such as angina pectoris, myocardial infarction, and cerebrovascular accident; and (7) comorbidities or mental health abnormalities that could affect patients' participation in the study. Patients were eliminated from the study if: (1) radical gastrectomy could not be completed; (2) end-to-side esophagojejunal anastomosis was not performed during the procedure; or (3) esophagojejunal anastomosis reinforcement was not possible. Double and a half layered esophagojejunal anastomosis was performed as follows: (1) Open surgery: the full thickness of the anastomosis is continuously sutured, followed by embedding the seromuscular layer with barbed or 3-0 absorbable sutures. The anastomosis is sutured with an average of six to eight stitches. (2) Laparoscopic surgery: the anastomosis is strengthened by counterclockwise full-layer sutures. Once the anastomosis has been sutured to the right posterior aspect of the anastomosis, the jejunum stump is pulled to the right and the anastomosis turned over to continue to complete reinforcement of the posterior wall. The suture interval is approximately 5 mm. After completing the full-thickness suture, the anastomosis is embedded in the seromuscular layer. Relevant data of patients who had undergone radical gastrectomy in the above 12 centers from June 2021 were collected and analyzed. The primary outcome was safety (e.g., postoperative complications, and treatment). Other studied variables included details of surgery (e.g., surgery time, intraoperative bleeding), postoperative recovery (postoperative time to passing flatus and oral intake, length of hospital stay), and follow-up conditions (quality of life as assessed by Visick scores).Result:[1] From June 2021 to September 2022,457 patients were enrolled, including 355 men and 102 women of median age 60.8±10.1 years and BMI 23.7±3.2 kg/m2. The tumors were located in the upper stomach in 294 patients, mid stomach in 139; and lower stomach in 24. The surgical procedures comprised 48 proximal gastrectomies and 409 total gastrectomies. Neoadjuvant chemotherapy was administered to 85 patients. Other organs were resected in 85 patients. The maximum tumor diameter was 4.3±2.2 cm, number of excised lymph nodes 28.3±15.2, and number of positive lymph nodes five (range one to four. As to pathological stage,83 patients had Stage I disease, 128 Stage II, 237 Stage III, and nine Stage IV. [2] The studied surgery-related variables were as follows: The operation was successfully completed in all patients, 352 via a transabdominal approach, 25 via a transhiatus approach, and 80 via a transthoracoabdominal approach. The whole procedure was performed laparoscopically in 53 patients (11.6%), 189 (41.4%) underwent laparoscopic-assisted surgery, and 215 (47.0%) underwent open surgery. The median intraoperative blood loss was 200 (range, 10–1 350) mL, and the operating time 215.6±66.7 minutes. The anastomotic reinforcement time was 2 (7.3±3.9) minutes for laparoscopic-assisted surgery, 17.6±1.7 minutes for total laparoscopy, and 6.0±1.2 minutes for open surgery. [3] The studied postoperative variables were as follows: The median time to postoperative passage of flatus was 3.1±1.1 days and the postoperative gastrointestinal angiography time 6 (range, 4–13) days. The median time to postoperative oral intake was 7 (range, 2–14) days, and the postoperative hospitalization time 15.8±6.7 days. [4] The safety-related variables were as follows: In total, there were 184 (40.3%) postoperative complications. These comprised esophagojejunal anastomosis complications in 10 patients (2.2%), four (0.9%) being anastomotic leakage (including two cases of subclinical leakage and two of clinical leakage; all resolved with conservative treatment); and six patients (1.3%) with anastomotic stenosis (two who underwent endoscopic balloon dilation 21 and 46 days after surgery, the others improved after a change in diet). There was no anastomotic bleeding. Non-anastomotic complications occurred in 174 patients (38.1%). All patients attended for follow-up at least once, the median follow-up time being 10 (3–18) months. Visick grades were as follows: Class I, 89.1% (407/457); Class II, 7.9% (36/457); Class III, 2.6% (12/457); and Class IV 0.4% (2/457).Conclusion:Double and a half layered esophagojejunal anastomosis in radical gastrectomy is safe and feasible.