Treatment Of Advanced Digestive Tract Tumor With PD-1 Inhibitor In 2 Cases And Literature Review

Objective:PD-1 is a member of the B7 receptor family.There are two ligands(PDL1 [also known as cd274] and PD-L2 [also nown as pddlg2])that bind to each other.These ligands can be generated and expressed by a variety of cell types.The PD-1-PD-L1 receptor-ligand axis has been shown to be extremely important for T cell failure,a state of immune dysfunction in patients with chronic infection or cancer.PD-1 down-regulates T-cell receptors and PIK3CA-AKT1 pathways through its ligands,and directly interacts with transcription factors(such as batf-par).Downstream targets of PD-1 bind to PD-1,diluting its inhibitory properties.Sintilimab(tyvyt <)is a complete human IgG4 monoclonal antibody that binds to programmed cell death receptor-1(PD-1),thus blocking the interaction between PD-1 and its ligands(PD-L 1and PD-L2),thus helping to restore the endogenous anti-tumor T cell response.At present,the application value of Sindili monoclonal antibody in solid tumors is still in the research stage,and a lot of clinical evidence is needed to further explore.At present,there are few reports about the application of anti-PD-1 antibody in solid tumors of digestive tract,but positive results have been reported in a small number of single-center studies of colorectal and esophageal cancer.Fortunately,most of these results indicate that anti-PD-1 antibody can significantly prolong the survival of patients.However,there is still a lack of systematic research on the application of advanced digestive tract tumors.Moreover,the interaction between tumor microenvironment and tumor cells is highly complex.Therefore,further studies are needed to reveal the mechanism of action of Sindilimab in the late digestive tract.Methods:In February 2019,Jinan Central Hospital admitted two patients with advanced digestive tract tumors,one male,68 years old.They were admitted becauseof "2 years of confirmed diagnosis of gastric cancer,more than 7 months of liver metastasis and multiple lymph node metastasis,more than 1 month of portal vein cancer thrombus and 3 days of abdominal pain".Positive examination:full abdomen,15 cm operation scar in mid-upper abdomen,tenderness under sword and right upper abdomen,active bowel sounds.Admission diagnosis:1.Targeted treatment of gastric antrum malignant tumors(adenocarcinoma,PT4N2M1,IV stage)after radical gastrectomy for gastric cancer after 6 cycles of local radiotherapy for hepatic metastasis,multiple lymph node metastasis and portal vein cancer thrombus after multi-cycle chemotherapy 2.Hypertension(grade 3,high risk)3.Gastric perforation repair 4.Appendicectomy.A 69-year-old male patient was admitted to the hospital because of "upper abdominal discomfort for 2 weeks,diagnosed as esophageal cancer for 1 week".Diagnosis:1.Esophageal malignant tumors(middle segment moderately differentiated squamous cell carcinoma,cTxNxM1,stage IV)secondary lung malignant tumors 2.Cerebral infarction 3.Paranasal sinusitis.Treatment:Case 1 was treated with 200 mg GTT q3 w of Sindilimab in 2019.02.22,2019.03.18,2019.04.10 and 2019.05.08 respectively,and symptomatic support was given during the treatment.After 3 cycles of immunotherapy,the whole abdomen enhanced CT showed that:compared with the anterior film(2019.02.21),after gastric cancer surgery and partial hepatectomy,the left hepatic lobe metastasis and invasion of pancreas,portal and retroperitoneal lymph node metastasis and involvement of left hepatic vein,left portal vein and hepatic artery were considered.The area of necrosis was narrowed slightly.2019.02.20 Saccharide antigen 19-9 was measured at1124.00U/ml and carcinoembryonic antigen 7.960ng/ml.2019.05.05 Saccharide antigen 19-9 and carcinoembryonic antigen 19-9 were measured at 332.70U/ml and7.960ng/ml respectively.Case 2 was treated with 200 mg d0+paclitaxel liposome 270 mg D1+nedaplatin 40 mg d2-4 of Sidilizumab in 2019.02.19,2019.03.12,2019.04.02 and 2019.04.23,respectively,supplemented with symptomatic treatment such as whitening,acid suppression,vomiting and rehydration.The results of auxiliary examination showed that WBC was 7.17*109/L and NEUT was 4.72*109/L on February 19,2019.Tumor markers were 6.23U/ml for carbohydrate antigen19-9,159.40ng/ml for carcinoembryonic antigen,9.56ng/ml for cytokeratin 19 fragment and 0.79ng/ml for squamous cell carcinoma-related antigen.On March 10,2019,routine blood tests showed WBC 7.58 *109/L,NEUT 4.43*109/L;tumor markers:carbohydrate antigen 19-9 7.75U/ml,carcinoembryonic antigen 109.10ng/ml,cytokeratin 19 fragment 2.45ng/ml,squamous cell carcinoma-related antigen 1.26ng/ml.On March 29,2019,routine blood tests showed WBC 7.02*109/L and NEUT 4.15*109/L;tumor markers:carbohydrate antigen 19-9,carcinoembryonic antigen 37.43 ng/ml,cytokeratin 19 fragment,squamous cell carcinoma-related antigen 1.18 ng/ml.On April 22,2019,routine blood tests showed WBC 7.43 *109/L and NEUT 5.24*109/L;tumor markers:carbohydrate antigen 19-95.74U/ml,carcinoembryonic antigen 9.93ng/ml,cytokeratin 19 fragment 1.43ng/ml,squamous cell carcinoma-related antigen 1.89ng/ml.After 2 cycles of immunotherapy,chest CT showed esophageal cancer,multiple nodules of varying sizes in both lungs,cavities in nodules,the largest of which was about 2 cm,and several small lymph nodes in mediastinum(compared with the previous chest CT of 2019.02.13,the lesions were slightly reduced).Conclusion:The combined therapy of anti-PD-1 monoclonal antibody and Sindiril monoclonal antibody combined with chemotherapy has achieved good therapeutic effect in 2 patients with advanced digestive tract tumors.The progress of tumors in patients is significantly inhibited,and the serum tumor markers are significantly decreased.These results suggest that PD-1 inhibitor has a good inhibitory effect on advanced digestive tract tumors.