| Objective:Liver cancer has the highest incidence and mortality rate among all types of malignant tumors,and at present,there is still a lack of effective treatment methods,and immunotherapy brings hope to some liver cancer patients.Pseudomonas aeruginosa-mannose sensitive hemagglutinin(PA-MSHA)can improve human immune status and has been used as adjuvant therapy for various malignancies.PA-MSHA is mainly administered by subcutaneous injection in the upper arm,and intraperitoneal spray has also been used as adjuvant therapy for gastric cancer and other PA-MSHA is mainly administered by subcutaneous injection in the upper arm.In this study,we investigated the effect of intraperitoneal PA-MSHA on the postoperative immune status of patients with hepatocellular carcinoma and evaluated the safety of intraoperative intraperitoneal PA-MSHA spraying by measuring the preoperative and postoperative immune-related indexes in the intraperitoneal PA-MSHA spraying group and the normal saline(NS)control group.Methods:Thirty-two cases of hepatocellular carcinoma that met the exclusion inclusion criteria in the Department of General Surgery,Second Hospital of Lanzhou University from February 2022 to January 2023 were collected,and the patients were randomly divided into 2 groups:the PA-MSHA intraperitoneal spraying group and the NS control group,with a total of 16 cases in each group.Patients in both groups underwent partial hepatectomy,and basic preoperative and postoperative clinical data and relevant immune indexes were collected from each group,mainly including:(1)basic patient data and tumor markers,prognostic nutritional index(PNI);(2)peripheral blood-related indexes:peripheral blood was drawn on preoperative day 1,postoperative day 3 and postoperative day 7,and enzyme-linked Enzyme-linked immunosorbent assay(ELISA)was performed to detect serum interleukin-8(IL-8),IL-10 and transforming growth factor-β(TGF-β)concentrations.Some patients were randomly selected to detect CD4~+T lymphocytes,CD8~+T lymphocytes,programmed cell death receptor-1(PD-1)positive CD4~+T lymphocytes(PD-1~+CD4~+T)and PD-1~+CD8~+T lymphocytes in peripheral blood lymphocyte subsets by flow cytometric assay.(3)Clinical safety-related indexes:all patients were tested for infection-related indexes(IL-6,procalcitonin(PCT),C-reactive protein(CRP)),liver and kidney function-related indexes on preoperative day 1,postoperative day 1,postoperative day 3 and postoperative day 7,and body temperature,abdominal drainage and postoperative flow were recorded for 7 days after surgery.The results of the study were as follows:the number of days of postoperative hospitalization,abdominal drainage and postoperative tube time,postoperative ventilation time,postoperative complications,and the number of days of postoperative hospitalization.Data analysis was performed using SPSS25.0 software.Results:1.effect of intraperitoneal spraying of PA-MSHA on peripheral blood lymphocyte and neutrophil indexes after primary liver cancer surgeryThe peripheral blood lymphocyte ratio decreased more significantly in the PA-MSHA intraperitoneal spraying group on postoperative day 1 and postoperative day 3(p<0.05),and the peripheral blood neutrophil ratio increased more significantly in the experimental group on postoperative day 3(p<0.05),and the neutrophil count in the experimental group was lower than that in the control group on postoperative day 7(p<0.05),but they were within the normal range.There was no statistical difference in the values of lymphocyte count,lymphocyte ratio,neutrophil count and neutrophil percentage change compared with preoperative values in the two groups at day 7postoperatively(p>0.05).2.Effect of PA-MSHA intraperitoneal spraying on peripheral blood T-lymphocyte-related indexes after primary liver cancer surgeryThe percentage of peripheral blood CD4~+T lymphocytes in the experimental group was lower(p<0.05)and the percentage of peripheral blood CD8~+T lymphocytes was less(p<0.05)on the third postoperative day compared with the NS control group;the percentage of peripheral blood CD8~+T lymphocytes in the experimental group increased on the seventh postoperative day,while the percentage of peripheral blood CD8~+T lymphocytes in the control group decreased(p<0.05).lymphocyte percentage in the experimental group increased,while that in the control group decreased(p<0.05).3.Effect of intraperitoneal spraying of PA-MSHA on peripheral blood IL-8,IL-10 and TGF-βafter primary hepatocellular carcinoma surgeryThe change value of IL-8 in peripheral blood of patients in the experimental group was lower than that in the control group on postoperative day 3 compared with preoperative;the concentration of IL-10 in peripheral blood of patients in the experimental group was lower than that in preoperative on postoperative day 3 and postoperative day 7(p<0.05),and the concentration of IL-10 in peripheral blood of patients in the experimental group was lower than that in the control group on postoperative day 3 and postoperative day 7(p<0.05).The peripheral blood TGF-βconcentration was higher in the experimental group than in the control group on the 7th postoperative day(p<0.05).4.The effect of intraperitoneal spraying PA-MSHA on liver and kidney function and infection indexes after primary liver cancer surgeryTBIL,DBIL,IBIL,AST,ALT were statistically different between patients in the experimental group and control group on postoperative day 1 and 3 compared with preoperative(p<0.05),γ-GT was not statistically different(p>0.05),on postoperative day 7 TBIL,IBIL,AST,γ-GT were not statistically different in the experimental group compared with preoperative,DBIL,ALT were There was a statistical difference(p<0.05)in the increase of TBIL,DBIL,IBIL,AST,ALT andγ-GT in the experimental group compared with the control group on postoperative day 1,day 3 and day 7,and there was no statistical difference(p>0.05)in the peripheral blood TBIL,DBIL,IBIL,AST,ALT andγ-GT in the control group.Compared with the control group,the change value of DBIL in the experimental group on postoperative day 3 was greater than that in the control group on preoperative day 1(p<0.05),and the rest of TBIL,DBIL,IBIL,AST,ALT,andγ-GT were not statistically different in postoperative change values(p>0.05).The maximum daily body temperature of patients in the experimental group was higher than that of the control group only on postoperative days 3 and 4(p<0.05).The urea nitrogen(Urea)of patients in the experimental group was higher on postoperative day 3 compared with preoperative day(p<0.05),and the Urea of the experimental group was higher than that of the control group on postoperative day 3(p<0.05);among the infection indexes,the CRP,IL-6 and PCT of patients in the experimental and control groups were higher than those before surgery(p<0.05);on postoperative day 1,the CRP,IL-6 and PCT of the experimental group were higher than those of the control group(p<0.05),and the changes of CRP,IL-6 and PCT were greater in the experimental group(p<0.05);on postoperative day 3,PCT was higher in the experimental group than in the control group(p<0.05);on postoperative day 7,there was no statistical difference between CRP,IL-6 and PCT of patients in the experimental group and the control group(p>0.05);on postoperative day 7,the changes of CRP,IL-6 and PCT of patients in both groups There was no statistical difference between the change values of CRP,IL-6,and PCT in the two groups on the 7th postoperative day compared with those before surgery(p<0.05).5.Comparison of postoperative abdominal drainage and hospitalization days of primary hepatocellular carcinoma with PA-MSHA sprayed in the peritoneal cavityThere were no statistical differences in the number of postoperative hospital days,total postoperative abdominal drainage,postoperative tube time and postoperative ventilation time between patients in the experimental group and patients in the NS control group(p>0.05).Conclusions:1.intraperitoneal spraying of PA-MSHA preparation decreased immunosuppressive cytokine IL-10 and increased CD8~+T lymphocyte ratio in patients with primary hepatocellular carcinoma after surgery,improved the immunosuppressive status of patients with primary hepatocellular carcinoma,and enhanced the anti-tumor immunity of the body.2.Intraperitoneal spraying of PA-MSHA preparation caused more significant increase in peripheral blood inflammation indexes CRP,IL-6 and PCT in patients with primary hepatocellular carcinoma in the short term,but no significant infection symptoms appeared in all patients.3.The safety of intraoperative PA-MSHA preparation for the adjuvant treatment of primary liver cancer by intraperitoneal spraying was good. |
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