ABSTRACT
Objective:To evaluate the risk factors of clinical cure and biochemical recurrence (BCR) after radical prostatectomy (RP).Methods:The clinical data of 896 patients who underwent RP at Peking University First Hospital from April 2001 to December 2020 were retrospectively analyzed. Average age was (65.90±6.3) years, median preoperative prostate specific antigen (PSA) was 10.75 (0.36-264.20) ng/ml, median prostate volume was 40.0 (12.0-220.9) ml, median PSA density (PSAD) was 0.27 (0.02-3.42) ng/(ml·g). Clinical staging: 432 cases in T 1c stage, 333 cases in T 2a/bstage, 76 cases in T 2c stage, and 55 cases in ≥T 3 stage. Preoperative Gleason score of biopsy: 193 cases in 3+ 3, 315 cases in 3+ 4, 162 cases in 4+ 3, 226 cases in ≥8. The RP surgery was operated by open or laparoscopic or robot-assisted approach. Clinical cure and BCR were used as the end points for analysis. Clinical cure was defined as a decrease in serum PSA level below 0.03 ng/ml 6 weeks after surgery. BCR was defined as the 2 consecutive serum PSA >0.2ng/ml during the follow-up after RP. Multivariate logistic regression was used to analyze the independent risk factors of clinical cure. The Kaplan-Meier method was used to draw the biochemical recurrence-free survival curve, the log-rank method was used for univariate analysis of BCR, and the Cox regression analysis was used for multivariate analysis. Results:All 896 patients were followed-up for 58 (5-241) months, 678 cases (75.7%) achieved clinical cure. Based on univariate analysis and multivariate analysis, among the preoperative indicators, whether the proportion of positive biopsy needles ≥33% ( P=0.007) and preoperative Gleason score of biopsy ( P=0.041) were independent risk factors of clinical cure. A total of 890 cases were included in the analysis of risk factors of BCR, of whom 172 cases (19.3%) had BCR. The 1-, 5-, and 10-year biochemical recurrence-free survival(BFS)rates were 98.1%, 83.1% and 68.4% respectively. The median BFS has not been reached, and the average BFS was 181 months (95% CI 172-189). The results of univariate and multivariate analysis showed that whether achieved clinical cure ( P=0.001) and postoperative pathological staging ( P<0.001) were independent risk factors of BCR. Conclusions:Whether the proportion of positive biopsy needles≥33% and preoperative Gleason score of biopsy were independent risk factors of clinical cure. Postoperative pathological staging and whether achieved clinical cure may be independent risk factors of BCR.
ABSTRACT
Objective To establish the mice model of immunological tolerance,and investigate the significance of haploidentical allogeneic lymphocytes infusion in induction of graft versus host disease and graft versus tumor in mice.Methods Sixty-four BALB/C female mice were randomly divided into 4 groups with 16 mice in each group.Control group:no special treatment was given after inoculation of tumor cells at the 4th day (CT26 colorectal cancer cell lines with mixture of 1 × 107/mL tumor cells suspension was inoculated to the right subcutaneous axillary of mice) ; Chemotherapy group:chemotherapy was applied at the 7th day after inoculation of tumor cells at the 4th day; DLI group:tumor cells were inoculated at the 4th day,and then haploid donor cells were infused at the 13th,15th and 17th day; Chemotherapy + DLI group:tumor cells were inoculated at the 4th day,chemotherapy was applied at the 7th day,and haploid donor cells were infused at the 13th,15th and 17th day.The pretreatment scheme included haploidentical allogeneic lymphocyte + ring ling amide + haploidentical allogeneic lymphocyte,and the chemotherapy regimen included peritoneal infusion of cyclophosphamide at the 3rd day after inoculation of tumor cells in mice.The time from the first day after vaccination to the day of death of mice and the mass of the tumors were detected to calculate the tumor inhibition rate.The clinical indexes of GVHD were observed,and clinical evaluation was made.The numbers of T lymphocytes in peripheral blood were detected by flow cytometry.Three mice were sacrificed in each group at the 15th day to make the tissue specimens,and they were observed under light microscope after HE staining.All data were analyzed using the analysis of variance or LSD-t test.Results The symptoms of GVHD of mice in the chemotherapy + DLI group were milder than those in other groups.The GVHD scores of the control group,chemotherapy group and the chemotherapy + DLI group were 2.3 ±0.6,1.5 ± 1.1,6.7 ±0.9 and 3.4 ±0.5,respectively,with significant difference between the 4 groups (F =148.68,P ＜ 0.05).The tumor masses of the control group,chemotherapy group,DLI group and the chemotherapy + DLI group were (3.40 ± 0.20) g,(0.80 ± 0.10) g,(2.20 ± 0.20) g and (0.50 ± 0.30) g,respectively,with significant difference between the 4 groups (F =149.17,P ＜ 0.05).The tumor inhibition rates of the control group,chemotherapy group,DLI group and the chemotherapy + DLI group were 0,77％ ± 9％,35％ ± 3％,85％ ± 44％.The levels of CD3 + of the control group,chemotherapy group,DLI group and the chemotherapy + DLI group were 52.3％ ± 2.9％,44.8％ ± 3.1％,62.9％ ± 3.5％,65.9％ ± 3.3％,respectively,with significant difference between the 4 groups (F =28.04,P ＜ 0.05).The levels of CD3 + CD4 + of the control group,chemotherapy group,DLI group and the chemotherapy + DLI group were 32.1％ ± 2.6％,27.1％ ± 1.1％,42.6％ ± 1.8％ and 41.7％ ± 2.4％,respectively,with significant difference between the 4 groups (F =40.29,P ＜ 0.05).The levels of CD3 + CD8 + of the control group,chemotherapy group,DLI group and the chemotherapy + DLI group were 22.7％ ± 2.2％,20.7％ ± 1.8％,26.7％ ± 0.8 ％ and 26.1％ ± 0.7％,respectively,with significant difference between the 4 groups (F =10.74,P ＜ 0.05).The levels of CD3 + CD4 + CD25 + of the control group,chemotherapy group,DLI group and the chemotherapy + DLI group were 8.7％ ±0.6％,6.6％ ±0.6％,11.2％ ±0.4％ and 13.3％ ± 0.7％,respectively,with significant difference between the 4 groups (F =82.88,P ＜ 0.05).Necrosis and bleeding of the tumor tissues were observed in all the 4 groups.Necrosis,shrinking of the tumor cells,inflammatory infiltration were observed in the DLI group and the chemotherapy + DLI group.Proliferation of lymphoid follicles was observed in the chemotherapy + DLI group.The survival time of mice in the control group,chemotherapy group,DLI group,chemotherapy + DLI group were (16.8 ± 2.5) days,(26.3 ± 2.9) days,(23.4 ± 2.5) days and (33.7 ± 4.6) days,respectively,with significant difference between the 4 groups (F =46.45,P ＜ 0.05).Conclusions (1) Pretreatment can induce specific immune tolerance in mice.(2) Haploidentical allogeneic lymphocyte infusion and chemotherapy have synergistic effects,joint application of haploidentical allogeneic lymphocyte infusion and chemotherapy can inhibit the proliferation of tumor cells and prolong the survival time of mice.(3) Chemotherapy can reduce the GVHD of haploidentical allogeneic lymphocyte infusion and enhance the GVT.(4) CD3 + CD4 + CD25 + T lymphocytes play important roles in decreasing GVHD.