RESUMO
Objective:To investigate the risk factors of urethrovesical anastomotic leakage after laparoscopic radical prostatectomy.Methods:The clinical data of 292 patients who underwent laparoscopic radical prostatectomy in the Tenth People's Hospital Affiliated to Tongji University from January to December 2021 were retrospectively analyzed. According to whether there was anastomotic leakage, the patients were divided into leakage group (27 cases) and non-leakage group (265 cases). There were no significant differences in age [(71.5±6.5) years vs. (70.2±6.4) years], body mass index [(24.5±3.6) kg/m 2 vs. (24.2±3.0) kg/m 2], prostate volume[40(27.3, 63.2)ml vs. 38(28.1, 56.2)ml], Gleason score, clinical stage, and risk classification between the leakage group and the non-leakage group ( P>0.05), but the total prostate-specific antigen in the leakage group was significantly higher than that in the non-leakage group[20.0 (9.6, 79.0) ng/ml vs. 13.7 (8.5, 25.0) ng/ml, P=0.049]. Propensity score matching (PSM) was used to match the above indicators between the leakage group and the non-leakage group as 1∶1, so that the baseline of the two groups was balanced. The perioperative indicators of the matched two groups of patients were compared and analyzed. Statistically significant indicators were selected and included in univariate and multivariate logistic regression to analyze the risk factors of anastomotic leakage after radical prostatectomy. Finally, the receiver operating characteristic (ROC) curve was drawn, and the area under the curve (AUC) was calculated. The accuracy of each factor in predicting urine leakage was obtained. Results:After PSM, 24 cases were successfully matched. The leakage group had shorter membranous urethral length (MUL) [(15.5±2.2)mm vs. (17.5±1.5)mm, P<0.001], thinner membranous urethral wall thickness (UWT) [(9.5±1.9)mm vs. (10.6±1.5)mm, P=0.024], longer anastomotic time of urethrovesical neck[(21.6±4.1)min vs. (16.9±2.9)min, P<0.001] and higher failure rate of water injection test [16.7% (4/24) vs. 4.2% (1/24), P=0.045] than the non-leakage group. There was no significant difference in other indicators between the two groups. The results of multivariate logistic regression analysis showed that short MUL ( OR=0.544, 95% CI 0.335-0.884, P=0.014), narrow UWT ( OR=0.538, 95% CI 0.313-0.924, P=0.025) and long anastomotic time of urethrovesical neck ( OR=1.519, 95% CI 1.122-2.110, P=0.009) were independent risk factors for anastomotic urine leakage. ROC curve analysis showed that the AUC of MUL, UWT, and anastomotic time were 0.789 (95% CI 0.651-0.927), 0.715 (95% CI 0.562-0.868), and 0.842 (95% CI 0.731-0.953), respectively. Conclusions:Narrow and short membranous urethra and long anastomosis time in patients with laparoscopic radical prostatectomy may be independent risk factors for postoperative anastomotic leakage, which may predict the occurrence of anastomotic leakage.
RESUMO
Owing to incurable castration-resistant prostate cancer (CRPC) ultimately developing after treating with androgen deprivation therapy (ADT), it is vital to devise new therapeutic strategies to treat CRPC. Treatments that target programmed cell death protein 1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved for human cancers with clinical benefit. However, many patients, especially prostate cancer, fail to respond to anti-PD-1/PD-L1 treatment, so it is an urgent need to seek a support strategy for improving the traditional PD-1/PD-L1 targeting immunotherapy. In the present study, analyzing the data from our prostate cancer tissue microarray, we found that PD-L1 expression was positively correlated with the expression of heterogeneous nuclear ribonucleoprotein L (HnRNP L). Hence, we further investigated the potential role of HnRNP L on the PD-L1 expression, the sensitivity of cancer cells to T-cell killing and the synergistic effect with anti-PD-1 therapy in CRPC. Indeed, HnRNP L knockdown effectively decreased PD-L1 expression and recovered the sensitivity of cancer cells to T-cell killing in vitro and in vivo, on the contrary, HnRNP L overexpression led to the opposite effect in CRPC cells. In addition, consistent with the previous study, we revealed that ferroptosis played a critical role in T-cell-induced cancer cell death, and HnRNP L promoted the cancer immune escape partly through targeting YY1/PD-L1 axis and inhibiting ferroptosis in CRPC cells. Furthermore, HnRNP L knockdown enhanced antitumor immunity by recruiting infiltrating CD8+ T cells and synergized with anti-PD-1 therapy in CRPC tumors. This study provided biological evidence that HnRNP L knockdown might be a novel therapeutic agent in PD-L1/PD-1 blockade strategy that enhanced anti-tumor immune response in CRPC.