Next-generation androgen receptor signaling inhibitors (ARSIs), such as enzalutamide (Enza) and darolutamide (Daro), are initially effective for the treatment of advanced prostate cancer (PCa) and castration-resistant prostate cancer (CRPC). However, patients often relapse and develop cross-resistance, which consequently makes drug resistance an inevitable cause of CRPC-related mortality. By conducting a comprehensive analysis of GEO datasets, CRISPR genome-wide screening results, ATAC-seq data, and RNA-seq data, we systemically identified PAK1 as a significant contributor to ARSI cross-resistance due to the activation of the PAK1/RELA/hnRNPA1/AR-V7 axis. Inhibition of PAK1 followed by suppression of NF-κB pathways and AR-V7 expression effectively overcomes ARSI cross-resistance. Our findings indicate that PAK1 represents a promising therapeutic target gene for the treatment of ARSI cross-resistant PCa patients in the clinic.Statement of significancePAK1 drives ARSI cross-resistance in prostate cancer progression.
Genetic factors coordinate with environmental factors to drive the pathogenesis of prostate adenocarcinoma (PRAD). SPOP is one of the most mutated genes and LRP5 mediates lipid metabolism that is abnormally altered in PRAD. Here, we investigated the potential cross-talk between SPOP and LRP5 in PRAD. We find a negative correlation between SPOP and LRP5 proteins in PRAD. SPOP knockdown increased LRP5 protein while SPOP overexpression resulted in LRP5 reduction that was fully rescued by proteasome inhibitors. LRP5 intracellular tail has SPOP binding site and the direct interaction between LRP5 and SPOP was confirmed by Co-IP and GST-pulldown. Moreover, LRP5 competed with Daxx for SPOP-mediated degradation, establishing a dynamic balance among SPOP, LRP5 and Daxx. Overexpression of LRP5 tail could shift this balance to enhance Daxx-mediated transcriptional inhibition, and inhibit T cell activity in a co-culture system. Further, we generated human and mouse prostate cancer cell lines expressing SPOP variants (F133V, A227V, R368H). SPOP-F133V and SPOP-A227V have specific effects in up-regulating the protein levels of PD-1 and PD-L1. Consistently, SPOP-F133V and SPOP-A227V show robust inhibitory effects on T cells compared to WT SPOP in co-culture. This is further supported by the mouse syngeneic model showing that SPOP-F133V and SPOP-A227V enhance tumorigenesis of prostate cancer in in-vivo condition. Taken together, our study provides evidence that SPOP-LRP5 crosstalk plays an essential role, and the genetic variants of SPOP differentially modulate the expression and activity of immune checkpoints in prostate cancer.
Tumor-associated macrophages (TAMs) promote tumor cell growth and metastasis in various human cancers. However, the role of TAMs in renal cell carcinoma (RCC) is rarely investigated. Herein, we observed that the infiltration of TAMs was obviously elevated in RCC tumor tissues, high infiltration of TAMs was closely associated with tumor progression and poor prognosis in RCC patients. In vitro assays further indicated that the conditioned medium of TAMs (TAMs CM) facilitated migration, invasion, and epithelial-mesenchymal transition (EMT) in RCC cells. Moreover, we found that IL-6 was involved in the functions of TAMs in RCC; IL-6 neutralizing antibody (IL-6NA) partly abolished the effect of TAMs on RCC cells. In addition, we demonstrated that TAMs might exert their roles by activating STAT3 signaling in RCC, and IL-6 was responsible for TAMs-induced STAT3 signaling activation. In conclusion, our results revealed that high infiltration of TAMs may promote RCC cells migration, invasion, and EMT via modulating IL-6/STAT3 signaling, further suggesting a potential of novel treatment strategies targeting TAMs or IL-6 for metastatic RCC.
ObjectiveTo identify less invasive and easily applicable serum cytokine-derived biomarkers which contribute to the diagnostic utility and risk assessment ability of the prostate health index (PHI) based multivariable model in grey zone aggressive prostate cancer (AG PCa) early detection. MethodsSerum 45 cytokines screening was performed in a small training cohort consisting of 10 sera by Luminex liquid array-based multiplexed immunoassays and identified TRAIL and IL-10 as new biomarkers for PHI diagnostic utility adjustment for further validation with a multivariable predictive model in a cohort including 79 aggressive prostate cancer patients and 209 benign prostatic hyperplasia or indolent PCa patients within the PSA grey zone. ResultsTRAIL and IL-10 were identified as potential serum biomarkers for AG PCa detection by the result of multi-cytokines screening in the univariate analysis, while multivariable logistic regression confirmed the AUC of the full risk predictive model (0.915) including tPSA, fPSA, PHI, TRAIL, and IL-10 was higher than various diagnostic strategies. DCA suggested a superior net benefit and indicated a good discriminative ability of the full risk model consistently with the result of the nomogram. ConclusionWe suggest a significant advantage for the PHI-based multivariate combinations of serum TRAIL and IL-10 comparing to PHI or other serum-derived biomarkers alone in the detection and risk stratification of grey zone AG PCa.
囊性肾癌是一类低度恶性潜能的复杂性肾肿瘤,约占肾脏肿瘤的4%.囊性肾癌的保肾手术挑战大,其囊壁薄,术中易破溃导致肿瘤细胞外溢可能,很难达到保肾手术的无瘤原则.本中心通过结合术前智能三维重建、解剖程序化操作、早期开放缝合技术等多种创新技术及方案,提高了囊性肾癌保肾手术的安全性和可行性.本文将从囊性肾癌的微创保肾手术角度,阐述囊性肾癌的术前评估、术中难点、术中技巧等方面,结合国内外文献及本中心诊疗经验进行深入探讨.
BackgroundEarly screening of clinically significant prostate cancer (csPCa) may offer opportunities in revolutionizing the survival benefits of this lethal disease. We sought to introduce a modified prostate health index density (mPHI) model using imaging indicators and to compare its diagnostic performance for early detection of occult onset csPCa within the prostate-specific antigen (PSA) gray zone with that of PHI and PHID.Methods and ParticipationBetween August 2020 and January 2022, a training cohort of 278 patients (total PSA 4.0–10.0 ng/ml) who were scheduled for a prostate biopsy were prospectively recruited. PHI and PHID were compared with mPHI (LDTRD×APD×TPV×PHI) for the diagnosis performance in identifying csPCa. Pathology outcomes from systematic prostate biopsies were considered the gold standard.ResultsThis model was tested in a training cohort consisting of 73 csPCa, 14 non-clinically significant prostate cancer(non-csPCa), and 191 benign prostatic hyperplasia (BPH) samples. In the univariate analysis for the PSA gray zone cohort, for overall PCa, the AUC of mPHI (0.856) was higher than PHI (0.774) and PHID (0.835). For csPCa, the AUC of mPHI (0.859) also surpassed PHI (0.787) and PHID (0.825). For detection of csPCa, compared with lower specificities from PHI and PHID, mPHI performed the highest specificity (76.5%), by sparing 60.0% of unnecessary biopsies at the cost of missing 11 cases of csPCa. The mPHI outperformed PHI and PHID for overall PCa detection. In terms of csPCa, mPHI exceeds diagnostic performance with a better net benefit in decision curve analysis (DCA) compared with PHI or PHID.ConclusionsWe have developed a modified PHI density (mPHI) model that can sensitively distinguish early-stage csPCa patients within the PSA gray zone.Clinical Trial RegistrationClinicalTrials.gov, NCT04251546.
目的:总结经腹膜外途径行单孔机器人辅助腹腔镜前列腺根治术的临床经验.方法:2021年6月至12月共为36例前列腺癌患者经腹膜外入路行单孔机器人辅助腹腔镜前列腺癌根治术.Gleason评分均≤7分,cTNM分期T2c期2例,余34例均为T2c期以下.20例患者行标准的筋膜外切除技术(第1组),10例患者行常规筋膜内切除技术(第2组),6例采用最大保留周围结构的筋膜内切除技术(第3组).结果:患者均顺利完成手术.第1组手术时间平均(75.5±15.5)min,第2组(105.6±18.8)min,第3组(85.6±16.8)min;术中出血量第1组平均(39.75±12.82)mL,第2组(82.5±12.08)mL,第3组(144.17±13.2)mL.术后6周复查总前列腺特异性抗原,均降至0.05 ng/mL以下.在尿控恢复方面,即刻尿控第1组为30%(6/20),第2组为70%(7/10),第3组为83.3%(5/6).第2组、第3组在性功能恢复方面优于第1组.结论:经腹膜外入路行单孔机器人辅助前列腺癌根治术可成为中低危局限性前列腺癌的常规治疗方案,术后瘤控良好,尤其常规筋膜内切除技术与最大保留周围结构的技术,在术后早期即刻尿控、性功能恢复方面可取得较好效果.
Non-clear renal cell carcinomas (nccRCCs) are less frequent in kidney cancer with histopathological heterogeneity. A better understanding of the tumor biology of nccRCC can provide more effective treatment paradigms for different subtypes. To reveal the heterogeneity of tumor microenvironment (TME) in nccRCC, we performed 10x sing-cell genomics on tumor and normal tissues from patients with papillary renal cell carcinoma (pRCC), chromophobe RCC (chrRCC), collecting duct carcinoma (CDRCC) and sarcomatoid RCC (sarRCC). 15 tissue samples were finally included. 34561 cells were identified as 16 major cell clusters with 34 cell subtypes. Our study presented the sing-cell landscape for four types of nccRCC, and demonstrated that CD8+ T cells exhaustion, tumor-associated macrophages (TAMs) and sarcomatoid process were the pivotal factors in immunosuppression of nccRCC tissues and were closely correlated with poor prognosis. Abnormal metabolic patterns were present in both cancer cells and tumor-infiltrating stromal cells, such as fibroblasts and endothelial cells. Combined with CIBERSORTx tool, the expression data of bulk RNA-seq from TCGA were labeled with cell types of our sing-cell data. Calculation of the relative abundance of cell types revealed that greater proportion of exhausted CD8+ T cells, TAMs and sarRCC derived cells were correlated with poor prognosis in the cohort of 274 nccRCC patients. To the best of our knowledge, this is the first study that provides a more comprehensive sight about the heterogeneity and tumor biology of nccRCC, which may potentially facilitate the development of more effective therapies for nccRCC.
目的 探讨智能互动定性定量分析(IQQA)技术应用于中度复杂性肾肿瘤腹腔镜肾部分切除术的可行性、安全性和有效性.方法 选择2018年1月—2019年6月收治的16例中度复杂性肾肿瘤(R.E.N.A.L评分>6?9分)患者,男10例、女6例,年龄为(55.8±8.3)岁,肾肿瘤R.E.N.A.L评分为(7.6±0.7)分.所有患者均于IQQA技术支持下行腹腔镜肾部分切除术.获取肾脏CTA检查的原始影像学数据,利用IQQA平台进行三维重建,通过操作平台多角度旋转、多层面系统化分析肾肿瘤与血管、集合系统的毗邻关系,进行手术规划和模拟,制订出个性化、精准的腹腔镜下肾部分切除术的方案.记录患者的手术时间、肾动脉阻断时间、术中出血量、术后引流管留置时间、术后并发症发生情况、术后住院天数,以及手术前和术后3个月血清肌酐水平、患肾肾小球滤过率(GFR).术后3个月随访时复查胸部CT、肾脏CT,观察肿瘤有无复发和转移.结果 16例患者均顺利完成手术,无1例患者中转开放性手术或改行根治性肾切除术.手术时间为(74.7±12.7)min,肾动脉阻断时间为(21.8±4.4)min,术中出血量为(63.8±38.9)mL;术后引流管留置时间为(6.3±1.6)d,术后住院时间为(6.9±1.7)d.术后患者均无出血、漏尿、感染、切口裂开、肺部感染等并发症发生.术后3个月血清肌酐水平为(80.6±11.4)μmol/L,与术前的(82.8±9.5)μmol/L的差异无统计学意义(P>0.05).术后3个月患肾GFR为(49.6±7.9)mL/min,显著低于术前的(56.0±6.9)mL/min(P<0.05).术后3个月患者胸部CT、肾脏CT检查均未见肿瘤复发和转移.结论 在IQQA技术辅助下对中度复杂性肾肿瘤行腹腔镜肾部分切除术更加精准,有利于提高中度复杂性肾肿瘤行腹腔镜肾部分切除术的成功率,患者肾功能得以较好的保护,该方法在技术上安全、可行.
Subsequently to the publication of the above article, an interested reader drew to the authors' attention that, on p. 1969, two pairs of panels shown for the DU145 data appeared to contain overlaps, such that they may have been derived from the same original source (specifically, relating to the shCon and the shSMC1A experiments). The authors have referred back to their original data, and realize that inadvertent errors were made during the assembly of these figures. The corrected version of Fig. 5, showing discrete representative images for the shCon and the shSMC1A experiments with the DU145 cell line, is shown on the next page. All the authors agree to this corrigendum. Note that the revisions made to this figure do not adversely affect the results reported in the paper, or the conclusions stated therein. The authors regret that Fig. 5 was not presented in its correct form in their paper, thank the Editor of International Journal of Oncology for granting them the opportunity to publish this corrigendum, and offer their apologies to the Editor and to the readers of the Journal. [the original article was published in International Journal of Oncology 49: 1963-1972, 2016; DOI: 10.3892/ijo.2016.3697].
目的:探讨腹腔镜保留肾单位手术中应用"2+1"缝合技术联合早期序贯开放血流法治疗T1b期单发肾肿瘤的安全性及疗效.方法:回顾分析2017年1月至2018年7月为22例T1b期单发肾肿瘤患者采用"2+1"缝合技术联合早期序贯开放血流法行腹腔镜保留肾单位手术的临床资料,肿瘤直径平均(5.4±0.8)cm,R.E.N.A.L评分平均(7.5±0.8)分.结果:患者均顺利完成手术,无一例中转开放手术.手术时间平均(136.5±31.2)min,术中出血量平均(135.0±40.6)mL,热缺血时间平均(15.0±2.3)min,术中、术后无一例输血,切缘均为阴性,术后均无漏尿、切口感染、患侧肾脏萎缩等并发症发生.结论:腹腔镜保留肾单位手术中应用"2+1"缝合技术联合早期序贯开放血流法治疗T1b期单发肾肿瘤,术中出血可控,热缺血时间可得到较好控制,手术安全、可靠.
Objective:To explore the safety and efficacy of laparoscopic non-blocking partial nephrectomy assisted by high power lateral green laser in the treatment of T 1a renal tumor. Methods:The clinical data of 10 patients with T1a stage renal tumor from February 2021 to April 2021 in department of urology, Gongli hospital affiliated to Naval Military Medical University were retrospectively analyzed. There were 7 males and 3 females, aged 47.0-74.0 years, with average of(58.8±9.7)years old. The diameter of the tumor ranged from 2.0 cm to 3.8 cm, with an average of (3.1±0.6)cm. There were 6 cases on the left side and 4 cases on the right side, locate on lumbar side in 9 cases and ventral sied in 1 case. The R. E.N.A.L score was 4.0-6.0, with an average of (5.0±0.8). The preoperative creatinine was 66.9-90.1μmol/L, with an average of (75.1±9.0)μmol/L, preoperative GFR of 44. 6- 67. 3 ml /min, with an average of(56.7±7.7)ml/min, preoperative hemoglobin level of 119.0-156.0g/L, with an average of (135.8±11.4)g/L. All patients underwent laparoscopic non-blocking partial nephrectomy assisted by 180w lateral green laser, free the surrounding area of the tumor fully and completely expose the renal tumor. The laser fiber was placed through the green laser hand piece, and the fiber was connected with normal saline to wash the strip. The initial green laser vaporization power was set at 80W, and the hemostasis power at 35W.About 3mm away from the edge of the tumor, and one optical fiber away from the renal parenchyma, the renal parenchyma was cut with 80W power. In order to reduce the interference by smoke, high-pressure flushing was used through the optical fiber while vaporizing, and an attractor was used to push and peel the tumor. In case of bleeding during operation, hemostatic power can be used to close the bleeding point and gradually advance until the tumor was completely removed. The wounds of renal inner medulla and renal outer cortex were continuously sutured in 1-3 layers with barbed suture. It involved 9 cases via retroperitoneal approach and 1 case via abdominal approach. The operation time, postoperative hemoglobin decrease, extraction time of negative pressure drainage, postoperative hospital stay, postoperative pathology and postoperative complications were recorded, and the serum creatinine level and GFR level of the affected side were followed up 1 month after operation.Results:All the operations were successfully completed, and there was no conversion to open surgery or radical nephrectomy. One case changed to scissors fast resection and sutured hemostasis due to severe intraoperative bleeding. The operation time was 90.0-120.0 min, with the average of (104.5±9.0)min. The postoperative hemoglobin level was 96.0-132.0g/L, with an average of (115.2±11.8)g/L, and the difference was statistically significant ( P<0.05). The postoperative hemoglobin decreased from 12.0g/L to 25.0g/L, with an average of (20.6±4.6)g/L. The time of vacuum drainage was 5.0-7.0 days, with an average of (5.7±0.7)d. Postoperative hospital stay was 6.0-8.0 days, with an average of (6.7±0.7)d. No bleeding, urinary leakage and other complications occurred in all patients. There were 7 cases of clear cell carcinoma, 2 cases of papillary renal cell carcinoma and 1 case of angiomyolipoma. All margins were negative. One month after operation, creatinine ranged from 66.0 to 90.4μmol/L, with an average of (76.8±8.3)μmol/L, which was not significantly different compared with that before operation ( P>0.05). One month after operation, GFR was 45.1-60.8 ml/min, and with an average of (55.5±4.7)ml/min, and there was no significant difference compared with preoperative data( P>0.05). Conclusions:For T 1aN 0M 0 stage and exophytic renal tumors, laparoscopic non-blocking partial nephrectomy assisted by lateral green laser is safe and effective.
Objective:To investigate the feasibility, safety and effectiveness of laparoscopic partial nephrectomy for cystic tumor of the renal hilus.Methods:The data of 6 patients with cystic tumor of renal hilus treated by laparoscopic partial nephrectomy in the three centers from January 2017 to December 2019 were analyzed retrospectively. There were 5 males and 1 females, with a median age of 45(10) years and body mass index of 23.3(1.5) kg/m2, maximum tumor diameter 3.7(0.4) cm, the R.E.N.A.L score 8.5(1.0), the tumor stage was T1. The preoperative creatinine level was 68(12) μmol/L. The glomerular filtration rate (GFR) was 47.3(5.5) ml/min. The hemoglobin level was 138(17) g/L. The success rate, opening rate, operation time, artery blocking time, intraoperative bleeding volume, postoperative drainage tube retention days, postoperative complications, postoperative hospital stay days, renal function and tumor prognosis indexes of 6 patients were collected for statistical analysis.Results:Laparoscopic partial nephrectomy was successfully completed in all patients, and there was no conversion to open surgery or radical nephrectomy. The median operation time was 112(20) min, the renal artery occlusion time was 34(7) min, the intraoperative hemorrhage was 33(22) ml, and the postoperative hospital stay was 6.5(1.0) d. There were no postoperative complications such as bleeding and urinary leakage. Postoperative pathology showed 5 cases of renal malignant tumor and 1 case of renal cyst. The surgical margin was negative. The median creatinine was 81(12) μmol/L in 3 months after operation, which had no significant difference compared with that before operation (P>0.05). The GFR of kidney in 3 months after operation was 37.0(4.4) ml/min, which had significant difference compared with that before operation (P<0.05). The hemoglobin level was 127(15) g/L after operation, and the difference was statistically significant compared with that before operation. After 3 months follow-up, no tumor recurrence or metastasis was found in CT.Conclusion:Laparoscopic partial nephrectomy is a feasible method for the patients with cystic renal carcinoma in the hilum of kidney, which is beneficial for the better protection of renal function and the exact perioperative effect.
目的 分析评估经尿道摩西技术钬激光前列腺剜除术(MoLEP)治疗长期维持抗凝治疗的良性前列腺增生(BPH)患者的有效性及安全性.方法 回顾性分析2019年4-9月海军军医大学公利医院行MoLEP术治疗41例BPH患者的临床资料,将长期抗凝治疗的15例BPH患者设为抗凝组,未服用抗凝剂26例患者设为未抗凝组.记录两组患者基本情况,比较两组术后血红蛋白下降量、手术时间、剜除时间、术后膀胱冲洗、留置导尿及住院时间;评估术中术后输血、二次出血、再住院、电切综合征、排尿困难、尿失禁等并发症情况;比较两组术前和术后3个月患者最大尿流率(Qmax)、国际前列腺症状评分(IPSS)、生活质量评分(QoL)、残余尿(PVR)变化情况,判断MoLEP对长期口服抗凝剂BPH患者的安全与疗效.结果 所有患者均顺利完成手术,无中转开放或经尿道前列腺电切术.抗凝组与未抗凝组患者术后血红蛋白下降量[(18.47±8.46)v s.(14.19±7.74)g/L]、手术时间[(62.00±20.16)vs.(58.88±16.56)min]、剜除时间[(43.67±16.50)vs.(40.50±14.40)min]、术后膀胱冲洗时间[(1.13±0.35)vs.(1.08±0.27)d]、术后留置导尿时间[(3.07±0.70)vs.(2.92±0.74)d]、术后住院时间[(4.07±0.70)vs.(3.92±0.74)d]差异均无统计学意义(P>0.05).两组术中、术后无输血、电切综合征发生,术后3月无二次出血、再入院、排尿困难、尿失禁患者.抗凝组与未抗凝组术后3个月Qmax[(18.81±5.67)vs.(17.39±3.78)mL/s]、IPSS评分[(5.8±2.8)vs.(6.5±2.8)]、QoL评分[(1.3±0.8)vs.(1.2±0.7)]、PVR[(12.53±20.69)vs.(10.50±12.15)mL]差异均无显著性(P均<0.05);但组内比较,术后3个月均优于术前,差异存在统计学意义(P<0.05).结论 MoLEP术中出血少,疗效确切,是值得推广的治疗口服抗凝剂患者安全有效的手术方式.
目的:探讨肾肿瘤悬吊法在“零缺血”腹腔镜下肾部分切除术中的应用价值.方法:回顾性分析2017年1月~2018年1月海军军医大学附属公利医院和海军军医大学附属东方肝胆外科医院12例患者应用肾肿瘤悬吊法在完全无肾动脉阻断的“零缺血”条件下开展腹腔镜下肾部分切除术,收集患者的一般临床基线资料,在后腹腔镜下采用肾肿瘤悬吊法行“零缺血”肾部分切除术:游离肾周脂肪暴露肾肿瘤,但保留肾肿瘤上方的脂肪.取肿瘤上方的脂肪向上提拉,用Hem-o-lock将肿瘤上方脂肪悬吊到上方筋膜、腹膜反折等组织(具体可根据术中情况评估选择)上,使肿瘤与肾脏之间保持一定的张力.使用腹腔镜剪刀在肿瘤周围0.5 cm左右处分离肿瘤,另外一个操作孔置入腹腔镜下吸引器,将肾脏创面的出血充分吸走,保持视野清晰并帮助调整瘤体方向,保证完整切除肿瘤,对肾脏创面进行连续缝合.收集12例患者的手术时间、肿瘤切除并缝合时间、术中出血量、术后引流管留置天数、术后并发症、术后住院天数等指标,记录术后6个月患肾肾小球滤过率(GFR)、血红蛋白及肌酐等相关实验室指标以及肿瘤学预后指标,进行统计分析.结果:12例患者均成功实施肾肿瘤悬吊法腹腔镜下“零缺血”肾部分切除术,无改行肾动脉阻断或者中转开放手术病例,手术成功率达100%,中位手术时间为105(70~135) min,中位肿瘤切除并缝合时间为17(14~25) min,中位术中出血量185(70~350) mL,中位术后引流管留置时间为5(4~6)d,中位术后住院天数为6(5~7)d,术后无出血、尿漏、感染、切口裂开等相关并发症.12例患者术后6个月复查肾脏CT、胸部CT等未见肿瘤复发、转移,术前以及术后6个月血红蛋白指标、肌酐水平、患肾GFR差异无统计学意义.结论:完全无阻断的“零缺血”腹腔镜下肾部分切除术术中应用肿瘤悬吊法能够保证手术的安全性和可行性,最大程度地保护肾功能,使患者在肾部分切除术中能够得到最大程度的获益.
目的:评估使用膀胱颈保留术(Bladder neck preservation,BNP)和最大尿道长度保留术(Maximal urethral length preservation,MULP)进行机器人辅助前列腺癌根治术(Robot-assisted radical prostatectomy,RARP)对术后早期尿控恢复的治疗意义.方法:回顾性分析2018~2019年本中心施行机器人前列腺癌根治术的患者信息,纳入标准为Gleason评分≤7(3+4)、≤cT2c分期以及PSA<20ng/ml,排除在磁共振成像显示膀胱颈或前列腺尖部受累的患者.共有24例患者接受联合保留最大尿道长度和膀胱颈的尿道重建术.尿控定义为不穿垫子或只穿一个安全垫.结果:拔除导尿管后即刻(术后2周),以及术后1个月、3个月和6个月的尿控率分别为12(50.0%)、18(75.0%)、20(83.3%)和23(95.8%),2例患者出现尿瘘(8.3%),未见手术切缘阳性病例.结论:对于Gleason评分≤7的局限性前列腺癌患者,联合使用BNP和MULP的尿道重建技术可实现RARP术后尿控快速恢复.
Laparoscopic partial nephrectomy (LPN) as a minimally invasive nephron-sparing surgery is gradually becoming the preferred surgical treatment forT1a renal carcinoma since it yields faster post-operative recovery and equivalent oncological outcomes to radical nephrectomy. However, it is difficult to performLPN for complex renal tumors, resulting in a longer warm ischemic time (WIT), which consequently affects the recovery of post-operative renal function.With the development of laparoscopic instruments and techniques and the accumulating experience of surgeons, theWIT during LPN may be shortened using anatomy-based early unclamping (EUC) after the placement of one or two running sutures on the tumor bed. In this study, we improved the closure techniques for LPN using EUC in patients with complex renal tumors and assessed their effectiveness.
Background: Cancer stem cells (CSCs) are biologically characterized by self-renewal, multi-directional differentiation and infinite proliferation, inducing anti-tumor drug resistance and metastasis. In the present study, we attempted to depict the baseline landscape of CSC-mediated biological properties, knowing that it is vital for tumor evolution, anti-tumor drug selection and drug resistance against fatal malignancy. Methods: We performed single-cell RNA sequencing (scRNA-seq) analysis in 15208 cells from a pair of primary and metastatic sites of collecting duct renal cell carcinoma (CDRCC). Cell subpopulations were identified and characterized by t-SNE, RNA velocity, monocle and other computational methods. Statistical analysis of all single-cell sequencing data was performed in R and Python. Results: A CSC population of 1068 cells was identified and characterized, showing excellent differentiation and self-renewal properties. These CSCs positioned as a center of the differentiation process and transformed into CDRCC primary and metastatic cells in spatial and temporal order, and played a pivotal role in promoting the bone destruction process with a positive feedback loop in the bone metastasis microenvironment. In addition, CSC-specific marker genes BIRC5, PTTG1, CENPF and CDKN3 were observed to be correlated with poor prognosis of CDRCC. Finally, we pinpointed that PARP, PIGF, HDAC2, and FGFR inhibitors for effectively targeting CSCs may be the potential therapeutic strategies for CDRCC. Conclusion: The results of the present study may shed new light on the identification of CSCs, and help further understand the mechanism underlying drug resistance, differentiation and metastasis in human CDRCC.
Objective To investigate the clinical feasibility and effectiveness of 3-D printing (3DP) combined with 3-D laparoscopic nephron-sparing surgery (LNSS) for partial endogenous renal cell carcinoma.Methods A retrospective analysis was made of the clinical data of 79 patients with partial endogenous renal cell carcinoma who were admitted to our department from July 2015 to October 2018.There were 46 males and 33 females.Their average age was (50.9 ± 7.9) years old,ranged from 33 to 68 years old.Tumor stages were T1aN0M0 in 53 cases and T1bN0M0 in 26 cases.The preoperative serum creatinine ranged from 40 to 107 μmol/L,with an average of (72.4 ± 14.2) μmol/L.The preoperative GFR ranged from 19 to 54 ml/min,with an average of (40.2 ± 6.2) ml/min.Thirty-four patients underwent 2-D laparoscopic nephron-sparing surgery (2DLNSS) based on preoperative enhanced CT scans.Forty-five patients underwent 3-D printing (3DP) based on three-dimensional reconstruction of renal CT scans.Seventeen patients underwent 2-D laparoscopic nephron-sparing surgery guided by 3-D printing model(3DP-2DLNSS),and 28 patients underwent 3-D laparoscopic nephron-sparing surgery guided by 3-D printing (3DP-3DLNSS).Serum creatinine levels ranged from 42 to 122 μmol/L with an average of (86.3 ± 14.8) μmol/L,and creatinine levels ranged from 8 to 66 μmol/L with an average of (19.1 ± 14.1) μmol/L.Six months after operation,the GFR of the kidney was 9-36 ml/min with an average of (21.4 ± 6.4)ml/min,and the fluctuation range was 6-40 ml/min with an average of (19.2 ± 8.8) ml/min.There was no statistical difference in the incidence of complications and pathological types after operation.Results There was no statistical difference in general data of preoperative patients.In intraoperative and post-operative statistics,the time of exploring renal artery was shorter than that of 2DLNSS (33.7 ± 7.5) min in 3DP-2DLNSS (28.3 ± 8.2,P =0.015) min and 3DP-3DLNSS (27.8 ± 6.5,P =0.002) min.In tumor detection time,3 DP-2DLNSS was shorter than 2DLNSS group (41.2 ± 6.6 vs.46.5 ± 6.9 min,P =0.012),and 3 DP-3DLNSS was shorter than 3DP-2DLNSS (35.4 ± 7.3 vs.41.2 ± 6.6 min,P =0.009).In warm ischemia time,3DP-2DLNSS min was shorter than 2DLNSS (23.5 ±9.7 vs.33.9 ±7.5 min P <0.001),and 3DP-3DLNSS was shorter than 3DP-2DLNSS (18.3 ± 4.6 vs.23.5 ± 9.7,P =0.023).In surgical time,3DP-2DLNSS (115.7 ± 23.0) min and 3DP-3DLNSS (103.3 ± 22.8) min were shorter than 2DLNSS (132.4 ± 28.9) min (P =0.031,P < 0.001).In intraoperative bleeding volume,3 DP-3 DLNSS was less than 2DLNSS (117.9 ± 17.9 vs.130.6 ± 16.8,P =0.009) ml.Fasting for 1 to 4 days after operation,with an average of (1.7 ± 0.8) days.The indwelling catheterization ranged from 1 to 8 days after operation,with an average of (3.9 ± 1.3) days.Negative pressure drainage was removed 2-9 days after operation,with an average of (4.9 ± 1.4) days.And the hospitalization 5-11 days after operation,with an average of (7.3 ± 1.5) days.Conclusions Preoperative 3D printing combined with intraoperative 3D laparoscopic nephron sparing surgery for partial endogenous renal tumors is safe and effective,which is superior to the previous CT scan alone and intraoperative 2D laparoscopic treatment.