The effect of holmium laser resection versus standard transurethral resection on non-muscle-invasive bladder cancer: a systematic review and meta-analysis.
- 作者列表："Li C","Gao L","Zhang J","Yang X","Liu C
:To explore the advantages and limitations of holmium laser resection of the bladder tumor (HOLRBT) versus standard transurethral resection of the bladder tumor (TURBT) in the treatment of non-muscle-invasive bladder cancer (NMIBC), the eligible studies were selected from the following databases: PubMed, Cochrane Library, and Embase. Studies comparing HOLRBT and TURBT for patients with NMIBC were included. The outcomes of interest were time of operation, catheterization and hospitalization, rates of recurrence, and perioperative complications, including obturator nerve reflex, bladder perforation, bladder irritation, and urethral stricture. Results of all data were compared and analyzed by Review Manager 5.3. A total of 9 comparative studies were finally included for this analysis. Pooled data demonstrated that HOLRBT significantly reduced the time to catheterization and hospitalization, the rate of recurrence in 2 years of follow-up, obturator nerve reflex, bladder perforation, and bladder irritation, compared with those in TURBT, respectively. However, no significant difference found between HOLRBT and TURBT in the time of operation, rate of recurrence in 1-year follow-up, and urethral stricture. The results of this research reached that HOLRBT would be a better choice than TURBT for patients with NMIBC.
: 为了探讨钬激光膀胱肿瘤切除术 (HOLRBT) 与标准经尿道膀胱肿瘤切除术 (TURBT) 治疗非肌层浸润性膀胱癌 (NMIBC) 的优势和局限性，从以下数据库中选择符合条件的研究: PubMed，Cochrane Library，和Embase。纳入了比较HOLRBT和TURBT治疗NMIBC患者的研究。感兴趣的结果是手术时间，导尿和住院，复发率和围手术期并发症，包括闭孔神经反射，膀胱穿孔，膀胱刺激和尿道狭窄。所有数据的结果由Review Manager 5.3进行比较和分析。最终纳入总共9项比较研究用于该分析。汇总数据表明，与TURBT相比，HOLRBT分别显著减少了导尿时间和住院时间、2年随访复发率、闭孔神经反射、膀胱穿孔和膀胱刺激。然而，HOLRBT和TURBT在手术时间、1年随访复发率和尿道狭窄方面无显著差异。本研究结果表明，对于NMIBC患者，HOLRBT将是比TURBT更好的选择。
METHODS:PURPOSE:Studies indicate that molecular subtypes in muscle invasive bladder cancer predict the clinical outcome. We evaluated whether subtyping by a simplified method and established classifications could predict the clinical outcome. MATERIALS AND METHODS:We subtyped institutional cohort 1 of 52 patients, including 39 with muscle invasive bladder cancer, an Oncomine™ data set of 151 with muscle invasive bladder cancer and TCGA (The Cancer Genome Atlas) data set of 402 with muscle invasive bladder cancer. Subtyping was done using simplified panels (MCG-1 and MCG-Ext) which included only transcripts common in published studies and were analyzed for predicting metastasis, and cancer specific, overall and recurrence-free survival. TCGA data set was further analyzed using the Lund taxonomy, the Bladder Cancer Molecular Taxonomy Group Consensus and TCGA 2017 mRNA subtype classifications. RESULTS:Muscle invasive bladder cancer specimens from cohort 1 and the Oncomine data set showed intratumor heterogeneity for transcript and protein expression. MCG-1 subtypes did not predict the outcome on univariate or Kaplan-Meier analysis. On multivariate analysis N stage (p ≤0.007), T stage (p ≤0.04), M stage (p=0.007) and/or patient age (p=0.01) predicted metastasis, cancer specific and overall survival, and/or the cisplatin based adjuvant chemotherapy response. In TCGA data set publications showed that subtypes risk stratified patients for overall survival. Consistently the MCG-1 and MCG-Ext subtypes were associated with overall but not recurrence-free survival on univariate and Kaplan-Meier analyses. TCGA data set included 21 low grade specimens of the total of 402 and subtypes associated with tumor grade (p=0.005). However, less than 1% of muscle invasive bladder cancer cases are low grade. In only high grade specimens the MCG-1 and MCG-Ext subtypes could not predict overall survival. On univariate analysis subtypes according to the Bladder Cancer Molecular Taxonomy Group Consensus, TCGA 2017 and the Lund taxonomy were associated with tumor grade (p <0.0001) and overall survival (p=0.01 to <0.0001). Regardless of classification, subtypes had about 50% to 60% sensitivity and specificity to predict overall and recurrence-free survival. On multivariate analyses N stage and lymphovascular invasion consistently predicted recurrence-free and overall survival (p=0.039 and 0.003, respectively). CONCLUSIONS:Molecular subtypes reflect bladder tumor heterogeneity and are associated with tumor grade. In multiple cohorts and subtyping classifications the clinical parameters outperformed subtypes for predicting the outcome.
METHODS::Acquired chemoresistance is a critical issue for advanced bladder cancer patients during long-term treatment. Recent studies reveal that a fraction of tumor cells with enhanced tumor-initiating potential, or cancer stem-like cells (CSCs), may particularly contribute to acquired chemoresistance and recurrence. Thus, CSC characterization will be the first step towards understanding the mechanisms underlying advanced disease. Here we generated long-term patient-derived cancer cells (PDCs) from bladder cancer patient specimens in spheroid culture, which is favorable for CSC enrichment. Pathological features of bladder cancer PDCs and PDC-dependent patient-derived xenografts (PDXs) were basically similar to those of their corresponding patients' specimens. Notably, CSC marker aldehyde dehydrogenase 1A1 (ALDH1A1), a critical enzyme that synthesizes retinoic acid (RA), was abundantly expressed in PDCs. ALDH1A1 inhibitors and shRNAs repressed both PDC proliferation and spheroid formation, whereas all-trans RA could rescue ALDH1A1 shRNA-suppressed spheroid formation. ALDH inhibitor also reduced the in vivo growth of PDC-derived xenografts. ALDH1A1 knockdown study showed that tubulin beta III (TUBB3) was one of the downregulated genes in PDCs. We identified functional RA response elements in TUBB3 promoter, whose transcriptional activities were substantially activated by RA. Clinical survival database reveals that TUBB3 expression may associate with poor prognosis in bladder cancer patients. Moreover, TUBB3 knockdown was sufficient to suppress PDC proliferation and spheroid formation. Taken together, our results indicate that ALDH1A1 and its putative downstream target TUBB3 are overexpressed in bladder cancer, and those molecules could be applied to alternative diagnostic and therapeutic options for advanced disease.
METHODS:OBJECTIVES:To evaluate the technical feasibility, oncological and functional outcomes of nerve sparing cystoprostatectomy (NSCP) and prostate capsule-sparing cystectomy (PCSC) for the treatment of organ-confined bladder cancer at a single referral centre. PATIENTS AND METHODS:From April 2001 to June 2012, 60 patients underwent PCSC and 47 were treated with NSCP. Inclusion criteria for PCSC were: fully informed consent for the well-motivated patient; negative transurethral resection of the bladder neck; normal prostatic specific antigen (PSA) level (defined as <4 ng/dL during the first year of the study, which was later lowered to 2.5 ng/dL); and normal transrectal ultrasonography, with biopsy for any suspicious nodule. Patients received a complete oncological and functional follow-up. The Kaplan-Meier method was used to depict survival outcomes after surgery. RESULTS:After a median follow-up of 73 and 62 months for PCSC and NSCP, respectively, the 5-year cancer-specific survival was 90% for the PCSC group and 78% for the NSCP group (P = 0.055). Considering complications within 30 days after surgery, 13% and 21% patients had Clavien ≥III complications in the PCSC and NSCP groups, respectively (P = 0.2). For functional outcomes, at 3 months after surgery, 54 (90%) and 24 (51%) patients reported full recovery of daytime urinary continence in the PCSC and NSCP groups, respectively (P < 0.001); and for erectile function recovery, 32 (53%) and four (9%) patients in the PCSC group and in the NSCP group were respectively potent without any treatment (P < 0.001). CONCLUSIONS:NSCP and PCSC are appropriate for a subset of patients with bladder cancer, with excellent oncological and functional results. These surgical procedures should be proposed to well-motivated patients.