Significance of age and comorbidity as prognostic indicators for patients with bladder cancer

The aim of this study was to determine the impact that age and comorbidity status have on both overall and bladder cancer-specific survival of bladder cancer patients. We obtained medical information pertaining to a population of 528 patients with newly diagnosed bladder cancer from Chung-Ang University Hospital cancer registry. The Adult Comorbidity Evaluation-27 （ACE-27） test, which has been previously validated in adult cancer patients, was used to assess comorbidity. We evaluated differences in the demographic and clinical characteristics of included patients, as well as differences in the treatments they received after categorizing them by age. The median age at the time of bladder cancer diagnosis of the entire cohort was 63 years, and the median follow-up time was 97 months. Of the 528 patients who were included in our study, 303 had at least one comorbid condition and 249 died during the follow-up period. When patients were stratified by age, we found that older patients had a higher proportion of severe comorbidities （P 〈 0.01） than younger patients, and that a lower proportion of them underwent radical cystec- tomy for invasive bladder cancer （IBC） （P 〈 0.01）. By multivariate analysis, we found that older age was predictive of lower overall survival （OS） and bladder cancer-specific survival （BCSS） rates among patients with superficial bladder cancer （SBC） and of lower OS rates among patients with IBC. We also found that moderate-severe comorbidity status and treatment through a bladder-conserving approach were predictive of lower OS and cancer-specific survival rates among patients with IBC. The disparity between overall deaths and bladder cancer deaths was shown in SBC and increased along with age and higher comorbidity. Age and comorbidity were found to be independent predictive factors of OS and BCSS among bladder cancer patients, and explained the disparity that we observed between overall bladder cancer-specific mortality rates.

Blockage of IGF-1R signaling sensitizes urinary bladder cancer cells to mitomycin-mediated cytotoxicity

A major problem which is poorly understood in the management of bladder cancer is low sensitivity to chemotherapy and high recurrence after transurethral resection. Insulin-like growth factor 1 receptor (IGF-1R) signaling plays a very important role in progression, invasion and metastasis of bladder cancer cells. In this study, we investigated whether IGF-1R was involved in the growth stimulating activity and drug resistance of bladder cancer cells. The results showed: The mRNAs of IGF-1, IGF-2 and IGF-1R were strongly expressed in serum-free cultured T24 cell line, whereas normal urothelial cells did not express these factors/receptors or only in trace levels; T24 cell responded far better to growth stimulation by IGF-1 than did normal urothelial cells; blockage of IGF1R by antisense oligodeoxynucleotide (ODN) significantly inhibited the growth of T24 cell and enhanced sensitivity and apoptosis of T24 cells to mitomycin (MMC). These results suggested that blockage of IGF-IR signaling might potentially contribute to the treatment of bladder cancer cells which are insensitive to chemotherapy.

Correlation of the amount of AgNORs with the grading and prognosis of bladder tumour

The number of AgNORs in the nucleolar organizer region was studied quantitativelyby one-step silver colloid technique in 6 samples obtained from normal bladder tissue,9 ofchronic cystitis and 56 of transitional cell carcinoma of bladder.The results revealed that meannumber of AgNORs per nucleus was not statistically different between normal bladder tissueand tissue from chronic cystitis,while there was a significant difference between normal or in-flammatory tissue and malignant tisssue on the one hand and between various grades of bladdertumor on the other.The results also indicated that mean number of AgNORs per nucleus wasclosely related to the prognosis of bladder tumor.So it is suggested that AgNOR counting bythe silver stain technique might play a role in the differenciation of benign and malignant lesionsand in grading and prognosis in bladder tumors.

Distribution and significance of oncogene C－erbB－1 and suppressor gene р53 in human bladder cancer

To study the relationship between oncogene C-erbB-1 and suppressor gene p53 and bladder cancer,oncogene C-erbB-1 and suppressor gene p53 were determined by immunohistochemistry in 58 cases of bladder cancer. In addition,on 30 of them in situ hybridization

Immediate cystectomy or conservative management for T_1 G_3 bladder cancer: A meta-analysis of general survival rate

Objective： The aim of this study was to compare the therapeutic effects of bladder preserving approach transurethral resection （TURBT） with additional intravesicel instillation versus immediate cystectomy in patients with newly diagnosed stage T1G3 bladder cancer. Methods： Clinical data of patients with newly diagnosed T1G3 bladder cancer underwent immediate cystectomy （Group A） or TURBT with additional intravesical instillation （Group B） was collected from online databases. Meta-analysis that recommended by Cochrane Collaboration was done for the data obtained. Publication bias was examined using a funnel plot. Results： Four trails, including 434 patients, were eligible for this study. The general mortality rate of group A （74/149 = 49.7%） and group B （102/285 = 35.8%） was calculated and compared in RevMan 4.2, which showed the difference on general mortality rate between the two groups was not statistical significant, with the pooled RR = 1.23 （95% CI 1.10-1.70, P 〉 0.05）. Conclusion： Compared with TURBT, immediate cystectomy may not reduce the general mortality rate to improve the forward survival rate.

Diagnosing upper tract urothelial carcinoma: A review of the role of diagnostic ureteroscopy and novel developments over last two decades

Objective: The role of ureteroscopy in the diagnosis of upper tract urothelial carcinoma is yet to be fully determined. We aimed to provide an up to date evaluation of its role and the emerging technologies in the field.Methods: A literature search of the last two decades (from 24th May, 2001 to 24th May, 2021) was carried out identifying 147 papers for potential inclusion within this narrative review.Results: Diagnostic ureteroscopy is undeniably useful in its ability to visualise and biopsy indeterminate lesions, and to risk stratify malignant lesions that may be suitable for kidney sparing surgery. However, an increased risk of intravesical recurrence following nephroureterectomy when a prior diagnostic ureteroscopy has been performed, inadequate sampling at biopsy, complications from the procedure, and difficult ureteric access are all potential drawbacks. Furthermore, whilst generally an accurate diagnostic procedure, it risks missing carcinoma in-situ lesions. Despite this, evidence shows that routine use of ureteroscopy changes the management of patients in a large proportion of cases, preventing unnecessary surgery or facilitating kidney sparing surgery. The overall rate of complications is low, and improved biopsy techniques and the use of tissue biomarkers for improved staging and grading are encouraging. The risks of delays to definitive management and post-ureteroscopy intravesical recurrence do not seem to affect survival, and trials are in progress to determine whether intravesical therapy can mitigate the latter. Further promising techniques are being investigated to improve shortcomings, particularly in relation to improved diagnosis of carcinoma in situ and preoperative staging.Conclusion: Ureteroscopy has a role in the diagnosis of upper tract malignancy, though whether it should be used routinely is yet to be determined.

Claudin-3在膀胱移行细胞癌中的表达及意义

目的通过检测Claudin-3 mRNA和蛋白在膀胱移行细胞癌(TCCB)组织中的表达,探讨其在膀胱移行细胞癌发生、发展中所起的作用。方法对56例TCCB患者肿瘤组织、17例非肿瘤膀胱移行上皮组织分别采用逆转录聚合酶链反应(RT-PCR)法检测Claudin-3 mRNA的表达,SP免疫组织化学法检测Claudin-3蛋白的表达。并分析Claudin-3 mRNA和蛋白的表达与TCCB的病理分级、临床分期的关系等。结果(1)TCCB组中Claudin-3 mRNA阳性率明显低于非肿瘤膀胱组织(P<0.05),且在不同临床分期、病理分级的TCCB组之间阳性率差异有统计学意义(P<0.05)。(2)TCCB组中Claudin-3蛋白表达水平明显低于非肿瘤膀胱组织,不同临床分期和病理分级肿瘤组织中Claudin-3蛋白表达的阳性率差异有统计学意义(P<0.05)。而在不同性别、年龄、单灶与多灶组间Claudin-3蛋白表达的阳性率差异无统计学意义(P>0.05)。在初发与复发组间Claudin-3蛋白表达的阳性率差异有统计学意义(P<0.05)。结论(1)TCCB组Claudin-3 mRNA和蛋白表达水平均明显低于非肿瘤组,提示Claudin-3与TCCB的发生密切相关,Claudin-3在膀胱肿瘤的发生中起抑制作用。(2)Claudin-3的转录表达与膀胱肿瘤的病理分级、临床分期、以及肿瘤复发均有显著相关。Claudin-3表达下调或缺失可能促使膀胱移行细胞癌恶性程度和复发率增高。

RhoGDI2基因抑制膀胱癌转移涉及基因和信号通路的生物信息学分析

目的利用生物信息学方法探讨Rho GTP酶GDP解离抑制因子2(rho GDP dissociation inhibitor 2,Rho GDI2)基因抑制膀胱癌转移涉及的基因和信号通路。方法从GEO datasets数据库搜索膀胱癌转移相关的全基因组表达谱芯片数据,使用GEO2R在线工具分析膀胱癌组织中Rho GDI2基因高表达组与低表达组之间的差异表达基因,再筛选出多组表达谱芯片数据中一致性上调或下调的基因,最后使用DAVID在线工具进行差异表达基因信号通路富集。结果得到Rho GDI2基因在膀胱癌组织中高表达组和低表达组一致性高的差异表达基因,其中A2M、CORO1A、ENC1、FGD3为上调基因中一致性高的差异表达基因。通过基因信号通路富集分析得到膀胱癌组织中Rho GDI2基因调控的主要信号通路为Vav-Rho A-ROCK-MLC和Ras-Raf-MEK。结论 Rho GDI2基因可能通过Vav-Rho A-ROCK-MLC和Ras-Raf-MEK信号通路调节肌丝蛋白、细胞骨架以及细胞的增殖、分化等,进而抑制膀胱癌转移。

直接还原法标记^(99m)Tc与抗人膀胱癌单克隆抗体BDI-1

通过２ － 巯基乙醇直接还原法将抗人膀胱癌单克隆抗体 Ｂ Ｄ Ｉ－ １ 与核素９９ｍ Ｔｃ 进行标记， 制备９９ ｍ Ｔｃ － Ｂ Ｄ Ｉ－ １ ． 优化条件后进行标记并进行一系列检测． 结果： 标记率为７２ ％ ， 经 Ｓｅｐｈａｄｅｘ 柱纯化后标记抗体的放化纯度高于９５ ％ ； 标记抗体的免疫活性分数为８７ ％ ， 与 Ｅ－ Ｊ细胞的结合率为９０ ％ ； 无毒、无菌、无热原． 结果表明： ２ － 巯基乙醇直接还原法将抗人膀胱癌单克隆抗体 Ｂ Ｄ Ｉ－ １ 与核素９９ ｍ Ｔｃ 进行标记为进一步进行膀胱癌的放射免疫显像诊断奠定了基础．

改良Indiana膀胱术的远期疗效观察

目的 :评价改良Indiana膀胱术的远期疗效。方法 :对 2 6例改良Indiana膀胱术术后患者的膀胱可控性、尿动力学、肾盂输尿管扩张、上尿路感染情况、血清电解质和肾功能进行随访。结果 :2 6例随访 1～ 7年 ,平均 3年。白天可控率 96 .2 % ;贮尿囊容量为 380～ 6 4 0ml,平均 5 4 2ml;贮尿囊内压力为 1 .2 1 5～ 3.2 2 4kPa ,平均1 .92 1kPa。B超、IVP造影示 3例输尿管扩张 ,经随访无加重。血清电解质及肾功能正常。结论 :改良Indiana膀胱术远期疗效可靠 ,并发症少 。

Comparisons of voided urine cytology, nuclear matrix protein-22 and bladder tumor associated antigen tests for bladder cancer of geriatric male patients in Taiwan, China

Aim： To compare the results of bladder tumor associated antigen （BTA TRAK）, nuclear matrix protein 22 （NMP 22） and voided urine cytology （VUC） in detecting bladder cancer. Methods： A total of 135 elderly male and 50 healthy volunteers enrolled in this study were classified into three groups： （i） 93 patients with bladder cancer; （ii） 42 patients with urinary benign conditions; and （iii） 50 healthy volunteers. BTA TRAK and NMP 22 kits were used to detect bladder cancer. Voided urine cytology was used to compare the sensitivity and specificity of the screening tests. Results： The sensitivity and specificity of cytology, BTA TRAK and NMP 22 were 24% and 97%, 51% and 73%, 78% and 73%, respectively. The level of NMP 22 increased with tumor grading. The BTA TRAK kit has the lowest sensitivity among the screening tests. The NMP 22 with the best sensitivity can be an adjunct to cytology for evaluating bladder cancer. Conclusion： The NMP 22 test has a better correlation with the grading of the bladder cancer than BTA TRAK. As cytology units are typically not available in hospitals or in outpatient clinics, NMP 22 might be a promising tool for screening bladder cancer.

Costimulatory Molecule B7-H1 on the Immune Escape of Bladder Cancer and Its Clinical Significance

B7-H1, a recently described member of the B7 family of costimulatory molecules, is thought to be involved in tumor immune escape by inducing T-cell apoptosis. In order to investigate the relationship between B7-H1 and immune escape of bladder cancer, B7-H1 expression in 50 cases of bladder cancer was detected by using immunohistochemical method. Survival curves were con- structed using the Kaplan-Meier method and independent prognostic factors were evaluated using the Cox regression model. Our results showed that the positive rate of B7-H1 immunostaining in normal bladder tissue and bladder cancer was 0 and 72% respectively. The expression of B7-H1 was strongly associated with the pathological grade, clinical stage and recurrence （P〈0.05）. The survival rate was significantly lower in patients with B7-H1 positive group than in those with B7-H1 negative group and multi-variable analysis revealed that B7-H1 could be regarded as an independent factor in evaluating the prognosis of bladder cancer. It is concluded that the expression of B7-H1 is strongly associated with neoplastic progression and prognosis of bladder cancer. The manipulation of B7-H1 may become a beneficial target for immunotherapy in human bladder cancer.

Correlative Expression of Glutathion S-Transferase-π and Multidrug Resistance Associated Protein in Bladder Transitional Cell Carcinoma

In order to elucidate the mechanisms of multidrug resistance (MDR) in bladder cancer, the expression of glutathione S-transferase-π (GST-π) and multidrug resistance associated protein (MRP) in tissue samples resected from 44 patients and 6 normal bladder mucosa as control was de- tected by using immunohistochemical method, and the results were analyzed by computer-assisted im- age analyzing system (IAS) to achieve semi-quantitative data. In addition, correlation between the expression of both factors was studied. The results showed that the positive expression rate of GST- π and MRP in bladder cancer was 72. 7 % (32/44) and 68. 2 % (30/44) respectively, significantly higher than those in normal bladder mucosa, being 16. 7% and 33. 3% respectively. The rate of GST-πpositive staining was increased correspondingly with tumor grade and stage elevated, being higher in recurrent tumors treated by chemotherapy, but not significantly (P>0. 05). There was no significant differences between the expression of MRP and tumors' behaviors and clinical characters. However, the results demonstrated that the correlation between the expression of both resistant fac- tors was very evident (r=0. 695, P<0. 0025). It was suggested that the activation of GST-π and MRP might occur during malignant transformation of normal mucosa, but tumors' differentiation and progression could not be the unique factors that influenced both overexpression. Chemotherapy might be another important reason. The correlation of both indicated that there was a common mech- anism regulating their expression probably, which made them play a pivotal role in chemotherapy drug resistance of bladder cancers.

Limited energy parametrial resection/dissection during modified laparoscopic nerve-sparing radical hysterectomy

Objective: The aim of this study was to investigate the feasibility of using ultrasonic scalpel combined with vascular clip in parametrial management,called limited energy parametrial resection/dissection(LEPRD),in laparoscopic nerve plane-sparing radical hysterectomy(NPSRH),a modified nerve-sparing radical hysterectomy(NSRH); and to evaluate its effectiveness in pelvic autonomic nerve preservation.Methods: From July 2012 to January 2016,257 consecutive patients with stage IB1 to IIA2 cervical cancer who underwent NPSRH were included in this study.Patients were divided into three cohorts according to the different parametrial resection modality.The clinical,pathological and surgery-related parameters were compared between the three groups.Short-and long-term postoperative bladder functions were evaluated.Results: LEPRD was attempted in 94 patients,and was successful in 65(69.1%) patients(LEPRD group).The remaining 29(30.9%) patients required bipolar coagulation after failure of vascular clipping(combined modality group).Routine bipolar cautery was used in the other 163 patients during the parametrial resection(bipolar group).The blood loss in the LEPRD group was significantly lower than those in the other two groups(P<0.001).The rate of successful Foley removal on postoperative day 7 was significantly higher in the LEPRD group than in the bipolar group(P=0.022).The incidence of chronic voiding dysfunction was significantly lower in the LEPRD group than in the bipolar group(P=0.019).Conclusions: It is feasible to perform LEPRD in NPSRH for cervical cancers.This kind of limited energy surgical technique is associated with less blood loss,and leads to improved postoperative bladder function.

Expression of Multidrug-associated Protein, P-glycoprotein, P53 and Bcl-2 Proteins in Bladder Cancer and Clinical Implication

The expression of multidrug resistant proteins in bladder cancer and clinical implication was studied. Expression of multidrug associated protein (MRP), P glycoprotein (P gp), P53 and Bcl 2 proteins were detected by using immunohistochemical method in 40 specimens of bladder transitional cell carcinoma. The results showed that the positive rate of MRP, P gp, P53 and Bcl 2 was 52.5 %, 57.5 %, 47.5 % and 62.5 % respectively. The positive rate of MRP, P gp, P53 and Bcl 2 in the grade Ⅰ, Ⅱ and Ⅲ of tumors was 46.3 %, 38.5 %, 38.5 %, 23.1 %; 52.9 %, 39.8 %, 47.1 %, 76.4 %; 60.0 %, 80.0 %, 60.0 %, 90.0 % respectively. The positive rate of MRP, P gp, P53 and Bcl 2 in 24 primary tumor specimens was 37.5 %, 41.7 %, 33.3 %, 45.8 % and that in 16 cases in recurrent specimens receiving chemotherapy 75.0 %, 81.3 %, 68.8 %, 87.5 % respectively. It was suggested the positive rate of MRP, P gp, P53 and Bcl 2 was increased with the advance of tumor grade. The positive rate of four proteins in all recurrent cases was significantly increased ( P <0.05). The expression of MRP, P gp, P53 and Bcl 2 proteins might be the important factors for chemotherapy failure.

Robot-assisted laparoscopic radical cystectomy with complete intracorporeal urinary diversion

Robot-assisted radical cystectomy with intracorporeal urinary diversion(RARCICUD)has only recently been explored as a viable surgical option for patients with muscle-invasive bladder cancer seeking satisfactory oncologic control while benefiting from minimally invasive surgical techniques.Inspired by earlier open and laparoscopic work,initial descriptions of RARC-ICUD were published in 2003,and have since been followed by multiple larger case series which have suggested promising outcomes for our patients.However,the rate of adoption has remained relatively slow when compared to other robotassisted procedures such as the radical prostatectomy,likely owing to longer operative times,operative complexity,costs,and uncertainty regarding oncologic efficacy.The operative technique for RARC-ICUD has evolved over the past decade and several high-volume centers have shared tips to improve efficiency and make the operation possible for a growing number of urologists.Though there are still questions regarding economic costs,effectiveness,and generalizability of outcomes reported in published data,a growing dataset has brought us ever closer to the answers.Here,we present our current operative technique for RARC-ICUD and discuss the state of the literature so that the urologist may hold an informed discussion with his or her patients.

Plasmacytoid Transitional Cell Carcinoma of Bladder： A Clinico-pathological Study and Review of Literatures

Objective： To study the pathologic features of plasmacytoid transitional cell carcinoma of the bladder, and to analyze the diagnostic features, criteria for differential diagnosis and the clinical significance of the tumor. Methods： Two cases of bladder plasmacytoid transitional cell carcinoma were studied. Routine paraffin sections with HE staining, Pap smear and immunohistochemistry by S-P method were observed under a light microscope. Pathological and clinical data were analyzed by comparison with early reported cases in literatures. Results： A characteristic feature of this tumor was of deep invasion in the lamina propria and/or muscularis propria, in addition to the component of carcinoma in situ in the mucosa, when tumors were diagnosed. The histological pattern and cytological features showed similarity to a plasmacytoid tumor. The tumor cells were strongly positive for AE1/AE3, CEA and CK18. The prognosis appeared to be worse than ordinary transitional cell carcinoma. Conclusion： The plasmacytoid transitional cell carcinoma of bladder is rare but has typical pathological, immunohistological and clinical features. Pathologists should be aware of this kind of primary tumor of bladder.

Clinical significance of elevation of serum CA125 level in patients with metastatic bladder carcinoma

Objective： To explore the clinical significance of the examination of serum CA125 level of patients with metastatic bladder carcinoma. Methods： Electrochemiluminescence technique was used to examine the serum CA125 concentration of 58 cases with metastatic bladder cancer. 30 cases of superficial bladder cancer and 8 cases of other urological diseases were collected as the control group. Results： Serum CA125 level in 39 （67.2%） out of 58 cases ranged from 36.7 U/mL to 1485.6 U/mL （mean 496.3 U/mL）, being higher than normal （〈 35 U/mL）. Serum CA125 level of metastatic bladder cancer patients was 324.5 U/mL, significantly higher than that in control group （P 〈 0.001）. Serum CA125 level of 10 patients after transurethral resection operation was significantly lower than that before operation （P 〈 0.05）. Serum CA125 level of 16 patients who refused further treatment significantly increased from 450.4 U/mL, to 505.8 U/mL （P = 0.041） 3 months after discharge from the hospital. Serum CA125 level of 17 patients significantly decreased from 475.8 U/L to 237.9 U/mL （P 〈 0.001 ） after bilateral iliac-artedal embolism treatment. Conclusion： CA125 may be a valuable marker for the judgment of advanced metastatic bladder cancer.

Superselective embolisation of bilateral superior vesical arteries for management of intractable hematuria in context of metastatic bladder cancer

Hematuria due to locally advanced or metastatic bladder cancer is a common condition and is often a management problem.Percutaneous embolisation is a mini-invasive option to handle this situation.We report a case of a patient with a metastatic bladder cancer and who presented with an abundant hematuria and severe anemia.After failure of endoscopic resections and“flush”of radiotherapy haemostatic and refusal of cystectomy by the patient,he was treated by superselective embolisation of bilateral superior bladder arteries with excellent immediate results.The technique is safe and effective in the short term.The longterm effectiveness requires further investigation.

Clinicopathologic Observation of 6 Cases with Neuroendocrine Carcinoma of the Urinary Bladder

OBJECTIVE To discuss the pathologic characteristics and theprognosis of neuroendocrine carcinoma of the bladder(NECB)in order to assist in making a precise diagnosis and to effectivelytreat the disease.METHODS Clinicopathologic features of the 6 cases with NECBwere analyzed retrospectively.The personal data of the patientsand the pathologic and immunohistochemical characteristics ofthe tumor were investigated.The follow-up of these patients wasconducted over a time period ranging from 3 months to 9 years.RESULTS Transurethral resection of the bladder tumorwas performed in all 6 patients.Based on the results of thepathologic examination,4 of the cases were diagnosed as smallcell neuroendocrine carcinoma and the other 2 were diagnosedas atypical carcinoid tumor.On immunohistochemical stainingall tumors expressed neuroendocrine markers includingneuronspecific enolase(CD56),synaptophysin(Syn)andchromogranin(CgA).In patients receiving partial cystectomyfollowed by postoperative chemotherapy,relapse was found in 4of the 6 cases on follow up.CONCLUSION NECB is a rare entity and a tumor with highmalignant potential and characteristic pathologic features.Hematuria is the cardinal symptom of NECB.Metastasis mayoccur at an early stage and the prognosis of the disease is poor.Final diagnosis of NECB depends on histopathologic examinationand immunohistochemical assays.Surgical excision combinedwith radiotherapy and chemotherapy is considered an effectivetreatment.