ATP—TCA技术指导浅表性膀胱癌术后灌注化疗的临床应用

目的：探讨生物荧光体外肿瘤药敏检测技术（ATP—TCA）在浅表性膀胱癌肿瘤细胞药敏试验中的应用,探讨该技术在指导膀胱癌个体化治疗上的应用价值。方法：对40例浅表性膀胱癌标本进行肿瘤细胞分离,原代培养,应用ATP—TCA技术检测肿瘤标本对五种常用化疗药物的敏感率和耐药率。试验组术后选用最敏感的化疗药物对患者常规行膀胱灌注化疗,对照组选择丝裂霉素进行术后常规化疗。术后随访2年,评价两组膀胱癌复发情况。结果：40例标本中,吡柔比星（THP）、羟基喜树碱（HCPT）、丝裂霉素（MMC）、表柔比星（EPI）、吉西他滨（GEM）的敏感率分别为75．0％、10．0％、5．0％、37．5％、10．0％,肿瘤细胞对五种化疗药物的敏感率和耐药率差异有统计学意义（P〈0．01）。膀胱肿瘤对化疗药物的敏感性存在个体差异。术后随访2年,药敏组膀胱癌复发率为17．5％（7／40）,对照组膀胱癌复发率为37．5％（15／40）。两组肿瘤复发率差异有统计学意义（P〈0．05）。结论：应用ATP—TCA技术检测出的药敏结果能够反映个体对化疗药物的敏感性,可以作为选择灌注化疗用药的理论基础,指导临床用药进行个体化治疗。同时,应用ATP—TCA技术指导临床膀胱癌术后灌注化疗,可显著降低浅表性膀胱癌患者术后复发率,提高临床疗效。     

Urinary bladder spindle-cell neoplasm concomitant with urothelial cancer

A postoperative spindle-cell neoplasm of the urinary bladder is an extremely uncommon lesion. The previous literature indicated that the neoplasm is an indolent, benign tumor and rarely exhibits clinically aggressive behavior. We report a 68-year-old male patient who underwent cystolithotomy for a huge urinary bladder stone. Two months later, he complained of progressively difficult micturition. Imaging studies revealed a huge invasive urinary bladder tumor, and a radical cystoprostatectomy with ileal conduit diversion was performed. The pathology report confirmed a spindle-cell tumor concomitant with a high-grade, papillary urothelial carcinoma. The patient recovered uneventfully, and there has been no tumor recurrence during ongoing follow-up (12 months).     

输尿管口旁浅表性膀胱肿瘤的微创治疗

目的：总结输尿管口旁浅表性膀胱肿瘤微创治疗的临床经验。方法：在连续硬脊膜外麻醉＋患侧闭孔神经阻滞麻醉下行内腔镜手术治疗输尿管口旁浅表性膀胱肿瘤患者25例,其中2l例肿瘤位于输尿管口周围2．0cm以内,但未累及输尿管口;4例肿瘤基底位于输尿管口内。经尿道先置人70。膀胱镜了解肿瘤具体情况,然后更换电切镜,从基底部将肿瘤及包括输尿管口在内的周围2cm正常膀胱黏膜快速一并完整切除。结果：25例手术均顺利结束,无出血、穿孔等并发症。25例均获得随访,时间为12～24个月,无输尿管口狭窄、闭锁、严重的膀胱输尿管反流、肾功能受损等并发症发生。结论：经尿道微创手术治疗输尿管口旁浅表性膀胱肿瘤,操作简单,创伤小,可代替开放性手术。     

Plasmacytoid urothelial carcinoma of the bladder

We report the first case of a pathological complete response for plasmacytoid urothelial carcinoma of the bladder. A 76-year-old man was diagnosed with plasmacytoid urothelial carcinoma (T4, N0, M0) by the microscopically plasmacytoid appearance of the specimen from the transurethral resection. Immunohistochemical studies were positive for epithelial markers and negative for lymphoid markers. Two cycles of systemic chemotherapy were performed with methotrexate, etoposide, vinblastine, and cisplatin, followed by radical cystectomy. The pathological examination revealed no residual cancer cells in the resected specimen.     

Mouse orthotopic models for bladder cancer research

Bladder cancer is a common malignancy in the urinary tract. Despite different therapeutic options, recurrence and progression of urothelial carcinoma after treatment is not uncommon. Novel therapeutic options of bladder cancer are urgently needed. The preclinical evaluation of new treatments requires an animal tumour model that mimics the human counterpart. To date, various animal orthotopic bladder cancer models have been described, but the reported rate of tumour ‘take’ is 30–100%. The establishment of reliable and reproducible animal models remains an ongoing challenge. We review different kinds of mouse models of orthotopic bladder cancer used in urothelial cancer studies, the methods of implantation, and the reported rate of tumour take. Significant progress has been made recently in noninvasive small animal‐imaging in tumour models. It is now possible for researchers to investigate the effects of studied agents by monitoring of in vivo tumour growth directly and noninvasively, as well as measuring a wide range of tumour‐related variables in small animals. We summarize the recent development in small‐animal imaging for tumour detection and quantification.     

Induction chemotherapy for unresectable urothelial carcinoma of the bladder

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? In resectable muscle‐invasive bladder cancer neoadjuvant chemotherapy followed by radical cystectomy confers to a significant 5% overall survival benefit. Less is known about induction chemotherapy followed by radical cystectomy in initially unresectable patients. Our retrospective analysis of a selected patient cohort suggests that patients with initially unresectable bladder cancer may benefit from this combined treatment approach.

OBJECTIVE

? To analyse the outcome in selected patients with initially unresectable or minimally metastatic muscle‐invasive urothelial bladder cancer who underwent induction chemotherapy (IC) followed by radical cystectomy (RC).

PATIENTS AND METHODS

? Thirty patients with initially unresectable, locally advanced or minimally metastatic bladder cancer underwent platinum‐based IC followed by RC with curative intent at our institution from 2000 to 2007. ? They received a median of four cycles (range 2–6 cycles) of cisplatin and gemcitabine (n= 19), carboplatin and gemcitabine (n= 9) or other platinum combinations (n= 2). ? We retrospectively analysed all 30 patients for complete pathological remission (pT0), disease free survival (DFS) and overall survival (OS). Chi‐square tests, Kaplan–Meier analyses, and Cox univariate modelling were used.

RESULTS

? Before IC, 30 patients were deemed unresectable because of locally advanced tumour classification (cT4, 18/30) and/or clinically suspected lymph node (LN) metastasis (21/30) or suspected distant metastasis (3/30). ? At re‐staging after IC there was a complete regression of all enlarged LN in 16/21 patients, a partial LN response in one patient or stable LN size in the remaining four patients. ? After RC, 9/30 (30%) of patients had attained pT0. ? The median follow‐up was 28 months (range 4–97 months). The 5‐year DFS and OS rates were 42% and 46%, respectively, for all patients. ? In the pT0 patients, the DFS (83%) and OS (71%) rates were significantly higher than in non‐pT0 patients.

CONCLUSION

? Patients undergoing IC followed by RC showed encouraging response and survival rates, suggesting that selected patients with initially unresectable bladder cancer benefit from this combined regimen.     

Risk factors for urothelial carcinoma of the prostate in patients undergoing radical cystoprostatectomy for bladder cancer

OBJECTIVE

To examine the risk factors for urothelial carcinoma (UC) involvement of the prostate in patients undergoing radical cystoprostatectomy (RCP) for bladder cancer, as such involvement has both prognostic and therapeutic implications.

PATIENTS AND METHODS

We examined 308 consecutive men from 1998 to 2005 who had RCP for UC of the bladder, with whole‐mount processing of their prostate. Prostatic involvement was categorized by site of origin (the bladder or the prostatic urethra) and, in the case of prostatic urethral origin, by depth of invasion, i.e. dysplasia/carcinoma in situ (CIS), involving the prostatic urethra, prostatic ductal invasion or prostatic stromal invasion. The impact of pathological characteristics was evaluated.

RESULTS

In all, 121 (39.3%) patients had some form of urothelial involvement of the prostate, of whom 59 (48.8%) had dysplasia/CIS of the prostatic urethra, 20 (16.5%) had ductal involvement and 32 (26.4%) had stromal involvement. Multivariate analysis showed that bladder CIS (odds ratio 2.0, 95% confidence interval, 1.2–3.6, P = 0.012) and trigonal involvement of bladder tumours (2.0, 1.1–3.7, P = 0.028) were independent risk factors for urothelial involvement of the prostate.

CONCLUSION

There was prostatic involvement with UC in nearly 40% of patients undergoing RCP. In this study CIS and trigonal involvement were independent predictors of risk, but were not adequate enough to accurately identify most patients who have UC within their prostate; further prospective studies are needed to more accurately predict risk factors and depth of invasion.     

膀胱腺癌的诊治(附23例报告)

目的 提高膀胱腺癌的诊断与治疗水平.方法 对1998年1月～2008年10月收治的23例膀胱腺癌患者临床资料进行回顾性分析.结果 2例患者失访,21例患者随访时间为5个月～10年.1年生存10例(47%),2年生存7例(33%),5年生存4例(19%).生存时间超过5年者均为早期患者.结论 早期诊断、选择合适的手术方式及术后辅助放化疗有益于改善患者预后.     

Secondary bladder cancer after upper tract urothelial carcinoma in the US population

Study Type – Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? It is known that a certain percentage of patients treated for upper tract urothelial carcinoma (UTUC) will go on to develop a secondary bladder cancer; however, the risk factors for developing a secondary bladder tumour have not been studied in a population‐based setting. Given the large changes in how UTUC has been diagnosed and managed in recent years, this study aimed to evaluate the natural history of UTUC in the US population over a 30‐year period, with a particular emphasis on the development of secondary bladder cancer.

OBJECTIVE

• ? To assess the natural history of upper tract urothelial carcinoma (UTUC) and the development of lower tract secondary cancer.

PATIENTS AND METHODS

• ? Patients diagnosed with UTUC between 1975 and 2005 were identified within nine Surveillance, Epidemiology and End Results registries.
• ? Baseline characteristics of patients with and without secondary bladder cancer were compared.
• ? A multivariate logistic regression model was fitted to test if the year of diagnosis predicted the likelihood of developing a secondary bladder cancer.

RESULTS

• ? Of the 5212 patients with UTUC, 242 (4.6%) had a secondary bladder cancer (range: 1.7–8.2%).
• ? There was a mean interval of 26.5 (95% CI: 22.2–30.8) months between cancer diagnoses.
• ? Compared with those without secondary tumours, patients with secondary bladder malignancy were more likely to present with larger tumours (4.2 vs 3.1 cm, P < 0.001) and with tumours located in the ureter (P < 0.001).
• ? Year of diagnosis was not a predictor of the likelihood of having a secondary bladder malignancy in a multivariate analysis controlling for demographic and tumour characteristics (odds ratio: 0.99; 95% CI: 0.95–1.03)

CONCLUSIONS

• ? Patients with larger urothelial tumours located in the ureter were those most likely to develop a secondary lower tract tumour.
• ? No longitudinal changes in the rate of secondary bladder cancer were noted among patients with UTUC over the 30‐year study period.

     

Management of superficial bladder cancer in Victoria: 1990 and 1995

BACKGROUND: A retrospective survey of medical practitioners was undertaken to describe the tumour characteristics, management and outcomes of all superficial bladder cancers newly diagnosed in 1990 and in 1995 in Victoria. METHODS: Cases were identified from the population cancer registry. The survey was conducted in 1999 and the cohort followed up until 2000 to obtain at least 5 years of follow-up data on all patients, in particular to identify recurrence of tumour as assessed at surveillance cystoscopy and progression to muscle invasive cancer. RESULTS: Tumour recurrence was observed in 390/610 patients (63.9%), of whom 56.9% had their recurrence noted at the first check cystoscopy. Ultimately 43 (6.3%) of patients progressed to invasive disease, with this subgroup demonstrating 5-year overall survival of 35% (95% confidence interval (CI) 21-49%). Ultimately survival was proportional to the extent of tumour invasion, being greater in low-risk patients (76%, 95% CI 72-80%, mucosal disease only) than in high-risk patients (46%, 95% CI 36-56%, lamina propria invasion noted at diagnosis). CONCLUSIONS: In low-risk subgroups of patients with superficial transitional cell carcinoma, the frequency of surveillance cystoscopy may be able to be reduced to levels in accordance with established European guidelines without a likely impact on patient survival. Where progression to muscle invasive disease does ensue, more aggressive management may be warranted in order to try to improve survival.     

膀胱癌手术常见并发症及其防治

膀胱癌手术根据肿瘤的类型包括经尿道膀胱肿瘤切除术和根治性膀胱切除术两大类,其手术并发症的发生较为常见。本文根据作者丰富的临床经历和手术经验,整理归纳了膀胱癌手术中各类常见的并发症,并总结了相应的防治方法,以期为泌尿外科临床医生在减少并发症发生率方面提供指导和帮助。     

Complications of intravesical therapy for urothelial cancer of the bladder

PURPOSE: Intravesical therapy is an integral part of treatment in patients with superficial urothelial carcinoma of the bladder. The American Urological Association and European Association of Urology guidelines on bladder cancer incorporate it for the treatment of superficial bladder cancer. Given the extensive use of intravesical immunotherapy and chemotherapy, it is essential for the practicing urologist to be aware of the local and systemic side effects of these therapies. MATERIALS AND METHODS: We reviewed the literature on intravesical immunotherapy and chemotherapy with particular emphasis on side effects, complications and their management. A Medline search of the English language literature for the last 25 years was done on Entrez PubMed and all relevant articles were studied in full. All side effects and complications were studied and their management was reviewed. RESULTS: Intravesical therapy for transitional cell carcinoma of the bladder is generally safe. There is a high incidence of local, usually self-limiting, relatively minor side effects and infrequent, potentially severe local and systemic side effects. Most side effects are avoidable. CONCLUSIONS: Although intravesical therapy is generally safe, local and systemic side effects occur and it is important to be aware of them. Identifying complications early, preventing them when possible and managing them efficiently are critical. Most complications are preventable. Knowing the risks and benefits of chemotherapeutic and immunotherapeutic agents may decrease the short-term and long-term toxicity of these agents. Adherence to guidelines may prevent inappropriate use, which can lead to unnecessary complications, resulting in bladder dysfunction and even cystectomy.     

Recurrence pattern for superficial bladder cancer

AIM: Patients with superficial bladder tumors sometimes have long recurrence-free intervals. We evaluated whether patients with long recurrence-free periods had subsequent recurrences. We also clarified how these patients should be followed. MATERIALS AND METHODS: We enrolled 244 patients with superficial bladder cancer (62 pTa and 182 pT1) treated by transurethral resection of bladder tumor (TURBT) and adjuvant chemotherapy with pirarubicin. Median follow up was 75.5 months. Patients were stratified by the length of their recurrence-free interval. RESULTS: Recurrences occurred in 124 patients (50.8%). Of 185 patients who did not have a recurrence for the first 3 years, subsequent recurrences occurred in 65 patients; in more than half the first recurrence developed after 5 years or more. Ta tumors had a low recurrence rate (14.5%) with the first recurrence often developing after a long recurrence-free period. Of 40 patients who remained recurrence-free for 3 years or more after at least one recurrence occurred, 16 patients (40%) had subsequent recurrences. Furthermore, most of these patients who remained free of recurrence for more than 5 years eventually had a recurrence. The overall progression rate was 15.6%, and this did not relate to the length of the recurrence-free interval. CONCLUSION: When patients did not have a recurrence for the first 3 years, tumors subsequently often recurred, even in pTa tumors. In patients with at least once recurrence, subsequent recurrences appear to occur irrespective of the length of the recurrence-free period. Thus, we recommend that all patients with superficial bladder tumors be followed for as long as possible.     

Management of BCG failures in superficial bladder cancer: a review

OBJECTIVE: Review management of bacillus Calmette-Guérin (BCG) failures in superficial bladder cancer. METHOD: Search of published literature and meeting abstracts. RESULTS: Patients in whom BCG fails are not a uniform group. Failure cannot be predicted but high-risk patients can be identified. In case of failure and progression the outcome is bad. Conservative but investigative alternatives are BCG/interferon-alpha, intravesical hyperthermia/chemotherapy, or photodynamic therapy. Standard treatment in failing patients remains cystoprostatectomy. CONCLUSION: BCG failures need careful and individualized therapy in experienced hands.     

膀胱部分切除术治疗肌层浸润性膀胱癌的再认识

膀胱癌是泌尿系统最常见的恶性肿瘤之一,对于肌层浸润性膀胱癌(MIBC)目前主要治疗方法是以手术治疗为主的综合治疗,标准手术治疗方式为根治性膀胱切除术(RC)合并盆腔淋巴结清扫,但该手术仍存在手术复杂、并发症多、术后生活质量差等不足,保留膀胱手术之一的膀胱部分切除术(PC)重新受到国内外学者的关注,有可能成为治疗MIBC的主要手术方法之一。     

Expression of thymidine phosphorylase in human superficial bladder cancer

BACKGROUND: The purpose of the present paper was to investigate the expression level of thymidine phosphorylase (TPase) in superficial bladder cancer tissues obtained by transurethral resection, and determine whether its expression correlates with tumor recurrence. METHODS: From March 1998 to December 2001, 99 patients with superficial bladder cancer were diagnosed and treated at eight affiliated hospitals. Tissue specimens obtained by transurethral resection of superficial bladder cancer (TURBT) were applied to immunohistochemical study using anti-TPase antibody as well as pathological diagnosis. The data were subjected to statistical analysis. RESULTS: Using MoAb 654-1 as the primary antibody, TPase was clearly stained in human bladder cancer tissues. The maximum TPase level measured by enzyme-linked immunosorbent assay (ELISA) method in normal bladder tissues was 18.7 U/mg protein. The TPase activity was 2.8-fold higher in tumors than in normal bladder samples (P = 0.037). The TPase positivity rates determined by immunohistochemical and ELISA methods were distinctly correlated (P = 0.046). For the recurrence-free rates in pT1 tumors treated by TURBT alone (n = 46), there were no statistically significant differences between Tpase-positive or -negative cases. CONCLUSIONS: The TPase expression determined by ELISA and immunohistochemistry is significantly up-regulated in superficial bladder tumors compared with normal bladder samples. However, TPase expression by immunohistochemistry is not a predictive index of recurrence-free rate for superficial bladder cancer treated with TURBT alone.     

浅表型膀胱癌P53过度表达的预后价值

用抗Ｐ５３单克隆抗体ＤＯ－７检测４９例浅表型膀胱癌病理蜡块，获总阳性率２８．６％，（１４／４９）。其中血管浸润组阳性率６０．０％（６／１０），显著高于无血管浸润组的２０．５％（８／３９，Ｐ〈０．０５）。病理分级Ｇ１阳性率１３．６％（３／２２）Ｇ２３８．９％（８／２１）Ｇ３５０．０％（３／６），总体构成比无统计学意义，初步随访结果表明，除病理分级外，Ｐ５３阳性及血管浸润与否均与疾病进展无相关性，但Ｐ     

非肌层浸润性膀胱尿路上皮癌预后的多因素Cox回归分析

目的:探讨影响非肌层浸润性膀胱尿路上皮癌(non-muscle invasive bladder cancer,NMIBC)预后的主要相关因素及其临床意义。方法:采用回顾性分析的方法,分析川北医学院附属医院2008年1月~2011年6月间收治的174例非肌层浸润性膀胱尿路上皮癌患者的临床病例资料。患者的临床病理特征(单因素)对肿瘤复发和进展风险的影响采用Kaplan-Meier法和log-rank检验评估。选择单因素分析有意义的变量分别对肿瘤复发、疾病进展进行Cox比例风险回归模型的多因素生存分析。结果:单因素分析表明患者年龄、肿瘤个数、肿瘤分期、分级、肿瘤生长部位、术后是否即刻灌注及既往复发情况七项因素与肿瘤复发显著相关(P0.05);肿瘤直径、肿瘤分期、分级、术后是否即刻灌注及既往复发情况五项因素与疾病进展相关(P0.05)。将上述各因素分别纳入Cox风险模型中得出各因素对肿瘤复发的相对危险度分别为:肿瘤分期(RR=2.041,P=0.046)、肿瘤分级(RR=1.548,P=0.037)、术后是否即刻灌注(RR=2.335,P=0.005)、既往复发情况(RR=1.484,P=0.048);各因素对疾病进展的相对危险度分别为:肿瘤分级(RR=3.019,P=0.006)、肿瘤直径(RR=5.062,P=0.005)、既往复发情况(RR=2.345,P=0.012)。结论:与非肌层浸润性膀胱尿路上皮癌术后复发密切相关的因素包括肿瘤分期、分级、术后是否即刻灌注及既往复发情况,而膀胱肿瘤的直径、分级及既往复发情况对患者肿瘤的进展影响最大。