Bladder preservation for locally advanced bladder cancer by transurethral resection, systemic chemotherapy and radiation

Twenty-three out of 31 patients with clinical T2-4a N0 M0 bladder cancer and given a trial of trimodality therapy including transurethral resection (TUR), systemic chemotherapy and radiation between 1991 and 2002 completed this therapy. The other 8 dropped out because of insufficient clinical effect. Local bladder recurrence was seen in 3 patients and the bladder preservation rate was 64.5%. Nineteen of the 23 patients showed a complete histological response on a subsequent TUR specimen, the other 4 were not examined for histological response. Thirteen of the 19 patients showed a complete histological response after maximal TUR and systemic chemotherapy, while 6 did after TUR, chemotherapy and radiotherapy. Bladder cancer was T2 in, 15, T3 in 1, and T4a in 3 patients. The CR rate for T2 cancer was significantly higher than that for T3-4a cancer. The 5-year disease-specific survival of the 23 patients treated with preservation therapy was 67.1%. Some of the patients with locally advanced bladder cancer may benefit from this preservation therapy.     

Three cases of small cell carcinoma of the urinary bladder: a case report

We report three cases of small cell carcinoma of the urinary bladder. Case 1: A 69-year-old man showed microscopic hematuria during follow up of prostate cancer of stage D2. The patient was diagnosed with small cell carcinoma of the urinary bladder at the stage of pT2N0M0. Complete remission was achieved by three courses of chemotherapy consisting of irinotecan and carboplatin. The patient was died by prostate cancer 16 months after the chemotherapy. Case 2: An 83-year-old woman presented with macroscopic hematuria. The patient was diagnosed with small cell carcinoma of the urinary bladder at the stage of pT2N0M0 and partial cystectomy was performed. The patient has been alive without any evidence of tumor recurrence at 6 months after surgery. Case 3: An 84-year-old man presented with macroscopic hematuria. The patient was diagnosed with small cell carcinoma of the urinary bladder at the stage ofcT3bN0M1 with multiple liver metastases. Complete remission was achieved by three courses of chemotherapy consisting of etoposide and carboplatin.     

The role of surveillance in the treatment of patients with muscle‐invasive bladder cancer after chemotherapy

Study Type – Prognosis (case series)
Level of Evidence 4

OBJECTIVE

To determine the survival of patients at our institution who were clinically tumour‐free (cT0) on re‐staging transurethral resection (TUR) after treatment with chemotherapy for muscle‐invasive bladder cancer.

PATIENTS AND METHODS

In all, 55 patients with muscle‐invasive, organ‐confined transitional cell carcinoma of the bladder were treated with TUR followed by systemic chemotherapy, over a 10‐year period. Patients were separated into two groups, those who were clinically T0 and those who showed persistent disease (>cT0) on re‐biopsy after chemotherapy. Overall and disease‐specific survival rates were calculated for the two groups. The cT0 group was further followed for tumour recurrence and clinical outcomes.

RESULTS

Thirty‐one patients (56%) were clinically T0 on TUR after chemotherapy; of these patients, 22 (71%) either died from other causes (with no disease recurrence) or are alive and with no evidence of disease at a mean follow‐up of 53 months. Twenty of the 31 patients (65%) have retained their bladder with no evidence of cancer recurrence at a mean follow‐up of 46 months. Disease‐free status (cT0) at the time of TUR after chemotherapy was associated with significantly higher overall and cancer‐specific survival (hazard ratio 3.40, P = 0.003; and 8.63, P = 0.001, respectively).

CONCLUSION

Previous studies suggest that surveillance can be a reasonable option for patients with muscle‐invasive transitional cell carcinoma of the bladder who show no evidence of disease on TUR after chemotherapy. Patients with persistent bladder cancer on re‐biopsy after chemotherapy tend to fare poorly even with immediate cystectomy.     

保留膀胱综合方法治疗肌层浸润性膀胱癌的疗效评价

目的探索保留膀胱手术＋膀胱内灌注化疗＋动脉灌注化疗治疗浸润性膀胱癌的临床疗效。方法 2003年5月至2012年2月,对经尿道膀胱肿瘤电切或膀胱部分切除后确诊为肌层浸润性膀胱癌（T2N0M0）的56例保留膀胱的患者,给予动脉灌注化疗加膀胱灌注化疗。结果 56例患者均获得随访,随访6～98个月,平均（36.0±3.2）个月,53例（94.6%）患者无复发及转移,3例（5.4%）分别在术后6、8、12复发,复发患者均给于全膀胱切除术,无死亡病例,没有明显并发症。结论保留膀胱手术后确诊的肌层浸润性膀胱癌患者,采用经髂内动脉灌注化疗＋膀胱内灌注化疗的联合治疗方法,能有效减少肿瘤复发,显著降低静脉化疗的副作用,提高患者的生活质量,患者易于接受,值得进一步探讨。     

Late metastases of prostatic adenocarcinoma to urinary bladder after radical prostatectomy: a case report]

We report a case of metastasis of prostatic cancer to urinary bladder. A 67-year-old man was admitted with a complaint of macroscopic hematuria, who had undergone radical prostatectomy and surgical castration for prostatic cancer (pT3N0M0) 53 months before. Computed tomographic (CT) scan revealed an invasive tumor on the right wall of the urinary bladder and swelling of paraaortic and pelvic lymph node metastases. These lesions were diagnosed as bladder tumor with lymph node metastases, and then transurethral biopsy of bladder tumor was performed. Because macroscopic hematuria could not be controlled and severe progressive anemia was found after the biopsy, simple cystectomy and bilateral cutaneoureterostomy were performed on the next day. Histopathological analysis showed that the tumor was adenocarcinoma, which was thought to be a metastatic tumor from the prostatic cancer.     

膀胱尿路上皮癌组织中HMGA2蛋白表达及其临床意义

目的 探讨高迁移率族蛋白A2(high mobility group protein A2,HMGA2)在膀胱癌组织中的表达情况,并分析其与临床病理特征及复发的关系.方法 膀胱尿路上皮癌标本148例,正常膀胱组织标本30例,采用免疫组织化学方法检测2组标本组织中HMGA2蛋白的表达,并结合临床资料进行分析.结果 正常膀胱组织中无HMGA2蛋白表达,肿瘤组织中随病理分级和分期增加,HMGA2蛋白相对表达量逐渐增高.HMGA2蛋白在G1、G2、G3组织中表达阳性率分别为21.3%、60.3%、82.1%,差异有统计学意义(P＜0.001).非肌层浸润性膀胱尿路上皮癌和肌层浸润性膀胱尿路上皮癌中HMGA2蛋白表达的阳性率分别为43.3%和72.7%,差异有统计学意义(P=0.003).随访2～95个月,复发64例,复发组与未复发组中HMGA2蛋白表达阳性率分别为54.7%和25.0%,差异有统计学意义(P=0.007).结论 HMGA2蛋白表达在膀胱癌组织中明显高于正常组织,HMGA2蛋白表达与膀胱癌的分级、分期、复发有关;与患者年龄、性别、肿瘤数目无相关性.检测HMGA2蛋白有助于膀胱癌的诊断及预后的评估.

Abstract：

Objective This study was to explore the expression and significance of HMA2 in bladder cancer , analyze its correlations to clinicopathologic and recurrence of bladder cancer. Methods The expression of HMGA2 protein in 148 specimens of bladder cancer and 30 specimens of normal bladder tissues was detected by immunohistochemtry, its correlations to clinicopathologic features was analyzed. Results There was no expression of HMGA2 protein in normal bladder tissues,while the expression level of HMGA2 protein was getting higher with the increase of tumor pathology grade and stage. The positive rate of HMGA2 protein was 21.3% in G1 bladder cancer, 60. 3% in G2 bladder cancer, 82.1% in G3 bladder cancer, its difference is significant (P＜0. 001). It was significantly lower in non-muscle invasive bladder cancer than in muscle invasive bladder cancer (43.3% vs 72. 7%, P=0. 003). The patients were followed up for 2～95 months, patients of recurrence was 64,HMGA2 protein expression was significantly higher in patients with recurrence than with non-recurrence (54.7% vs 25.0%, P=0. 007). Conclusions The expression of HMGA2 protein was highly in bladder cancer, the positive rate of HMGA2 protein expression was related with classification,TMN stage and recurrence, but not with sex, age, tumor number (P＞0. 05). The detection of the expression of HMGA2 protein is in favor of diagnosis and prognostic evaluation of bladder cancer.     

p53PIN3基因多态性与膀胱移行细胞癌发病风险关系的研究

目的:探讨p53第3内含子16bp插入/缺失多态性与膀胱移行细胞癌发病风险的关系。方法:采用序列特异性引物,以PCR方法检测90例膀胱移行细胞癌患者和110例健康对照个体外周血DNA p53基因第3内含子的基因型。结果:膀胱癌组与对照组p53基因第3内含子16bp插入或缺失序列(PIN3)的A、A′等位基因频率分别83.33%、11.67%及96.36%、3.64%,两组比较差异有统计学意义(P<0.05);两组中三种基因型频率分别为76.67%、23.33%、0和92.73%、7.27%、0,分布差异有统计学意义(P<0.05)。膀胱移行细胞癌按临床分期比较:浅表性癌、浸润性癌突变与野生基因型差异有统计学意义(P<0.05);按病理分级比较:G1～G2、G3突变与野生基因型差异有统计学意义(P<0.05);按性别和年龄分组:两组突变与野生基因型频率比较差异均无统计学意义(P>0.05)。结论:p53第3内含子16bp插入/缺失多态性与膀胱癌发病风险存在相关性,可能是膀胱移行细胞癌患病的易感基因。     

两种方法行THP膀胱内灌注预防膀胱癌术后复发的疗效观察

目的：探讨膀胱癌术后大剂量吡喃阿霉素（THP）膀胱内灌注时保留时间对肿瘤复发和对人体安全性的差异。方法：将45例浅表性膀胱癌经尿道膀胱肿瘤电切术或膀胱部分切除术病人随机分对照组（24例）、观察组（21例），二术后2周开始应用THP（40mg/40ml）膀胱内灌注，观察组灌注后药物在膀胱内保留30min；对照组保留2h。结果：两组病人随访7－26个月，复发率比较，P＞0．05，差异无显著性意义；所有病人均能耐受THP膀胱内灌注；两组灌注后不同保留时间全身不良反应比较，均P＞0．05，差异无显著性意义；尿频、尿痛等膀胱刺激症和迟发性不良反应（尿道狭窄和前列腺炎）两组比较，P＜0．05，观察组明显低于对照组。结论：膀胱癌术后应用THP膀胱内灌注预防肿瘤复发效果显著，药物在膀胱内保留时间短，对膀胱、尿道刺激性小，不良反应少。     

Assessment of QOL and survival for patients undergoing radical cystectomy or bladder preservation for invasive bladder cancer]

PURPOSE: In this study, we have retrospectively compared patient backgrounds, prognosis and QOL (quality of life) in patients with invasive bladder cancer treated by radical cystectomy or by bladder preservation. PATIENTS AND METHODS: This study enrolled recent 30 cases from each institutions, totally 120 cases from four institutions. All patients were diagnosed with invasive bladder cancer in stage T 2 or T 3, N 0, M 0. The patients planned for preserving the bladder were treated with a combination of intra-arterial chemotherapy and radiation as an induction therapy. The questionnaire used to assess QOL was the EORTC QLQ-C 30 (Japanese-language edition). RESULTS: Radical cystectomy was selected as the initial treatment in 60 cases (the planned radical cystectomy group). Bladder preservation was planned but the presence of residual tumors after induction therapy underwent radical cystectomy in 18 cases (the preservation-radical cystectomy group). Bladder preservation was achieved in 42 cases (the preservation group). In a comparison of background factors, histologically grade 3 tumor and cases with histology other than transitional cell carcinoma, were significantly common in the planned radical cystectomy group. Because this study is not an randomized test, it is difficult to compare the outcomes between the patients treated by radical cystectomy or by bladder preservation. However, it is indicated that the candidates for bladder preservation therapy exist among the patients with T 2 or T 3, N 0, M 0 bladder cancer. Quality of life, as evaluated from global QL and from physical, cognitive, and emotional function, tended to be better in the patients with their bladder, although no difference was noted among the groups with regard to life role or social function. Symptoms such as sleep disturbance and diarrhea were common in the radical cystectomy groups, and financial impact, constipation, appetite loss, and dyspnea also tended to more frequently affect patients in these groups. CONCLUSION: Our results indicate that bladder preservation treatment using an induction therapy is one of option of the treatment for clinically T 2 or T 3, N 0, M 0 bladder cancer. We need a prospective randomized study with a long-term follow-up to elucidate true candidates for this treatment.     

茶多酚对人膀胱癌细胞光动力学杀伤效应的影响

目的 :探讨茶多酚对人膀胱癌细胞叶绿素衍生物光动力学杀伤效应的影响。 方法 :采用MTT比色分析法 ,判断茶多酚影响体外人膀胱癌T -2 4和SCaBER细胞光动力学的杀伤效应。 结果:与单纯光动力学作用组比较 ,茶多酚能显著减弱叶绿素衍生物光动力学对两种人膀胱癌细胞的损伤 (P <0 0 5,0 0 1) ,茶多酚的作用时间与光动力学对T -2 4细胞杀伤效应呈负相关 ,而与SCaBER细胞却无相关性。 结论 :茶多酚具有较强的缓解膀胱肿瘤细胞光动力学杀伤效应的作用     

Adenovirus mediated gelsolin gene therapy for orthotopic human bladder cancer in nude mice

PURPOSE: Gelsolin is an actin regulatory protein that is undetectable or reduced in human bladder tumors compared with normal epithelial cells. Whether the over expression of gelsolin could inhibit tumor growth was investigated in an orthotopic bladder cancer nude mouse model using recombinant adenovirus encoding wild-type gelsolin (Ad-GSN). MATERIALS AND METHODS: The 2 human bladder cancer cell lines KU-7 and UMUC-2 were transduced with Ad-GSN in vitro. Flow cytometric analysis was done to examine the cell cycle after transducing the adenovirus. Cell growth was compared with control groups of these cells transduced with adenovirus containing the Escherichia coli beta-galactosidase gene Ad-betagal. In vivo KU-7 cells were introduced into the bladder of nude mice (day 0), followed by 3 injections into the urethra (days 2 to 4) with Ad-GSN or Ad-betagal (1 x 10 pfu). At 8 days after initial adenovirus exposure (day 10) each bladder was sectioned and stained, and the mass of the tumor was digitally determined. RESULTS: Bladder cancer cell growth (KU-7 and UMUC-2) was inhibited after these cells were transduced with Ad-GSN in vitro. Based on flow cytometric analysis over expression of gelsolin may cause these cells to arrest or delay at the G2/M phase of the cell cycle. In the orthotopic bladder cancer model the mass of the tumor was approximately 90% less in Ad-GSN treated animals than in controls. CONCLUSIONS: Ad-GSN provides a significant tumor suppressive effect on human bladder cancer cells in this orthotopic nude mouse model. Adenovirus mediated over expression of gelsolin may be useful therapy for human bladder cancer.     

新辅助介入化疗联合微创手术治疗浸润性膀胱癌

目的 探讨新辅助介入化疗联合腔内手术治疗浸润性膀胱癌的临床效果.方法 对31例确诊为肌层浸润性膀胱癌（T2~4/G1~3）的患者行新辅助性介入化疗,先经股动脉入髂内动脉,尽可能到达供应肿瘤血管,给予丝裂霉素10 mg,吉西他宾1.0/m2,顺铂90 mg,明胶海绵暂时性封堵后拔管,1周后行经尿道膀胱肿瘤汽化电切术,术后即刻用丝裂霉素200 mg或吡柔比星40 mg膀胱灌注.结果 21例治疗1次,7例治疗2次（间隔1个月）,3例治疗3次（间隔1~2个月）.31例随访4个月~4年,平均36个月,2例术后6、10个月复发,再次重复治疗,1例因盆腔转移治疗2次后拒绝治疗,半年后死于肺转移,其余未见肿瘤复发.结论 对于局限浸润性膀胱癌的患者,采用新辅助性经髂内动脉插管介入化疗联合腔内手术治疗疗效满意.     

Laparo-endoscopic single-site (LESS) radical nephrectomy with renal vein thrombectomy: initial report

Background

The aim of the following study is to evaluate the advancement of incidentally diagnosed prostate cancer in specimen after cystoprostatectomies caused by muscle-invasive bladder cancer. Secondly we assessed the survival in patients after radical cystoprostatectomy whose postoperative specimen was characterized by the presence of co-existing prostate cancer or prostate infiltration by urothelial bladder cancer.

Methods

Between 1993 and 2009 a total of 320 patients with muscle-invasive bladder cancer underwent cystoprostatectomy. The first analyzed group consisted of 52 patients with bladder cancer infiltrating prostate, while the second group consisted of 21 patients with co-existing prostate cancer. In all patients cancer specific survival and progression were analyzed. Average follow up was 75.2 months (range: 0 - 181).

Results

Cancer-specific survival was significantly shorter in group I (p = 0.03). Neoplastic progression in patients from group I was observed in 42.2% of patients, while in patients from group II in 23.6% of patients (p = 0.04). No statistical difference was observed in the percentage of positive lymph nodes between the groups (p = 0.22). The median Gleason score in patients with co-existing prostate cancer was equal to 5. The stage of prostate cancer pT₂/pT₃ was equal to 20 (96%)/1 (4%) patients. 12 (57%) prostate cancers were clinically insignificant. Biochemical recurrence occurred in 2 (9%) patients.

Conclusions

1. Incidentally diagnosed prostate cancer in specimen after cystoprostatectomies is frequently clinically insignificant and characterized by low progression.
2. Patients with bladder cancer infiltrating prostate are characterized by higher percentage of progression and death in comparison with patients with co-existing prostate cancer.

     

浅表性膀胱癌保留膀胱术后预后影响因素分析

目的 探讨浅表性膀胱肿瘤术后预后的各种影响因素.方法 回顾性分析186例浅表性膀胱肿瘤患者保留膀胱手术治疗的资料,研究肿瘤临床病理特征及治疗措施对手术预后的影响.结果本组病例中,复发65例,初诊时为多发、大于3 cm、病理为G2级以上的高危肿瘤复发率分别要高于单发、小于3 cm、病理为C1级的中低危肿瘤;对于保留膀胱的...     

Fibulin-5表达对膀胱癌细胞迁移和侵袭能力的影响

目的 探讨fibulin-5表达在膀胱尿路上皮癌中的影响作用. 方法 经尿道切除获取膀胱尿路上皮癌标本20例,其中低级别(G_1和G_2)13例、高级别(G_3)7例.蛋白质印迹法检测fibulin-5在膀胱尿路上皮癌和正常膀胱黏膜组织中的表达.将PCR扩增的fibulin-5 cDNA克隆到pMD-19T载体中,构建p-EGFP-fibulin-5质粒.脂质体介导法将p-EGFP-fibulin-5质粒转染到人膀胱癌5637细胞株内,流式细胞仪分选,经G418筛选形成稳定的表达克隆.Boyden小室法检测未转染、转染空载体和转染fibulin-5的膀胱癌细胞迁移和侵袭能力. 结果 正常膀胱黏膜、低级别和高级别膀胱尿路上皮癌组织中fibulin-5蛋白相对表达量分别为1.16±0.28、0.57±0.32和0.44±0.42.与正常膀胱黏膜相比,膀胱癌组织中fibulin-5蛋白表达显著下调(P<0.01),低级别和高级别癌之间差异无统计学意义(P>0.05).转染成功的膀胱癌5637细胞显示绿色荧光.未转染、转染空载体和转染fibulin-5的膀胱癌细胞的迁移细胞数分别为136.9±5.7、139.3±7.7和127.6±3.1,侵 袭细胞数分别为31.7±4.7、31.5±4.8和8.05±3.1.转染fibulin-5后膀胱癌细胞侵袭力明显降低 (P<0.01),其迁移力虽低于对照组但差异无统计学意义(P>0.05). 结论 Fibulin-5蛋白表达减 少可能是膀胱癌发生和发展的机制之一,过表达fibulin-5可以抑制膀胱癌细胞侵袭力.     

Small cell neuroendocrine carcinoma of the urinary bladder: a case report]

A 60-year-old male was referred to our hospital with a complaint of asymptomatic gross hematuria. Cystoscopic examination revealed a non-papillary broad-based tumor on the posterior wall of the urinary bladder. Computed tomography revealed no evidence of metastases. Transurethral resection of bladder tumor (TUR-BT) was performed and muscle invasion was detected by histological examination of the specimen. Total cystectomy and ileal conduit formation were performed at the preoperative diagnosis of T2-3N0M0. Hematoxylin-eosin staining of the specimen revealed small cancer cells with hyperchromatic nucleus and scanty cytoplasm growing in the muscle layer of the urinary bladder and in the left obturator lymph nodes. Immunohistochemistry for neurospecific enolase showed diffuse staining in the cytoplasm of cancer cells, and ultrastructural study showed dense core granules. From these findings, the patient was diagnosed with small cell neuroendocrine carcinoma of the urinary bladder at the stage of pT3bpN1M0. Three courses of adjuvant chemotherapies with cis-platinum (CDDP) and etoposide were administered. The patient is still alive with no evidence of any recurrence at 22 months after the operation. This case suggests that treatment with combined total cystectomy and adjuvant CDDP and etoposide chemotherapies is effective against neuroendocrine carcinoma of the urinary bladder with regional lymph node metastases.     

上尿路移行细胞癌术后发生膀胱癌的危险因素分析

目的探讨上尿路移行细胞癌临床与病理特点及对术后膀胱癌发生及预后的影响.方法对133例肾盂和(或)输尿管癌病例的临床特点与术后发生膀胱癌以及预后情况分别应用Cox比例风险模型分析,作Kaplan-Meier曲线并行LogRank检验.结果133例患者接受根治手术后发生膀胱癌者40例,占30.1%.原发上尿路肿瘤数目、分期和有无同发膀胱癌对术后发生膀胱癌有显著影响,风险度>1,回归系数>0,二者间相关系数小.应用LogRank检验显示原发肿瘤为单发者术后无膀胱癌发生的机率低于多发者(P=0),随着病理分期的升高,膀胱癌发生率随之增加(P＝0.0039).首次发生膀胱癌者有92.5%在2年之内.原发肿瘤数目、分期、有无同发膀胱癌以及术后膀胱癌发生间隔时间对存活率有显著影响,四种因素的相关系数小.结论原发上尿路肿瘤的数目、分期和有无同发膀胱癌为术后发生膀胱癌的危险因素;原发肿瘤数目、分期、有无同发膀胱癌以及术后膀胱癌发生间隔时间对存活率有显著影响.     

Usefulness of PSA screening in outpatients with bladder cancer: Preliminary results

BACKGROUND: We performed prostate-specific antigen (PSA) screening and evaluated its usefulness in outpatients with bladder cancer who may have an elevated risk for prostate cancer. METHODS: Sixty-one new or followed-up outpatients with bladder cancer were examined between September 1999 and December 2000 in the Department of Urology, Gunma University Hospital, Japan. PSA was measured after informed consent was obtained, and patients in whom the PSA level was 4.1 ng/mL or higher were selected for thorough examination. In the examination, one examiner performed DRE (digital rectal examination) and, based on DRE and TRUS (transrectal ultrasonography) findings, determined whether prostate biopsy was indicated. RESULTS: The average age of the 61 cases was 69.1 +/- 8.6 years, and the average PSA level was 3.5 +/- 5.8 ng/mL. The PSA level was 4.1 ng/mL or higher in 11 (18.0%) patients, nine of whom underwent six-sextant biopsy under TRUS guidance. Of these nine cases, four (6.6%) were diagnosed as having prostate cancer. The Gleason score was 7 in three cases and 9 in one case. The clinical stage was T2N0M0 in three cases and T3N0M0 in one case. CONCLUSIONS: On PSA screening in patients with bladder cancer and patients with a history of transurethral resection of the bladder tumor (TUR-BT), prostate cancer was found in 6.6%. This rate is higher than in the general population. These cancers were classified into intermediate to high-risk groups, and the prognosis of prostate cancers could be more important than those of the bladder cancers in two cases (50%). We conclude that PSA screening for inpatients with bladder cancer may be useful.     

光动力疗法对人膀胱癌细胞胞内游离钙的影响

目的:探讨光动力学作用后的膀胱癌细胞(T-24和SCaBER)胞内钙离子浓度的变化.方法:采用MTT比色分析法判断光动力学对体外人膀胱癌T-24和SCaBER细胞的杀伤效应.同时应用激光共聚焦显微镜和Fluo-3/AM探针技术测定光动力学作用后细胞内钙离子的浓度.结果:T-24和SCaBER细胞内钙离子有明显升高,与对照组比较差异有显著意义(P＜0.001).结论:光动力学作用后细胞内钙离子超载可能在细胞死亡中发挥重要作用.