Experimental rat bladder urothelial cell carcinoma models

Bladder cancer is a major public health problem. Currently available therapeutic options seem to be unable to prevent bladder cancer recurrence and progression. To enable preclinical testing of new intravesical therapeutic agents, a suitable bladder tumor model that resembles human disease is highly desirable. The aim of this topic paper was to discuss the problems associated with current in vivo animal bladder tumor models, focusing on the orthotopic syngeneic rat bladder tumor model. In the second part of the paper the development of a potential new orthotopic rat bladder tumor model is described.     

膀胱癌染色体微卫星不稳定性及杂合性丢失

目的　探讨染色体微卫星不稳定性（ ＭＳＩ） 及杂合性丢失（ＬＯＨ） 在膀胱癌早期诊断中的意义。　方法　运用位于４ 、５ 、９ 、２１ 号染色体上的四对微卫星标志,结合ＰＣＲ 银染技术,分别检测２２例膀胱癌患者肿瘤组织及尿脱落细胞染色体ＭＳＩ及ＬＯＨ。　结果　肿瘤及尿液标本ＭＳＩ的发生率分别为２３ ％ 、１９ ％ ,ＬＯＨ 发生率分别为４１ ％ 、１８ ％ ,至少有一个位点出现ＭＳＩ或ＬＯＨ 分别为５９ ％ 及３２ ％ 。不同年龄、性别、临床分期、肿瘤组织分级的患者ＭＳＩ与ＬＯＨ 的发生率差异均无显著性（ Ｐ＞０ ．０５） 。　结论　检查尿液中肿瘤脱落细胞的ＭＳＩ及ＬＯＨ 可能成为膀胱癌筛选及监测复发的辅助方法。     

Plasmacytoid urothelial carcinoma of the urinary bladder report of seven new cases

INTRODUCTION: Plasmacytoid urothelial carcinoma (PUC) is a rare tumor of the urinary bladder. Its clinical and histopathological features have not been well characterized. In this study we report seven cases of PUC from our institution. MATERIALS AND METHODS: A pilot case of PUC was recently diagnosed at our institution. Cases of urothelial carcinoma (UC) were reviewed for a period of seven years to identify PUC. Representative sections from each case of PUC were submitted for immunohistochemical studies. Clinical charts were reviewed. RESULTS: There were a total of seven cases of PUC out of 260 cases of invasive urothelial carcinoma. The common type of urothelial carcinoma (CUC) was present in focal areas in five cases. Cases with extensive PUC showed coarse and indurated mucosal folds and thickened bladder walls, with no grossly identifiable tumor. Urine cytology showed a scant number of atypical single cells, frequently without tumor diathesis, leading to a shortfall in the positive cytological diagnosis. Histologically, PUC appeared as dyscohesive, plasmacytoid cells with eccentric nuclei, extending widely into the bladder walls and extensively into adjacent pelvic organs. CONCLUSION: PUC is a distinct clinical and pathological subtype of urothelial carcinoma. The clinical presentation is frequently late due to the frequent absence of hematuria and indurated mucosal surface at cystoscopy. The disease followed an ominous course with recurrence in all the patients, and with patient death.     

The role of WNT signalling in urothelial cell carcinoma

Urothelial cell carcinoma (UCC) of the bladder is one of the most common malignancies, causing considerable morbidity and mortality worldwide. It is unique among the epithelial carcinomas as two distinct pathways to tumourigenesis appear to exist: low grade, recurring papillary tumours usually contain oncogenic mutations in FGFR3 or HRAS whereas high grade, muscle invasive tumours with metastatic potential generally have defects in the pathways controlled by the tumour suppressors p53 and retinoblastoma. Over the last two decades, a number of transgenic mouse models of UCC, containing deletions or mutations of key tumour suppressor genes or oncogenes, have helped us understand the mechanisms behind tumour development. In this summary, I present my work investigating the role of the WNT signalling cascade in UCC.     

A rare case of synchronous association of chromophobe renal cell carcinoma with urothelial carcinoma of urinary bladder

Introduction

Chromophobe renal cell carcinoma accounts for 3–5% of all RCCs. However, its association with urothelial carcinoma of urinary bladder has never been reported. We report a case of synchronous association of chromophobe RCC with low grade urothelial carcinoma of urinary bladder.

尿沉渣微卫星检测在膀胱移行细胞癌诊断中的价值

目的　探讨微卫星不稳定性（ ＭＳＩ） 检测在膀胱移行细胞癌（ＴＣＣ） 诊断中的价值。　方法　采用ＰＣＲ 扩增、聚丙烯酰胺凝胶电泳、银染等技术。选用了２０ 种微卫星标记物对５０ 例ＴＣＣ 进行分析（ 每例均包括血、尿及肿瘤组织３ 种标本） 。　结果　５０ 例尿标本中４７ 例发生ＭＳＩ，阳性率为９４ ％ ，每例患者尿中微卫星改变均与原发肿瘤标本一致。　结论　尿沉渣ＭＳＩ检测技术是诊断膀胱肿瘤敏感有效的、无损伤的方法之一。     

Nomogram for predicting survival of postcystectomy recurrent urothelial carcinoma of the bladder

Purpose

We aimed to identify prognostic clinicopathological factors and to create a nomogram able to predict overall survival (OS) in recurrent urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC).

尿微卫星不稳定性研究对膀胱肿瘤诊断的探讨

目的：探讨尿微卫星不稳定性改变(MSI)与膀胱移行细胞癌(TCC)临床病理特征的关系及其在早期诊断中的价值。方法：选择36例TCC患者5个微卫星位点,应用聚合酶链反应-变性聚丙烯酰胺凝胶银染法分析尿微卫星的改变。结果：36例中有22例(61．11%)出现微卫星不稳定性改变(LOH/MSI),并与肿瘤的分期、分级无关(P＞0．05);尿脱落细胞学检查的阳性率为22．22%(8/36),两者相比差异有统计学意义(P＜0．05)。结论：尿沉渣微卫星不稳定性分析对膀胱癌的早期诊断有一定的意义,是尿脱落细胞学检查的重要补充。所选微卫星位点为本地区膀胱癌的进一步研究奠定了基础。     

The relationship between the expression of E-cadherin and tumor recurrence and progression in high-grade stage T1 bladder urothelial carcinoma

Objective To evaluate the relationship between the expression of E-cadherin (E-CD) and tumor recurrence and progression in patients with high-grade stage T1 urothelial carcinoma of bladder. Methods Fifty-two patients who had primary high-grade stage T1 urothelial carcinoma were enrolled to the study. The pathologic specimens of patients were evaluated and staged as T1a and T1b according to muscularis mucosae involvement by the tumor. The immunohistochemical demonstration of E-CD was accomplished by using immunoperoxidase method and all the specimens were examined under light microscope for E-CD level. Results The mean age of the patients was 64.0 ± 7.7 (range 36–81) years. The mean follow-up period was 56.4 ± 19.4 (range 14–84) months. Among 52 patients, 27 (52%) of them were stage T1b and 25 (48%) were T1a tumors. The recurrence rates for T1a and T1b groups were 52% (n = 13) and 92.6% (n = 25), respectively (P < 0.05). The expression of E-CD was homogenous in 52% of pT1a and 14.8% of T1b tumors (P < 0.05). In T1a group with recurrence, homogeneous E-CD staining ratio was 30.7% (n = 4/13), but it was 75% (n = 9/12) in T1a patients without recurrence (P < 0.05). In T1b group with recurrence, the homogenous expression of E-CD was 12% (n = 3/25) and the expression of E-CD was heterogenous in 88% (n = 22/25) of them (P < 0.05). In T1a group, progression of the disease was detected in 28% (n = 7/25) of the patients, but disease progression was seen in 55.5% (n = 15/27) of T1b group patients (P < 0.05). In T1a group with progression, heterogeneous E-CD staining ratio was 85.7% (n = 6/7), but it was 80% (n = 12/15) in T1b patients with progression. The effects of tumor number, tumor size and carcinoma in situ presence on recurrence were evaluated within each group. It was determined that parameters such as tumor number and tumor size had no significant effect on recurrence of the groups. The mean survival rates were statistically different between the groups. On multivariate analysis only E-cadherin expression (P = 0.012, odds ratio 6.291, 95% confidence interval for odds ratio 1.303–4.72) and tumor stage (P = 0.003, odds ratio 11.58, 95% confidence interval for odds ratio 2.446–8.542) remained independently significant as predictors of recurrence. Conclusion E-CD expression was decreased in pathologic specimens of bladder tumor patients with muscularis mucosae involvement and this condition correlated well with tumor recurrence.     

Radical cystectomy for urothelial carcinoma of the bladder without neoadjuvant or adjuvant therapy: long-term results in 1100 patients

Background

The optimal treatment strategy for muscle-invasive bladder cancer (BCa) remains controversial.

Objective

Better define the long-term outcomes of radical cystectomy (RC) alone for BCa and determine the impact of pathologic downstaging after transurethral resection in a large and homogeneous single-center series.

Design, setting, and participants

A cohort of 1100 patients undergoing RC with pelvic lymph node dissection (PLND) without neoadjuvant therapy for urothelial carcinoma of the bladder between January 1, 1986, and December 2009 was evaluated. Patients with other than metastases to the pelvic lymph nodes were excluded. Median age was 65 yr. Clinical course, pathologic characteristics, and long-term outcomes were evaluated. Follow-up was obtained until December 2009 with a median of 38 mo and a completeness of 96.5%.

Intervention

RC with PLND; urinary diversion with ileal neobladder whenever possible.

Measurements

Primary end points were disease-specific survival (DSS), recurrence-free survival (RFS), and overall survival (OS) according to the tumor stage of the RC specimen versus the maximum tumor stage. The log-rank test was used to compare subgroups.

Results and limitations

The 30-d (90-d) mortality rate was 3.2% (5.2%). The 10-yr OS, DSS, and RFS rates were 44.3%, 66.8%, and 65.5%, respectively. Based on the tumor stage of the RC specimen, the 10-yr DSS rate was pT0/a/is/1 pN0: 90.5%, pT2a/b pN0: 66.8%, pT3a/b pN0: 59.7%, pT4a/b pN0: 36.6%, and pTall pN+: 16.7%. Downstaging by transurethral resection of the prostate was observed in 382 patients. Patients with maximum tumor stage pT2a/b pN0 had distinctly better 10-yr DSS rates than those with pT2a/b pN0 in the RC specimen: pT2a pN0: 92.2% versus 73.8%; pT2b: 75.0% versus 62.0%. A total of 49% female and 80% male patients received an ileal neobladder.

Conclusions

This contemporary and homogeneous single-center series found acceptable OS, DFS, and RFS for patients undergoing RC. Pathologic downstaging had a significant impact on survival.     

肾细胞癌的微卫星不稳定性研究

目的　探讨微卫星不稳定性在肾细胞癌发生发展中的作用及其与临床病理指标的关系。　方法　应用ＰＣＲ 方法检测了３４ 例新鲜肾细胞癌标本中不同染色体上的１５ 个微卫星位点。　结果　３４ 例肾癌中有１５ 例（４４％ ）表现为微卫星不稳定性，并多见于晚期肿瘤（Ⅲ～Ⅳ期） 。　结论　微卫星不稳定性较广泛地存在于肾细胞癌中，可能与肿瘤发展相关。     

膀胱癌患者尿脱落细胞中Survivin的检测及其临床应用

目的通过对膀胱移行细胞癌（TCCB）患者尿脱落细胞中Survivin蛋白和其mRNA表达的检测，以探讨其在膀胱肿瘤早期诊断中的应用价值。方法分别采用免疫组织化学sP法和巢式逆转录-聚合酶链反应（Nested RT-PCR）方法检测48例TCCB、16例对照组（其中5例膀胱外泌尿系肿瘤患者、5例非肿瘤泌尿系疾病患者及6例健康者）尿脱落细胞Survivin的蛋白和mRNA表达，同时行尿脱落细胞学检查。结果48例TCCB患者中尿脱落细胞Survivin蛋白与mRNA阳性表达率分别为42例（87．5％），47例（97．9％）；对照组仅1例BPH患者mRNA阳性表达（3．1％）。TCCB组与对照组Survivin阳性率比较差异有统计学意义（P〈0.01）。免疫组织化学和RT—PCR法检测尿液中Survivin的敏感性和特异性分别为87．5％、97．9％和72．7％、93．8％。而尿脱落细胞学检查阳性率为28例（58．3％），其敏感性和特异性分别为58．3％和100．0％。结论尿脱落细胞Survivin检测诊断TCCB敏感性和特异性均较高，且无创，无痛苦，可作为早期诊断TCCB的敏感指标，其中RT-PCR检测方法敏感性更高。     

Detection of urothelial carcinoma,upper tract urothelial carcinoma,bladder carcinoma,and urothelial carcinoma with gross hematuria using selected urine-DNA methylation biomarkers: A prospective,single-center study

Introduction

Hematuria is the most common symptom of urothelial carcinomas (UC) but is often idiopathic. Cystoscopy is expensive which involves considerable patient discomfort, and conventional urine cytology for noninvasive UC detection and disease monitoring suffers from poor sensitivity. We aim to evaluate the performance of genes selected from a previous study in detecting UC, especially among patients with gross hematuria, as well as upper tract urothelial carcinoma (UTUC) and bladder carcinoma separately, in voided urine samples.

Urinary markers in bladder cancer

OBJECTIVES: Many markers for the detection of bladder cancers have been tested. Almost all urinary markers reported are better than cytology with regard to sensitivity, but they score lower in specificity. The purpose of this review is to highlight the most important urinary biomarkers studied and reported recently. METHODS: Literature on bladder cancer markers has been reviewed regularly in the last few years. In the current review we have tried to summarise the most recent literature of urinary markers. RESULTS: The results of this review show that the first-generation urinary markers did not add much to urinary cytology. The current generation of markers is promising but larger clinical trails are needed. The future of marker development is bright with new techniques emerging, but the perfect marker is still to be found. CONCLUSION: Currently, no single marker can yet guide us in surveillance and lower the frequency of urethrocystoscopy.     

Clinico-pathological features of bladder carcinoma: Experience from a tertiary care hospital of Pakistan

Bladder carcinoma is most common urological malignancy in Pakistan. The objective of the study was to determine the clinico-pathological characteristics of histologically confirmed bladder carcinoma at a tertiary care hospital of South Punjab, Pakistan. Methods: In two hundreds and twenty one patients (172 male and 49 female) bladder carcinoma was diagnosed from Jan 1998 to June 2005. All patients were evaluated with regards to clinical presentation, cystoscopic findings and histo-pathological data. Results: Male female ratio was 3.5:1. The median age was 58 years (range 18–87 years). 65% men had history of cigarette smoking while 51% women had long history of smokeless tobacco (nasal snuff or chewable) use. Most patients presented with painless hematuria. Primary transitional cell carcinoma was the most common (i.e. 96%) histological variety of bladder carcinoma. 63% patients had muscle invasive disease at the time of presentation. Even in superficial bladder carcinoma, most patients had invasion of lamina propria (pT1 disease). Conclusion: More than 90% of primary bladder carcinoma are of transitional cell variety and over 60% having muscle invasive disease at the time of diagnosis. Even in patients with superficial disease, majority (i.e. 98%) have invasion of lamina propria.     

GC化疗方案在不同转移性尿路上皮癌中的临床疗效观察

目的总结吉西他滨+顺铂(Gemcitabine+Cisplatin,GC)化疗方案在尿路上皮癌(urothelialcellcarcinoma,UCC)中的临床治疗效果,以期提高晚期UCC患者的生存质量。方法回顾分析52例转移性UCC患者接受GC方案化疗后的临床资料。化疗效果参照实体瘤的疗效评价标准进行评价,化疗毒副作用按照WHO化疗毒副作用分级标准进行评价。结果 GC方案对转移性UCC患者总有效率为48.1%,其中单纯淋巴结转移患者的化疗有效率为64.3%,脏器转移者仅为29.2%。化疗中44.2%的患者出现Ⅱ度以上的骨髓抑制。随访时间平均17.6个月。统计分析表明单纯淋巴结转移较脏器转移患者化疗效果更好,生存期更长。结论 GC方案对晚期UCC的化疗效果肯定,化疗毒副作用小,但是要准确评估患者的体能状态和肾功能,谨慎选择合适的化疗对象。     

Blood- and tissue-based biomarkers for prediction of outcomes in urothelial carcinoma of the bladder

ObjectivesUrothelial carcinoma of the bladder (UCB) is a highly heterogeneous malignancy that causes significant morbidity and mortality. Standard pathologic features (stage, grade, and nodal status) are insufficient to predict accurately a patient's outcome. Biomarkers could help clinicians provide individualized prognostications and allow risk-stratified clinical decision making regarding surgical and medical treatment. This review summarizes the existing tissue- and blood-based biomarkers in UCB.Material and methodsA PubMed/Medline search was conducted to identify original articles regarding molecular biomarkers and UCB. Searches were limited to papers published in English. Keywords included urothelial carcinoma, bladder cancer, transitional cell, biomarker, marker, staining, cystectomy, recurrence or progression, survival, prediction, and prognosis.ResultsThe articles with the highest level of evidence were selected and reviewed, with the consensus of all the authors of this paper.ConclusionsThere is no doubt that a panel of biomarkers would eventually improve our clinical decision making regarding treatment and follow-up. However, to date, no biomarker panel is yet validated for daily clinical practice.     

WISP1 genetic variants as predictors of tumor development with urothelial cell carcinoma

Objectives

Urothelial cell carcinoma (UCC) of the urinary bladder is a major malignancy of the genitourinary tract. Etiological factors, such as the environment, ethnicity, genetics, and diet, contribute to UCC carcinogenesis. WNT1-inducible signaling pathway protein 1 (WISP1), also known as CCN4, a cysteine-rich protein belonging to the Cyr61, CTGF, Nov (CCN) family of matricellular proteins, has many developmental functions and might be involved in carcinogenesis. This study investigated WISP1 single-nucleotide polymorphisms to evaluate UCC susceptibility and clinicopathological characteristics.

Human TLR gene family members are differentially expressed in patients with urothelial carcinoma of the bladder

Purpose

Toll-like receptors (TLRs) have an important role in the activation of both innate and adaptive immunity in response to pathogens and endogenous danger signals from damaged or dying cells. The aim of this study was to determine the relationship between urothelial carcinoma (UC) and TLR expression.