Patterns of failure and influence of potential prognostic factors after surgery in transitional cell carcinoma of the upper urinary tract

Background  We investigated the long-term outcome of upper urinary tract transitional cell carcinoma (TCC) after surgery. Methods  The study population comprised 114 surgically treated patients with upper urinary tract TCC treated at Jikei University Hospital between March 1990 and December 2004. All these patients underwent radical surgery without any type of neoadjuvant therapy. Patterns of failure and patient survival were compared with clinicopathological parameters. Results  The 5- and 10-year overall survival (OAS) rates for the patients were 85% (95% confidence interval [CI], 81%–89%) and 76% (95% CI, 69%–83%). To date, 19 patients (16.7%) have experienced distant or lymph node metastasis at a mean of 13.3 months following surgery (range, 1 to 50 months). The site of the primary tumor did not affect patient survival (P > 0.05). Both lymphovascular involvement (LVI) and positive lymph nodes were found to have poor prognosis in univariate analysis (P = 0.004 and P < 0.0001). Multivariate analysis indicated pathological stage and bladder recurrence (bladder recurrence being a better prognostic factor) to be independent predictors of metastasis-free survival, but not of OAS or cause-specific survival (CSS). Conclusion  Pathological stage and bladder recurrence were found to be the predictors of metastasis-free survival in this study. Further searching for reliable biomarkers is needed to accurately predict the prognosis of this malignancy.     

Recurrence risk factors in patients with transitional cell carcinoma of bladder

Objective： To study recurrence factors and set up a model to evaluate the prognosis of patients with bladder cancer. Methods： An analysis on recurrence-related factors was made by Cox＇s proportional hazards model analysis and logistic multiple linear regression model analysis in 212 patients with transitional cell carcinoma treated surgically from 1995-2001. These factors included clinical and pathologic figures. Results： The most important factor is metastasis to the regional lymph nodes, the Hazards ratio is 6.6 （P=0.0004）, followed by multiple tumors （Hr=2.255, P〈0.0001）, tumor in trigone and bladder neck （Hr=2.053, P〈0.0001）, stage （Hr=2.057, P〈0.0001）, grade （Hr=1.569, P=0.0081）, intravesical chemotherapeutic instillations （Hr-0.559, P=0.0011） and hematuria （Hr=0.762, P=0.0076）. A predicting equation was established, and the predicting values were calculated according to the individual features of patients. The predicting and actual values were compared, and the sensitivity, specificity and overall concordance were 83.5%, 67.6% and 80.1% respectively. Conelusion：The evaluation of prognosis could be made quite accurately based on these factors.     

Prognostic relevance of disseminated tumour cells in bone marrow of patients with transitional cell carcinoma

ObjectiveThis prospective study is the first immunocytochemical investigation of the frequency and prognostic value of CK+ tumour cells in the bone marrow of patients with transitional cell carcinoma (TCC).MethodsBone marrow aspirates from 228 TCC patients were taken preoperatively. Cytospins were made and stained by immunocytochemistry using the monoclonal antibodies CK2 and A45-B/B3. 27 patients with no evidence of any malignant disease served as control group.ResultsCK+ tumour cells were detected in 28% (63/228) of the TCC patients. No CK+ cells (0/27) were detected in the control group. In multivariate analysis the detection of ⩾3 CK+ cells in bone marrow was an independent prognostic factor (hazard ratio = 2.7, p < 0.05) in patients with T2–4 tumour classification.ConclusionDisseminated CK+ cells play a role in the biology of tumour spread of TCC, and their immunocytochemical detection can be useful in assessing the prognosis of TCC patients with an invasive tumour.     

野生型PTEN基因高表达对膀胱移行细胞癌EJ细胞的抑癌作用

目的 探讨外源性野生型人酪氨酸磷酸酶（PTEN）基因的高表达对膀胱移行细胞癌EJ细胞的抑癌作用。方法 利用携带人PTEN基因的野生型、磷酸酶域突变型质粒体外分别转染人膀胱移行细胞癌EJ细胞。Western blot检测目的基因PTEN的表达,观察细胞形态变化及超微结构变化;MTIO法检测细胞增殖率及转染细胞对吡柔比星（THP）和丝裂霉素（MMC）的敏感性;Western blot法检测bcl-2蛋白的表达。以空载质粒作为对照。结果 质粒转染后,EJ细胞的PTEN蛋白表达上升75．0％。转染野生型质粒后,EJ细胞异型性低,出现典型凋亡小体,细胞增殖率下降40．1％,bcl-2蛋白表达被下调,并提高了对THP和MMC的敏感性。而转染突变型质粒的EJ细胞则无此作用。结论 野生型PTEN基因在体外对膀胱移行细胞癌EJ细胞增殖有明显抑制作用,诱导细胞凋亡,磷酸酶域突变型PTEN基因无此作用。野生型PTEN的抑癌作用可能与其对bcl-2蛋白表达的下调有关。     

纤维粘连蛋白在膀胱移行细胞癌中的表达

本文应用ＡＢＣ免疫组织化学方法对４９例膀胱移行细胞癌中的纤维粘连蛋白（ＦＮ）作了研究。结果发现：ＦＮ的分布形式有细胞周、间质及细胞浆三种形式：随着移行细胞癌组织学分级的增高，细胞周ＦＮ及间质ＦＮ逐渐减少，而胞浆ＦＮ则有所增加。结果提示：这些变化可能是膀胱移行细胞癌浸润转移的重要基础；并可能与预后有一定关系。     

MMP2活性测定在判断膀胱移行细胞癌侵袭性中的意义

背景与目的:活性基质金属蛋白酶2(matrixmetalloproteinase2,MMP2)在细胞外基质(extracellularmatix,ECM)和基底膜(basementmembrane,BM)降解、促进肿瘤的侵袭转移中具有重要作用,但在膀胱移行细胞癌(bladdertransitionalcellcarcinoma,BTCC)中MMP2活性与其侵袭性的关系尚不清楚。本研究旨在探讨活性MMP2对判定BTCC侵袭性的意义。方法:运用半定量明胶酶谱法对20例BTCC组织和4例正常膀胱粘膜组织中活性MMP2的含量进行检测,并对结果进行分析。结果:20例BTCC组织中19例检测到MMP2的活性,随着BTCC分级和侵袭能力的增强,MMP2活性亦明显升高,11例G1期肿瘤MMP2比活为(8896.5±1655.6)(mg·ml-1)-1,5例G2期肿瘤比活为(18355.6±5307.1)(mg·ml-1)-1,3例G3期肿瘤比活为(26467.1±4705.6)(mg·ml-1)-1;10例Tis～T1期肿瘤比活为(7843.4±1515.4)(mg·ml-1)-1,9例T2～T4期肿瘤比活为(21295.6±3297.9)(mg·ml-1)-1。正常膀胱粘膜组织中MMP2为阴性。结论:活性MMP2在BTCC进展中具有重要作用。     

uPA、uPAR与尿路移行细胞癌侵袭行为的相关性研究

背景与目的:丝氨酸蛋白水解酶的uPA(urokinase-typeplasminogenactivator)uPAR(urokinase-typeplasminogenactivatorreceptor)作用系统被认为在细胞外基质和基底膜的降解、促进肿瘤侵袭转移过程中起核心作用,本研究旨在探讨uPA、uPAR在尿路移行细胞癌组织中的表达及其与肿瘤侵袭行为的关系。方法:应用免疫组织化学PicTureTM通用型二步法检测50例肾盂输尿管癌及40例膀胱癌组织中uPA和uPAR的表达水平及分布。结果:uPA和uPAR在正常肾盂、输尿管、膀胱组织中未见表达,在癌组织中的表达明显高于癌旁组织;G1级uPA和uPAR的阳性率分别为33.33%、50.00%,G3级分别为88.47%和96.15%;Ta～T1期的分别为37.50%和50.00%,T4期均为100.0%;在高分级、高分期肿瘤组织中,uPA和uPAR的阳性率明显升高(P<0.05),且uPA阳性与uPAR阳性高度相关(rs=0.979)。结论:uPA、uPAR的共同表达是尿路移行细胞癌的特征之一,且与分级和分期密切相关,在尿路移行细胞癌浸润和转移中可能具有重要作用。     

Dysfunction of natural killer cells in patients with transitional cell carcinoma

Previous studies had established that transforming growth factor-β1 (TGF-β1) is highly expressed in bladder tumor, facilitating progression and spreading of the cancerous cells. Here, we report that both the number and the cytotoxic function of natural killer (NK) cells are decreased in patients with superficial transitional cell carcinoma (TCC). In consistent with previously reported findings, the plasma TGF-β1 concentration is also elevated in patients with superficial TCC. In vitro, the cytotoxic function of NK cells was impaired by the presence of TGF-β1. Hence, our data suggested elevated concentration of serum TGF-β1 in loss of NK cytotoxicity in superficial TCC patients, implicating altered innate immunity may correlate with the incidence of TCC.     

组织蛋白酶D在肾盂输尿管移行细胞癌中表达的意义

目的：探讨组织蛋白酶D在上尿路移行细胞癌中表达的临床意义。方法：应用免疫组织化学ABC法，对组织蛋白酶D在43例肾盂、输尿管移行细胞癌中的表达进行检测。结果：肿瘤细胞阳性表达19例（44．2％）；间质细胞阳性表达14例（32．6％）。两表达与肿瘤分级、分期无显差异（P＞0．05）。间质细胞组织蛋白酶D阳性表达的患术后肿瘤复发明显高于阴性表达（P＜0．05），且5年生存期明显低于阴性表达（P＜0．05）。结论：上尿路移行细胞癌间质细胞组织蛋白酶D的检测，对术后肿瘤复发、生存期的判断具有一定的临床价值，可能用作判断预后的指标之一。     

人膀胱癌组织中细胞外基质金属蛋白酶诱导因子的表达

背景与目的:基质金属蛋白酶(matrix metalloproteinases,MMPs)在恶性肿瘤的发生、浸润和转移中发挥关键作用,肿瘤细胞表达的细胞外基质金属蛋白酶诱导因子(extracellular matrix metalloproteinase inducer,EMMPRIN)司以诱导间质成纤维细胞合成MMPs,从而促进肿瘤的浸润和转移。本研究拟通过检测EMMPRIN在人膀胱癌组织和正常膀胱粘膜中的表达,探讨EMMPRIN在膀胱癌发生、浸润和转移中的作用。方法:应用免疫组化SP方法检测EMMPRIN在45例膀胱癌组织和9例正常膀胱粘膜中的表达,并与临床病理指标结合起来分析。结果;EMMPRIN蛋白定位于癌细胞的胞膜和胞浆,阳性率为73.3％,正常膀胱粘膜和肿瘤间质均为阴性表达。EMMPRIN在Ⅱ、Ⅲ级和术后复发组的阳性表达率分别为84.0％、84.6％和100％,高于Ⅰ级和无复发组(分别为14.3％和55.6％)(P<0.05);在淋巴结转移组的强阳性表达率(85.7％)高于无淋巴结转移组(23.7％)(P<0.05)。结论:EMMPRIN在人膀胱癌组织中过度表达,与膀胱癌的恶性程度有关,可作为判断膀胱 癌是否具备高侵袭转移潜能的指标。     

膀胱移行细胞癌Langerhans细胞的研究

膀胱移行细胞癌Ｌａｎｇｅｒｈａｎｓ细胞的研究图１正常膀味粘膜，ＬＣ位于粘膜下间质内，与移行细胞紧密相靠（ＳＩ。Ｏ２００Ｘ）图２移行细胞癌Ⅰ级，癌巢及周围淋巴组织中均可见到ＬＣ（Ｓ１０Ｏ２００×）图３移行细胞癌Ⅱ级，ＬＣ浸润于癌巢中（Ｓ１００２００×）...     

骨形成蛋白7重组腺病毒的构建及诱导成骨的研究

目的探讨骨形成蛋白7（BMP7）重组腺病毒异位诱导成骨的作用。方法将BMP7基因克隆到转移载体pAdTrack-CMV中,在细菌BJ5183中与pAdEasy腺病毒基因组进行同源重组,得到BMP7重组腺病毒基因组,通过转染HEK293细胞包装出重组腺病毒,然后在裸鼠小腿肌肉中进行异位诱导成骨实验。结果经过PCR及酶切鉴定证明获得了BMP7转移质粒pAdTrack-BMP7和BMP7重组腺病毒基因组,并包装出重组腺病毒。组织学观察显示2周时实验局部大量纤维样细胞聚集,软骨细胞分化;5周时骨小梁形成,软骨细胞已退化。结论BMP7重组腺病毒的构建以及其异位诱导成骨的成功,为BMP7基因治疗的研究提供了确切的实验依据。     

Tumor lysis syndrome after treatment with gemcitabine for metastatic transitional cell carcinoma

Tumor lysis syndrome is a set of life threatening complication that can arise from treatment of high tumor burden, drug sensitive, and rapidly proliferating neoplasm particularly of hematological origin. It is rarely described in patients with solid tumors. We report the first case of tumor lysis syndrome in a man with metastatic renal pelvic transitional cell carcinoma after gemcitabine treatment. Despite aggressive therapy, he died 2 weeks after TLS was diagnosed. Our experience demonstrates that administration of gemcitabine for metastatic renal pelvic transitional cell carcinoma may induce acute tumor lysis syndrome, which necessitates frequent laboratory monitoring and prompt initiation of appropriate therapeutic measures.     

尿移行细胞癌巴氏染色色度学定量研究

目的定量揭示尿移行细胞癌巴氏染色的色度学特征,筛选对移行细胞癌诊断分类有重要价值的色度学参数。方法取尿脱落细胞中正常的移行细胞（NTC）、结构不良移行细胞（DTC）以及移行细胞癌细胞（TCC）,用计算机图像分析技术分别测试细胞的色度学参数,包括细胞浆的红、绿、蓝三基色（Rp、Gp、Bp）和细胞核的红、绿、蓝三基色（Rn、Gn、Bn）,对测试结果进行单因素方差分析和组间两两比较（SNK-q检验法）。结果Rp、Rn、Gp、Gn、Bp、Bn从正常细胞、结构不良细胞、癌细胞依次减小,单因素方差分析示差异有统计学意义（P=0.001）,组间两两比较示各组间差异有统计学意义。结论尿移行细胞巴氏染色中的色度学参数Rp、Rn、Gp、Gn、Bp、Bn在各组移行细胞间有显著性差异,这些参数及其差异可用于判别尿脱落细胞的研究。     

Development of multiple transitional cell carcinomas in the urinary tract

The multiplicity of transitional cell carcinomas in the renal pelvis, ureter and bladder was analyzed in terms of (1) tumor configuration, i.e., papillary, nodular cancers, (2) associated mucosal changes such as carcinoma in situ (CIS) and dysplasia and (3) the possible involvement of human papillomavirus (HPV) in the development of multiple papillary cancers in the bladder. The incidences of concurrent or subsequent bladder cancer in renal pelvic cancer and/or ureteral cancer cases were 7/31 (22%) for renal pelvic cancer, 17/28 (60%) for ureteral cancer and 10/15 (67%) for renal pelvic and ureteral cancer. In 33 cases of renal pelvic and/or ureteral cancer occurring since 1978, 67% of the papillary and 13% of the nodular cancers in the upper tract exhibited a simultaneous or later development of bladder cancer. In 211 cases of bladder cancer for which cystectomy was performed, 77% of the papillary cancers arose in multiple form, 57% being associated with CIS and/or dysplasia, whereas 72% of the nodular cancers developed singly, 55% being associated with CIS and/or dysplasia. No positive signals hybridizing to HPV types 1, 5, 6, 11, 16, 17, 18, 20, 33 and 38 were detected in any of 19 papillary bladder cancers and 13 specimens of normal bladder mucosa under conditions of low stringency, suggesting that HPV may not be a factor in multiple bladder tumor development. Definite findings from the present study are: (1) there is multiple development of papillary cancers but they remain superficial, whereas nodular cancers develop singly and are invasive, (2)) there was no steady tendency towards a relation between multiplicity and associated mucosal changes, (3) HPV was not, to our knowledge, involved in the multiple development of papillary cancers in the bladder.     

Real-world Outcomes in Advanced Urothelial Cancer and the Role of Neutrophil to Lymphocyte Ratio

Introduction

In the first- and second-line metastatic urothelial carcinoma (mUC) treatment setting, we investigated real-world outcomes and evaluated the prognostic role of neutrophil to lymphocyte ratio (NLR).

Metastasis to the ovaries from transitional cell carcinoma of the bladder and renal pelvis: a report of two cases

Ovarian metastases from a primary urinary tract carcinoma are extremely rare. This can be difficult to distinguish from transitional cell carcinomas (TCC) of ovarian origin because of histologic similarity. A 65-year-old woman who was diagnosed with renal pelvis TCC 4 months prior was referred for evaluation of a left ovarian mass. A 47-year-old woman who underwent radical cystectomy due to bladder TCC 1 year ago was referred because of a right ovarian mass. Both patients underwent a bilateral salpingo-oophorectomy. The tumor cells had morphology identical to those of the primary urinary tract tumors. Gynecologic oncologists should consider metastatic TCC of the ovary from urinary tract origin, as well as breast, and gastrointestinal tract origins.     

Caspase-3与Bcl-2蛋白在膀胱移行细胞癌中的表达及意义

背景和目的:肿瘤的发生是细胞异常增生和凋亡不足的结果。以往研究认为凋亡的发生与Caspase-3和Bcl-2蛋白有密切的联系。本研究拟通过检测Caspase-3和Bcl-2蛋白在膀胱移行细胞癌中的表达,探讨其在膀胱移行细胞癌发生、发展中的意义。方法:采用免疫组织化学(SP)法,对52例膀胱移行细胞癌组织和10例正常膀胱粘膜组织中的Caspase-3及Bcl-2蛋白表达情况进行检测。结果:膀胱移行细胞癌组织中的Caspase-3蛋白表达率(53.8%,28/52)明显低于正常膀胱粘膜组织(90.0%,9/10),Caspase-3的蛋白表达与膀胱移行细胞癌的病理分级有关(P<0.05),但与临床分期没有明显的联系;膀胱移行细胞癌组织中的Bcl-2蛋白表达率(51.9%,27/52)明显高于正常膀胱粘膜组织(20.0%,2/10),且Bcl-2蛋白表达情况与病理分级、临床分期均无关(P>0.05)。在正常膀胱粘膜中Caspase-3与Bcl-2的蛋白表达呈负相关(rs=-0.659,P<0.01)。结论:Caspase-3蛋白的高表达与Bcl-2蛋白的低表达在膀胱癌的发生和细胞凋亡的调控方面可能起着重要作用。     

膀胱癌组织中MMP-2与TIMP-2 mRNA的表达及临床意义

目的 探讨基质金属蛋白酶-2(MMP-2)及其组织抑制因子-2(TIMP-2)mRNA在膀胱癌组织中的表达,以及与膀胱癌侵袭、转移和复发的关系。方法 应用半定量PCR和实时定量PCR(RQ-PCR)方法,检测10例正常膀胱组织和45例膀胱移行细胞癌组织中MMP-2和TIMP-2 mRNA的表达。结果 半定量PCR显示MMP-2、TIMP-2在膀胱正常组织中均呈阴性表达,而在45例膀胱癌组织中,MMP-2阳性率为66.7%(30/45),TIMP-2为57.8%(26/45)。定量PCR检测显示MMP-2表达量随肿瘤病理分级和临床分期的升高而增加,在复发病例中也增加,其组间差异有统计学意义(P＜0.05);TIMP-2的表达量随病理分级和临床分期的升高而降低,而且组间差异有统计学意义(P＜0.05),而在初发复发病例的组间差异无统计学意义(P＞0.05)。结论 MMP-2和TIMP-2对于膀胱癌的侵袭、转移和复发发挥了重要作用;MMP-2可能对判断膀胱癌的预后有一定的指导意义。     

髓母细胞瘤的CT诊断(附50例分析)

 目前CT在诊断髓母细胞瘤方面虽有经验，但也经常遇到一些非典型CT表现的特殊病例误诊为其他颅内肿瘤。为进一步提高髓母细胞瘤的CT诊断水平，对经CT检查，并经手术病理证实的50例髓母细胞瘤总结如下。