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H Barton Grossman

Publications and source records attributed to H Barton Grossman.

At least 19 recordsLinked to original sources
PubMed2007

Genetic polymorphism in bladder cancer.

Individual variation in the genetic constitution of humans may affect the host responses to constant assaults from exogenous and endogenous carcinogens, which will eventually impact cancer risk, disease prognosis and clinical outcome. Bladder cancer is one of the most common cancers in the world. In this review, the published research articles studying the association between genetic polymorphisms and bladder cancer risk and disease progression are summarized. Genetic polymorphisms are categorized based on their primary cellular functions: genes in carcinogen metabolism, DNA repair, cell cycle control, inflammation, apoptosis, methylation, genes functioning as G proteins, and cell adhesion molecules. Furthermore, we discuss a number of limitations of current genetic susceptibility research and suggest future directions in molecular epidemiology study. This review presents an overview of current molecular epidemiology of bladder cancer and provides a useful resource for understanding the pathogenesis of bladder cancer.

Apoptosis↗
PubMed2007

High-order interactions among genetic variants in DNA base excision repair pathway genes and smoking in bladder cancer susceptibility.

Cancer is a common multifactor human disease resulting from complex interactions between many genetic and environmental factors. In this study, we used a multifaceted analytic approach to explore the relationship between eight single nucleotide polymorphisms in base excision repair (BER) pathway genes, smoking, and bladder cancer susceptibility in a hospital-based case-control study. Overall, we did not find an association between any single BER gene single nucleotide polymorphism and bladder cancer risk. However, in stratified analysis, the OGG1 S326C variant genotypes in ever smokers (odds ratio, 0.74; 95% confidence interval, 0.56-0.99) and ADP-ribosyltransferase (ADPRT) V762A variant genotypes in never smokers (odds ratio, 0.58; 95% confidence interval, 0.37-0.91) conferred a significantly reduced risk. Using logistic regression, we observed that there was a two-way interaction between ADPRT V762A and smoking status. We next used classification and regression tree analysis to explore high-order gene-gene and gene-environment interactions. We found that smoking is the most important influential factor for bladder cancer risk. Consistent with the above findings, we found that the ADPRT V762A was only significantly involved in bladder cancer risk in never smokers and the OGG1 S326C was only significantly involved in ever smokers. We also observed gene-gene interactions among OGG1 S326C, XRCC1 R194W, and MUTYH H335Q in ever smokers. Using multifactor dimensionality reduction approach, the four-factor model, including smoking status, OGG1 S326C (rs1052133), APEX1 D148E (rs3136820), and ADPRT762 (rs1136410), had the best ability to predict bladder cancer risk with the highest cross-validation consistency (100%) and the lowest prediction error (37.02%; P < 0.001). These results support the hypothesis that genetic variants in BER genes contribute to bladder cancer risk through gene-gene and gene-environmental interactions.

Algorithms↗
PubMed2006

Matrix metalloproteinase polymorphisms and bladder cancer risk.

Matrix metalloproteinases (MMP) contribute to tumor microenvironment and are associated with bladder cancer. A study examining the association between MMP polymorphisms and bladder cancer risk has never been published. We analyzed the association of 11 single nucleotide polymorphisms (SNPs) and one microsatellite polymorphism in MMP genes MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, and MMP-12 with bladder cancer risk in 560 Caucasian patients and 560 controls matched on age, gender, and ethnicity. Individual, combination, haplotype, and diplotype analyses were done. No associations between individual MMP polymorphisms and overall bladder cancer risk were seen. The MMP-9 microsatellite > or =24 CA repeat allele and the MMP-12-82 GG polymorphisms were associated with invasive bladder cancer risk [odds ratio (OR), 2.60; 95% confidence interval (95% CI), 1.07-6.26; and OR, 4.59; 95% CI, 1.21-17.32, respectively]. Smoke-stratified analyses revealed several associations between MMP polymorphisms, alone and in combination, with bladder cancer risk, particularly in light smokers. Linkage disequilibrium was seen in all of the MMP-1, MMP-3, MMP-8, and MMP-12 SNPs and in four of five MMP-9 polymorphisms tested. Several MMP-9 haplotype and diplotypes were associated with overall and invasive bladder cancer risk. Our study suggests that genetic variations in the MMP family are associated with bladder cancer risk. Heavy carcinogen exposure may overwhelm some of the genetic effects of MMP polymorphisms. Our study confirms the importance of taking a multigenic pathway-based approach to risk assessment.

Case-Control Studies↗
PubMed2006

Genotypes, haplotypes and diplotypes of XPC and risk of bladder cancer.

Xeroderma pigmentosum complementation group C (XPC) is responsible for DNA damage recognition in the initial steps of the nucleotide excision repair pathway. Genetic variations in the XPC gene may be associated with impaired protein function and increased risk for bladder cancer. To elucidate the roles of common polymorphisms of XPC in the etiology of bladder cancer, we conducted a hospital-based case-control study including 578 Caucasian incident bladder cancer patients and 578 age- and gender-matched Caucasian controls. We analyzed the associations of the genotypes, haplotypes and diplotypes of three XPC polymorphisms, Ala499Val (C-->T), PAT (-/+) and Lys939Gln (A-->C), with the risk of bladder cancer. No significant association was found for any individual polymorphism. However, the C-C and T-A (indicated as in the order of Ala499Val-PAT-Lys939Gln) haplotypes were associated with reduced bladder cancer risks, with odds ratios (ORs) of 0.51 [95% confidence interval (CI) = 0.34-0.78] and 0.79 (0.60-1.04), respectively. The protective effects were more evident in men, people younger than 59 years, and ever-smokers. We also found that four diplotypes were significantly associated with reduced bladder cancer risk, with ORs (and 95% CIs) of 0.53 (0.34-0.82) for C-A/T-A, 0.48 (0.27-0.84) for C-A/C-C, 0.18 (0.053-0.60) for C-C/C-C and 0.57 (0.36-0.90) for C+C/C+C. These results suggest that sequence variants in the XPC gene might modulate the risk of bladder cancer.

Aged↗
PubMed2006

Relevance of extracapsular extension of pelvic lymph node metastasis in patients with bladder cancer treated in the contemporary era.

BACKGROUND: Previous reports have suggested that extracapsular extension (ECE) is a prognostic factor in patients with urothelial carcinoma who have positive lymph nodes at the time of radical cystectomy. In the current study, the relevance of ECE in patients treated in the contemporary era was evaluated. METHODS: A database search from 1993 to 2003 revealed 150 patients with pN+M0 disease detected after radical cystectomy; of these, 108 patients did not receive neoadjuvant chemotherapy and form the basis of the current report. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) data were analyzed by the Kaplan-Meier method, with log-rank tests used to evaluate associations between survival and variables studied. RESULTS: Five-year OS, DSS, and RFS rates were 30.9%, 45.5%, and 29.7%, respectively. Adjuvant chemotherapy was administered to 70% of patients. On multivariate analysis, adjuvant chemotherapy was significantly associated with prolonged OS, DSS, and RFS (P </= .01). For patients overall and when stratified by pN status, the presence of ECE of lymph node metastasis was not found to be significantly associated with OS (P = .52), DSS (P = .43), or RFS (P = .83). CONCLUSIONS.: The current study suggests that ECE is not an independent prognostic factor in a contemporary series of patients with positive lymph nodes at radical cystectomy. This might be reflective of a paradigm shift that encompasses the adoption of multimodal therapy.

Aged↗
PubMed2006

Clinical model of lifetime cost of treating bladder cancer and associated complications.

OBJECTIVES: To estimate the lifetime cost of bladder cancer and the contribution of complications to the total costs. METHODS: We reviewed the medical records of a retrospective cohort of 208 patients with bladder cancer who registered at our comprehensive cancer center from 1991 to 1999. We multiplied the number of resources used during management of bladder cancer by their unit charges. We converted charges into costs using the Medicare cost-to-charge ratio and inflated these to 2005 U.S. dollars. We estimated future costs by creating two extreme hypothetical scenarios. In the best-case scenario, we assumed patients with superficial disease developed recurrences at the cohort's mean rate and that patients with muscle-invasive disease were disease free after definitive therapy. Survival was based on the U.S. life expectancy in both cases. In the worst-case scenario, we assumed patients with superficial disease developed muscle-invasive disease and that all patients subsequently died of bladder cancer. RESULTS: The average cost of bladder cancer was 65,158 dollars among the cohort patients. Sixty percent of this cost (39,393 dollars) was associated with surveillance and treatment of recurrences, and 30% (19,811 dollars) was attributable to complications. The lifetime cost of bladder cancer was lower for the worst-case scenario (99,270 dollars) than for the best-case scenario (120,684 dollars). However, a greater proportion of the costs were attributable to complications with the worst-case scenario (43%, 42,290 dollars) compared with the best (28%, 34,169 dollars). CONCLUSIONS: The management of bladder cancer and its associated complications results in a major economic burden. More cost-effective surveillance strategies and approaches for preventing complications are crucial to minimizing the disease's clinical and economic consequences.

Aged↗
PubMed2006

Comparing the effect of ATRA, 4-HPR, and CD437 in bladder cancer cells.

Clinical trials have explored the use of natural and synthetic retinoids for the prevention of bladder cancer recurrence. Natural retinoids have been shown to inhibit bladder cancer growth. Here, we compared the effects of natural and synthetic retinoids in bladder cancer cells. Bladder cancer cell lines were treated with all-trans-retinoid acid (ATRA), N-4-hydroxyphenyl-retinamide (4-HPR) and 6-[3-(1-adamantyl)-4 hydroxyphenyl]-2-naphthalene carboxylic acid (CD437). Their effects on cell growth, apoptosis, cell cycle, gene expression, and retinoid acid receptors (RARs) and the JWA-retinoid response gene were assessed. Most of the bladder cancer cells were resistant to ATRA (1 and 10 microM). 4-HPR inhibited cell growth by 90% at 10 microM; however, CD437 showed the same effect at 1 microM. 4-HPR and CD437 increased G1 and decreased S phase. The three retinoids differentially affected p53, RARs, and JWA. Only CD437 increased Caspase 3 expression. The results demonstrated that 4-HPR and CD437 were more potent growth inhibitors and apoptosis inducers than ATRA. However, 4-HPR was effective at a concentration at least 10 microM. The in vitro results suggested the higher dose of 4-HPR in chemoprevention trial be considered.

Antineoplastic Agents↗
PubMed2006

Bladder cancer risk as modified by family history and smoking.

BACKGROUND: The familial risk of bladder cancer (BC) is not well understood and, to date, little attention has been paid to the joint effect of smoking and family history in modifying the risk of BC. The authors investigated the role of family history in association with the risk of BC. METHODS: Case and control probands were identified as part of an on-going BC case-control study. The relative risk associated with a family history of BC was estimated. RESULTS: In total, 713 cases and 658 controls were included. In a case-control analysis, compared with individuals who never smoked and who had no family history of BC, probands who had smoked and who also had a positive family history were at 5.31-fold increased risk of BC (P for interaction = .04). The 713 case probands and the 658 controls reported 5160 and 4816 first-degree relatives, respectively. Compared with never-smoking relatives who had probands diagnosed with BC at an older age (age >65 years), ever-smoking relatives who had probands diagnosed at a younger age (ages 40-65 years) showed a 6.89-fold (95% confidence interval, from 2.25-fold to 21.12-fold) increased risk. Similar results were obtained for the joint effects of family history of BC and smoking. CONCLUSIONS. The current results indicated that a positive family history of BC may have interacted with smoking habits to increase the risk of BC in the study population.

Aged↗
PubMed2006

Mutations within the kinase domain and truncations of the epidermal growth factor receptor are rare events in bladder cancer: implications for therapy.

PURPOSE: It has previously been reported that the patient response to gefitinib depends on the presence of mutations within the kinase domain of epidermal growth factor receptor (EGFR) or the expression of its truncated form, EGFR variant III (EGFRvIII). The focus of this study was to determine if these alterations are present within the tyrosine kinase and ligand-binding domain of EGFR in urothelial carcinoma. EXPERIMENTAL DESIGN: The kinase domain found within exons 18 to 21 of the EGFR from 11 bladder cancer cell lines and 75 patient tumors were subjected to automated sequencing. EGFRvIII expression was determined by immunohistochemistry using a urothelial carcinoma tissue microarray, and its expression was subsequently verified by reverse transcription PCR, real-time PCR, and Western blot analysis, using an EGFRvIII-transfected glioblastoma cell line and glioblastoma tumors as positive controls. RESULTS: Our analysis failed to detect mutations within the tyrosine kinase domain of EGFR in the 11 cell lines and 75 patients tested. The initial analysis of EGFRvIII expression by immunohistochemistry revealed that at least 50% of the patient tumors expressed EGFRvIII in a urothelial carcinoma tissue microarray. Conflicting reports exist, however, regarding the extent of EGFRvIII expression in tissues owing to the specificity of the antibodies and the methodologies used. Therefore, we sought to validate this observation by reverse transcription PCR, real-time PCR, and Western blot analysis. In these assays, none of the samples were positive for EGFRvIII except for control transfectants and glioblastomas. CONCLUSIONS: When our results are taken together, we conclude that alterations within the tyrosine kinase domain and expression of EGFRvIII are rare events in bladder cancer. The present study has clinical implications in selecting tyrosine kinase inhibitors for the therapy of urothelial carcinoma.

Blotting, Western↗
PubMed2006

Bladder cancer predisposition: a multigenic approach to DNA-repair and cell-cycle-control genes.

The candidate-gene approach in association studies of polygenic diseases has often yielded conflicting results. In this hospital-based case-control study with 696 white patients newly diagnosed with bladder cancer and 629 unaffected white controls, we applied a multigenic approach to examine the associations with bladder cancer risk of a comprehensive panel of 44 selected polymorphisms in two pathways, DNA repair and cell-cycle control, and to evaluate higher-order gene-gene interactions, using classification and regression tree (CART) analysis. Individually, only XPD Asp312Asn, RAG1 Lys820Arg, and a p53 intronic SNP exhibited statistically significant main effects. However, we found a significant gene-dosage effect for increasing numbers of potential high-risk alleles in DNA-repair and cell-cycle pathways separately and combined. For the nucleotide-excision repair pathway, compared with the referent group (fewer than four adverse alleles), individuals with four (odds ratio [OR] = 1.52, 95% CI 1.05-2.20), five to six (OR = 1.81, 95% CI 1.31-2.50), and seven or more adverse alleles (OR = 2.50, 95% CI 1.69-3.70) had increasingly elevated risks of bladder cancer (P for trend <.001). Each additional adverse allele was associated with a 1.21-fold increase in risk (95% CI 1.12-1.29). For the combined analysis of DNA-repair and cell-cycle SNPs, compared with the referent group (<13 adverse alleles), the ORs for individuals with 13-15, 16-17, and >or=18 adverse alleles were 1.22 (95% CI 0.84-1.76), 1.57 (95% CI 1.05-2.35), and 1.77 (95% CI 1.19-2.63), respectively (P for trend = .002). Each additional high-risk allele was associated with a 1.07-fold significant increase in risk. In addition, we found that smoking had a significant multiplicative interaction with SNPs in the combined DNA-repair and cell-cycle-control pathways (P<.01). All genetic effects were evident only in "ever smokers" (persons who had smoked >or=100 cigarettes) and not in "never smokers." A cross-validation statistical method developed in this study confirmed the above observations. CART analysis revealed potential higher-order gene-gene and gene-smoking interactions and categorized a few higher-risk subgroups for bladder cancer. Moreover, subgroups identified with higher cancer risk also exhibited higher levels of induced genetic damage than did subgroups with lower risk. There was a significant trend of higher numbers of bleomycin- and benzo[a]pyrene diol-epoxide (BPDE)-induced chromatid breaks (by mutagen-sensitivity assay) and DNA damage (by comet assay) for individuals in higher-risk subgroups among cases of bladder cancer in smokers. The P for the trend was .0348 for bleomycin-induced chromosome breaks, .0036 for BPDE-induced chromosome breaks, and .0397 for BPDE-induced DNA damage, indicating that these higher-order gene-gene and gene-smoking interactions included SNPs that modulated repair and resulted in diminished DNA-repair capacity. Thus, genotype/phenotype analyses support findings from CART analyses. This is the first comprehensive study to use a multigenic analysis for bladder cancer, and the data suggest that individuals with a higher number of genetic variations in DNA-repair and cell-cycle-control genes are at an increased risk for bladder cancer, confirming the importance of taking a multigenic pathway-based approach to risk assessment.

Aged↗
PubMed2006

Surveillance for recurrent bladder cancer using a point-of-care proteomic assay.

CONTEXT: At least 50% of patients with a history of bladder cancer have recurrences, so rigorous surveillance is necessary. Cystoscopy is standard but can fail to detect some bladder cancers, so a urine test is frequently part of the evaluation. OBJECTIVE: To investigate whether a point-of-care proteomic test that measures the nuclear matrix protein NMP22 in voided urine could improve detection of recurrence during monitoring of patients with a history of bladder cancer. DESIGN, SETTING, AND PATIENTS: From September 2001 to February 2002, 23 academic, private practice, and hospital facilities in 9 US states prospectively enrolled 668 consecutive patients with a history of bladder cancer in this cross-sectional study. Patients provided a voided urine sample for analysis of NMP22 protein and cytology prior to cystoscopy. MAIN OUTCOME MEASURES: Diagnosis of bladder cancer recurrence, based on cystoscopy with biopsy, was accepted as the reference standard. The performance of the NMP22 test was compared with voided urine cytology as an aid to detection. Testing for the NMP22 tumor marker was conducted in a blinded manner. RESULTS: Bladder cancer was diagnosed in 103 patients. Cystoscopy alone identified 91.3% of the cancers (94/103; 95% confidence interval [CI], 84.1%-95.9%). The combination of cystoscopy with the NMP22 assay detected 99.0% of the malignancies (102/103; 95% CI, 94.7%-100%; P = .005). The NMP22 assay detected 8 of 9 cancers that were not visualized during initial cystoscopy, including 7 that were high-grade. The sensitivity and specificity of the NMP22 test alone were 49.5% (51/103; 95% CI, 39.5%-59.5%) and 87.3% (493/565; 95% CI, 84.2%-89.9%), respectively. Voided cytology detected only 3 of the malignancies missed during initial cystoscopy and did not significantly increase the sensitivity of cystoscopy (94.2%; 95% CI, 87.7%-97.8%; P = .08). CONCLUSION: The noninvasive point-of-care assay for elevated urinary NMP22 protein can increase the ability to detect recurrent bladder cancer, with test results available during the patient visit.

Adult↗
PubMed2006

Neoadjuvant chemotherapy for bladder cancer.

The 30-45% failure rate after radical cystoprostatectomy mandates that we explore and optimize multimodal therapy to achieve better disease control in these patients. Cisplatin-based multi-agent combination chemotherapy has been used with success in metastatic disease and has therefore also been introduced in patients with high-risk but non-metastatic bladder cancer. There is now convincing evidence that chemotherapy given pre-operatively can improve survival in these patients. In this review we establish the need for peri-operative chemotherapy in bladder cancer patients and summarize the evidence for the efficacy of neoadjuvant chemotherapy. The advantages and disadvantages of neoadjuvant versus adjuvant chemotherapy are discussed, and the main shortcomings of both--treatment-related toxicity and the inability to prospectively identify likely responders--are presented. Finally, a risk-adapted approach to neoadjuvant chemotherapy is presented, whereby the highest risk patients are offered treatment while those unlikely to benefit are spared the treatment-related toxicity.

Chemotherapy, Adjuvant↗
PubMed2006

Upper urinary tract tumors with nontransitional histology: a single-center experience.

OBJECTIVES: To review our experience with patients with upper urinary tract tumors of nonurothelial origin. Upper urinary tract tumors of nonurothelial origin are uncommon entities. To our knowledge, no series of patients with these neoplasms has been published in the past decade. METHODS: We reviewed the records at the University of Texas M. D. Anderson Cancer Center from 1990 to 2004 to identify patients with primary nonurothelial tumors of the upper urinary tract. We reviewed the patient records to collect data on tumor subtype, treatment, recurrence, and survival. RESULTS: Sixteen patients (1.9% of our database of patients with upper urinary tract tumors) were identified; 12 had squamous cell carcinoma, 2 had adenocarcinoma, 1 had sarcomatoid carcinoma, and 1 had small cell carcinoma. The tumors were located in the renal pelvis in 10 and the ureter in 6. Of the 16 patients, 15 had been treated with nephrectomy or nephrouterectomy and 1 with chemotherapy and radiotherapy. Fifteen of the tumors were pathologic Stage T3 or worse. Ten patients received adjuvant chemotherapy. Of the 16 patients, 9 died (1 of unknown causes), 4 were alive without disease, 2 were alive with disease, and 1 was alive at last follow-up with the disease status unknown. The median follow-up was 30.1 months, the median overall survival time was 11.3 months, and 1-year survival rate was 46%. The median recurrence-free survival time and 1-year recurrence-free survival rate were 5.8 months and 38%, respectively. CONCLUSIONS: Primary nonurothelial carcinomas of the renal pelvis and ureter are rare. Our analysis suggests a poor prognosis for most patients with these pathologic types, probably resulting from the advanced stage at diagnosis and poor responses to systemic therapy.

Carcinoma↗
PubMed2006

Immediate versus staged urethrectomy in patients at high risk of urethral recurrence: is there a benefit to either approach?

OBJECTIVES: To compare treatment-related outcomes of immediate and staged urethrectomy in patients at high risk of urethral recurrence. METHODS: We retrospectively identified 76 male patients with cystectomy for transitional cell carcinoma of the bladder who had undergone urethrectomy in the absence of established urethral recurrence. Concomitant cystoprostatectomy and urethrectomy was performed in 57 patients and staged urethrectomy in 19 patients. The criteria for staged urethrectomy were the presence of a positive urethral margin or established transitional cell carcinoma of the urethra in the cystectomy specimen. The mean interval from cystectomy to staged urethrectomy was 4.7 months (range 1.4 to 14). RESULTS: The most common pathologic finding of the urethrectomy specimens was prostatic duct involvement (31.6%) in the immediate urethrectomy group and Stage pT0 in the delayed urethrectomy group (73.7%). No statistically significant difference in disease-specific survival was noted between the immediate and staged groups (P = 0.14). Similarly, no difference was noted in postoperative complication rates or total operative blood loss (P = 0.77 and P = 0.64, respectively). However, a slight benefit for immediate urethrectomy was noted in the total duration of hospitalization (P = 0.01). The presence of local or distant recurrence was a predictor of disease-specific survival (P = 0.02 and P = 0.02, respectively). CONCLUSIONS: Immediate and staged urethrectomy appear to be similar in surgical morbidity and disease-specific survival. A benefit was noted for the immediate group in the total duration of hospitalization. The development of local or distant recurrence was a predictor of poor survival.

Adult↗
PubMed2006

Chemoprevention of bladder cancer.

Chemoprevention of cancer can be accomplished using primary, secondary, or tertiary strategies. Tertiary chemoprevention has been the predominant approach for bladder cancer and addresses the need for preventing the occurrence of second primary cancers in patients who have previously been treated for cancer. Because non-muscle-invasive bladder cancer is associated with a high risk of recurrence, tertiary chemoprevention has been studied in this population. Although considerable preclinical data has demonstrated the feasibility of this approach, application to the clinical setting has met with limited success. This review discusses chemoprevention of bladder cancer and focuses on the drugs used in chemoprevention investigations and clinical study design.

Humans↗
PubMed2006

Characterization of a panel of cell lines derived from urothelial neoplasms: genetic alterations, growth in vivo and the relationship of adenoviral mediated gene transfer to coxsackie adenovirus receptor expression.

PURPOSE: Cell lines have become an essential component for the investigation of cancer. We have developed a panel of cell lines derived from human urothelial cancers and we describe some of their important characteristics. MATERIALS AND METHODS: Ten human urothelial cancer cell lines were characterized by their growth in athymic nude mice, CAR expression and their susceptibility to adenoviral mediated transfer of the green fluorescence protein gene. TP53 mutation status and immunochemical analysis of p53, pRB and p16 were also examined. RESULTS: Five cell lines rapidly produced tumors in athymic nude mice. Two cell lines produced tumors in 1 month, 1 produced them in 3 months and 2 were nontumorigenic. The cell lines varied in CAR expression and in their susceptibility to adenoviral mediated gene transduction. There was no direct correlation between CAR expression and susceptibility to adenoviral mediated gene transduction. Seven cell lines had TP53 mutations, of which 2 had large deletions and did not express p53 protein by immunostaining. All cell lines expressed abnormal pRB by immunochemical analysis (3 had no staining and 7 had homogenously strong staining) and 8 did not express p16 (7 showed homogeneously strong pRB staining). CONCLUSIONS: Our panel of 10 human urothelial cell lines differed in genetic alterations, growth in nude mice, susceptibility to adenoviral mediated gene transduction, and expression of p53, p16 and pRB. The availability of various urothelial cancer cell lines with differing genotypic and phenotypic features will facilitate further research into bladder cancer.

Adenoviridae↗
PubMed2006

The case for early cystectomy in the treatment of nonmuscle invasive micropapillary bladder carcinoma.

PURPOSE: Micropapillary bladder carcinoma is a rare variant of UC. Due to paucity of data regarding treatment outcomes, patients with nonmuscle invasive micropapillary UC often receive intravesical therapy in an attempt at bladder preservation. MATERIALS AND METHODS: We reviewed the records of all patients evaluated at our institution who had micropapillary UC of the bladder. Of these, 44 had nonmuscle invasive disease at presentation and form the basis of this report. RESULTS: Mean patient age was 64.3 years (range 45 to 81) with a male-to-female ratio of 13:1. Stage distribution at presentation was 5 Ta (11%), 4 CIS (9%) and 35 T1 (80%). Median CSS was 81 months. Kaplan-Meier estimates of 5 and 10-year CSS rates were 64% and 26%, respectively. Intravesical BCG therapy was attempted in 27 patients (61%). Of these 27 patients, 67% (18 of 27) had progression (cT2 or greater), including 22% in whom metastatic disease developed. Only 19% of patients (5 of 27, all T1) remain disease-free with an intact bladder at a median followup of 30 months. A total of 30 patients (68%) underwent cystectomy. Among patients who underwent cystectomy after progression (18), median CSS was 61.7 months with no patient surviving 10 years, whereas among those undergoing cystectomy as initial therapy (12), median survival was not reached and the 10-year CSS rate was 72%. CONCLUSIONS: Intravesical BCG therapy appears to be ineffective against micropapillary UC. Our results suggest that the optimal treatment strategy for nonmuscle invasive micropapillary UC is radical cystectomy performed before progression.

Aged↗