microRNA expression profile in a large series of bladder tumors: identification of a 3-miRNA signature associated with aggressiveness of muscle-invasive bladder cancer.

The aim of this study was to evaluate the expression levels of microRNAs (miRNAs) in bladder tumors in order to identify miRNAs involved in bladder carcinogenesis with potential prognostic implications. Expression levels of miRNAs were assessed by quantitative real-time RT-PCR in 11 human normal bladder and 166 bladder tumor samples (86 non-muscle-invasive bladder cancer (NMIBC) and 80 muscle-invasive bladder cancer (MIBC)). The expression level of 804 miRNAs was initially measured in a well-defined series of seven NMIBC, MIBC and normal bladder samples (screening set). The most strongly deregulated miRNAs in tumor samples compared to normal bladder tissue were then selected for RT-PCR validation in a well-characterized independent series of 152 bladder tumors (validation set), and in six bladder cancer cell lines. Expression levels of these miRNAs were tested for their association with clinical outcome. A robust group of 15 miRNAs was found to be significantly deregulated in bladder cancer. Except for two miRNAs, miR-146b and miR-9, which were specifically upregulated in MIBC, the majority of miRNAs (n = 13) were deregulated in the same way in the two types of bladder tumors, irrespective of pathological stage : three miRNAs were upregulated (miR-200b, miR-182 and miR-138) and the other 10 miRNAs were downregulated (miR-1, miR-133a, miR-133b, miR-145, miR-143, miR-204, miR-921, miR-1281, miR-199a and miR-199b). A 3-miRNA signature (miR-9, miR-182 and miR-200b) was found to be related to MIBC tumor aggressiveness and was associated with both recurrence-free and overall survival in univariate analysis with a trend to significance in the multivariate analysis (p = 0.05). Our results suggested a promising individual prognostic value of these new markers.

Genomic expression and single-nucleotide polymorphism profiling discriminates chromophobe renal cell carcinoma and oncocytoma.

BACKGROUND: Chromophobe renal cell carcinoma (chRCC) and renal oncocytoma are two distinct but closely related entities with strong morphologic and genetic similarities. While chRCC is a malignant tumor, oncocytoma is usually regarded as a benign entity. The overlapping characteristics are best explained by a common cellular origin, and the biologic differences between chRCC and oncocytoma are therefore of considerable interest in terms of carcinogenesis, diagnosis and clinical management. Previous studies have been relatively limited in terms of examining the differences between oncocytoma and chromophobe RCC. METHODS: Gene expression profiling using the Affymetrix HGU133Plus2 platform was applied on chRCC (n = 15) and oncocytoma specimens (n = 15). Supervised analysis was applied to identify a discriminatory gene signature, as well as differentially expressed genes. High throughput single-nucleotide polymorphism (SNP) genotyping was performed on independent samples (n = 14) using Affymetrix GeneChip Mapping 100 K arrays to assess correlation between expression and gene copy number. Immunohistochemical validation was performed in an independent set of tumors. RESULTS: A novel 14 probe-set signature was developed to classify the tumors internally with 93% accuracy, and this was successfully validated on an external data-set with 94% accuracy. Pathway analysis highlighted clinically relevant dysregulated pathways of c-erbB2 and mammalian target of rapamycin (mTOR) signaling in chRCC, but no significant differences in p-AKT or extracellular HER2 expression was identified on immunohistochemistry. Loss of chromosome 1p, reflected in both cytogenetic and expression analysis, is common to both entities, implying this may be an early event in histogenesis. Multiple regional areas of cytogenetic alterations and corresponding expression biases differentiating the two entities were identified. Parafibromin, aquaporin 6, and synaptogyrin 3 were novel immunohistochemical markers effectively discriminating the two pathologic entities. CONCLUSIONS: Gene expression profiles, high-throughput SNP genotyping, and pathway analysis effectively distinguish chRCC from oncocytoma. We have generated a novel transcript predictor that is able to discriminate between the two entities accurately, and which has been validated both in an internal and an independent data-set, implying generalizability. A cytogenetic alteration, loss of chromosome 1p, common to renal oncocytoma and chRCC has been identified, providing the opportunities for identifying novel tumor suppressor genes and we have identified a series of immunohistochemical markers that are clinically useful in discriminating chRCC and oncocytoma.

Conformal radiotherapy for detectable PSA following radical prostatectomy: efficacy and predictive factors of recurrence.

INTRODUCTION: Many studies have analyzed outcomes following salvage radiation therapy (RT) after biochemical recurrence--defined as the presence of detectable serum prostate-specific antigen (PSA)--following radical prostatectomy (RP). However, the management of patients with detectable PSA following RP, which is not specific for tumor recurrence, is a matter of debate. This study aimed to evaluate oncological results of three-dimensional conformal RT (3D-CRT) in patients who had biochemical recurrence. MATERIALS AND METHODS: The study included patients who underwent RP, who had a postoperative PSA level--determined between 2 and 4 months after surgery--that was greater than 0.1 ng/ml, and who subsequently received monotherapy with 3D-CRT on the prostate bed. The patients' clinical, characteristics and the pathological characteristics of their biopsy specimens were recorded. The main endpoint was biochemical failure after 3D-CRT, defined as three consecutive elevated PSA levels. RESULTS: The tumors in the 46 patients included 4 (9%) pT2a, 7 (15%) pT2b, 14 (30%) pT2c, 10 (22%) pT3a, 10 (22%) pT3b, and 1 (2%) pT4 tumor. The Gleason score was 7 or higher in 37 patients (80%). Positive surgical margins were seen in 37 patients (80%). The patients had a median postoperative PSA level of 0.29 ng/ml (range, 0.1-5.8 ng/ml) and a median PSA doubling time (PSADT) before RT of 6 months (range, 1-53 months). The rate of biochemical recurrence free survival after 3D-RT was 66% at 30 months. Preoperative PSA, PSADT before RT, and D'Amico scores were significantly associated with biochemical failure after 3D-CRT (p < 0.05). CONCLUSIONS: In cases of persistent PSA following RP for prostate cancer, 3D-CRT can be used as monotherapy with a significant chance of recurrence free survival. Preoperative PSA, PSADT before RT, and D'Amico score are predictive factors of recurrence following RT.

A comparative study of prostate cancer detection and management in China and in France.

OBJECTIVE: To compare the detection and management of prostate cancer in one French and six Chinese urological institutions. PATIENTS AND METHODS: All the patients subjected to prostate biopsy for suspected prostate cancer in six Chinese urological institutions and in the department of urology of the Cochin hospital, France, between January 2003 and December 2005 were included. The characteristics of patients and tumors, and the management of prostate cancer were then analyzed. RESULTS: In the Chinese institutions, 95.8% of patients undergoing prostate biopsy presented with urinary disorders. The rate of abnormal digital rectal examination (DRE) ranged from 29.2% to 45.1%. In the French institution, 72.7% of prostate biopsies were performed as a result of prostate cancer screening, and the rate of abnormal DRE was 16.8%. In the Chinese institutions, a total of 979 patients underwent prostate biopsy, with median PSA values varying between 10.2 ng/ml and 33 ng/ml among the institutions. Overall, 408 cases of prostate cancer were diagnosed, with median PSA values varying between 24.3 ng/dl and 174.9 ng/dl and 19.4% of tumors were clinically localized. In the French institution, 565 patients underwent prostate biopsy, with a median PSA value of 7.4 ng/ml and 251 cases of prostate cancer were diagnosed, with a median PSA value of 8.1 ng/ml and 80.9% of tumors were clinically localized. In the Chinese institutions, the majority of patients received surgical or medical castration. The rate of patients subjected to surgical castration varied between 24.2% and 100%. Radical prostatectomy (RP) was performed in only three Chinese hospitals, in which the percentage of patients treated with RP varied between 12.1% and 31.1%. In the French institution, RP was the most common treatment of prostate cancer (43.8% of patients). CONCLUSION: In China, most patients subjected to prostate biopsy suffer from urinary symptoms and have elevated PSA levels. The lack of mass screening for prostate cancer results in a high rate of advanced tumors with nodal involvement and/or metastases. RP is rarely performed in Chinese hospitals, and castration represents the usual treatment of prostate cancer.

Large-scale real-time reverse transcription-PCR approach of angiogenic pathways in human transitional cell carcinoma of the bladder: identification of VEGFA as a major independent prognostic marker.

BACKGROUND: Actors of the angiogenesis pathways are targets for the new promising targeted therapies already used in several malignancies. In bladder cancer, antiangiogenic molecules could also add to already existing treatment options. OBJECTIVE: To evaluate the involvement of angiogenesis pathways in bladder carcinogenesis and identify new molecular markers having a clinical implication. DESIGN, SETTING, AND PARTICIPANTS: Expression levels of 40 genes involved in angiogenesis were assessed by quantitative real time RT-PCR in 157 urothelial tumour bladder samples obtained from patients who underwent transurethral bladder resection or radical cystectomy between 2001 and 2005. Pathologic tumour staging showed: 73 non-muscle-invasive bladder tumours (30 low-grade pTa, 14 high-grade pTa, and 29 high-grade pT1), and 84 muscle-invasive tumours (> or = pT2), all of high grade. RT-PCR results were associated with a survival analysis. RESULTS AND LIMITATIONS: VEGFA, MET, CXCR4, and IL8 were significantly overexpressed in tumour samples as compared to normal bladder tissue. VEGFA overexpressions were found in 89% of non-muscle-invasive and 66% of muscle-invasive tumour samples. In univariate analysis, for invasive tumours, VEGFA overexpression was associated with a poorer outcome in both overall and disease-free survival (p=0.011 and 0.026 respectively) at a 13-mo median follow-up. Multivariate analysis retained T stage, N status, and VEGFA overexpression as independent prognostic factors in both overall and disease-free survival (p=0.02 and p=0.04, respectively, for VEGFA). CONCLUSIONS: This study shows that, in bladder cancer, VEGFA status could be used as a prognostic factor at the individual level. VEGFA overexpression could guide a rationalized use of the costly antiangiogenic therapies which could therefore become part of the treatment options in bladder cancer.

Selecting patients for exclusive permanent implant prostate brachytherapy: the experience of the Paris Institut Curie/Cochin Hospital/Necker Hospital group on 809 patients.

PURPOSE: The aim of this study was to analyze overall and relapse-free survival in a cohort of 809 patients, 34% of whom corresponded to a higher-risk group than American Brachytherapy Society (ABS) criteria. METHODS AND MATERIALS: Between January 1999 and September 2004, 809 patients were treated with permanent loose 125 iodine seed implantation (IsoSeed Bebig, Eckert and Ziegler) by the Paris Institut Curie, Cochin Hospital, and Necker Hospital group. Of these 809 patients, 533 (65.9%) corresponded exactly to ABS criteria. Two hundred and seventy-six patients (34.1%) had a prostate-specific antigen (PSA) level between 10 and 15, or a Gleason score of 7, or both (non-ABS group). RESULTS: Overall 5-year survival was 98%, with no difference between the ABS group and the non-ABS patient subgroups (p = 0.62).Five-year relapse-free survival was 97% in the ABS group; it was significantly lower (p = 0.001) in the non-ABS group but remained satisfactory at 94%. On subgroup analysis, the results appeared to be better for the subgroup of patients with PSA 10-15 than for the subgroup with a Gleason score of 7. CONCLUSIONS: Our results suggest that selected patients in the intermediate-risk group of localized prostate cancers can be safely proposed as recipients of permanent implant brachytherapy as monotherapy.

Predictive factors for progression in patients with clinical stage T1a prostate cancer in the PSA era.

OBJECTIVE: In the literature, most data regarding the outcome of patients with clinical stage T1a prostate cancer were established before the prostate-specific antigen (PSA) era. The aim of our study was to determine the predictive factors of progression in patients with T1a prostate cancer diagnosed in the PSA era. METHODS: Consecutive patients (n=144) with newly diagnosed T1a prostate cancer (tumor involving < or =5% of the resected prostatic tissue) were included. None of them was treated before evidence of tumor progression confirmed by prostate needle biopsies. The associations between tumor characteristics and time to cancer progression were assessed using Cox regression analysis. RESULTS: With a mean follow-up of 5.1 yr, 30 patients (21%) experienced cancer progression. Five adverse parameters were significantly associated with cancer progression: preoperative PSA> or =10 ng/ml, postoperative PSA> or =2 ng/ml, prostate weight > or =60 g, weight of resected tissue > or =40 g, and Gleason score> or =6. The 5-yr progression rate was 12% if fewer than two of these parameters were present, whereas it was 47% if two or more parameters were present (p<0.001). CONCLUSION: In the PSA era the risk of progression associated with T1a prostate cancer can be predicted using five criteria, and two groups of patients can be defined. The patients at low risk of progression may be good candidates for surveillance. In those with a high risk of progression, a more aggressive treatment should be discussed.

[The low weight of the prostate is an independent risk factor for positive surgical margins on radical prostatectomy specimens]. / Le faible poids de la prostate est un facteur de risque indépendant de marges chirurgicales positives sur pièce de prostatectomie radicale.

OBJECTIVE: The presence of positive surgical margins (PSM) on radical prostatectomy specimen is predictive of biological recurrence. Our objective was to analyze the influence of prostate weight on surgical margins status after radical prostatectomy. PATIENTS AND METHODS: A cohort of 295 patients operated consecutively between 1998 and 2004 at our institution was prospectively studied. The variables significantly associated with the surgical margins status in univariate analysis were used for multivariate analysis. RESULTS: The overall rate of PSM was 23% (9% for pT2 patients). Parameters significantly associated with surgical margins status were preoperative PSA (p = 0.02), number of positive biopsy cores (p = 0.04), pathological stage (p < 0. 001), and Gleason score on radical prostatectomy specimen (p < 0. 001). In addition, patient age and surgical specimen weight were conversely associated with surgical margins status (p = 0.008 and p = 0.001, respectively). In multivariate analysis, only three parameters were found to be independent factors of PSM: the pathological stage (p < 0. 001), the patient age (p = 0. 02), and the surgical specimen weight (p = 0.02). PSM rates were 6% and 25% in patients with prostate > 70g and < 70g, respectively (p = 0.008), and 15% and 28% in those with prostate weight > or = 50g and < 50g, respectively (p = 0.015). CONCLUSION: Low prostate weight is an independent risk factor of PSM. Patients with prostate weight > or = 70g should be considered at low risk of PSM, while those with prostate weight < 50g are at high risk of PSM.

Survival analysis of 130 patients with papillary renal cell carcinoma: prognostic utility of type 1 and type 2 subclassification.

OBJECTIVES: To evaluate the prognostic significance of subtyping papillary renal cell carcinoma (PRCC) into type 1 and type 2 tumors. METHODS: From 1995 to 2004, 1358 patients underwent surgery for renal cell carcinoma, of whom 130 had PRCC alone on the specimen. The tumor characteristics, including their subtype, were analyzed; small basophilic cells and large eosinophilic cells were defined type 1 and type 2 tumors, respectively. Survival analyses were performed retrospectively. RESULTS: Of the 130 patients (110 men and 20 women, mean age 60.6 +/- 15.3 years) with PRCC, 102 underwent radical nephrectomy (78.4%) and 28 underwent partial nephrectomy (21.6%). The median tumor size was 4.5 cm (range 0.5 to 21). The comparison of the 68 (52.3%) type 1 PRCCs and 62 (47.7%) type 2 PRCCs revealed that type 2 tumors were associated with a greater stage and grade and microvascular invasion significantly (P <0.001) more often. The median follow-up was 48 months (range 2 to 111). Of the 130 patients, 22 died of cancer-specific causes, 5 (7%) with type 1 and 17 (27%) with type 2 tumors (P = 0.002). The overall and disease-free survival rate was 89% and 92% in type 1 tumors and 55% and 44% in type 2 tumors, respectively. Univariate analysis identified tumor type, stage (P <0.001), grade (P <0.001), microvascular invasion (P <0.001), an absence of foam cells (P <0.001), the presence of sarcomatoid cells (P = 0.001), and tumor necrosis (P = 0.007) as prognostic factors. Multivariate analysis retained tumor type (P = 0.034) and TNM stage (P <0.001). CONCLUSIONS: The results of our study have shown that histologic subtyping of PRCC allows for the identification of an independent prognostic factor.

Identification of risk factors for voiding dysfunction following TVT placement.

OBJECTIVE: To determine preoperative risk factors of postoperative voiding dysfunction after tension-free vaginal tape (TVT) procedure. METHODS: In 2004, 100 patients with genuine stress urinary incontinence underwent surgery by the TVT procedure. Preoperative and postoperative urodynamic study was performed for each patient. Postoperatively, patients' perception of result and quality of life were assessed on two validated scales, namely, Mesure du Handicap Urinaire (MHU) and Ditrovie. Voiding dysfunction was defined by a postoperative peak flow rate of <15 ml/s at 3 mo. Clinical and urodynamic parameters were compared and analysed. RESULTS: At 3 mo, 20 patients (20%) showed evidence of voiding dysfunction despite the absence of clinical symptoms in 14 of them (70%). Multivariate analysis showed that age (p<0.038) and preoperative peak flow rate (p<0.001) were independent risk factors for voiding dysfunction. Parity, menopausal status, body mass index, and maximal urethral closure pressure were not statistically related to the risk of voiding dysfunction. CONCLUSIONS: This study confirms the existence of an important rate of postoperative voiding dysfunction, mostly asymptomatic, and identifies age and preoperative maximal peak flow rate as independent preoperative risk factors. Identification of voiding dysfunction in patients may lead to better follow-up and early detection of late potential complications of suburethral procedures.

Age difference between patient and partner is a predictive factor of potency rate following radical prostatectomy.

PURPOSE: We evaluated the influence of partner age on postoperative erectile function in patients who underwent bilateral nerve sparing radical prostatectomy for localized prostate cancer. MATERIALS AND METHODS: The study group was a cohort of 240 consecutive patients treated with radical prostatectomy with a minimum 1-year followup. None had received adjuvant therapy. Evaluation was done by questionnaires mailed to a third party. Potency was defined by erection sufficient for sexual intercourse with vaginal penetration. A total of 200 patients were evaluable. RESULTS: The postoperative potency rate in 189 preoperatively sexually active patients was 59%. On univariate analysis patient age and the age difference between patient and partner were significantly associated with the potency rate following surgery, that is 60.8 and 6.8 years in the preserved potency group and 63.3 and 4.2 years in the impotent group (p <0.001 and p = 0.02, respectively). On multivariate analysis age difference was a predictive factor of postoperative potency independent of patient age (p = 0.008). Age difference was also an independent predictor of potency with and without aid (p = 0.037 and 0.002, respectively). CONCLUSIONS: To our knowledge this is the first study to identify the influence of age difference between patient and partner on potency preservation following radical prostatectomy. Age difference was a significant predictive factor of maintaining postoperative potency independent of patient age. We suggest that partner age difference should be reported in radical prostatectomy outcomes series because it influences postoperative potency rates. It is a new prognostic factor that might help counseling patients preoperatively.

[Bilateral pyelonephritis and emphysematous cystitis: an exceptional association]. / Pyélo-urétéronéphrite bilatérale et cystite emphysémateuses: une association exceptionnelle.

The authors report the case of a patient hospitalized for bilateral pyelonephritis and emphysematous cystitis requiring bilateral nephrostomy. This rare disease occurs in diabetic patients and is essentially due to Escherichia coli and Klebsiella pneumoniae. Treatment consists of antibiotics and renal drainage or nephrectomy. The prognosis is poor with a mortality rate greater than 50%.

Management of a malignant urinary fistula by ureteral embolization with coils.

We report the case of a 42-year-old man with a synovial sarcoma of the prostate, metastatic at presentation, who after aggressive chemotherapy followed by extensive surgery developed a complex pelvic fistula involving the lower ureter, bladder, and enteral structures. The patient was a poor candidate for surgery because of his short life expectancy and poor health status. Conservative management with bilateral nephrostomy tubes did not allow sufficient fistulous output for symptomatic relief. Using the percutaneous access already in place, we performed bilateral ureteral embolization with coils. Complete ureteral occlusion was obtained with a minimally invasive procedure and allowed total symptomatic relief.

[Sarcomatoid carcinoma with heterologous osteoid differentiation]. / Carcinome sarcomatoïde de vessie à différenciation ostéosarcomateuse.

Sarcomatoid carcinomas of the bladder with heterologous osteoid differentiation are exceptional, aggressive tumors with a poor prognosis. We report a new case, and discuss the clinical and pathological characteristics of this tumor.

Can pT0 stage of prostate cancer be predicted before radical prostatectomy?

OBJECTIVES: To report our experience with biopsy-proven pT0 prostate cancer over the last 10 yr. METHODS: We retrospectively analysed a series of 1950 consecutive patients treated with radical prostatectomy (RP) for clinically localized prostate cancer between 1996 and 2005 at our institution. The patients without residual tumour on RP specimen were defined as pT0 patients. The group of pT0 patients was compared with a control group of 295 patients operated consecutively during the same period. RESULTS: Overall, 11 (0.5%) patients were classified as pT0 on pathologic examination of the RP specimen. There was no pT0 tumour in the control group. Among the pT0 patients, five characteristics were particularly frequent: T1c clinical stage (90.9%), prostate-specific antigen (PSA) or=60 g (100%). All these characteristics were present in 8 of the 11 (72.7%) pT0 patients, while they were present in only 12 of the 295 (4.1%) controls. These parameters, when combined together, had a sensitivity of 72%, a specificity of 96%, and an accuracy of 99% for the prediction of pT0 stage. With a mean follow-up of 30 months after RP, no pT0 patient had clinical or biologic evidence of prostate cancer. CONCLUSIONS: In our experience, the rate of pT0 tumours after RP is 0.5%. The combination of clinical stage, preoperative PSA, number of positive biopsy cores, Gleason score, and prostate weight could help to predict pT0 stage after RP.

Is quantitative real-time RT-PCR an adjunct to immunohistochemistry for the evaluation of ErbB2 status in transitional carcinoma of the bladder?

OBJECTIVE: To test different approaches of evaluation of the ErbB2 status in a large series of human transitional cell carcinoma (TCC) of the bladder with the prospect of finding targeted therapies. METHODS: ErbB2 status of 73 human TCC samples was analyzed by both immunohistochemistry (IHC) and by quantification of mRNA levels of expression using real-time reverse transcription-polymerase chain reaction (RT-PCR). Additionally, 18 bladder samples were studied for ERBB2 gene amplification by real-time quantitative PCR. RESULTS: Twenty-five tumors (34.2%) overexpressed ERBB2 mRNA compared to normal bladder samples; this alteration appeared in low-grade and low-stage tumors (pTaG1). Twenty-four (32.9%) tumors showed moderate (++) or strong (+++) immunostaining. A very strong agreement was found between the two methods (kappa = 0.97, 95% confidence interval, 0.90-1). ErbB2 status was not associated with tumor stage. Of the 18 bladder samples tested for ERBB2 gene amplification, only one showed ERBB2 DNA amplification. CONCLUSIONS: ErbB2 overexpression occurs in about one third of bladder TCCs. This overexpression can be detected by RT-PCR with a very good correlation with IHC. RT-PCR can therefore be used for cases considered doubtful on IHC rather than gene amplification studies because, in TCC, gene amplification is not the predominant mechanism of both mRNA and protein overexpression. Accurate quantification of ErbB2 status is mandatory for the use of anti-ErbB2-targeted therapies in bladder TCC.

Gene expression profiling of ERBB receptors and ligands in human transitional cell carcinoma of the bladder.

PURPOSE: The ErbB driven growth pathway has been implicated in most human epithelial malignancies. Therefore, its blockade is a promising therapeutic strategy and several candidate drugs are currently undergoing clinical trials. Paradoxically little is known of the expression pattern or clinical significance of the 4 ErbB receptors and their 11 ligands in TCC of the bladder. MATERIALS AND METHODS: To obtain further insight into the molecular pathogenesis of TCC we used quantitative real-time reverse transcriptase-polymerase chain reaction assay to quantify mRNA expression of the 4 ERBB and their 11 known ligand genes, including recently described EPGN/epigen, in 73 tumor samples. RESULTS: The level of mRNA of 4 ligand genes (EGF, NRG1, NRG2 and NRG3) was extremely low, that is detectable but not quantifiable. Six genes were over expressed (ERBB2, TGFA, HB-EGF, AREG, EREG and EPGN), 3 were under expressed (ERBB1, ERBB4 and NRG4) and 2 were over or under expressed (ERBB3 and BTC). ERBB2 and AREG expression differed between early stage tumors (pTa grade 1) and normal samples. The most marked differences in expression were ERBB3, EREG and NRG4 between superficial and muscle invasive tumors (p = 0.0069, 0.00007 and 0.0000001, respectively), and TGFA and NRG4 between low and high grade superficial tumors, and between pT1 or greater and pTa tumors. CONCLUSIONS: This study shows the involvement of the ERBB family and ligand genes in TCC. Most receptor and ligand genes are deregulated at different stages of carcinogenesis, implying that they should be studied simultaneously. Quantitative real-time reverse transcriptase-polymerase chain reaction could be used to determine ErbB signaling pathway status in individuals with a view to tailored therapy.

Management of prostate cancer in China: a multicenter report of 6 institutions.

PURPOSE: In China the incidence of prostate cancer (PCa) is low and sparse data are available regarding its management. We analyzed the management of PCa at 6 Chinese urological institutions. MATERIALS AND METHODS: A retrospective analysis was performed of 431 consecutive patients treated for PCa at 6 Chinese institutions, including 5 in the divisions of Shanghai and 1 in the province of Chongqing, between January 2000 and December 2004. Tumor characteristics, therapeutic options and patient outcomes were recorded. RESULTS: At diagnosis median patient age was 72 years and median prostate specific antigen was 46.1 ng/ml. Most PCa cases were revealed by urinary symptoms (75.9%) or bone pain (12.8%). PCa was palpable on digital rectal examination in 74% of cases. At least 44 patients (10.2%) had metastases to lymph nodes at diagnosis and 112 (26%) had bone metastases. A total of 236 patients underwent bilateral orchiectomy and 100 received medical hormone therapy, which in 75% consisted of antiandrogen alone. At a median followup of 16.8 months 60% of these patients experienced biological recurrence. Radical prostatectomy was performed in 24 patients as monotherapy or in combination with bilateral orchiectomy. No patient with clinically localized PCa experienced biological recurrence after radical prostatectomy. CONCLUSIONS: The management of PCa in China differs from that in Western countries. To date surgical castration represents standard treatment. Screening detection of PCa could help detect earlier stage tumors and improve the outcome in patients.

Combination of gemcitabine and oxaliplatin in urothelial cancer patients with severe renal or cardiac comorbidities.

Clinical trials in urothelial cancer exclude a large population of patients. An observational study evaluated the behavior of frail patients not eligible for cisplatin- or carboplatin-based regimens. Urothelial cancer patients requiring chemotherapy with either chronic renal failure (creatinine clearance <60 ml/min), and/or performance status (PS) > or =2 and/or cardiac dysfunction were prospectively observed. The treatment associated gemcitabine 1200 mg/m and oxaliplatin 85 mg/m, bimonthly (GO). Over 2 years, 31 of 45 (69%) patients with urothelial cancer requiring chemotherapy were not eligible for cisplatin- or carboplatin-based chemotherapy. Sixteen (52%) had a PS > or =2, 23 (74%) had creatinine clearance <60 ml/min, and 20 (65%) had an underlying cardiopathy. A total of 178 cycles of GO were administered (median 6 per patient, range 2-12). No aggravation of renal or cardiac status was noted. Acute grade 3 and 4 neutropenia and thrombocytopenia were observed in 16 and 13% of patients, respectively, with one febrile neutropenia. The median progression-free and overall survival values were 4.2 and 9.5 months, respectively. The majority of urothelial cancer patients have severe renal or cardiac comorbidities, and we conclude that in this subset of patients the combination of gemcitabine and oxaliplatin is well tolerated, and its clinical activity warrants further evaluation.

Serum levels of vascular endothelial growth factor in patients undergoing prostate biopsy for suspicion of prostate cancer.

OBJECTIVES: To analyze the correlation between serum levels of vascular endothelial growth factor (VEGF) and biopsy findings in patients with a suspicion of prostate cancer. METHODS: Serum levels of VEGF were measured on frozen, archival serum obtained before prostate biopsy in 47 patients with clinical and/or biologic suspicion of prostate cancer. VEGF-A levels were measured using an enzyme-linked immunosorbent assay. RESULTS: The prostate biopsies showed cancer in 27 patients (group 1) and benign tissue in the remaining 20 patients (group 2). No statistically significant difference was found between the two groups in age, digital rectal examination findings, total prostate-specific antigen (PSA) levels, free PSA levels, and complexed PSA levels. The mean prostate volume was significantly lower in group 1 (45.5 g versus 53.9 g; P = 0.04), and the mean percentage of free PSA (free PSA/total PSA) was significantly lower in group 1 (11.3% versus 19%; P = 0.0003). Serum VEGF-A levels were not significantly different between the two groups. The mean VEGF level was 90.6 pg/mL in group 1 and 107.9 pg/mL in group 2 (P = 0.55). Multivariate analysis showed that VEGF-A levels were not predictive of prostate cancer. CONCLUSIONS: Our findings suggest that serum VEGF-A is not helpful to predict prostate cancer in patients with clinical and/or biologic suspicion of prostate cancer.