Association of oncofetal protein expression with clinical outcomes in patients with urothelial carcinoma of the bladder.

PURPOSE: Oncofetal proteins are expressed in the developing embryo. Oncofetal protein expression correlates with the clinical outcome of nonmuscle invasive bladder urothelial carcinoma. IMP3, MAGE-A, glypican-3 and TPBG are oncofetal proteins that have not been well characterized in urothelial carcinoma of the bladder. MATERIALS AND METHODS: We investigated the expression of these 4 proteins and their association with clinical outcomes using tissue microarrays from 384 consecutive patients treated with radical cystectomy between 1988 and 2003 at 1 academic center. We stained for IMP3, MAGE-A, glypican-3 and TPBG. Univariable and multivariable Cox regression analyses were done to evaluate the association of oncofetal protein expression with disease recurrence and cancer specific mortality. RESULTS: IMP3, MAGE-A, glypican-3 and TPBG were expressed in 39.5%, 45%, 6% and 85% of urothelial bladder carcinomas, respectively. Expression was tumor specific and did not correlate with pathological features except for TPBG. At a median followup of 128 months 176 patients (46%) experienced disease recurrence, 175 (45.5%) had died of the disease and 96 (27.5%) had died of another cause. On univariable analysis IMP3 and MAGE-A expression was associated with an increased risk of disease recurrence (p <0.001 and 0.03) and cancer specific mortality (p = 0.004 and 0.03, respectively). On multivariable Cox regression analysis adjusted for the effects of standard clinicopathological features IMP3 and MAGE-A expression was independently associated with disease recurrence (p = 0.004, HR 1.55, 95% CI 1.15-2.11 and p = 0.02, HR 1.44, 95% CI 1.05-1.99, respectively) but not with cancer specific mortality. CONCLUSIONS: Oncofetal proteins are commonly and differentially expressed in urothelial carcinoma of the bladder compared to normal urothelium. IMP3 and MAGE-A expression was associated with disease recurrence and cancer specific mortality but glypican-3 and TPBG expression was not.

The feasibility of ureteral tissue engineering using autologous veins: an orthotopic animal model with long term results.

BACKGROUND: In an earlier study we demonstrated the feasibility to create tissue engineered venous scaffolds in vitro and in vivo. In this study we investigated the use of tissue engineered constructs for ureteral replacement in a long term orthotopic minipig model. In many different projects well functional ureretal tissue was established using tissue engineering in animals with short-time follow up (12 weeks). Therefore urothelial cells were harvested from the bladder, cultured, expanded in vitro, labelled with fluorescence and seeded onto the autologous veins, which were harvested from animals during a second surgery. Three days after cell seeding the right ureter was replaced with the cell-seeded matrices in six animals, while further 6 animals received an unseeded vein for ureteral replacement. The animals were sacrificed 12, 24, and 48 weeks after implantation. Gross examination, intravenous pyelogram (IVP), H&E staining, Trichrome Masson's Staining, and immunohistochemistry with pancytokeratin AE1/AE3, smooth muscle alpha actin, and von Willebrand factor were performed in retrieved specimens. RESULTS: The IVP and gross examination demonstrated that no animals with tissue engineered ureters and all animals of the control group presented with hydronephrosis after 12 weeks. In the 24-week group, one tissue engineered and one unseeded vein revealed hydronephrosis. After 48 weeks all tissue engineered animals and none of the control group showed hydronephrosis on the treated side. Histochemistry and immunohistochemistry revealed a multilayer of urothelial cells attached to the seeded venous grafts. CONCLUSIONS: Venous grafts may be a potential source for ureteral reconstruction. The results of so far published ureteral tissue engineering projects reveal data up to 12 weeks after implantation. Even if the animal numbers of this study are small, there is an increasing rate of hydronephrosis revealing failure of ureteral tissue engineering with autologous matrices in time points longer than 3 months after implantation. Further investigations have to prove adequate clinical outcome and appropriate functional long-term results.

[Why outpatient surgery does not work in hospitals - or medical practices - as yet]. / Ambulantes Operieren: Warum es im Krankenhaus (noch) nicht klappt ­ und in der Praxis auch nicht.

High costs in the German health care system and a lack of nursing staff make a shift from inpatient to outpatient treatment unavoidable. The new catalogue announced for outpatient surgical procedures will contain up to 50% of all procedures in urology. In anticipation of these major changes, neither hospitals nor medical practices are able to prepare adequately since the precise catalogue, the infrastructural changes required, and the rules of remuneration have not yet been clarified. Without some degree of certainty for planning, nobody will be able or willing to invest into future structures.

Intensifying the saturation biopsy technique for detecting prostate cancer after previous negative biopsies: a step in the wrong direction.

OBJECTIVE: To report the results using an extensive saturation biopsy in men with negative prostate biopsies but in whom there is still a clinical suspicion for carcinoma. PATIENTS AND METHODS: Between February 1999 and October 2004 we offered 40 patients (median age 63 years) an extensive saturation biopsy if there was clinical suspicion of prostate cancer after previous negative prostate biopsies. The median (range) number of cores taken was 64 (39-139) and was adjusted to the size of the prostate. All patients received general or spinal anaesthesia. RESULTS: Of the 40 patients, 18 (45%) had carcinoma in at least one core; 16 had a radical prostatectomy, which showed pT2a, pT2b, pT2c, pT3a and pT3b adenocarcinoma of the prostate in three, four, six, two and one patients, respectively. Brachytherapy and external radiation were the therapies of choice in the other patients. Sixteen patients had marked haematuria after the biopsy procedure. CONCLUSION: There is no significant increase in the cancer detection rate in an extensive saturation-biopsy regimen compared to published series with fewer cores, but the morbidity increased.

Loss of SPINK1 expression is associated with unfavorable outcomes in urothelial carcinoma of the bladder after radical cystectomy.

BACKGROUND: We assessed the association of serine protease inhibitor Kazal type I (SPINK1) expression with clinicopathologic outcomes in urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC). MATERIALS AND METHODS: Tissue microarrays comprising 438 consecutive UCB patients treated with RC between 1988 and 2003 and 62 cases of normal urothelium controls were evaluated for SPINK1 protein expression by immunohistochemistry (IHC). Semiquantitative evaluation was performed by 2 pathologists blinded to clinical outcomes (loss of expression: <50% cells or intensity 0-2). RESULTS: In normal urothelium, SPINK1 expression was noted in umbrella cells of 32 of 62 controls (52%); 254 RC patients (57.9%) exhibited loss of SPINK1 expression. Loss of SPINK1 expression was significantly associated with higher pathologic stages (P = 0.002) and presence of lymph node metastasis (P = 0.04). At a median follow-up of 130 months (IQR: 98.4), loss of SPINK1 expression was associated with an increased risk of disease recurrence (P = 0.02) and cancer-specific mortality (P = 0.03). On multivariable analysis that adjusted for the effects of standard clinicopathologic parameters, SPINK1 was not an independent predictor of disease recurrence (P = 0.09) or cancer-specific mortality (P = 0.12). CONCLUSIONS: Over half of UCB patients treated with RC exhibit loss of SPINK1 expression. Loss of SPINK1 correlates with features of biologically aggressive UCB. Although SPINK1 expression did not have independent prognostic value in RC patients, it may serve as a biomarker for tumor staging and may be useful as an adjunct in clinical decision-making.

Pathological T0 prostate cancer without neoadjuvant therapy: clinical presentation and follow-up.

INTRODUCTION AND OBJECTIVES: Radical prostatectomy is a standard therapy for patients with prostate cancer diagnosed by prostatic needle biopsy, prostate cytology, transurethral resection of the prostate or prostatectomy. In a small group of patients no tumour can be found in the radical prostatectomy specimen. These cases are classified as stage pT0. The aim of this study was to evaluate the clinical presentation of this entity and their prognosis. MATERIAL AND METHODS: In a nation-wide database the clinical data of 3609 patients with prostate cancer were collected. 28 patients (0.8%) were staged as pT0 in the radical prostatectomy specimen. The data included age, prostate specific antigen (PSA), and pathological report at diagnosis, histology of the radical prostatectomy specimen and follow-up data. RESULTS: The diagnosis was made by TURP (transurethral resection of the prostate) in 15, prostatectomy in 2, needle biopsy in 11, and cytology in 2 patients. For patients who underwent TURP or prostatectomy the preoperative staging was T1a in 10 and T1b in 5 cases. 12 patients diagnosed by biopsy or cytology were classified T2a and one patient after biopsy as T2b. 9 patients had a GI- and 19 a GII-tumour, GIII-pattern was not represented. The mean age at diagnosis was 64.7 years (range 53-79 years). The PSA at the time of diagnosis was <4ng/ml in 8 cases; 4-10ng/ml in 16 cases and >10ng/ml in 4 patients. One patient presented with a micrometastasis in a single lymph node. Median follow-up was 62 months (19-150). All patients had undetectable PSA levels following surgery. No patient presented with clinical or biochemical progression. One patient died with no evidence of disease at 133 months after radical prostatectomy. CONCLUSIONS: None of the clinical parameters had a strong association with a pathologically proven T0 situation after radical prostatectomy in this setting. Interestingly no patient had a high-grade tumour. None of the patients classified as pT0 had a biochemical or clinical relapse during follow-up.

Outcome in patients with seminal vesicle invasion after radical cystectomy.

PURPOSE: We evaluated the impact of seminal vesicle invasion by transitional cell carcinoma of the bladder in a large cystectomy series. MATERIALS AND METHODS: Between January 1985 and February 2002, 1,125 cystectomies were performed at our 2 institutions. In 68 male patients there was pathologically proved tumor extension to the perivesical fat, prostatic stroma and/or seminal vesicles, including group 1: 38 to the prostatic stroma alone, group 2-12 to the seminal vesicles alone, and group 3-18 to the seminal vesicles and prostatic stroma. Complete followup was available for all patients. Overall disease specific and progression-free survival rates were calculated using the Kaplan-Maier-Method. Survival rates were compared using the log rank test. RESULTS: The overall 5-year survival rate for all 68 patients was 23.1%. The 5-year disease specific survival rates were 41.1%, 0% and 0%, and the 5-year progression-free survival rates were 32.1%, 0% and 0% for groups 1 to 3, respectively. Survival was significantly decreased in patients with seminal vesicle infiltration with or without prostatic stromal infiltration compared with prostatic involvement alone. This difference was independent of lymph node status in groups 1 versus 2 and 3. CONCLUSIONS: Seminal vesicle invasion by bladder carcinoma has a significant impact on disease specific and progression-free survival compared with prostatic stromal involvement alone.

Carbon-11 acetate positron emission tomography can detect local recurrence of prostate cancer.

We investigated the potential of [(11)C]acetate positron emission tomography (PET) to detect local recurrence in prostate cancer (PCA) in patients with increasing PSA following complete prostatectomy. A total of 31 patients were studied and compared with the results of transrectal ultrasound (TRUS) combined with biopsy and clinical follow-up. Whole-body PET scan was performed 5 min after injection of 0.8 GBq [(11)C]acetate and completed within 1 h. Focally increased tracer uptake below the urinary bladder or in an abdominal lymph node region was considered as relapse. TRUS followed by biopsy verified recurrence in 18 patients and ruled it out in 13 patients. PET demonstrated local recurrence in 15 out of the aforementioned 18 patients. PET also demonstrated distant lymph node involvement and bone metastases in five patients each. No focal [(11)C]acetate uptake was demonstrated in the prostate bed in patients with negative biopsy. These patients had no evidence of disease during 6 months of follow-up. In the subgroup of patients with PSA <2.0 ng/ml ( n=8), five patients had positive PET findings, with four of them verified by biopsy. It is concluded that [(11)C]acetate PET is a promising new tool for the diagnosis of PCA recurrence and can influence patient management.