Outcomes of an enhanced recovery after radical cystectomy program in a prospective multicenter study: compliance and key components for success.

OBJECTIVE: To investigate the effect of an Enhanced Recovery After Surgery (ERAS) program on complications and length of stay (LOS) after radical cystectomy (RC) and to assess if the number and type of components of ERAS play a key role on the decrease of surgical morbidity. MATERIALS AND METHODS: We analyzed the data of 277 patients prospectively recruited in 11 hospitals undergoing RC initially managed according to local practice (Group I) and later within an ERAS program (Group II). Two main outcomes were defined: 90-day complications rate and LOS. As secondary variables we studied 90-day mortality, 30-day readmission and transfusion rate. RESULTS: Patients in Group II had a higher use of ERAS measures (98.6%) than those in Group I (78.2%) (p < 0.05). Patients in Groups I and II experienced similar complications (70.5% vs. 66%, p = 0.42). LOS was not different between Groups I and II (12.5 and 14 days, respectively, p = 0.59). The risk of having any complication decreases for patients having more than 15 ERAS measures adopted [RR = 0.815; 95% confidence interval (CI) 0.667-0.996; p = 0.045]. Avoidance of transfusion and nasogastric tube, prevention of ileus, early ambulation and a fast uptake of a regular diet are independently associated with the absence of complications. CONCLUSIONS: Complications and LOS after RC were not modified by the introduction of an ERAS program. We hypothesize that at least 15 measures should be applied to maximize the benefit of ERAS.

[Effectiveness and tolerability of zoledronic acid in the treatment of metastatic prostate cancer]. / Efectividad y tolerabilidad del acido zoledrónico en el tratamiento del cancer de próstata metastásico.

OBJECTIVES: To assess the effectiveness and tolerability of zoledronic acid in prostate cancer patients with bone metastases at the hormone-sensitive (HS) and hormone-independent (HI) stages. MATERIALS AND METHODS: A nationwide, observational, prospective, open and multi-centre trial was devised, with a total of 218 male patients diagnosed with prostate cancer at the HS stage (36%) or HI stage (64%) who were administered zoledronic acid (4 mg/IV/month for 6 months) in addition to their specific oncological treatment. Effectiveness was assessed by the following means: 1) Assessment of the improvement in pain and mobility; 2) Incidence and time to onset of skeletal-related events (SREs) and 3) Analysis of bone markers. Tolerability was assessed by means of registering the number and type of adverse effects. A satisfaction survey was carried out amongst the patients after the end of the trial. RESULTS: Out of the 218 patients, 170 (78%) were evaluable for effectiveness. A decrease in pain ratings at rest and during movement was observed in all patients, whether in the HS or HI groups (p < 0.0001). Improved mobility was observed likewise (p = 0.005), as was quality of life. The global incidence of skeletal events was 11.2%, with a time to onset of SREs of 10.7 months. There were no significant differences observed between HS vs. HI patients. Osteolysis markers (N-telopeptide) decreased significantly with the treatment across both the HS and HI groups. For safety reasons. 212 patients were evaluable (97.2%). The incidence of adverse drug reactions was 16% (34/212) and was found to be significantly higher in HS patients (22.4%) compared with HI patients (11.9%). Overall, the tolerability of zoledronic acid was good, with no significant morbidity in either group (HS and HI). 66% of the patients reported feeling satisfied or very satisfied. CONCLUSIONS: Zoledronic acid proved effective in the relief of pain, improving mobility and quality of life as well as reducing or delaying the occurrence of skeletal-related events in prostate cancer patients presenting metastatic bone disease, regardless of the phase, whether HS or HI, they found themselves in. Tolerability and patient satisfaction were rates as good.

Validation of the prostate health index in a predictive model of prostate cancer. / Validación del índice de salud prostática en un modelo predictivo de cáncer de próstata.

OBJECTIVES: To validate and analyse the clinical usefulness of a predictive model of prostate cancer that incorporates the biomarker «[-2] pro prostate-specific antigen¼ using the prostate health index (PHI) in decision making for performing prostate biopsies. MATERIAL AND METHODS: We isolated serum from 197 men with an indication for prostate biopsy to determine the total prostate-specific antigen (tPSA), the free PSA fraction (fPSA) and the [-2] proPSA (p2PSA). The PHI was calculated as p2PSA/fPSA×√tPSA. We created 2 predictive models that incorporated clinical variables along with tPSA or PHI. The performance of PHI was assessed with a discriminant analysis using receiver operating characteristic curves, internal calibration and decision curves. RESULTS: The areas under the curve for the tPSA and PHI models were 0.71 and 0.85, respectively. The PHI model showed a better ability to discriminate and better calibration for predicting prostate cancer but not for predicting a Gleason score in the biopsy ≥7. The decision curves showed a greater net benefit with the PHI model for diagnosing prostate cancer when the probability threshold was 15-35% and greater savings (20%) in the number of biopsies. CONCLUSIONS: The incorporation of p2PSA through PHI in predictive models of prostate cancer improves the accuracy of the risk stratification and helps in the decision-making process for performing prostate biopsies.

Bicalutamide (Casodex) 150 mg plus standard care in early non-metastatic prostate cancer: results from Early Prostate Cancer Trial 24 at a median 7 years' follow-up.

Trial 24, one of three ongoing trials in the Early Prostate Cancer programme, is evaluating the efficacy and tolerability of bicalutamide (Casodex) 150 mg following standard care (radiotherapy, radical prostatectomy or watchful waiting) in patients with early, non-metastatic prostate cancer. At 7 years' median follow-up, addition of bicalutamide significantly improved objective progression-free survival (PFS) for patients with locally advanced disease, reducing the risk of progression by 34% versus standard care alone (hazard ratio 0.66; 95% confidence interval 0.55, 0.79; P<0.001). In localized disease, a significant difference in objective PFS was not found. There was no significant difference in overall survival.

Do we need new high-risk criteria for surgically treated renal cancer patients to improve the outcome of future clinical trials in the adjuvant setting? Results of a comprehensive analysis based on the multicenter CORONA database.

BACKGROUND: Since there is still an unmet need for potent adjuvant strategies for renal cancer patients with high progression risk after surgery, several targeted therapies are currently evaluated in this setting. We analyzed whether inclusion criteria of contemporary trials (ARISER, ASSURE, SORCE, EVEREST, PROTECT, S-TRAC, ATLAS) correctly identify high-risk patients. METHODS: The study group comprised 8873 patients of the international CORONA-database after surgery for non-metastatic renal cancer without any adjuvant treatment. Patients were divided into potentially eligible high-risk and assumable low-risk patients who didn't meet inclusion criteria of contemporary adjuvant clinical trials. The ability of various inclusion criteria for disease-free survival (DFS) prediction was evaluated by Harrell's c-index. RESULTS: During a median follow-up of 53 months 15.2% of patients experienced recurrence (5-year-DFS 84%). By application of trial inclusion criteria, 24% (S-TRAC) to 47% (SORCE) of patients would have been eligible for enrollment. Actual recurrence rates of eligible patients ranged between 29% (SORCE) and 37% (S-TRAC) opposed to <10% in excluded patients. Highest Hazard Ratio for selection criteria was proven for the SORCE-trial (HR 6.42; p < 0.001), while ASSURE and EVEREST reached the highest c-index for DFS prediction (both 0.73). In a separate multivariate Cox-model, two risk-groups were identified with a maximum difference in 5-year-DFS (94% vs. 61%). CONCLUSION: Results of contemporary adjuvant clinical trials will not be comparable as inclusion criteria differ significantly. Risk assessment according to our model might improve patient selection in clinical trials by defining a high-risk group (28% of all patients) with a 5-year-recurrence rate of almost 40%.

Identification and functional properties of the pituitary adenylate cyclase activating peptide (PAC1) receptor in human benign hyperplastic prostate.

Pituitary adenylate cyclase activating peptide (PACAP) is a novel neuropeptide with regulatory and trophic functions that is related to vasoactive intestinal peptide (VIP). Here we investigate the expression of specific PACAP receptors (PAC1) and common VIP/PACAP receptors (VPAC1 and VPAC2) in the human hyperplastic prostate by immunological methods. The PAC1 receptor corresponded to a 60-KDa protein whereas the already known VPAC1 and VPAC2 receptors possessed molecular masses of 58 and 68 KDa, respectively. The heterogeneity of VIP/PACAP receptors in this tissue was confirmed by radioligand binding studies using [125I]PACAP-27 by means of stoichiometric and pharmacological experiments. At least two classes of PACAP binding sites showing different affinities could be resolved, with Kd values of 0.81 and 51.4 nM, respectively. The order of potency in displacing [125I]PACAP-27 binding was PACAP-27 approximately equal to PACAP-38 > VIP. PACAP-27 and VIP stimulated similarly adenylate cyclase activity, presumably through common VIP/PACAP receptors. The PAC1 receptor was not coupled to activation of either adenylate cyclase, nitric oxide synthase, or phospholipase C. It appears to be a novel subtype of PAC1 receptor because PACAP-27 (but not PACAP-38 or VIP) led to increased phosphoinositide synthesis, an interesting feature because phosphoinositides are involved via receptor mechanisms in the regulation of cell proliferation.

Effect of flutamide-induced androgen-receptor blockade on adenylate cyclase activation through G-protein coupled receptors in rat prostate.

The effect of the antiandrogen flutamide on the prostatic vasoactive intestinal peptide (VIP) receptor/effector system was studied in rats. Rats were s.c. injected with a daily dose of flutamide (15 mg/kg B.W.) or vehicle for 14 days. Drug treatment resulted in histological evidence of gland involution and increased plasma membrane fluidity as estimated by fluorescence spectroscopy. The number of VIP receptors and the stimulatory effect of VIP on adenylate cyclase activity in prostatic membranes decreased in flutamide-treated rats. However, the pattern of forskolin stimulation of the enzyme activity was not modified by this drug. Androgen-receptor blockade by flutamide also decreased the prostatic levels of alpha(s,) alpha(i1/2), and alpha(i3/0) G-protein subunits, as estimated by an immunological procedure. Whereas apoptotic DNA fragmentation was evidenced in prostate from 3-day castrated animals, a heterogeneous electrophoretic pattern was observed after flutamide treatment. Thus, androgen-receptor blockade by flutamide results in an important impairment of the components of the VIP receptor/effector system in rat prostate as well as in a modification of their coupling extent, which is presumably due to differences observed in plasma membrane fluidity. These results represent a crosstalk in the prostate between two mechanisms of signal transduction involved in cell proliferation.

Bicalutamide ('Casodex') 150 mg in addition to standard care in patients with nonmetastatic prostate cancer: updated results from a randomised double-blind phase III study (median follow-up 5.1 y) in the early prostate cancer programme.

Trial 24 is one of three placebo-controlled trials within the ongoing bicalutamide ('Casodex') Early Prostate Cancer (EPC) programme evaluating bicalutamide 150 mg/day in addition to radical prostatectomy, radiotherapy or watchful waiting for T1b-4, any N, M0 prostate cancer. In Trial 24, at 5.1 y median follow-up, the addition of bicalutamide significantly (P < 0.0001) improved objective progression-free survival (PFS) and prostate-specific antigen PFS compared with standard care alone. There was no significant difference in overall survival (P = 0.746). In the context of the whole EPC programme, long-term bicalutamide is not appropriate for localised disease, yet provides advantages in delaying disease progression in patients with locally advanced prostate cancer.

[Importance of heterotrimeric G proteins in prostate cancer molecular biology]. / Importancia de las proteínas G heterotriméricas en la biología molecular del cáncer de próstata.

OBJECTIVE: To deep in the knowledge of the involvement of G-protein alphas and alphai subunits in human prostate cancer. METHODS: Prostate tissue from 9 patients undergoing radical prostatectomy for prostate cancer and 5 controls undergoing cystoprostatectomy for bladder carcinoma. G-protein alphas and alphai subunits were studied for expression (mRNA by RT-PCR and protein by Western-blot), functionality (adenylyl cyclase activity, AC) and possibility of mutations (analysis with restriction enzymes and cDNA sequentiation). RESULTS: At mRNA level, the expression of alphas, alphai1, alphai2 y alphai3 was detected in healthy and cancerous tissues. At protein level, the expression of alphas y alphai1,2 diminished (25% and 40%, respectively) in prostate cancer. The expression of alphai3/0 also diminished, whereas that of beta subunit was not modified. Basal AC activity in adenocarcinoma membranes was 40% inferior to the control. Digestion with restriction enzymes Eag I or AlwN I did not allow to locate mutations in alphas. However, digestion at alphai2 level with BstU I enzyme served to observe a change of Gln205 (CAG triplet) to Pro (CCG). CONCLUSIONS: The functionality and expression of heterotrimeric G proteins are selectively modified in human prostate adenocarcinoma, occurring in addition some punctual mutation. The observed substitution of Gln205 by Pro may result in a low GTPase activity for alphai2 that, therefore, is stabilized in its active form.

The association between metabolic syndrome and prostate cancer: Effect on its aggressiveness and progression.

OBJECTIVES: To evaluate the impact of metabolic syndrome and its individual components on prostate biopsy findings, the radical prostatectomy specimen and on biochemical recurrence. MATERIAL AND METHODS: An observational study was conducted of 1319 men who underwent prostate biopsy between January 2007 and December 2011. The impact on the biopsy findings, the radical prostatectomy specimen and biochemical recurrence was evaluated using logistic regression and Cox regression. RESULTS: Of the 1319 patients, 275 (21%) had metabolic syndrome, and 517 prostate cancers were diagnosed. A greater percentage of metabolic syndrome was found among patients with prostate cancer than among patients without prostate cancer (25% vs. 18%; P=.002). Poorer results were found in the radical prostatectomy specimens (Gleason score ≥ 7, P<.001; stage ≥ T2c, P<.001; positive surgical margins, P<.001), and there was a greater percentage of biochemical recurrence in patients with metabolic syndrome than in those without metabolic syndrome (24% vs. 13%; P=.003). Metabolic syndrome behaved as an independent predictive factor of finding a Gleason score ≥ 7 for the specimen, as well as for finding a specimen stage ≥ T2c. Metabolic syndrome was also able to independently predict a greater rate of biochemical recurrence (OR: 3.6, P<.001; OR: 3.2, P=.03; HR: 1.7; respectively). CONCLUSIONS: Metabolic syndrome is associated with poorer findings in the radical prostatectomy specimens and is an independent prognostic factor of biochemical recurrence.

Evolution of the patient characteristics of candidates for radical prostatectomy and the results obtained with the technique.

OBJECTIVES: To evaluate the oncological profile and risk of biochemical recurrence of patients with prostate cancer who underwent radical prostatectomy based on the time period in which the patients were operated. To evaluate the differences in prostate-specific antigen (PSA) at diagnosis of patients with or without biochemical recurrence based on these time periods. MATERIAL AND METHODS: Observation carried forward study of a cohort of 972 radical prostatectomies performed during 3 time periods (1994-2000, 2001-2006, 2007-2011). The importance of PSA at diagnosis on the time periods and on biochemical recurrence was assessed using a generalized linear model. The independent predictive behavior of biochemical recurrence was analyzed using Cox regression. RESULTS: The median follow-up was 38 (16-76) months. PSA levels at diagnosis were higher in the period 1994-2000 (12.97ng/mL, P<.001). Seventy-two percent of the patients from the period 2007-2011 were diagnosed as clinical stage T1c (P<.001), compared with 55% from the period 1994-2000. The percentage of extracapsular extension in the specimen decreased from 27% to 18% from the period 1994-2000 to the period 2007-2011 (p<.001). The percentage of patients with biochemical recurrence went from 38% to 14% from the first to the third period (P>.001). The difference between PSA levels at diagnosis for the patients with or without biochemical recurrence was independent of the period (P=.84). The period during which surgery was performed was not an independent predictive factor for biochemical recurrence (P=.09). CONCLUSIONS: Patients from the 2007-2011 period had less extracapsular disease in the radical prostatectomy. The period was not an independent predictive factor for biochemical recurrence.

Effects of the luteinising hormone-releasing hormone (LH-RH) agonist leuprolide on adenylyl cyclase regulation through G-protein coupled receptors in rat ventral prostate.

Luteinising hormone-releasing hormone (LH-RH) agonists are widely used for the therapy of advanced prostate cancer through the suppression of testosterone secretion. Furthermore, recent studies indicate the existence of prostate LH-RH receptors coupled to signalling pathways resulting in direct antiproliferative effects. In order to shed light on the mechanisms through which these compounds inhibit prostate cell growth, we investigated the effects of leuprolide (a LH-RH agonist) treatment of rats compared with the effects of surgical castration on the behaviour of G-protein coupled receptors acting through adenylyl cyclase in the ventral prostate. Important decreases of both plasma testosterone levels and ventral prostate weight were observed 5 weeks after subcutaneous (s.c.) injection of a leuprolide-depot preparation (1.5 mg/kg body weight (b.w.)) or 5 days after bilateral gonadectomy. However, leuprolide treatment increased the number of vasoactive intestinal peptide (VIP) receptors and the ability of this neuropeptide to stimulate adenylyl cyclase activity in prostate membranes, whereas surgical castration decreased both parameters. Moreover, leuprolide resulted in significant increases of prostate alpha(s) and alpha(i1-3) (but not alpha(i1) and beta) G-protein levels, while the four G-protein subunits were overexpressed after gonadectomy. The estimation of alpha(s) and alpha(i) activity by experiments with Gpp[NH]p and forskolin indicated a potentiation of the two arms of adenylyl cyclase regulation in leuprolide-treated rats. Present observations suggest that leuprolide treatment leads to an antimitogenic response by acting mainly through the activation of Gi proteins negatively coupled to adenylyl cyclase.

Estrogen receptors alpha and beta in the normal, hyperplastic and carcinomatous human prostate.

Two different estrogen receptors (ER-alpha and ER-beta) have been described, which are differentially involved in regulating the normal function of reproductive tissues. ER-alpha was considered for a long time to be the only estrogen receptor, and it has been detected in the stromal cells of the human prostate but not in the epithelium. To obtain new information about the differential effects of both receptor types, we have investigated their localization in normal prostates, benign prostatic hyperplasia (BPH), and prostatic cancer (PC) by immunohistochemistry, ELISA and Western blot. Epithelial immunostaining was absent in normal prostates and was present in BPH (10% of cells) and PC (80% of cells), whereas about 15% of stromal cells were positively immunostained for ER-alpha in the three types of prostatic specimens studied. Epithelial immunostaining for ER-beta was detected in normal prostates (13% of cells), BPH (30% of cells) and PC (79% of cells), whereas stromal immunostaining for ER-beta was absent in normal and hyperplastic prostates and was present in PC (12% of cells). The complementary presence of both receptor types in the normal prostate (ER-beta in the epithelium and ER-alpha in the stroma) might explain the mechanism of estrogen action in the development of BPH. The increased epithelial immunostaining for both ER-alpha and ER-beta in BPH and PC suggests that the involvement of estrogen receptors in hyperplasia and cancer concerns mainly the epithelium.

One-incision nephroureterectomy endoscopically assisted by transurethral ureteral stripping.

OBJECTIVES: Ureteral endoscopic surgery has been proposed as the first step of nephroureterectomy, either open or laparoscopic, to obviate the low abdominal incision. We present our experience with a technique of one-incision nephroureterectomy endoscopically assisted by transurethral ureteral stripping. METHODS: Standard nephrectomy is performed after placement of a Chevassu ureteral catheter. The lumbar ureter is sectioned and the catheter tip tied to the top of the distal portion of the ureter, which is later intussuscepted when the catheter is pulled out. Transurethral resection through the muscular wall and into the perivesical fat is performed around the everted ureteral orifice, and the bladder spontaneously closes with an indwelling Foley catheter. Since 1989, we have used this technique in 21 patients with urothelial malignancies of the renal pelvis or calyces (15 patients), renal cell carcinoma (2 patients), renal cholesteatoma (1 patient), or reflux nephropathy (3 patients). RESULTS: Two patients required a low abdominal incision for removal of retained ureter after unsuccessful stripping. The rest underwent this procedure without complications or adverse effects. Mean follow-up was 44.6 +/- 11.4 months (range 4 to 76). Three patients presented with bladder tumor but no recurrences were detected in the resected area of the bladder or the retroperitoneum. CONCLUSIONS: Endoscopically assisted nephroureterectomy allows removal of an adequate cuff of bladder with the distal ureter and generally obviates extending the incision or performing a second one. It can be an attractive option in selected cases, without apparent risk of neoplastic urine contamination in the retroperitoneum.

Adenocarcinoma of the rete testis.

To date, no studies have evaluated adenocarcinoma of the rete testis statistically, because reports have been limited to single cases or series of 2 cases only. Univariate and multivariate analyses on disease-free survival have been performed after combining all data available in the literature with our own. Information about disease-free survival has been collected in 38 patients. As many as 40% of them died within the first year of diagnosis. Three and 5-year disease-free survival was 49% and 13%, respectively. We have not detected any difference in survival between age groups or side of the lesion. Similarly, statistical difference cannot be proved between survival of tumors with nodular infiltrating or cystic growth pattern, although it has been suggested that these two varieties represent different tumor types from a gross and microscopic morphologic point of view. Univariate analysis reveals that tumor stage, tumor size, and therapy may have an influence on survival. Tumors that are organ-confined and small lesions (testicular mass < 5 cm in maximum diameter) behave definitely better than those disseminated at diagnosis or of a bigger size. Surprisingly, tumor size is not associated with tumor stage or histologic growth pattern (nodular infiltrating versus predominantly cystic). With regard to therapy, cases in which RPLND has been performed as part of the therapy behave better in univariate analysis, while patients who receive radiation do worse. Most probably these facts reflect that patients with clearly advanced disease where local control cannot be achieved by surgery tend to undergo palliative treatment by radiation. On the other hand, RPLND tends to be performed in patients in whom there is no evidence of distant spread. Therefore, it would really be the primary stage that would set the prognosis rather than the consequent treatment, and neither radiation therapy nor RPLND would be true independent variables. Similarly, no significant difference is observed when patients receive chemotherapy. Cox's regression analysis reveals size of the testicular tumor as the only independent predictor of survival. Stage at diagnosis does not have an influence by itself and neither does any form of therapy. In this sense, the negative effect of radiotherapy is eliminated. We are aware that the results drawn from a literature review are far from ideal, but there is not enough evidence to suggest an optimal sequence of treatment for this rare malignancy. To date, no effective chemotherapy has been found. Whenever the tumor is resectable, there appears to be merit in an RPLND.(ABSTRACT TRUNCATED AT 400 WORDS)

Muscularis mucosa differentiates two populations with different prognosis in stage T1 bladder cancer.

OBJECTIVES: Contrary to previous belief, the existence of a muscularis mucosa in the human urinary bladder has now been well described. Although the degree of development of this structure seems variable, it can frequently be used to differentiate two levels within the subepithelial connective tissue: the lamina propria and the submucosa. The present study evaluates whether this morphologic feature is potentially useful for the identification of two populations with Stage T1 bladder cancer: those with tumor invasion confined to the lamina propria (pT1A) and those with tumors infiltrating into the submucosa (pT1B). METHODS: A series of 170 Stage T1 papillary bladder tumors was analyzed pathologically to identify the level of subepithelial connective tissue invasion. Both the reproducibility of such a differentiation and its prognostic implication were evaluated using Kaplan-Meier survival estimates and the Cox regression model. RESULTS: In specimens from transurethral resection, categorization into T1A or T1B could be performed in 98 of 170 cases (58% of specimens). Such differentiation proved to be of prognostic value with significantly different 5-year survivals between the two subcategories (pT1A [n = 50] vs pT1B [n = 49]) (log-rank, P < 0.02). Cox's regression analysis of pT1 subcategory and grade was performed in the 99 cases in which the differentiation between pT1A/pT1B could be made. This demonstrated that the depth of subepithelial connective tissue invasion was an independent prognostic factor (P < 0.05). CONCLUSIONS: The depth of tumor infiltration can be assessed in a considerable proportion of Stage T1 bladder neoplasms. The present study validates the prognostic significance of such a distinction both by Mantel-Haenszel life table method and Cox's regression analysis.

Immunoexpressions of p21, Rb, mcl-1 and bad gene products in normal, hyperplastic and carcinomatous human prostates.

A comparative study of the expression of p21, Rb, mcl-1, and bad gene products, which are involved in the control of the cell cycle, was performed in normal, hyperplastic, and carcinomatous human prostates by means of a semiquantitative immunochemical study. This included Western blot, ELISA, and immunohistochemistry procedures. In normal prostates, immunoexpression of the four gene products was scanty or absent. In men with benign prostatic hyperplasia, immunoreactions to the four proteins studied were found in many epithelial cells and some stromal cells. In prostatic carcinoma, the immunostaining pattern was as in hyperplastic prostates but the numbers of both epithelial and stromal cells were higher. Present results indicate that immunoexpression of p21, Rb (both the phosphorylated and dephosphorylated forms), mcl-1, and bad gene products are markedly increased in prostates with proliferative alterations but that these proteins do not discriminate between benignant (hyperplasia) and malignant (adenocarcinoma) prostatic tumours, although immunoexpression is higher in prostatic carcinoma.

Retroperitoneal fibrosis in a patient with Parkinson's disease treated with pergolide.

We describe a 68-year-old patient with Parkinson's disease who developed retroperitoneal fibrosis during pergolide treatment. Because pergolide is an ergot derivative, it could be related to the development of this complication.

In vivo proton magnetic resonance spectroscopy of diseased prostate: spectroscopic features of malignant versus benign pathology.

In vivo Proton Magnetic Resonance Spectroscopy appears potentially useful for non-invasive discrimination between benign prostatic hyperplasia (BPH) and prostate carcinoma (PC). Aiming to delimit the range within which spectra from one or the other pathology should occur, and establish extreme spectroscopic features of malignant versus benign prostate disease, we performed endorectal proton MR spectroscopy on 20 patients severely affected of either benign prostatic hyperplasia (BPH) (n = 10) or prostate cancer (PC) (n = 10). They were selected on the basis of the large volume and homogeneity of their lesions, which were histologically confirmed after spectroscopy. Consequently, high-quality short-TE proton spectra with well-resolved metabolite signals, and practically free of volume averaging issues were obtained in all cases. Apart from the typical citrate, creatine, and choline signals of prostate spectra, both BPH and PC spectra showed a peak centered at 3.6 ppm which was assigned to myo-inositol. The intensity of this contribution was found significantly increased in PC cases compared to BPH. Possible relationships between neoplastic transformation and the metabolic pathways in which myo-inositol participates are discussed. Average spectroscopic profiles were calculated for both advanced pathologies, and showed obvious differentiated features. In quantitative terms, the ratio of citrate to choline peak areas as well as that of creatine to myo-inositol appeared as the most convenient to discriminate between advanced PC cases (both ratios below 1.0) and advanced BPH cases (both ratios above 1.0).

[Cytogenetic analysis of transitional cell carcinoma of the bladder, stage B (pT2-3a/pN0)]. / Análisis citogenético del carcinoma de células transicionales de vejiga estadio B (pT2-3a/pN0).

Muscle-invading urothelial carcinoma of the bladder, stage B of the Jewett-Marshall Scale (T2-T3a/pN0), treated effectively with radical cystectomy, is known to be a highly curable disease. But certain difficulties arise when it comes to apply the traditional morphological factor to the prognosis of this population, partly due to their relative small numbers and the lack of prospective studies on the subject. Apart from the presence or absence of lymph invasion, it is unclear whether the prognostic factors of poor evolution in tumours are also valid in more invasive lesions. This paper presents the cytogenetic study conducted in 7 patients with Stage B urothelial carcinoma in cystectomy portions. All of them showed favourable evolution except for one case with associated profusion of marker chromosomes and tetraploidy. As it has already been shown in Stage T1 vesical carcinoma, this association almost certainly carries a major predictive value of poor prognosis in the muscle-invading localized disease.