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
Abstract 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%.
To evaluate the impact of metabolic syndrome and its individual components on prostate biopsy findings, the radical prostatectomy specimen and on biochemical recurrence.
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.
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).
Metabolic syndrome is associated with poorer findings in the radical prostatectomy specimens and is an independent prognostic factor of biochemical recurrence.
We have synthesized the principal advances in the field of the study of epigenetics and specifically DNA methylation regarding the diagnosis of urological neoplasms.
Review of the literature (PubMed, ...MEDLINE and Cochrane) on the study of DNA methylation in urological neoplasms (prostate cancer, bladder cancer, renal cancer and testicular cancer), considering all the studies published up to January 2013.
It was possible to determine the state of methylation of many genes in our tumor samples. When these were compared with healthy tissue samples, it was possible to define the specific aberrant methylation patterns for each type of tumor. The study and definition of specific abnormal methylation patterns of each type of tumor is a tool having potential utility for diagnosis, evaluation, prediction of prognosis and treatment of the different forms of genitourinary cancer. The analysis of gene methylation in urine after micturition or post-prostatic massage urine, semen, in the wash plasma or fluid from prostatic biopsies may allow early detection of bladder, prostate, renal and testicular cancer. In each one of the neoplasms, an epigenetic signature that may be detected in the DNA has been identified, obtained from very scarce or not at all invasive specimens, with potential in the diagnosis and evaluation of prognosis. Validation of these studies will confirm the accuracy, effectiveness and reproducibility of the results available up to now. Criteria have still not been developed that determine if a gene panel provides sufficient information in the health care practice to guide an unequivocal diagnosis or therapeutic conduct. More studies are needed to compare sensitivity, specificity, positive and negative predictive value of the test in each case. Multicenter studies analyzing the real reproducibility of these results in a clinical setting also do not exist.
The study of aberrant DNA methylation in biological specimens of patients has an enormous potential for the early diagnosis and screening of genitourinary neoplasms. A larger number of studies is needed to be able to define the series of genes that would mean unequivocal signatures of malignancy. This methodology also has potential when defining prognostic groups and potential of response to different therapies.
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.
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.
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).
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.
To study prostate and seminal vesicle anatomy in viable motheaten (mev) with mutations in PTPN6 gene leading to a severe reduction in the activity of protein tyrosine phosphatase SHP-1. Homozygous ...mev mice exhibit multiple anomalies that include immunodeficiencies, increased proliferation of macrophage, neutrophil, and erythrocyte progenitors, decreased bone density and sterility.
We analyzed macro- and microscopic anatomy of the seminal vesicle and prostate macro- and microscopic anatomy of 5 mev/mev and 8 wt/wt adult 7 week old mice. Computerized morphometric analysis was performed to measure the relative changes appearing in the epithelial volume of the different prostatic lobes.
All mice studied revealed normal genital organs (penis, testis, epididymis, vas deferens) and bladder. The seminal vesicle was absent in all mev/mev individuals analyzed, being normal and very noticeable in wt/wt mice. The different glands that compose the prostatic complex (anterior, ventral and dorso-lateral prostate) were atrophied in mev/mev mice: anterior prostate 0.4 times, ventral 0.19 times, dorsal 0.35 times and lateral 0.28 times those of the respective regions in wt/wt mice. Microscopically, mev/mev mice revealed scarce and large prostatic ducts, acini severely atrophic with empty lumen and scarce loose epithelial component forming tufts and infoldings, and hyperplastic changes in fibromuscular stroma.
The prostate of mev/mev mice exhibits signs of aberrant differentiation and the resulting phenotype may be related to the loss of function of SHP-1. Prostatic anomalies in these mice affect, together with defects in sperm maduration, for their sterility. These data suggest SHP-1 plays an important role in prostate epithelial morphogenesis.
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.
Objectives. To investigate the efficacy and tolerability of bicalutamide (Casodex) as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with localized or ...locally advanced (T1b-T4, any nodal status, M0) prostate cancer.
Methods. This was a multicenter, prospective, randomized, double-blind, placebo-controlled trial in Europe, South Africa, Australia, and Mexico and is part of the Casodex Early Prostate Cancer program.
Results. A total of 3603 men were randomized to receive bicalutamide (n = 1798) or placebo (n = 1805). The patient demographics were well balanced between the two groups. Prior therapy of curative intent had been given to 64% of the patients (prostatectomy 44%, radiotherapy 18%, and prostatectomy and radiotherapy 2%) and 36% had been monitored with watchful waiting. After a median follow-up of 2.6 years and a median exposure to the study drug of 2.2 years, a significant 43% reduction in the risk of objective progression was observed for the bicalutamide group compared with the placebo group (hazard ratio 0.57, 95% confidence interval 0.48 to 0.69,
P ≪0.0001). The time to prostate-specific antigen doubling was significantly delayed for the bicalutamide group compared with the placebo group (hazard ratio 0.37, 95% confidence interval 0.32 to 0.43,
P ≪0.001). The survival data were immature, with 7.2% overall mortality. The most frequently reported adverse events with bicalutamide were gynecomastia alone (17.4%), breast pain alone (17.6%), and gynecomastia with breast pain (47.5%).
Conclusions. Bicalutamide 150 mg daily as immediate therapy, alone or as adjuvant to treatment of curative intent, significantly reduced the risk of disease progression in patients with localized or locally advanced prostate cancer. Longer follow-up is underway to assess any benefit in overall survival.
To validate and analyze the clinical usefulness of a predictive model of prostate cancer that incorporates the biomarker “-2 pro prostate-specific antigen” using the prostate health index (PHI) in ...decision making for performing prostate biopsies.
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.
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.
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.
Validar y analizar la utilidad clínica de un modelo predictivo de cáncer de próstata que incorpora el biomarcador «–2 proantígeno prostático específico» a través del índice de salud prostática (PHI) en la toma de decisión para realizar una biopsia de próstata.
Se aisló suero de 197 varones con indicación de biopsia de próstata para la determinación del antígeno prostático específico total (tPSA), fracción libre de PSA (fPSA) y -2 proPSA (p2PSA); el PHI se calculó como p2PSA/fPSA×√tPSA. Se crearon 2 modelos predictivos que incorporaban variables clínicas junto a tPSA o a PHI. Se evaluó el rendimiento de PHI usando análisis de discriminación mediante curvas ROC, calibración interna y curvas de decisión.
Las áreas bajo la curva para el modelo tPSA y el modelo PHI fueron de 0,71 y 0,85, respectivamente. PHI mostró mejor capacidad de discriminación y mejor calibración para predecir cáncer de próstata, pero no para predecir un grado de Gleason en la biopsia ≥7. Las curvas de decisión mostraron un beneficio neto superior del modelo PHI para el diagnóstico de cáncer de próstata cuando el umbral de probabilidad está entre 15 y 35% y un mayor ahorro (20%) en el número de biopsias.
La incorporación de p2PSA a través de PHI a los modelos predictivos de cáncer de próstata mejora la exactitud en la estratificación del riesgo y ayuda en la toma de decisión sobre realizar una biopsia de próstata.
Determine whether the overexpression p53, MIB-1 and PECAM-1 of protein levels is of interest in predicting the prognosis of transitional cell carcinoma of the upper urinary tract (TCC-UUT) with the ...primary seat in the renal pelvis.
A univariate and multivariate analysis was conducted for prognosis prediction in a series of 82 patients with TCC-UUT of the renal pelvis who had no metastases at diagnosis (N0/Nx M0) and were treated exclusively with nephroureterectomy. We assessed clinicopathological parameters (age, gender, tumor grade and extent, histological variety, growth pattern, vascular invasion, infiltration of the renal parenchyma, tumor necrosis) and the immunohistochemical expression of p53, MIB-1 (ki-67) and PECAM-1 (CD31) in sections performed with tissue microarray (TMA).
A total of 47.6% of the patients had high-grade lesions according to the USIP-WHO classification. The growth pattern was flat in 15.85%. The distribution by T category was: 3.7% pTa, 51.2% pT1, 11% pT2, 29.3% pT3 and 4.9% pT4. The mean follow-up was 46.8+38.5 (range, 4-172) months. The median survival was reached at 57 (95% CI 44-63) months. The univariate analysis revealed that survival in these patients is associated with tumor size (P=.028), histological variety (P<.0001), growth pattern (P<.0001), grade (P<.0001), pT (P=.01), vascular invasion (P=.025), necrosis (P=.004) and overexpression of p53 (P=.0006), PECAM-1 (P=.0036) and MIB-1 (P=.0038). The Cox regression model showed that high-grade (HR, 4.2; 95% CI 1.28-13.79; P=.018), flat growth pattern (HR, 2.52; 95% CI 1.05-6.03; P=.038) and p53 overexpression (HR, 2.8; 95% CI 1.22-6.44; P=.015) were independent predictors.
Histological grade, tumor growth pattern and p53 overexpression were established as the primary predictors of prognosis for primary TCC-UUT of the renal pelvis. The independent value of MIB-1 observed in other studies was not reproduced in this study.
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