Comorbidity and performance indices as predictors of cancer-independent mortality but not of cancer-specific mortality after radical cystectomy for urothelial carcinoma of the bladder.

BACKGROUND: Comorbidity and performance indices allow assessment of preoperative health status. However, the optimal tool for use in patients with urothelial carcinoma of the bladder (UCB) who are undergoing radical cystectomy (RC) has not yet been established. OBJECTIVE: To evaluate correlation of Adult Comorbidity Evaluation-27 (ACE27), Charlson Comorbidity Index, Age-Adjusted Charlson Comorbidity Index, Eastern Cooperative Oncology Group performance status, and American Society of Anesthesiologists (ASA) score with survival. DESIGN, SETTING, AND PARTICIPANTS: A retrospective multicenter study was carried out on 555 unselected consecutive patients who underwent RC for UCB from 2000 to 2010. INTERVENTION: RC with pelvic lymph node dissection in patients with UCB without neoadjuvant chemotherapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox regression models were calculated with established variables to assess predictive capacity for cancer-specific mortality (CSM) and cancer-independent mortality (CIM). RESULTS AND LIMITATIONS: All indices were independent predictors for CIM but not for CSM. The ASA score was the only index that significantly increased the predictive accuracy of the predefined CIM model (+2.3%; p=0.045). To create a clinically valuable tool, we devised a weighted prognostic model including age and the best prognosticators within the performance and comorbidity scores (ASA/ACE27 0-1/2-3). A 3-yr CIM rate of 8%, 26%, and 47% was calculated for the low-, intermediate-, and high-risk groups, respectively. Patients >75 yr of age with ASA 3/4 and ACE27 >1 exhibited a CIM risk seven times greater than patients ≤75 yr with ASA 1/2 and ACE27 0/1. This study is limited by the short follow-up and its retrospective nature. CONCLUSIONS: Comorbidity and performance assessment is mandatory in the preoperative prediction of CIM for patients undergoing RC for UCB. The present results indicate that the ASA score is the tool of choice. External and prospective validation is warranted.

[Science in the crosshairs of enlightenment. Significance of hypothetical thinking]. / Wissenschaft im Fadenkreuz der Aufklärung. Zur Tragweite des hypothetischen Denkens.

To further the enlightenment primarily or even only by means of science was the hope of most representatives of the movement of the enlightenment which gave its name to a whole period of European cultural history. Only a few of its representatives, like Montesquieu and Rousseau, doubted for good reasons, whether and how the goals of the enlightenment can be reached at all by the means of science alone. In his Discours préliminaires to the Encyclopédie D'Alembert still wanted to limit science proper to the narrower field of those kinds of research which were strictly based on observations and calculations alone. In this way he remained committed to Descartes' ideal method of receiving authentic knowledge only by deduction from evident axioms or fundamental theorems. Pascal's casual discovery of the calculation of probabilities allowed to apply mathematics on the hidden laws of the apparent casualties of the human life world. Bacon's project of empirical science as a rational and methodological art of conducting experiments could replace the methodological ideal of science more geometrico. Lichtenberg's refined sensibility for the subjunctive linguistic forms of hypothetical thinking indicates a new understanding of inventing and testing hypotheses as the two most important methods of the experimental sciences when compared to the formal sciences of logic and mathematics. Whoever is studying the history of science of modern times in the cross wire of the enlightenment, will realize soon that science has always been in need of being illuminated about its own chances, risks and side effects. The project of enlightenment through science had to be complemented by the project of an enlightenment about science right from its beginning. Because of the implicit risks and side effects the project of enlightenment has to be enlightenment despite of science and because of science. On the one hand, as a special form of human practice the sciences are directed towards theoretical goals and practical purposes such that their agents cannot be conscious of all aspects of their practices in advance and reflect about all of them at the same time. On the other hand, the agents of such scientific practices are rarely trained, to analyze the cognitive implications of their own actions with the conceptual means of philosophical analysis. Furthermore, the agents of scientific research are hardly able to foresee the theoretical results of their research or even predict the chances and risks of eventual applications with the methods of the social sciences. Despite of the chastening experiences with the ambivalence of the theoretical results and practical applications of the modern sciences and despite of the illuminating effects of modern history and theory of science, contemporary scientists are not fully conscious yet of what they are really doing and what science really is. The contemplative ideal of scientific investigations for their own sake has been replaced in modern times by the practical ideal of scientific research in the service of humanity. The emancipation of the modem sciences from philosophical authorities and religious institutions has freed at first the sciences from alien restrictions to their self-chosen objects and purposes of research. However, the increasing economic constraints and the political dependences prevented even more so that scientists could realize the autonomy which the representatives of the enlightenment had been hoping for. KANT defined the goal of enlightenment as "man's emergence from his self-incurred immaturity". Quoting HORACE'S Sapere aude! he appealed to the courage of his comrades to use their own reason without the guidance of others in philosophical and especially in religious matters. Intellectual maturity as the proper goal of the enlightenment remained to be an undelivered promise despite of the emancipation of the sciences from traditional philosophical authorities and religious institutions. It is not only arguable whether or not enlightenment in this understanding is possible for most people, but also whether it is even desirable for all people considering the implicit ambivalence of the modern sciences. Kant's main philosophical works can be adequately interpreted as the first and unique attempt to understand the potential of the cognitive capacities of human beings about the chances and risks of enlightenment itself by means of a critical inquiry. This holds especially for the practical fruits of the enlightenment as, e.g., with respect to the emancipation from superstition and the appeal to religious tolerance, to the republican idea of the state and the establishment of civil and human rights, to the humanization of the law and execution of legal penalty as well as the unalienable rights of each individual human being.

High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European multicentric study.

PURPOSE: To describe the safety and efficacy of high-intensity focused ultrasound (HIFU) for the treatment of prostate cancer as assessed in a Phase II/III prospective multicentric clinical trial. PATIENTS AND METHODS: Patients (N = 402) presenting with localized (stage T(1-2)N(0-x)M(0)) prostate cancer between 1995 and 1999 at six European sites who were not candidates for radical prostatectomy were treated with HIFU under general or spinal anesthesia. Their mean age was 69.3 +/- 7.1 (SD) years, the mean prostate volume 28.0 +/- 13.8 cc, and the mean serum prostate specific antigen (PSA) concentration 10.9 +/- 8.7 ng/mL. Nearly all (92.2%) of the patients had one to four positive biopsy samples at baseline. The Gleason scores were 2 to 4 for 13.2% of the patients, 5 to 7 for 77.5%, and 8 to 10 for 9.3%. During the follow-up, random sextant biopsies and serum PSA measurements were performed. Any positive sample in biopsies performed after the last treatment session resulted in a "HIFU failure" classification. RESULTS: The patients received a mean of 1.4 HIFU sessions. The mean follow-up duration was 407 days (quartile 1 135 days, median 321 days, quartile 3 598 days). The negative biopsy rate observed in the T1-2 primary-care population was 87.2%. These results were also stratified according to the usual disease-related risk classification, and as much as a 92.1% negative biopsy rate was observed in low-risk patients. Nadir PSA results correlated with prostate size and the clinical procedure. CONCLUSION: These short-term results obtained on a large cohort confirm that HIFU is an option to be considered for the primary treatment of localized prostate cancer.