L.A. Rioja

The use of neural networks and logistic regression analysis for predicting pathological stage in men undergoing radical prostatectomy: a population based study.

PURPOSE Clinical under staging occurs in 40% to 60% of patients who undergo radical prostatectomy for prostate cancer. To decrease under staging several methods of predicting pathological stage preoperatively have been developed based on statistical logistic regression analysis and neural networks. To our knowledge none has been validated in our homogeneous regional patient population to date. We created logistic regression and neural network models, and implemented and adapted them into our practice. We also compared the 2 methods to determine their value and practicality in daily clinical practice. We present the results of our novel approach for predicting pathological staging of prostate adenocarcinoma. MATERIALS AND METHODS Between 1986 and 1999, 600 white men from the Aragon region of Spain underwent surgery for prostate cancer; of whom 468 were selected for study. Predictive study variables included patient age, clinical stage, biopsy Gleason score and preoperative prostate specific antigen (PSA). The predicted result included in analysis was organ confined or nonorgan confined disease. Data were analyzed by multivariate logistic regression and a supervised neural network (multilayer perceptron and radial basis function). Results were compared by comparing the areas under the receiver operating characteristics curves. RESULTS We generated 5 logistic regression models. The model created with clinical staging, Gleason biopsy score and PSA distributed in 5 categories (p <0.001) with an area under the receiver operating characteristics curve of 0.840 proved to be most predictive of pathological stage. Similarly of the 6 neural network models evaluated the radial basis function model, which included age, clinical stage, Gleason biopsy score and preoperative PSA distributed in 5 categories with an area under the curve of 0.882, proved the most predictive but not superior to the logistic regression model. The difference in the area under the curves in the 2 chosen models was 0.042 (p = 0.1). CONCLUSIONS It is possible to generate useful predictive models of organ confined disease using logistic regression or neural networks with high indexes of clinical and statistical validity. However, using these variables neural networks did not prove to be better than logistic regression analysis. Therefore, better predictive variables must be identified, preferably nonlinear characteristics with respect to the probability of organ confined tumor, to generate better predictive models using neural networks.

Improved Prediction of Biochemical Recurrence After Radical Prostatectomy by Genetic Polymorphisms

PURPOSE Single nucleotide polymorphisms are inherited genetic variations that can predispose or protect individuals against clinical events. We hypothesized that single nucleotide polymorphism profiling may improve the prediction of biochemical recurrence after radical prostatectomy. MATERIALS AND METHODS We performed a retrospective, multi-institutional study of 703 patients treated with radical prostatectomy for clinically localized prostate cancer who had at least 5 years of followup after surgery. All patients were genotyped for 83 prostate cancer related single nucleotide polymorphisms using a low density oligonucleotide microarray. Baseline clinicopathological variables and single nucleotide polymorphisms were analyzed to predict biochemical recurrence within 5 years using stepwise logistic regression. Discrimination was measured by ROC curve AUC, specificity, sensitivity, predictive values, net reclassification improvement and integrated discrimination index. RESULTS The overall biochemical recurrence rate was 35%. The model with the best fit combined 8 covariates, including the 5 clinicopathological variables prostate specific antigen, Gleason score, pathological stage, lymph node involvement and margin status, and 3 single nucleotide polymorphisms at the KLK2, SULT1A1 and TLR4 genes. Model predictive power was defined by 80% positive predictive value, 74% negative predictive value and an AUC of 0.78. The model based on clinicopathological variables plus single nucleotide polymorphisms showed significant improvement over the model without single nucleotide polymorphisms, as indicated by 23.3% net reclassification improvement (p = 0.003), integrated discrimination index (p <0.001) and likelihood ratio test (p <0.001). Internal validation proved model robustness (bootstrap corrected AUC 0.78, range 0.74 to 0.82). The calibration plot showed close agreement between biochemical recurrence observed and predicted probabilities. CONCLUSIONS Predicting biochemical recurrence after radical prostatectomy based on clinicopathological data can be significantly improved by including patient genetic information.

Malignant mesothelioma of the tunica vaginalis. Report of a case without risk factors and review of the literature.

Malignant mesothelioma of the tunica vaginalistestis is an aggressive tumour with localrecurrence being distant metastases the mainfeature of the clinical course. Usually appearsover the fourth decade, having a strongrelationship with occupational exposure toasbestos and long lasting hydrocele. Weintroduce a case of a 78-year-old caucasianmale who developed a malignant mesotheliomawithout personal history of hydrocele orexposure to asbestos. A revision of the currentliterature is performed to summarize the recenttherapeutic options as well as new diagnostictools.

Adult hydrocele and spermatocele.

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Evaluation of the duration of ureteral stenting following endopyelotomy: Animal study

Background: The purpose of the present paper was to evaluate whether it is possible to reduce the duration of ureteral stenting following endopyelotomy, and thus reduce side‐effects.

Atypical small acinar proliferation Review of a series of 64 patients

Objective. To study the evolution of 64 patients initially diagnosed with ASAP (atypical small acinar proliferation). Material and methods. Between 1998 and the end of 2003, 64 patients were diagnosed at our centre with ASAP. Results. The mean age of the patients assessed was 69 years (SD 6.4 years), the median prostate-specific antigen (PSA) level was 7.1 ng/ml (range 2–39 ng/ml) and 25% of the patients had a suspicious rectal examination. These 64 patients were subjected to re-biopsy. At re-biopsy, we diagnosed 27 patients (42%) with prostate adenocarcinoma. We classified patients into two groups depending on whether they did (n=27) or did not (n=37) have tumours. There were no significant differences in median PSA level between the two groups. The rectal examination was suspicious in 14% of patients without tumours and in 39% with tumours. Radical prostatectomy was applied to 20/28 patients (71%) diagnosed with prostate cancer. In these 20 patients, the median tumour volume was 0.4 cm3 (range 0.1–3.2 cm3) and 44% of the tumours were significant. The 37 patients with an unsuspicious histology were subjected to follow-up for a median of 12 months (range 1–30 months). The median PSA level in these patients was 5.7 ng/ml (range 0.8–28 ng/ml). A third biopsy was performed in three of these patients in view of an elevated PSA level, and one result was positive. Conclusions. In our experience, a pathological result of ASAP is associated with a definitive diagnosis of prostate cancer in 42% of cases. Moreover, a significant cancer was found in 44% of patients subjected to radical prostatectomy. We therefore systematically perform repeat biopsies on all patients with a histological result of ASAP.

Epidermal naevus syndrome (Solomon's syndrome) associated with bladder cancer in a 20-year-old female

Epidermal naevus syndrome was first described by Solomon et al. in 1968, based on a study of 12 patients. Herein we report the case of a 20‐year‐old female diagnosed with epidermal naevus syndrome at the age of 3 years. Subsequently she experienced several different symptoms and at the last exploration a suspicious lesion was found in her bladder. The definitive pathology diagnosis was transitional cell carcinoma of the bladder, which is extremely rare in patients aged <21 years. It seems that this neoplastic lesion was directly related to the essential pathology of the patient, namely epidermal naevus syndrome.

Association of steroid and xenobiotic receptor (SXR) and multidrug resistance 1 (MDR1) gene expression with survival among patients with invasive bladder carcinoma

What’s known on the subject? and What does the study add?

Significance of Protein p53 Overexpression in the Clinical Course of High-Risk Superficial Bladder Cancer

Objectives: This is a retrospective study in which the long-term biological behavior of 67 ‘high-risk’ superficial bladder tumors and the prognostic relevance (prediction of disease recurrence and progression) of the determination of the p53 phenotype in these cases were studied. Material and Methods: 67 tumors with a ‘high risk’ of progression were selected from the 1,103 transurethral resections for bladder cancer carried out in 640 patients in this center between 1987 and 1992. These included 39 T1G3, 14 Tis (isolated or associated with Ta-T1, non-G3 tumors), and 14 Ta-T1, non-G3 tumors with submucosal lymphatic affection (L+). The median follow-up of these cases was 69.7 months. An immunohistochemical technique with monoclonal antibodies (DO-7) was used to detect the p53 phenotype in paraffin-fixed material. Results: Tumor recurrence occurred in 31 patients (46.3%) and local or distant progression in 14 (20.9%). Radical cystectomy was carried out in 16 (23.9%) cases. p53 overexpression of ≧20% (‘p53+’) was detected in 40 tumors (59.7%). The rate of recurrence and progression, the disease and progression-free intervals, cancer-specific survival, disease-free survival and progression-free survival were similar in the 3 tumor groups (in all cases, p > 0.05). There were no significant differences in the overexpression of protein p53, using the standard cutoff point of 20% stained nuclei, on comparing the same variables in the whole group of 67 patients (in all cases, p > 0.05). Conclusion: The detection of protein p53 was not found to be of use in the retrospective prediction of disease progression or survival in ‘high-risk’ superficial bladder cancer.

New combined approach in metallic ureteral stenting to avoid urothelial hyperplasia: study in swine model.

PURPOSE We assessed the therapeutic value of a new treatment option for ureteral strictures that may avoid urothelial hyperplasia, which is the main cause of metallic stent failure. MATERIALS AND METHODS We used 24 pigs in this study. An experimental model of ureteral stricture was induced in all animals. Obstruction was confirmed by ultrasound and retrograde ureteropyelogram 6 weeks after model creation. The pigs were then randomly allocated to 2 experimental groups. Therapy involved placement of a 6 × 30 mm metallic ureteral covered stent in the ureteral stricture in group 1 and subsequent endoureterotomy at the ureteral segments adjacent to the 2 ends of the stent in group 2. A double pigtail stent was then deployed for 3 weeks. Completion studies 6 months after therapy included retrograde ureteropyelogram, endoluminal ultrasound and ureteroscopy to assess urothelial hyperplasia formation. RESULTS At the end of the study evidence of urothelial hyperplasia was seen in 50% of the pigs in group 1 and in 29% in group 2. Four and 2 cases of cranial stent migration in groups 1 and 2, respectively, were seen at 6 months. Hyperplasia and renal involvement were statistically significantly different between the groups with more damage in group 1 than in group 2. CONCLUSIONS Hyperplasia was markedly reduced when ureteral peristalsis was inhibited by endoureterotomy at the area of interaction between the stent and the ureter.