ABSTRACT Purpose: The 8th edition of the TNM has been updated and improved in order to ensure a high degree of clinical relevance. A major change in prostate includes pathologically organ - confined disease to be considered pT2 and no longer subclassified by extent of involvement or laterality. The aim of this study was to validate this major change. Materials and Methods: Prostates were step - sectioned from 196 patients submitted to radical prostatectomy with organ confined disease (pT2) and negative surgical margins. Tumor extent was evaluated by a semiquantitative point count method. The dominant nodule extent was recorded as the maximal number of positive points of the largest single focus of cancer from the quadrants. Laterality was considered as either total tumor extent (Group 1) or index tumor extent (Group 2). Time to biochemical recurrence was analyzed with the Kaplan - Meier product limit analysis and prediction of shorter time to biochemical recurrence with Cox proportional hazards model. Results: In Group 1, 43 / 196 (21.9%) tumors were unilateral and 153 / 196 (78.1%) bilateral and in Group 2, 156 / 196 (79.6%) tumors were unilateral and 40 / 196 (20.4%) bilateral. In both groups, comparing unilateral vs bilateral tumors, there was no significant clinicopathological difference, and no significant association with time as well as prediction of shorter time to biochemical recurrence following surgery. Conclusions: Pathologic sub - staging of organ confined disease does not convey prognostic information either considering laterality as total tumor extent or index tumor extent. Furthermore, no correlation exists between digital rectal examination and pathologic stage.

ABSTRACT Introduction: In view of the detailed histologic evaluation of prostate cancer (PC), it is usually advisable to provide a “second opinion” to confirm diagnosis. This study aimed to compare the Gleason score (GS) of initial diagnosis versus that of histopathologic review of patients with PC. The secondary objective was to compare initial GS versus histopathologic review versus post - surgical histopathology. Material and methods: Retrospective study based on chart review of patients with PC that attended the Uro - oncology Department of Hospital das Clínicas - UNICAMP - Campinas, Brazil, from April, 2002, to April, 2012. Data were divided in groups: patients with biopsies performed elsewhere, biopsies after pathological review and histopathological results following retropubic radical prostatectomy (RRP). These were evaluated in relation to GS difference using Fleis's Kappa concordance coefficient. Results: 402 PC patients, with a median age of 66 years, were evaluated. Reviewed GS showed worsening, with accuracy of 61.2%, and Kappa concordance value = 0.466. Among 143 patients submitted to surgery, GS varied widely, regarding initial evaluation, review and post - surgical RRP. Joint concordance of evaluations was weak (Kappa = 0.216), mainly due to almost no existence concordance between initial evaluation and following RRP (Kappa = 0.041). Conclusion: There is a great histopathological variation of initial GS versus reviewed GS. There is also a better correlation of reviewed GS and post - surgical GS than with initial GS. The second opinion by an uropathologist improves diagnosis and should be advised for better therapeutic decision.

ABSTRACT Purpose To find any influence on prognostic factors of index tumor according to predominant location. Materials and Methods Prostate surgical specimens from 499 patients submitted to radical retropubic prostatectomy were step-sectioned. Each transverse section was subdivided into 2 anterolateral and 2 posterolateral quadrants. Tumor extent was evaluated by a semi-quantitative point-count method. The index tumor (dominant nodule) was recorded as the maximal number of positive points of the most extensive tumor area from the quadrants and the predominant location was considered anterior (anterolateral quadrants), posterior (posterolateral quadrants), basal (quadrants in upper half of the prostate), apical (quadrants in lower half of the prostate), left (left quadrants) or right (right quadrants). Time to biochemical recurrence was analyzed by Kaplan-Meier product-limit analysis and prediction of shorter time to biochemical recurrence using univariate and multivariate Cox proportional hazards model. Results Index tumors with predominant posterior location were significantly associated with higher total tumor extent, needle and radical prostatectomy Gleason score, positive lymph nodes and preoperative prostate-specific antigen. Index tumors with predominant basal location were significantly associated with higher preoperative prostate-specific antigen, pathological stage higher than pT2, extra-prostatic extension, and seminal vesicle invasion. Index tumors with predominant basal location were significantly associated with time to biochemical recurrence in Kaplan-Meier estimates and significantly predicted shorter time to biochemical recurrence on univariate analysis but not on multivariate analysis. Conclusions The study suggests that index tumor predominant location is associated with prognosis in radical prostatectomies, however, in multivariate analysis do not offer advantage over other well-established prognostic factors.

ABSTRACT Introduction Endometriosis is a disease with causes still unclear, affecting approximately 15% of women of reproductive age, and in 1%-2% of whom it may involve the urinary tract. The bladder is the organ most frequently affected by endometriosis, observed around 85% of the cases. In such cases, the most effective treatment is partial cystectomy, especially via videolaparoscopy. Study Objective, Design, Size and Duration In order to identify and delimit the extent of the intravesical endometriosis lesion, to determine the resection limits, as well as to perform an optimal reconstruction of the organ aiming for its maximum preservation, we performed a cystoscopy simultaneously with the surgery, employing a modified light-to-light technique in 25 consecutive patients, from September 2006 to May 2012. Setting Study performed at Campinas Medical Center – Campinas – Sao Paulo – Brazil.Participants/materials, setting and methods: Patients aged 27 to 47 (average age: 33.4 years) with deep endometriosis with total bladder involvement were selected for the study. The technique used was conventional laparoscopy with a transvaginal uterine manipulator and simultaneous cystoscopy (the light-to-light technique). A partial videolaparoscopic cystectomy was performed with cystoscopy-assisted vesical reconstruction throughout the entire surgical time. The lesions had an average size of 2.75cm (ranging from 1.5 to 5.5cm). The average surgical time was 137.7 minutes, ranging from 110 to 180 minutes. Main Results Postoperative follow-up time was 32.4 months (12-78 months), with clinical evaluation and a control cystoscopy performed every six months. No relapse was observed during the follow-up period. Conclusions A cystoscopy-assisted partial laparoscopic cystectomy with a modified light-to-light technique is a method that provides adequate identification of the lesion limits, intra or extravesically. It also allows a safe reconstruction of the organ aiming for its maximum preservation.

ABSTRACT Introduction and Objectives: Reactive Stroma (RStr) is observed in many human cancers and is related to carcinogenesis. The objectives of the present study were to stablish a relationship of the RStr microenvironment with prostate cancer (Pca) through a morphological and molecular characterization, and to identify a possible relationship between RStr with worse prognosis factors and occurrence of malignant prostatic stem cells. Materials and Methods: Forty prostatic samples were selected from men with Pca diagnosis submitted to radical prostatectomy; they were divided in two groups: Group-1 (n=20): samples without reactive stroma; Group-2 (n=20): samples of PCa with intense stroma reaction. Prostatic samples were evaluated for RStr intensity by Masson Trichromic stain and posteriorly submitted to histopathological and immunohistochemistry analysis for antigens: α-actin, vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA, AR, Erα and ERβ. Results: Reactive stroma with intense desmoplastic reactivity was significantly more frequent in intermediate (Gleason 7, 3+4) and high grade tumors (Gleason 7, 4+3). The group with intense stromal reactivity showed significant higher levels of Vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA and ERα. Conclusions: It can be concluded that RStr may be a predictive marker of Pca progression, since it was associated with increase of growth factors, imbalance of androgen and estrogen receptors and presence of malign prostatic stem cells.

Objective The aim of active surveillance of early prostate cancer is to individualize therapy by selecting for curative treatment only patients with significant cancer. Epstein’s criteria for prediction of clinically insignificant cancer in surgical specimens are widely used. Epstein’s criterion “no single core with >50% cancer” has no correspondence in linear extent. The aim of this study is to find a possible correspondence. Materials and Methods From a total of 401 consecutive patients submitted to radical prostatectomy, 17 (4.2%) met criteria for insignificant cancer in the surgical specimen. The clinicopathologic findings in the correspondent biopsies were compared with Epstein’s criteria for insignificant cancer. Cancer in a single core was evaluated in percentage as well as linear extent in mm. Results Comparing the clinicopathologic findings with Epstein’s criteria predictive of insignificant cancer, there was 100% concordance for clinical stage T1c, no Gleason pattern 4 or 5, ≤2 cores with cancer, and no single core with >50% cancer. However, only 25% had density ≤0.15. The mean, median and range of the maximum length of cancer in a single core in mm were 1.19, 1, and 0.5-2.5, respectively. Additionally, the mean, median, and range of length of cancer in all cores in mm were 1.47, 1.5, and 0.5-3, respectively. Conclusion To pathologists that use Epstein’s criteria predictive of insignificant cancer and measure linear extent in mm, our study favors that “no single core with >50% cancer” may correspond to >2.5 mm in linear extent.

Purpose To compare dietary, lifestyle, clinical, anthropometric, genetic and prostatic features of Brazilian Indians and non-Indians (Amazon). Methods 315 men, 228 Indians and 89 non-Indians, ≥40 years old were submitted to digital rectal examination, serum prostate specific antigen (PSA), testosterone, TP53 and GSTP1 genotyping, anthropometric, lifestyle, dietary, personal and familial medical history. Prostatic symptoms were evaluated with the International Prostate Symptom Score (IPSS). Results Macuxis and Yanomamis represented 43.6% and 14.5% of Indians respectively who spontaneously referred no prostate symptoms. Mean IPSS was 7, range 3-19, with only 15% of moderate symptoms (score 8-19); Mean age was 54.7 years, waist circumference 86.6 cm, BMI 23.9 kg/m2. Yanomamis presented both lower BMI (21.4 versus 24.8 and 23.3, p=0,001) and prostate volume than Macuxis and “other ethnic groups” (15 versus 20, p=0.001). Testosterone (414 versus 502 and 512, p=0.207) and PSA (0.48 versus 0.6 and 0.41, p=0.349) were similar with progressive PSA increase with aging. Val/Val correlated with lower PSA (p=0.0361). Indians compared to control population presented: - TP53 super representation of Arg/Arg haplotype, 74.5% versus 42.5%, p<0.0001. -GSTP1 Ile/Ile 35.3% versus 60.9%; Ile/Val 45.9% versus 28.7%; Val/Val 18.8% versus 10.3%; p=0.0003. Conclusions Observed specific dietary, lifestyle, anthropometric and genetic profile for TP53 and GSTP1 may contribute to Brazilian Indian population prostate good health.

Objectives At present there are several drugs for the treatment of advanced renal cell carcinoma (ARCC). The main objective of this work was to perform a systematic review (SR) and meta-analysis (MA) of clinical randomized studies that compared target cell therapies (TCT). Materials and Methods SR identified clinical randomized trials that compared TCT versus interferon-alpha in the treatment of patients with ARCC. In order to analyze efficiency, it was evaluated free-survival progression (FSP), total survival (TS) and response rate (RR). Results In relation to first line treatment, seven studies of TCT were identified using sunitinib, sorafenib, bevacizumab and temsirolimus; and two studies with sorafenib and everolimus for second line treatment. Relative risk (RRi) of MA for FSP of first line therapies was: 0.83, CI = 0.78-0.87, I2 = 94% and p < 0.00001. Best results of RR of specific FSP among studies were: 0.38, sunitinib, CI = 0.25-0.58, bevacizumab, 0.62, CI = 0.47-0.83; and temsirolimus, 0.78, CI = 0.70-0.87. MA didn't show any benefit regarding TS of first line treatment of all analyzed drugs. As for RR significant results were: sunitinib, 3.83 CI = 2.86-5.12; bevacizumab, 2.52 CI = 1.78-3.57 and bevacizumab, 1.97 CI = 1.43-2.71. Conclusions: For first line treatment, sunitinib was the most effective TCT in relation to FPS; there was no alteration of TS and RR was small but significant for sunitinib and bevacizumab. Available studies could not conclude any results for second line treatments.

Objective There is evidence that reactive stroma in different cancers may regulate tumor progression. The aim of this study is to establish any possible relation of reactive stroma grading on needle prostatic biopsies to biochemical recurrence. Materials and Methods The study group comprised 266 biopsies from consecutive patients submitted to radical prostatectomy. Reactive stroma was defined as stroma surrounding neoplastic tissue and graded as 0 (absent), 1 (slight), 2 (moderate), and 3 (intense) according to tumor stroma area relative to total tumor area. Results From the total of 266 needle prostatic biopsies, 143 (53.8%), 55 (20.7%), 54 (20.3%), and 14 (5.3%) showed grades 0, 1, 2, and 3, respectively. Increasing reactive stroma grade was significantly associated with clinical stage T2, higher preoperative PSA, higher biopsy and radical prostatectomy Gleason score, more extensive tumors in radical prostatectomy, and pathologic stage > T2. Only grade 3 was significantly associated with time and risk to biochemical recurrence. On multivariate analysis only preoperative PSA and 2 methods of biopsy tumor extent evaluation were independent predictors. Conclusion Increasing reactive stroma grade on biopsies is significantly associated with several clinicopathologic adverse findings, however, only grade 3 predicts time and risk to biochemical recurrence following radical prostatectomy on univariate but not on multivariate analysis. We have not been able to show that reactive stroma grade 3 on biopsies is an independent predictor of biochemical recurrence beyond that of preoperative PSA and other pathologic findings on biopsy.

Objective Systematic review of literature and meta-analysis to evaluate the results of magnetic resonance image 1.5T with endorectal coil in the diagnosis and evaluation of extra-prostatic extension and involvement of seminal vesicles of prostate cancer, compared to the histopathological results of the radical prostatectomy specimen. Materials and Methods It was conducted a systematic review of literature and meta-analyses of all studies data published after 2008. In those studies, the patients with prostate cancer with indication to radical prostatectomy were submitted to magnetic resonance image (MRI) at pre-operatory period and the results were compared to those of histopathological studies after the surgery. The selected terms for research included prostate cancer, magnetic resonance, radical prostatectomy, and prostate cancer diagnosis, in the databases EMBASE, LILACS, PUBMED/MEDLINE and Cochrane Library. The data were collected using a specific qualitative instrument and the meta-analysis data were presented in the forest plot graphics, homogeneity test and sROC curves and funnel plot. Results A total of seven studies were included, with a total of 603 patients. Among these studies, six evaluated the value of MRI for the detection of prostate cancer, and the median sensitivity of meta-analysis was 0.6 and specificity 0.58, but with heterogeneity among the studies. Three studies evaluated extra-prostatic extension with a median sensitivity of 0.49, specificity 0.82 and heterogeneity only for sensitivity. Three studies evaluated invasion of seminal vesicles, with median sensitivity of 0.45 and specificity 0.96, with heterogeneity in both analysis. Conclusion Magnetic resonance of 1.5T with endocoil showed low values of sensitivity and specificity for the diagnosis and staging of prostate cancer. The reviewed studies showed a significant heterogeneity among them. The best observed result was MRI specificity for invasion of seminal vesicles. More studies are necessary to evaluate new techniques and parameters before recommending the routine use of MRI in clinical practice.

ObjectiveTo perform a systematic review and meta-analysis of all randomized controlled trials comparing the efficacy of Sipuleucel-T versus placebo for asymptomatic or minimally symptomatic metastatic castration-refractory prostate cancer (mCRPC).Materials ans MethodsSeveral databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The endpoints were overall survival (OS), time to progression (TTP) and side effects. We performed a meta-analysis (MA) of the published data. The results are expressed as Hazard Ratio (HR) or Risk Ratio (RR), with their corresponding 95% confidence intervals (CI 95%).ResultsThe final analysis included 3 trials comprising 737 patients. The TTP was similar in patients who received Sipuleucel-T or placebo (fixed effect: HR = 0.89; CI 95% = 0.75 to 1.05; p = 0.16), with no heterogeneity detected on this analysis (Chi2 = 2.14, df = 2 (P = 0.34); I2 = 6%). The results showed a higher overall survival in patients treated with Sipuleucel-T (fixed effect: HR = 0.74; CI 95% = 0.61 to 0.89; p = 0.001; NNT = 3). We found no heterogeneity on this analysis either (Chi2 = 1.46, df = 2 (P = 0.48); I2 = 0%). The incidence of adverse events (grade > 3) was the same in both groups.ConclusionSipuleucel-T prolongs overall survival in patients with asymptomatic or minimally symptomatic mCRPC.

PURPOSE: The amount of extraprostatic extension and positive surgical margin correlates in most studies with biochemical recurrence following radical prostatectomy. We studied the influence of focal and diffuse extraprostatic extension and positive surgical margins on biochemical progression using a simple method for quantification. MATERIALS AND METHODS: A total of 360 prostates were step-sectioned and totally processed from 175 patients with stage T1c and 185 patients with clinical stage T2 submitted to radical retropubic prostatectomy. Extraprostatic extension was stratified into 2 groups: present up to 1 quadrant and/or section from the bladder neck or apex (Group 1, focal) and in more than 1 quadrant or section (Group 2, diffuse); and, positive surgical margin present up to 2 quadrants and/or sections (Group 1, focal) and in more than 2 quadrants or sections (Group 2, diffuse). The Kaplan-Meier product-limit analysis was used for the time to biochemical recurrence, and an univariate and multivariate Cox stepwise logistic regression model to identify significant predictors. RESULTS: Extraprostatic extension was found in 129/360 (35.8%) patients, 39/129 (30.2%) in Group 1 and 90/129 (69.8%) in Group 2. In univariate analysis but not in multivariate analysis, patients showing diffuse extraprostatic extension (Group 2) had a significant higher risk to develop biochemical recurrence in a shorter time. Positive surgical margin was present in 160/360 (44.4%) patients, 81/160 (50.6%) patients in Group 1 and 79/160 (49.4%) patients in Group 2. Patients with diffuse positive surgical margins (Group 2) had a significant higher risk in both univariate and multivariate analyses. Diffuse positive surgical margin was the strongest predictor on both analyses and an independent predictor on multivariate analysis. CONCLUSION: Diffuse extraprostatic extension in univariate analysis and positive surgical margins on both univariate and multivariate analyses are significant predictors of shorter time to biochemical progression following radical prostatectomy.

PURPOSE: Perineural invasion (PNI) on needle prostatic biopsies (NPB) has been controversial as a marker of extraprostatic extension and consequently for planning of nerve-sparing radical prostatectomy (RP). The aim of this study was to find whether tumor extent on NPB influences the value of PNI to predict stage > pT2 on RP. MATERIALS AND METHODS: This retrospective study was based on 264 consecutive patients submitted to radical retropubic prostatectomy. Their NPB were matched with whole-mount processed and totally embedded surgical specimens. Tumor extent on NPB was evaluated as the percentage of linear tissue in mm containing carcinoma in all cores. Considering the median value, patients were stratified into 2 groups: harboring less or more extensive tumors on NPB. Univariate and multivariate logistic regression analyses were used to relate stage > pT2 to PNI and other clinical and pathological variables. RESULTS: In patients with more extensive tumors, PNI was predictive of stage > pT2 in univariate analysis but not in multivariate analysis. In less extensive tumors, PNI showed no association between any clinical or pathological variables studied; no difference in the time to biochemical progression-free status compared to patients without PNI; and, no predictive value for pathological stage > pT2 on both univariate and multivariate analyses. CONCLUSION: Tumor extent on NPB influences the predictive value of PNI for pathologic stage > pT2 on RP. With a higher number of small tumors currently detected, there is no evidence that perineural invasion should influence the decision on preservation of the nerve during radical prostatectomy.

Testicular tumors represent the most common type of solid neoplasia in men aged between 18 and 35 years. Its cure rate is approximately 90%1,2. In some cases, tumoral vascular invasion can occur and demands surgical ressection to stop disease progression and prevent thromboembolic events. That is the only valuable therapeutic choice although it is a high risk procedure. We present a case report of a patient who underwent successful chemotherapy and surgery for a right-sided testicular tumor associated with an inferior vena cava tumor thrombus extending from the renal vein to the right atrium and extensive retroperitoneal lymph node disease.

Los tumores testiculares son el tipo más frecuente de neoplasia sólida en los varones de 18 a 35 años de edad. Su tasa de curación aproximada es del 90%1,2. En algunos casos puede producirse invasión vascular del tumor, que exigirá resección quirúrgica para detener la progresión de la enfermedad y prevenir episodios tromboembólicos. La cirugía es la única opción terapéutica válida, aunque el procedimiento entraña un riesgo elevado. Presentamos el caso clínico de un paciente sometido con éxito a quimioterapia y cirugía por un tumor del testículo derecho asociado con un trombo tumoral en la vena cava inferior que se extendía desde la vena renal a la aurícula derecha y linfadenopatía retroperitoneal extensa.