Continence criteria of 193 618 patients after open, laparoscopic, and robot-assisted radical prostatectomy.

OBJECTIVES: To apply a new evidence-gathering methodology, called reverse systematic review (RSR), to analyse the influence of different continence classification criteria on urinary continence rates among open retropubic radical prostatectomy (RRP), laparoscopic RP (LRP) and robot-assisted RP (RARP). MATERIALS AND METHODS: A search was carried out in eight databases between 2000 and 2020 through systematic reviews (SRs) studies referring to RRP, LRP or RARP (80 SRs). All references used in these SRs were captured referring to 910 papers in an overall database called the 'EVIDENCE Database'. A total of 422 studies related to post-RP urinary continence were selected for the final analysis, totalling 782 reports referring to 193 618 patients. RESULTS: Overall, 206 (26.4%) reports for RRP, 243 (31.0%) reports for LRP, and 333 (42.6%) reports for RARP were found. Mean overall continence rates, respectively for RRP, LRP and RARP, were: 42%, 34% and 42% at 1 month; 62%, 64% and 65% at 3 months; 73, 77 and 79% at 6 months; and 81%, 85% and 86% at 12 months. The most used criterion was 'No pad' (53.3%), followed by 'Safety pad' (19.3%), 'Not described' (10.6%), and 'No leak' (9.9%). 'No pad' showed the lowest discrepancy in continence rates in each period compared to the overall average for each technique, demonstrating less ability to influence the final results favouring any of the techniques. CONCLUSION: The RSR demonstrated that the 'No pad' criterion was the most used in the literature and showed the lowest bias capable of influencing the results and favouring any of the techniques and is the fairest option for future comparisons.

Prognostic significance of architectural subtypes of Gleason grade 4 prostate cancer in radical prostatectomy: A semiquantitative method of evaluation.

Studies have shown that Gleason grade 4 extent as well as architectural subtypes provide prognostic information. We aimed to evaluate the influence on biochemical recurrence following radical prostatectomy of patients with organ-confined tumor, Gleason score 7, and negative surgical margins. Total tumor extent, Gleason grade 4 total extent and the extent of each architectural subtype (fused glands, poorly defined glands, cribriform glands, and glomeruloid glands) were evaluated by a semiquantitative point-count method using different colors to identify each subtype. Microscopic morphology of glomeruloid glands was considered regardless of morphology: size (small or large), attachment (narrow or extensive), and cribriform or solid intraluminal protrusion. Gleason grade 4 total extent significantly predicted shorter time to biochemical recurrence in univariate and multivariate analysis. Stratifying extent, Gleason grade 4 with >30% of the total grade 4 extent was significantly predictive for time of recurrence. Considering architectural subtypes, cribriform and glomeruloid glands but not fused and poorly formed glands extent, significantly predicted shorter time to recurrence in univariate analysis. An important issue related to the studies on prognostic significance of Gleason grade 4 subtypes is the lack of uniformity in the definition of microscopic morphology of the subtypes particularly of the glomeruloid architecture.

The TNM 8th edition: Validation of the proposal for organ - confined (pT2) prostate cancer.

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.

Does index tumor predominant location influence prognostic factors in radical prostatectomies?

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.

Prostate total tumor extent versus index tumor extent--which is predictive of biochemical recurrence following radical prostatectomy?

PURPOSE: It is controversial whether tumor extent in radical prostatectomies predicts biochemical recurrence following surgery. We compared the predictive value of total tumor extent vs dominant nodule (index tumor) extent. MATERIALS AND METHODS: A mean of 32 paraffin blocks was processed from prostate surgical specimens step sectioned at 3 to 5 mm intervals from 300 patients treated with radical retropubic prostatectomy. Each transverse section was subdivided into 2 anterolateral and 2 posterolateral quadrants. Tumor extent was evaluated by a semiquantitative point count method. Dominant nodule extent was recorded as the maximal number of positive points of the largest single focus of cancer in the quadrants. Time to biochemical recurrence was analyzed by Kaplan-Meier product limit analysis. Prediction of shorter time to biochemical recurrence was determined by univariate and multivariate Cox proportional hazards models. RESULTS: Except for age and race, total and index tumor extent was significantly associated with higher preoperative prostate specific antigen, clinical stage T2, pathological stage greater than T2, positive surgical margins and higher radical prostatectomy Gleason score. Total and index tumor extent was significantly associated with time to biochemical recurrence in Kaplan-Meier estimates. Total and index tumor extent significantly predicted shorter time to biochemical recurrence on univariate analysis but only index tumor extent was an independent predictor of time to biochemical recurrence on multivariate analysis. CONCLUSIONS: The study indicates that any tumor extent estimate in surgical specimens should be related to the dominant nodule (index tumor) and not to total tumor extent.

Controversial predictors of biochemical recurrence after radical prostatectomy: a study from a Latin American (Brazilian) institution.

PURPOSE: To analyze controversial clinicopathologic predictors of biochemical recurrence after surgery: age, race, tumor extent on surgical specimen, tumor extent on needle biopsy, Gleason score 3 + 4 vs 4 + 3, and amount of extent of extraprostatic extension and positive surgical margins. MATERIALS AND METHODS: The needle biopsies and the correspondent surgical specimens were analyzed from 400 patients. Time to recurrence was analyzed with the Kaplan-Meier curves and risk of shorter time to recurrence using Cox univariate and multivariate analysis. RESULTS: Except for age, race, maximum percentage of cancer per core, and number of cores with cancer, all other variables studied were significantly predictive of time to biochemical recurrence using the Kaplan-Meier curves. In univariate analysis, except for focal extraprostatic extension, age, race, focal positive surgical margins, and maximum extent and percentage of cancer per core, all other variables were significantly predictive of shorter time to recurrence. On multivariate analysis, diffuse positive surgical margins and preoperative PSA were independent predictors. CONCLUSIONS: Young patients and non-whites were not significantly associated with time to biochemical recurrence. The time consuming tumor extent evaluation in surgical specimens seems not to add additional information to other well established predictive findings. The higher predictive value of Gleason score 4 + 3 = 7 vs 3 + 4 = 7 discloses the importance of grade 4 as the predominant pattern. Extent and not simply presence or absent of extraprostatic extension should be informed. Most tumor extent evaluations on needle biopsies are predictive of time to biochemical recurrence, however, maximum percentage of cancer in all cores was the strongest predictor.

Adenocarcinoma on needle prostatic biopsies: does reactive stroma predicts biochemical recurrence in patients following radical prostatectomy?

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.

Radical Prostatectomy Technique Dispute: Analyzing Over 1.35 Million Surgeries in 20 Years of History.

Systematic reviews (SR) produce the best evidence comparing open (RRP), laparoscopic (LRP), and robotic (RARP) radical prostatectomy (RP). However, the hyperfiltration of evidence generates very specific scenarios that reduce the power of extrapolation. To compare RP evidence regarding demographics using a new methodology called reverse systematic review (RSR). Between 2000 and 2020, 8 databases were searched for SR studies on RRP, LRP, or RARP. All references were captured and analyzed over time in 80 SR. Total of 1724 reports (nr = 752, 43.7% for RARP; nr = 559, 32.4% for RRP; nr = 413, 23.9% for LRP) described 1,353,485 patients (881,719, 65.1% RRP; 366,006, 27.0% RARP; 105,760, 7.8% LRP). Patients/center/year was higher in RARP compared to LRP and RRP, median 50.0, 40.0, and 36.66, respectively, P < .001. Surgeons per study was lesser in RARP and LRP compared to RRP, median 2.0, 2.0, and 6.0, respectively, P < .001. Study duration and follow-up in years was shorter in RARP compared to LRP and RRP, median 2.6, 3.0, and 4.0, respectively, P < .001. Cumulative RARP reports predominate in North America (55.7%, nr = 468) and Asia (47.8%, nr =129), while LRP predominate in Europe (42.3%, nr =230) and RRP in Oceania (45.1%, nr = 23). After 2010 all continents began to accumulate more patients in the robotic approach. Potential biases related to shorter follow-up, greater volume centers, and surgeons were identified favoring the RARP. Analyzing the context of the available evidence is essential to compare techniques. Influenced by economic and scientific interests, robotic surgery was developed in centers with a higher volume of surgeries, characterizing potential biases when comparing techniques in the clinical shared decision.

Influence of focal and diffuse extraprostatic extension and positive surgical margins on biochemical progression following radical prostatectomy.

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.

Correlation between genetic and environmental risk factors for age-related macular degeneration in Brazilian patients.

PURPOSE: To analyze the correlations between age-related macular degeneration (AMD) and genetic and environmental risk factors for in a Brazilian population. DESIGN: Cross-sectional study with a control group. METHODS: We collected data on 236 participants 50 years of age or older (141 with AMD and 95 controls without the disease). Data was obtained using a questionnaire and included information on demographics, ocular and medical history, family history of AMD, lifestyle, and smoking and drinking habits. Genetic evaluations included direct sequencing for the LOC387715 (rs10490924) variant, as well as PCR and enzymatic digestion for the CFH Y402H (rs1061170) and HTRA1 (rs11200638) variants. We performed a risk assessment of environmental risk factors and genetic variants associated with AMD and determined correlations between AMD and the data collected using multiple linear regression analysis. RESULTS: Of the 141 AMD cases, 99 (70%) had advanced AMD in at least one eye (57% neovascular AMD and 13% geographic atrophy), and 42 (30%) had not-advanced AMD. Family history of AMD (OR: 6.58; 95% CI: 1.94-22.31), presence of cardiovascular disease (CVD) (OR: 2.39; 95% CI: 1.08-5.28), low physical activity level (OR: 1.39; 95% CI: 0.82-2.37), and high serum cholesterol (OR: 1.49; 95% CI: 0.84-2.65) were associated with an increased risk for AMD. There was a significant association between CVD and incidence of advanced AMD (OR: 2.29; 95% CI 0.81-6.44). The OR for the risk allele of the LOC387715 gene, the CFH gene and the HTRA1 gene were 2.21 (95% CI: 1.47-3.35), 2.27 (95% CI: 1.52-3.37), and 2.76 (95% CI: 1.89-4.03), respectively. In the stepwise multiple linear regression analyses, the HTRA1 and CFH risk alleles, family history of AMD, the LOC387715 risk allele, and CVD were associated with an increased risk of AMD for a total of 25.6% contribution to the AMD phenotype. CONCLUSIONS: The analysis correlating environmental and genetic risk factors such as family history of AMD, and CVD and the variants of HTRA1, CFH, and LOC387715 genes showed an expressive contribution for the development of AMD among this admixed population.

Does tumor extent on needle prostatic biopsies influence the value of perineural invasion to predict pathologic stage > T2 in radical prostatectomies?

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.

Turner's syndrome and subclinical autoimmune thyroid disease: a two-year follow-up study.

Although autoimmune thyroid disease (AITD) is frequent in Turner's syndrome (TS), followup studies are scant, and there are none regarding subclinical thyroiditis. We investigated thyroid function and morphology in 17 patients with TS (mean age 14.6 years) with transient and asymptomatic variations of TSH and/or thyroid hormones. Our 2-year follow-up included measurements of TSH, free T4, T3 and TPO and Tg antibodies, ultrasound (US) (first and last evaluations) and scintigraphy (first evaluation). Thyroid volume was evaluated relative to the patients' stature. Fourteen had abnormal hormones, including four with hypothyroidism and one with hyperthyroidism, ten had positive antibodies, and all had abnormalities on US; uptake was normal in 14/16. Abnormal hormones were independent of antibodies, number of US findings, age, time of disease and volume. At the end of the follow-up, antibodies were associated with a high number of abnormal US features, particularly heterogeneous texture. Our results indicate that recurring thyroid hormone variations in TS are due to chronic AITD.

The impact of the 2005 international society of urological pathology consensus conference on standard Gleason grading of prostatic carcinoma in needle biopsies.

PURPOSE: At an International Society of Urological Pathology consensus conference in 2005 the Gleason grading system for prostatic carcinoma underwent its first major revision. We compared the concordance of pattern and change of prognostic groups for the conventional and the modified Gleason grading, and checked the discriminative power of the modified Gleason grading. MATERIALS AND METHODS: The grading was based on 172 prostatic needle biopsies of patients subsequently undergoing radical prostatectomy. Four prognostic Gleason grading groups were considered, divided into scores of 2-4, 5-6, 7 and 8-10. To check the discriminative power of the modified Gleason grading we compared the time of biochemical (prostate specific antigen) progression-free outcome according to prognostic groups between standard and revised grading. RESULTS: The greatest impact of the International Society of Urological Pathology consensus recommendations for Gleason grading was seen on the secondary pattern which had the lowest percentage of concordance and was reflected in a change toward higher Gleason prognostic groups. Of 172 patients in whom the Gleason prognostic group was changed (to higher grades) based solely on the consensus criteria, 46 (26.7%) had higher preoperative prostate specific antigen, more extensive tumors and positive surgical margins, and higher pathological stage. The revised Gleason grading identified in this series a higher number of patients in the aggressive prognostic group Gleason score 8-10 who had a significantly shorter time to biochemical progression-free outcome after radical prostatectomy (log rank p = 0.011). CONCLUSIONS: The findings of this study indicate that the recommendations of the International Society of Urological Pathology are a valuable refinement of the standard Gleason grading system.

Iatrogenic and non-iatrogenic positive margins: incidence, site, factors involved, and time to PSA progression following radical prostatectomy.

INTRODUCTION: There are conflicting data regarding the incidence, site and prognostic significance of positive margins resulting from iatrogenic incision into the prostate (pT2+) or non-iatrogenic inability to excise extraprostatic extension (EPE) of tumor. MATERIALS AND METHODS: The surgical specimens were whole-mount processed. Nerve-sparing, tumor extension and Gleason score were considered possible factors involved in positive margins. Time to PSA progression was studied using a Kaplan-Meier product-limit analysis. RESULTS: Positive margins resulted from iatrogenic incision in 61/230 (26.52%) prostates and from EPE in 34/230 (14.78%) prostates. The site most frequently involved in pT2+ prostates was the posterolateral quadrants (40.98%); in cases with EPE both anterolateral and posterolateral quadrants (67.65%) were most frequently involved. Positive margins occurred equally in patients with and without nerve-sparing in both groups. Tumors were significantly more extensive and with higher Gleason score in patients with EPE. Time to PSA progression was similar in patients with pT2+ versus EPE and no invasion of the seminal vesicle, but was significantly shorter in patients with EPE and invasion of the seminal vesicle. CONCLUSION: The frequency of positive margins in our institution was similar to others with large experience in performing radical prostatectomies. The higher frequency of posterolateral quadrants in iatrogenic positive margins is probably related to the preservation of adjacent vital structures and not to nerve-sparing surgery. A trend for a decreasing frequency of non-iatrogenic surgical margins may be explained by the marked increase of clinical stage T1c in recent years. More-extensive tumors and higher Gleason scores seem to influence only non-iatrogenic positive margins. Biochemical (PSA) progression in EPE must be studied by stratifying the patients into two groups: with and without seminal vesicle invasion.

Surgical margins in radical prostatectomy: a comparison between retropubic and laparoscopic surgery.

OBJECTIVES: To compare positive surgical margins in both radical retropubic prostatectomies and laparoscopic surgery in two reference centres in Brazil. MATERIALS AND METHODS: One hundred and seventy nine pathological studies from patients, who underwent radical prostatectomy due to prostate adenocarcinoma, 89 submitted to retropubic surgery and 90 to laparoscopic surgery, were analyzed. Inclusion criteria Patients with PSA

[Evidences for subclinic chronic autoimmune thyroid disease in girls with Turner Syndrome]. / Evidências de doença tireóidea auto-imune crônica subclínica em portadoras da Síndrome de Turner.

Patients with Turner syndrome (TS) frequently exhibit transient, recurrent and asymptomatic variations of TSH and/or thyroid hormones (TH). This work was carried out to evaluate thyroid function and structure in patients with TS who had had such variations in hormone concentrations. Our sample comprised 24 patients, 17 less than 20-years old. Evaluation included serum levels of TSH, free T4, total T3, TPO and Tg autoantibodies, thyroid ultrasound (US) and scintigraphy with 99mTc-pertechnetate. Thirteen patients had abnormal TSH and/or TH levels; 23 exhibited US features compatible with chronic thyroid disorder, particularly thyromegaly (established according to volume expected for stature) and heterogeneous echogenicity. Uptake was normal in 21 cases and tracer distribution was homogeneous in 22. The finding of abnormal hormone concentrations was independent of age, length of time since the first similar finding, thyroid autoantibodies, number of abnormalities at US and abnormal scintigraphic findings. Patients aged more than 20 years had higher frequency of thyroid antibodies and heterogeneous echogenicity, and thyroid volume was significantly correlated to length of time since detection of the first hormone variation, indicating progressive thyroid disease. These results suggest that subclinical thyroid dysfunction in TS is due to chronic autoimmune thyroid disease.

Prostatic atrophy: immunohistochemical study of hypoxia induced factors.

BACKGROUND: There is evidence that chronic local ischemia may be one possible etiology of prostatic atrophy (PA). Our aim was to study the expression of hypoxia induced factors in areas of PA. DESIGN: The immunohistochemical expression of hypoxia-inducible factor-1 alpha (HIF-1) and vascular endothelial growth factor (VEGF) was studied in atrophic acini of 33 needle prostatic biopsies. Prostatic atrophy was the only diagnosis in these biopsies. For HIF-1alpha, a total of 27,158, 10,060 and 9920 nuclei were counted in atrophic acini, acini with squamous metaplasia, and acini without squamous metaplasia surrounding acute infarct, respectively. For VEGF, a total of 24,966, 9849 and 9918 nuclei were counted for the same acini. A total of 1326 nuclei were counted in acini of the needle biopsy used as negative control. The Student's test for independent samples with significance level at 5% (p<0.05) was used to compare the mean ratio (MR) of positive nuclei over total nuclei for HIF-1 and VEGF. RESULTS: For HIF-1, 108 (MR=0.004), 6877 (MR=0.68), and 6566 (MR=0.66) nuclei were positive in atrophic acini, acini with squamous metaplasia, and acini without squamous metaplasia surrounding acute infarct, respectively. There was a highly significant difference (p<0.001) between atrophic acini and acini surrounding acute infarct. For VEGF, 139 (MR=0.05), 5926 (MR=0.60), and 4948 (MR=0.50) nuclei were positive in the same acini. The difference was highly significant (p<0.001). All 1326 nuclei counted in the needle biopsy with essentially normal findings were negative for HIF-1 and VEGF. CONCLUSIONS: This study showed that prostatic atrophic acini are not on acute ischemia. However, local chronic ischemia cannot be ruled out. Experimental data showed that on chronic ischemia, the signal triggering HIF-1alpha accumulation may disappear despite continuous hypoxia suggesting that compensatory mechanisms triggered during prolonged hypoxia may be able to restore normal tissue oxygen levels.

Factors associated with the reduction of bone density in patients with gonadal dysgenesis.

OBJECTIVE: To correlate bone mineral density (BMD) in women with primary hypoestrogenism caused by 46,XX pure gonadal dysgenesis or Turner's syndrome with age, age at estrogen therapy initiation, length of estrogen use, and body mass index (BMI). DESIGN: Cross-sectional study. SETTING: Academic tertiary-care hospital. PATIENT(S): Thirty-eight women, aged 16 to 35 years (mean, 24.6 years), affected by these genetic disorders. INTERVENTION(S): Measurement of lumbar spine and femoral neck BMD using double x-ray absorptiometry. The results were correlated with the control variables by using Pearson's coefficient of correlation. Variables associated with BMD were evaluated by multiple linear regression analysis. MAIN OUTCOME MEASURE(S): Bone mineral density. RESULT(S): Bone mineral density of the lumbar spine showed that 90% of the women presented osteopenia or osteoporosis. The femoral neck was affected in 55% of these women. The length of estrogen therapy and the BMI showed a positive association with BMD at the lumbar spine and femoral neck, respectively. CONCLUSION(S): Women affected by pure gonadal dysgenesis or Turner's syndrome presented a marked decrease in BMD of the lumbar spine and femoral neck. Medical attention for their diagnosis and early hormone replacement therapy are advised.

Prostate cancer with bladder neck involvement: pathologic findings with application of a new practical method for tumor extent evaluation and recurrence-free survival after radical prostatectomy.

BACKGROUND: Recent studies have questioned the high risk for disease recurrence in cases of bladder neck involvement by prostate cancer (pT4 disease). DESIGN: The study was based on 141 patients submitted to radical prostatectomy. PSA-recurrence was defined as 0.5 ng/ml or rising at three different examinations. Bladder neck invasion was correlated to Gleason score (<7 or > or =7), urethral or lateral positive surgical margins, tumor size (extensive or not extensive) using a new simple point-count method, race and preoperative PSA levels (<10 or > or =10 ng/ml). The mean and median follow-up periods were 17.2 and 15 months (range 3-55). Recurrence-free survival curves were constructed using the Kaplan-Meier survival method with tests of significant differences based on the log-rank statistic. RESULTS: Bladder neck invasion was seen in 30/141 (21.27%) patients; 9 (6.38%) had also concomitant positive surgical margins in the sections. Extraprostatic extension was seen in 39/141 (27.65%) and seminal vesicle invasion in 18/141 (12.76%) patients. Patients with bladder neck invasion significantly correlated to Gleason score (P = 0.04), preoperative PSA (P < 0.001), and tumor extension (P= 0.04). No correlation was found to age (P = 0.44), race (P = 0.12) and positive urethral or lateral margins (P = 0.32). The PSA-recurrence relative risk in patients with bladder neck invasion was 0.17 (P = 0.68), with extraprostatic extension 0.53 (P = 0.47) and with seminal vesicle invasion 5.76 (P = 0.02). CONCLUSIONS: Bladder neck involvement correlates with pathologic unfavorable findings on radical prostatectomy specimens as well as to preoperative PSA levels. However, the PSA-recurrence risk associated with bladder neck involvement (pT4) was similar to extraprostatic extension (pT3a) and substantially lower than seminal vesicle invasion (pT3b). The findings favor a need for downstaging of bladder neck involvement in the next version of the TNM system. The method proposed for tumor extent evaluation is simple and accessible to all pathologists working in routine pathology laboratories.

The TNM 8th edition: Validation of the proposal for organ - confined (pT2) prostate cancer

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.