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 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.

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.

CONTEXTUALIZAÇÃO:O câncer de mama é a neoplasia maligna mais frequente na população feminina brasileira. Nos últimos anos, houve grande evolução das técnicas cirúrgicas e aumento do número de cirurgias conservadoras da mama, entretanto a morbidade imediata ou tardia após a cirurgia, sob a forma de comprometimento funcional e dor, ainda é um significativo problema clínico.OBJETIVO: Verificar a relação entre o comprometimento funcional tardio do membro superior e a qualidade de vida de mulheres submetidas à cirurgia do câncer de mama.MÉTODO: Participaram da pesquisa 81 mulheres com tempo decorrido de cirurgia variando entre um a cinco anos. Realizou-se levantamento das queixas referidas pelas pacientes em relação ao membro superior e foram aplicados os questionários Disabilities of the Arm, Shoulder and Hand (DASH) e European Organization for Research and Treatment of Cancer (EORTC QLQC-30 e BR23).RESULTADOS: A correlação entre o escore DASH e o tempo decorrido de cirurgia demonstrou que, quanto maior este último, maiores são as dificuldades de funcionalidade dos membros superiores das pacientes entrevistadas (r=0,459; p<0,0001). Houve correlação estatisticamente significativa entre o escore DASH e a qualidade de vida relacionada à saúde.CONCLUSÃO:O comprometimento funcional tardio apresentou impacto significativo na função do membro superior, na vida cotidiana e na qualidade de vida relacionada à saúde das mulheres que foram submetidas à cirurgia do câncer de mama.

BACKGROUND: Breast cancer is the most common malignancy in Brazilian women. In recent years, there has been great progress in and an increasing number of breast-conserving surgical techniques; however, immediate or late morbidity after surgery, in the form of functional impairment and pain, remains a significant clinical problem.OBJECTIVE: To investigate the relationship between late upper limb functional impairment and the quality of life in women subjected to breast cancer surgery.METHOD: A total of 81 women participated in the study, with the length of time since surgery ranging from one to five years. A survey of upper limb complaints reported by patients was conducted, and the questionnaires Disabilities of the Arm, Shoulder, and Hand (DASH) and the European Organization for Research and Treatment of Cancer (EORTC QLQC-30 and BR23) were applied.RESULTS: The correlation between the DASH score and the length of time since surgery determined that the longer the time since surgery, the greater the difficulties in functionality of the upper limb (r=0.459; p<0.0001). A statistically significant correlation was observed between the DASH score and health-related quality of life.CONCLUSION: Late functional impairment had a significant impact on upper limb function in everyday life and health-related quality of life for women who underwent breast cancer surgery.

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.

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.

OBJECTIVE: There is evidence showing that Gleason grading of prostatic adenocarcinoma is one of the most powerful predictors of biological behavior and one of the most influential factors used to determine treatment for prostate cancer. The aim of the current study was to compare the Gleason score for needle biopsy to the Gleason score for the correspondent surgical specimen, find any possible difference in the biochemical (PSA) progression following surgery in upgraded cases, correlate Gleason score in the specimens to several clinicopathologic variables, and compare outcomes between patients with low-grade vs. high-grade Gleason and Gleason scores 3+4 vs. 4+3. MATERIALS AND METHODS: The study population consisted of 200 consecutive patients submitted to radical prostatectomy. Biochemical progression was defined as PSA > 0.2 ng/mL. Time to PSA progression was studied using the Kaplan-Meier product-limit analysis. RESULTS: In 47.1% of the cases, there was an exact correlation and 40.6% of cases were underestimated in the biopsies. Half of the tumors graded Gleason 6 at biopsy were Gleason score 7 at surgery. These upgraded tumors had outcomes similar to tumors with Gleason score 7 in both biopsy and surgery. There was a positive correlation of high-grade Gleason score in the surgical specimens to higher preoperative PSA, more extensive tumors, positive margins and more advanced pathologic staging. Tumors with a Gleason score > 7 have lower PSA progression-free survival vs. Gleason scores < 7. In this series, there was no significant difference when comparing Gleason scores of 3+4 vs. 4+3. CONCLUSIONS: The findings support the importance of Gleason grading for nomograms, which are used by clinicians to counsel individual patients and help them make important decisions regarding their disease.

INTRODUCTION: Chronic inflammation of longstanding duration has been linked to the development of carcinoma in several organ systems. It is controversial whether there is any relationship of inflammatory atrophy to prostate cancer. It has been suggested that the proliferative epithelium in inflammatory atrophy may progress to high-grade prostatic intraepithelial neoplasia and/or adenocarcinoma. The objective of our study is to compare on needle prostate biopsies of patients showing cancer the topographical relation of inflammatory atrophy and atrophy with no inflammation to adenocarcinoma. MATERIALS AND METHODS: The frequency and extent of the lesions were studied on 172 needle biopsies of patients with prostate cancer. In cores showing both lesions, the foci of atrophy were counted. Clinicopathological features were compared according to presence or absence of inflammation. RESULTS: Considering only cores showing adenocarcinoma, atrophy was seen in 116/172 (67.44%) biopsies; 70/116 (60.34%) biopsies showed atrophy and no inflammation and 46/116 (39.66%) biopsies showed inflammatory atrophy. From a total of 481 cores in 72 biopsies with inflammatory atrophy 184/481 (38.25%) cores showed no atrophy; 166/481 (34.51%) cores showed atrophy and no inflammation; 111/481 (23.08%) cores showed both lesions; and 20/481 (4.16%) showed only inflammatory atrophy. There was no statistically significant difference for the clinicopathological features studied. CONCLUSION: The result of our study seems not to favor the model of prostatic carcinogenesis in which there is a topographical relation of inflammatory atrophy to adenocarcinoma.

O seguimento de pacientes com síndrome de Turner (ST) freqüentemente revela alterações transitórias, recorrentes e assintomáticas de TSH e/ou hormônios tireóideos (HT). Neste trabalho foram avaliadas estrutura e função da tireóide em portadoras da ST com história de alterações prévias desses hormônios. A casuística incluiu 24 pacientes, 17 com menos de 20 anos, avaliadas laboratorialmente pelas concentrações séricas de TSH, T4 livre, T3 e anticorpos anti-TPO e anti-Tg, e morfologicamente por ultra-sonografia (USG) e cintilografia com pertecnetato-99mTc. Havia alterações de TSH e/ou HT em 13 casos, e em 23 havia alterações USG compatíveis com doença crônica da tireóide, particularmente tireomegalia (estabelecida de acordo com o volume esperado para a estatura) e heterogeneidade do parênquima. A captação foi normal em 21 casos e a distribuição do radiofármaco, homogênea em 22. As alterações hormonais foram independentes da idade, do tempo de evolução, da presença de anticorpos, do número de anomalias USG e de alterações cintilográficas. Pacientes maiores de 20 anos apresentaram maior freqüência de anticorpos e de hipoecogenicidade do parênquima, e houve correlação positiva entre o volume tireóideo e o tempo de evolução, indicando comprometimento progressivo da glândula. Esses resultados sugerem que as alterações encontradas decorram de doença tireóidea auto-imune crônica.

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.

PURPOSE: A recent study has found that PSA recurrence rate for clinical T1c tumors is similar to T2 tumors, indicating a need for further refinement of clinical staging system. To test this finding we compared clinicopathologic characteristics and the time to PSA progression following radical retropubic prostatectomy of patients with clinical stage T1c tumors to those with stage T2, T2a or T2b tumors. MATERIALS AND METHODS: From a total of 186 consecutive patients submitted to prostatectomy, 33.52% had clinical stage T1c tumors, 45.45% stage T2a tumors and 21.02% stage T2b tumors. The variables studied were age, preoperative PSA, prostate weight, Gleason score, tumor extent, positive surgical margins, extraprostatic extension (pT3a), seminal vesicle invasion (pT3b), and time to PSA progression. Tumor extent was evaluated by a point-count method. RESULTS: Patients with clinical stage T1c were younger and had the lowest mean preoperative PSA. In the surgical specimen, they had higher frequency of Gleason score < 7 and more organ confined cancer. In 40.54% of the patients with clinical stage T2b tumors, there was extraprostatic extension (pT3a). During the study period, 54 patients (30.68%) developed a biochemical progression. Kaplan-Meier product-limit analysis revealed no significant difference in the time to PSA progression between men with clinical stage T1c versus clinical stage T2 (p = 0.7959), T2a (p = 0.6060) or T2b (p = 0.2941) as well as between men with clinical stage T2a versus stage T2b (p = 0.0994). CONCLUSION: Clinicopathological features are not similar considering clinical stage T1c versus clinical stages T2, T2a or T2b.

OBJECTIVE: It is controversial whether age is associated with higher grade and worse outcome. Some studies have not found age to be related to outcome nor younger age to be associated with better response to therapy. MATERIALS AND METHODS: The study population consisted of 27 patients aged 55 years or younger and 173 patients 56 years or older submitted to radical prostatectomy. The variables studied were preoperative PSA, time to PSA progression following radical prostatectomy and pathologic findings in surgical specimens: Gleason score, Gleason predominant grade, positive surgical margins, tumor extent, extraprostatic extension (pT3a), and seminal vesicle invasion (pT3b). RESULTS: Comparing patients aged 55 years or younger and 56 years or older, there was no statistically significant difference for all variables studied: preoperative PSA (p = 0.4417), Gleason score (p = 0.3934), Gleason predominant grade (p = 0.2653), tumor extent (p = 0.1190), positive surgical margins (p = 0.8335), extraprostatic extension (p = 0.3447) and seminal vesicle invasion (p > 0.9999). During the study period, 44 patients (22%) developed PSA progression. No difference was found in the time to biochemical progression between men aged 55 years or younger and 56 years or older. CONCLUSION: Our findings suggest that age alone do not influence the biological aggressiveness of prostate cancer.