Capsular Involvement Research Articles

Clinical staging error in prostate cancer: localization and relevance of undetected tumour areas

To describe the localization and to assess the clinical implications of areas of undetected prostate cancer in radical prostatectomy (RP) specimens, focusing on patients with unilaterally negative preoperative biopsy cores. The study included 149 of 559 consecutive patients (26.7%) who had RP for prostate cancer. Unilateral prostate cancer was diagnosed from prostate biopsies, taken by several physicians, but > or = pT2c disease was present in the RP specimen. The prostate was dissected by standardized transversal cuts and tumour areas were mapped by one genitourinary pathologist. To estimate the tumour size and location, areas of prostate cancer were transferred to a digital grid database representing the prostate by 794 units. The most frequent location of undetected prostate cancer was in the dorsalateral region and in the apex of the prostate. The mean tumour volume of the false-negative lobe was significantly lower than contralaterally (18.9 vs 47.5 units, P < 0.001). In 36 of 149 patients (24.2%), the tumour volume on the negative biopsy side was equal or higher than on the positive biopsy side; in the final RP specimen, 60 patients (40.3%) had capsular involvement on the negative biopsy side. Significantly many patients with newly diagnosed prostate cancer remain clinically understaged. The apical and dorsolateral region of the prostate are not adequately represented in current biopsy strategies. Undetected tumour areas are often clinically significant by size and capsular involvement, indicating a direct clinical implication when planning nerve-sparing RP or focal therapy. Our results show a continuing need for optimized and standardized biopsy protocols.

Patient risk stratification using Gleason score concordance and upgrading among men with prostate biopsy Gleason score 6 or 7

Purpose To define the impact of discordant Gleason sum (GS) between prostate biopsy (Pbx) tissue and radical prostatectomy (RP) specimen among men initially diagnosed with Gleason 6 or 7 prostate adenocarcinoma. Materials and methods We evaluated patients diagnosed with GS 6 or 7 and treated primarily with RP. We defined the frequency of GS discordance between Pbx and RP pathology reports. We analyzed pretreatment parameters associated with GS discordance and compared immediate postprostatectomy outcome variables across patient groups defined by their GS and concordance. We then conducted survival analysis for biochemical recurrence across patient groups defined by their GS and concordance status. Results Among patients with GS 6 on Pbx, 681/1,847 (36.86%) patients were upgraded to GS 7 or higher after RP. Surgical margin, capsular involvement, seminal vesicle, and nodal involvement status were more favorable in patients with concordant Pbx and RP specimen with GS 6 ( P < 0.0001). Patients with smaller transrectal ultrasound (TRUS) prostate volume were found to have higher PSA densities and were more likely to be upgraded at RP. Multivariate survival analysis also predicted fewer biochemical recurrence events over time in men with concordant Pbx tissue and RP specimen of GS 6 vs. 6/7 or 7/7 ( P = 0.0025) controlling for other relevant covariates. Conclusions GS discordance between Pbx tissue and RP specimens among prostate cancer patients initially diagnosed with either GS 6 or 7 adenocarcinoma of the prostate is substantial. This discordance has potential clinical significance in predicting oncologic outcomes.

Prognostic Value of Capsular Invasion for Localized Clear-Cell Renal Cell Carcinoma

BackgroundThe impact of capsular invasion on the survival of patients undergoing surgery for renal cell carcinoma (RCC) has attracted little attention in the literature and remains controversial. ObjectivesTo evaluate the value of capsular invasion, without perirenal fat invasion, on the prognosis of patients with localized clear-cell RCC. Design, setting, and participantsBetween 1984 and 2007, we retrospectively reviewed the records of 317 consecutive patients with localized clear-cell RCC (pT1–T2N0M0) who underwent radical nephrectomy or nephron-sparing surgery at our institution. Overall, 299 patients were eligible for the study. We analyzed clinical (presentation and body mass index [BMI]) and pathologic (tumor size, Fuhrman nuclear grade, collecting system invasion, microvascular invasion, and capsular involvement) parameters. MeasurementsRecurrence-free survival (RFS) and cancer-specific survival (CSS) were investigated using the Kaplan-Meier method, and the Cox regression model was used to determine the significant prognostic factors based on multivariate analysis. Results and limitationsRenal capsular invasion was observed in 106 of 299 patients (35.5%). Capsular invasion had a statistically significant association with age, symptomatic presentation, tumor diameter, pathologic stage, collecting system invasion, and microvascular invasion. The mean follow-up was 60.5 mo (range: 1–249). The 5-yr RFS and CSS rates for tumors with capsular invasion were significantly lower compared with rates for tumors without invasion (77.7% vs 92.3% and 85.5% vs 95.7%, respectively; p=0.0004). Multivariate analysis showed that BMI (hazard ratio [HR]=0.19), stage (HR=2.45), and capsular invasion (HR=3.36) were independent prognostic factors of disease recurrence. With respect to CSS, BMI (HR=0.20), tumor size (HR=1.13), and capsular invasion (HR=4.03) were the factors related to death. Nevertheless, we recognize that these findings may be limited by the study’s retrospective, single-institution design. ConclusionsOur findings suggest that capsular invasion is associated with poor survival in patients with localized clear-cell RCC.

Criteria in Sentinel Lymph Nodes of Melanoma Patients that Predict Involvement of Nonsentinel Lymph Nodes

Previous studies described various criteria in sentinel lymph nodes (SLN) of melanoma patients that predict the involvement of further, nonsentinel lymph nodes (NSLN). Such criteria may facilitate the selection of patients who might benefit from a completion lymph node dissection (CLND). However, it is currently unclear which parameters are most important. A total of 180 melanoma patients with positive SLNB and subsequent CLND were investigated. Histopathologic parameters in the SLN were systematically evaluated and compared with regard to NSLN positivity. Twenty-eight of these patients (16.0%) had positive NSLN. By univariate analysis several criteria with regard to tumor burden and location of melanoma cells in the SLN correlated with NSLN involvement, such as positivity by hematoxylin-eosin (H&E) staining (P < .001), largest diameter of clusters (P < .001), capsular involvement (P = .001), extranodal extension (P < .001), and tumor penetrative depth (P < .001). Multivariate analysis revealed three independent parameters: (1) positivity of the SLN by H&E staining (versus by immunohistochemistry alone), (2) relative tumor burden > 10% of total lymph node tissue, and (3) perinodal intralymphatic tumor. In 23 of 28 patients with positive NSLN the SLN was positive by H&E staining, in 15 of 28 patients the relative tumor burden was > 10%, and 13 of 28 showed perinodal intralymphatic tumor. In 5 of 28 patients with NSLN involvement, these three parameters were negative. Histopathologic examination of the SLN can identify patients at risk for NSLN positivity.

Neoadjuvant Chemohormonal Therapy in Poor-Prognosis Localized Prostate Cancer

To conduct a trial of neoadjuvant chemohormonal therapy and radical prostatectomy for patients with poor-prognosis localized prostate cancer (prostate-specific antigen [PSA] value 20 ng/mL or greater, Gleason score 8 or higher, and clinical stage T2c or greater), who are at high risk for local and systemic relapse. Complete androgen blockage and four cycles of docetaxel (70 mg/m2) on day 2 and estramustine (280 mg three times daily) on days 1 to 5 every 21 days were given to 22 patients before radical prostatectomy and nerve preservation. Patient characteristics, as median (range), were as follows: age 61 (49 to 70) years, PSA value 21.2 (3.2 to 71.6) ng/mL, and Gleason sum 7 (6 to 9). Clinical stage was T3a-c in 14 patients (64%), T2c in 4 (18%), T2b in 3 (14%), and T1c in 1 (4%). Presurgery characteristics after chemohormonal therapy were as follows: PSA value 0.21 (0.05 to 0.6) ng/mL, clinical stage T1c in 14 patients (63.7%), T2a in 6 (27.3%), and T3a in 2 (9%). The pathologic specimens revealed viable disease in all patients, organ-confined disease in 14 (63.6%), specimen-confined disease in 16 (72.7%), seminal vesicle disease in 9 (40.9%), and lymph node involvement in 4 (18.1%). To date, at a median follow-up of 23.6 (12.1 to 54.7) months, 10 patients (45.4%) relapsed, with PSA doubling time of 1.5 (0.4 to 34.3) months. Of the relapsed patients, 8 (89%) had organ/specimen involvement. The neoadjuvant chemohormonal approach with nerve-preservation surgery is feasible in patients with poor-prognosis localized prostate cancer. It leads to clinical tumor downstaging. The pattern of relapse suggests that local therapy, with radiotherapy for patients with surgical or capsular involvement, and additional systemic therapy should be integrated.

Expression of X-Linked Inhibitor of Apoptosis Protein Is a Strong Predictor of Human Prostate Cancer Recurrence

The X-linked inhibitor of apoptosis protein (XIAP) is associated with cell survival by blocking caspase-mediated apoptosis. We examined the expression patterns of XIAP with regard to human prostate cancer, predicting that XIAP status may predict cancer recurrence and/or clinical outcome. Immunohistochemistry was done on tissue microarrays constructed from 226 primary prostate cancer specimen. The protein expression distribution was examined across the spectrum of epithelial tissues and its association with standard clinicopathologic covariates and tumor recurrence was examined in 192 outcome-informative patients. The mean XIAP expression was significantly higher in prostate cancer compared with prostatic intraepithelial neoplasia (PIN), normal, and benign prostatic hyperplasia. We observed that XIAP is an independent predictor of tumor recurrence in multivariate Cox proportional hazards analysis in all patients as well as after substratifying by Gleason score. Interestingly, patients with high XIAP levels had a much lower probability of tumor recurrence than those with lower XIAP expression. Even patients with high-grade tumors who had higher XIAP levels had a lower risk of recurrence compared with any patient whose tumors express lower XIAP. XIAP is expressed at higher levels in prostate cancers compared with matched normal tissues. High XIAP expression is strongly associated with a reduced risk of tumor recurrence and is not directly associated with Gleason score, tumor stage, capsular involvement, or preoperative prostate-specific antigen status, suggesting that it is a novel prognosticator and a potential target for prostate cancer diagnosis and therapy. Significantly, these findings provide important and extensive validation of previous results.

Prognostic Significance of Isolated HMB45 or Melan A Positive Cells in Melanoma Sentinel Lymph Nodes

The detection of micrometastases (defined as groups of malignant cells) in the sentinel lymph node (SLN) is an important prognostic tool in melanoma. The use of immunohistochemistry with melanocytic markers such as HMB45 and Melan A increases the detection rate of micrometastases but there are also cases with isolated immunohistochemically positive cells (IPC). To determine the prognostic significance of isolated HMB45 and/or Melan A positive cells in melanoma SLN, we compared the clinical course of 47 patients with IPC to 308 patients with negative SLN and to 122 patients with micrometastases. The mean follow-up was 38.1 months. By Kaplan-Meier analyses, relapse free survival and overall survival of patients with IPC were similar to SLN negative patients, whereas patients with micrometastases had a significantly worse relapse free survival and overall survival. In the 47 patients with IPC, 6 relapses (12.8%) and 3 melanoma-related death (6.4%) occurred, in the SLN negative patients 36 relapses (11.7%) and 17 melanoma-related deaths (5.5%), in the patients with micrometastases 46 relapses (37.7%) and 29 melanoma-related deaths (23.8%). Prognosis of patients with IPC in SLN did not correlate with type of positive staining (HMB45, Melan A, or both), capsular involvement, number of cells, presence of cytologic atypias of IPC, or tumor penetrative depth. In conclusion, with short-term follow-up IPC in melanoma SLN are without prognostic significance.

Prognostic relevance of capsular involvement and collecting system invasion in stage I and II renal cell carcinoma

To define the prognostic relevance of capsular involvement (invasion with no penetration) and collecting-system invasion in patients with stage I (pT1N0M0) and stage II (pT2N0M0) renal cell carcinoma (RCC), by evaluating the outcome of patients treated with nephrectomy. In all, 519 patients from a kidney cancer database treated with nephrectomy for stage I and II RCC between 1985 and 2005 were assessed retrospectively. The primary endpoint was recurrence-free survival time. The prognostic relevance of capsular involvement and collecting-system invasion were examined using univariate and multivariate survival analysis. Capsular involvement and collecting-system invasion were evident in 112 (21.6%) and 39 (7.5%) patients, respectively. Capsular involvement was associated with higher Fuhrman grades and larger tumours. The incidence of collecting-system invasion was higher in patients with microvascular invasion. The median follow-up was 49 months. In univariate analysis, patients with capsular involvement and collecting-system invasion had a worse prognosis than patients without (P = 0.007 and <0.001, respectively). In multivariate analysis, capsular involvement (hazard ratio 1.84, P = 0.036) and collecting-system invasion (3.78, P < 0.001) were independent prognostic factors of recurrence-free survival. Interestingly, there was no survival difference between patients with capsular involvement in stage I/II and patients with invasion of perinephric tissue (pT3aN0M0). These findings suggest that capsular involvement and collecting-system invasion are poor prognostic findings in stage I and II RCC. They should both be considered when planning the follow-up. A revised pT3a stage including patients with capsular involvement could improve its prognostic validity.

Flap endonuclease 1 is overexpressed in prostate cancer and is associated with a high Gleason score

To investigate the expression and potential clinical usefulness of structure-specific flap endonuclease 1 (FEN-1) in human primary prostate cancer using tissue microarray technology, as FEN-1 was recently identified to be overexpressed in CL1.1, the most aggressive clone generated from the hormone-refractory prostate cancer cell line CL1. Immunohistochemistry was performed on tissue microarrays constructed from paraffin-embedded specimens of primary prostate cancer from 246 patients who had had a radical prostatectomy. Prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH) and normal prostate epithelium were represented on the array. FEN-1 nuclear expression was scored based on the percentage of target cells staining positively, and correlated with Gleason score, preoperative prostate-specific antigen (PSA) level and pathological stage. The time to PSA recurrence was also analysed. The mean expression of FEN-1 was significantly higher in cancer (36.7%) than in normal (13.2%), BPH (4.5%) and PIN (15.4%) specimens (P < 0.001). FEN-1 expression was significantly correlated with Gleason score (ó = 0.23, P = 0.002). A higher preoperative serum PSA level (P = 0.015), Gleason score > or = 7 (P < 0.001), seminal vesicle invasion (P < 0.001) and capsular involvement (P = 0.004) were associated with PSA recurrence, whereas FEN-1 expression was not. In a multivariate analysis, only Gleason score > or = 7 (P < 0.001), seminal vesicle invasion (P = 0.005) and capsular involvement (P = 0.009) were retained as independent predictors for PSA recurrence. FEN-1 is overexpressed in prostate cancer compared with matched normal prostate, and its expression increases with tumour dedifferentiation, as shown by increasing Gleason score. These results suggest that FEN-1 might be a potential marker for selecting patients at high risk, and a potential target for prostate cancer diagnosis and therapy.

Splenectomy in cytoreductive surgery for advanced ovarian cancer

To evaluate the series of advanced ovarian cancer patients who underwent splenectomy as part of their surgery, a retrospective file review of 258 ovarian cancer cases were examined. There were 13 cases that underwent splenectomy. These patients constitute 5% of all and 8.8% of the advanced ovarian cancer patients. Seven cases had splenectomy as part of their initial cytoreductive surgery while 6 had surgery for recurrent disease. Splenectomy was performed to resect hilar and/or capsular involvement in 9 (69%) cases, while in 3 cases (23%) splenic injury during adjacent tumoral resection required splenectomy. One patient had splenectomy for infarcts and died after the surgery with systemic complications nonrelated to the surgery. No other serious morbidity was detected. Median survival of the patients was 34 months (1-120 months) from the initial diagnosis. Median survival was 18 months (1-78 months) after the splenectomy. Three patients were still alive with no evidence of disease 2, 5 and 6.5 years after the splenectomy. Splenectomy is a feasible and safe procedure. However, it should be reserved for patients in whom optimal cytoreductive results could be achieved.

Prostate Stem Cell Antigen Expression is Associated With Gleason Score, Seminal Vesicle Invasion and Capsular Invasion in Prostate Cancer

Few successful therapeutic options exist for men who present with metastatic prostate cancer (CaP) or for the 30% with recurrence. The development and characterization of molecular markers are vital to the development of prognostic and therapeutic modalities in CaP. We investigated the expression and potential clinical usefulness of prostate stem cell antigen (PSCA) in CaP using tissue microarrays. Immunohistochemical analysis using a PSCA monoclonal antibody was performed on tissue microarrays constructed from paraffin embedded specimens from 246 patients who underwent radical retropubic prostatectomy. PSCA staining was correlated with established prognostic factors, such as Gleason score, prostate specific antigen (PSA), and seminal vesicle invasion. In addition, recurrence-free survival was analyzed. A high PSCA intensity of 3 was associated with adverse prognostic features, such as Gleason score 7 and above (p = 0.001), seminal vesicle invasion (p = 0.005) and capsular involvement (p = 0.033). On univariate analysis tumors with a PSCA intensity of 3 carried an increased risk of PSA recurrence (p = 0.031, HR 1.77, 95% CI 1.05 to 2.96). However, after adjusting for these variables a PSCA intensity of 3 was no longer an independent predictor of PSA recurrence. We found that high PSCA intensity is significantly associated with adverse prognostic features such as high Gleason score and extra-organ disease. The results of this study suggest that PSCA is a promising tumor marker for the selection of patients at high risk but additional studies are necessary to assess the usefulness of PSCA in patient biopsies.

Risk factors for malignancy in multinodular goitres

Background. Multinodular goitre (MNG) is quite often associated with thyroid carcinoma, but the risk factors for malignancy are not well known. The aim is to analyse patients with thyroid carcinoma associated with MNG to determine the clinical risk factors for malignancy. Method. From a series of 672 MNGs we analysed a subgroup of 59 patients presenting with an associated thyroid carcinoma. The variables analysed were age, sex, family history, cervical radiation therapy, residence in areas of endemic goitre, prior thyroid surgery, time of evolution, asymptomatic status, hyperthyroidism, compressive syndromes, intrathoracic prolongation, goitre consistency and cervical adenopathies. These were compared to MNGs not developing malignancy using the Chi-squared test, Student's t test and a logistic regression test. Results. Of the 59 cases, 37 corresponded to a microcarcinoma (≤1 cm). The most common histological type was papillary ( n=48), followed by follicular ( n=6). In 20 cases the carcinoma was multifocal, and capsular involvement was noted in 16 patients, lymph node involvement in five and vascular involvement in another five. The multivariate analysis confirmed the following as independent variables associated with the presence of carcinoma: family history of thyroid pathology (RR=1.6), history of cervical radiation therapy (RR=1.8), recurrent goitre (RR=2.1) and presence of adenopathies on physical exploration (RR=1.6). Conclusion. The risk factors for carcinoma associated with MNG are family history of thyroid pathology, personal history of cervical radiation therapy, prior surgery and presence of cervical adenopathies.

Use of algorithms as determinants for individual patient decision making: national comprehensive cancer network versus artificial neural networks

The National Comprehensive Cancer Network (NCCN) developed a series of algorithms based on expert opinion to guide the treatment of patients with prostate cancer. These algorithms define acceptable treatment options according to the risk of disease recurrence and the life expectancy of the patient. However, practicing clinicians are expected to use medical judgment when making actual treatment decisions. Many clinical and pathologic variables affect patient prognosis, which, in turn, influences the treatment and surveillance of patients. Artificial neural networks (ANNs) offer promise for improving the predictive value of traditional statistical modeling. ANN models have been designed that predict risk of lymph node spread and capsular involvement during disease staging, risk of disease recurrence after prostatectomy, and overall and cause-specific survival. This article provides a review of guidelines, such as NCCN and ANN, used for the management of prostate cancer and suggests that group-level recommendations based on these algorithms or other decision trees may misrepresent individual patient preferences for treatment. Patients and their clinicians need to consider available prognostic information, including clinical status, pathologic variables, and comorbidities, and then select a reasonable treatment approach that maximizes outcome and quality of life according to the preferences of each patient.

Avaliação da incidência e do comportamento do câncer de tireóide em pacientes com doença de graves submetidos a tireoidectomia

A fim de avaliar a incidência, comportamento, evolução clínica e determinação de possíveis fatores preditivos da associação entre carcinoma de tireóide (CT) e Doença de Graves (DG), analisamos os prontuários de todos os pacientes submetidos à tireoidectomia para tratamento definitivo de DG em 2 hospitais universitários, entre 01/79 e 11/02. Dos 341 pacientes identificados, o exame histológico das peças cirúrgicas revelou CT em 7 (2,1%). A idade dos pacientes do grupo sem CT variou de 13 a 79 anos (mediana: 34) e naqueles com CT variou de 19 a 50 anos (mediana: 29), sem diferença significativa entre os grupos. Havia 293 mulheres (87,7%) e 41 homens (12,3%) no grupo sem CT e 5 mulheres (71,5%) e 2 homens (28,5%) no grupo com CT. O tipo histológico presente em todos os casos foi carcinoma papilífero de tireóide (CPT), sendo um caso de CPT multicêntrico sem acometimento extra-tireoidiano, 2 casos de variante folicular com 8 e 25mm de diâmetro, sem invasão capsular, um caso de CPT clássico com 15mm de diâmetro e nos 3 restantes, microcarcinoma (&lt;10mm de diâmetro). O acompanhamento dos pacientes variou de 6 a 16 anos, e nenhum apresentou recorrência local da doença, ou metástases à distância. Nesta casuística, a incidência de CT em pacientes operados por DG foi concordante com dados da literatura. Não observamos agressividade maior do que a usual, talvez pela grande freqüência de carcinomas ocultos.

An Unusual-Appearing Metanephric Adenoma: Features Distinguishing It From Other Small Blue Cell Tumors in the Adult Kidney

This article reports a “small blue cell tumor” with an unusual microscopic appearance in an asymptomatic 63-year-old man. Examination of the right partial nephrectomy specimen showed a 5 × 3 × 3-cm mass with fleshy cut surface and focal necrosis. The mass was confined in the kidney with no margin involvement. Microscopically, the peripheral part of the tumor showed bland-appearing small blue cells forming tightly packed small acini, a feature typical of metanephric adenoma. The central portion had larger blue cells arranged as crowded long tubular or somewhat papillary structures. Mitoses and small necrotic foci also were seen occasionally in the central portion. No lymphovascular invasion or capsular involvement was identified. All the tumor cells were positive for keratin markers (AE1/AE3 and CAM5.2). All the peripheral cells and 20% of the central cells were reactive with vimentin. Cells at both the peripheral and central portions stained negatively for neuroendocrine markers (synaptophysin and chromogranin). Differential diagnosis includes several small blue cell tumors that can be found in the adult kidney. The pertinent literature is reviewed.

Quantitative analysis of the extent of extracapsular invasion and its prognostic significance: a prospective study of 170 cases of carcinoma of the larynx and hypopharynx.

The extracapsular spread of disease in modal metastasis of head and neck tumors is an important prognostic factor. However, the implications of the degree of capsular involvement are rarely mentioned. This is a prospective study which intends to investigate the role of transcapsular spread in metastatic lymph nodes on the outcome of patients with laryngeal or hypopharyngeal carcinoma. This is a prospective study of 170 consecutive cases of previously untreated patients with squamous cell carcinoma of the larynx or the hypopharynx treated from January 1981 through January 1988 at the Head and Neck Service of the Heliópolis Hospital Complex, São Paulo, Brazil. In an attempt to understand better the influence of the extension of capsular lymph node involvement on recurrence and actuarial survival rates, the Kaplan-Meier method and Mantel-Cox test were used. The nodal cervical relapse was associated only to a macroscopic transcapsular spread (confidence interval, 1.7-7.0). When the carcinoma was confined to the lymph node or only a microscopic transcapsular spread was present, no statistically significant differences were found in recurrence or in death rates. The 5-year global and disease-free actuarial survival rates were, respectively, 52.0% and 56.8% for cases without metastasis and 5.8% and 10.2% when macroscopic transcapsular spread was present (p < .0001). The capsular rupture was the most important independent prognostic factor associated with the N categories of the TNM clinical classification and with metastatic lymph node diameter. The risks of recurrence and death are higher when there is macroscopic extracapsular extension. When the tumor is confined to the lymph node or shows a microscopic invasion beyond the capsule, there are no statistically significant differences in risk rates. The risk of capsular rupture is related to the N category of the classification TNM and the diameter of the metastatic lymph node, from 3 cm and larger.

Morphologic changes induced by neoadjuvant androgen ablation may result in underdetection of positive surgical margins and capsular involvement by prostatic adenocarcinoma

Objectives Neoadjuvant androgen ablation (NAAA) causes significant cytoarchitectural changes in both benign and malignant prostatic epithelial cells that may contribute to underdetection of prostate cancer capsular involvement and positive surgical margins. Methods The aim of this study is to determine the ability of cytokeratin immunohistochemistry to enhance the determination of pathologic stage of prostate cancer following NAAA. Results Cytokeratin AE1/AE3 immunohistochemistry identified 6 (27.3%), 15 (68.2%), 5 (22.7%), and 5 (22.7%) cases of organ-confined disease, capsule penetration, positive surgical margin, and seminal vesicle involvement, respectively, as compared with 10 (45.5%), 10 (45.5%), 3 (13.6%), and 5 (22.7%) cases by hematoxylin-eosin (H&E) staining, respectively. Two cases without detectable tumor by H&E staining had demonstrable residual tumor by cytokeratin immunohistochemical staining. Conclusions Cytokeratin immunohistochemistry revealed more extensive intracapsular, capsular, and extracapsular tumor involvement and higher rate of positive surgical margin than did conventional H&E staining. Therefore, the beneficial pathologic effects of NAAA observed may, in part, be attributable to the artifact of observation.

REICAP: prospective epidemiologic study of prostate cancer in Italy. Preliminary results. Ricerca Epidemiologica Italiana sul Carcinoma Prostatico.

Prostatic carcinoma is a common disease of aging male subjects. Owing to structural population changes, its incidence is increasing, making it a major social problem. Epidemiological studies are useful but often do not fully rely on clinical data. The purpose of the present study was to investigate characteristics of prostatic carcinoma from both a clinical and epidemiological point of view. A multiphased clinicoepidemiological study was initiated in Italy, involving 26 urological centers operating in districts where national tumor registries are active. Demographic and clinical data on stage, pathology, prostate-specific antigen (PSA), and first-line treatment of 819 patients recruited during the prospective 1-year clinical phase of the study were examined. The study showed that most patients with prostate carcinoma were symptomatic, that incidental cases were 10% and distant metastases were present at first observation in 15.3% of patients. PSA within the normal range was found in about 60% of incidental cases and in about a third of stage B cases. Most patients were treated with hormonal therapy. Radical surgery showed a limited incidence of capsular involvement and lymph node metastases. These preliminary data show that in Italy, prostate carcinoma is diagnosed mainly when symptoms are present and that in 53% of cases the disease is locally advanced or disseminated. Treatment appears quite homogeneous for advanced cases but controversies exist for stage A1 (19% treated with hormones, 23% with radical surgery and 52% with watchful waiting), for stage A2 (52% treated with hormones, 23% with watchful waiting), and for stage B (58% of B2 treated with hormones against 27% only treated with radical prostatectomy). A special analysis is planned to investigate the cause of the low incidence of capsular invasions and D1 in operated cases.

Prognostic significance of capsular invasion and capsular penetration in patients with clinically localized prostate cancer undergoing radical prostatectomy.

One hundred thirty patients with an observed follow-up of more than 10 years after radical prostatectomy were restaged with regard to local extent of the tumor in relation to the prostate capsule. Of 112 patients with surgically staged negative pelvic lymph nodes, 62 had a tumor-free prostate capsule, 24 had capsular invasion without penetration, and 26 had tumors extending through the capsule of the prostate. Observed overall and disease-free 10-year-survival rates were 79% and 69.4%, respectively, in patients with absence of capsular involvement and 70.8% and 66.7%, respectively, in patients with capsular invasion alone. In patients with capsular penetration, however, the survival rates significantly decreased to 57.7% (P = 0.018) and to 38.5 (P = 0.017), respectively. The overall progression rate was found to be significantly higher in patients with tumors extending through the prostatic capsule (46.2%), as compared to those with absence of capsular involvement (21%; P = 0.014) as well as to those with capsular invasion alone without penetration (25%; P = 0.034). Thus, in contrast to capsular invasion alone, capsular penetration means a poor prognostic indicator, which accounts for a reduced survival expectancy and a higher progression rate following radical prostatectomy. Therefore, tumors with capsular invasion and those with capsular penetration should not be grouped together in the same tumor stage as done in the 1987 edition of the TNM tumor classification system.

Extent of pontine pyramidal tract Wallerian degeneration and outcome after supratentorial hemorrhagic stroke.

Pyramidal tract Wallerian degeneration has been detected on magnetic resonance imaging (MRI) as T2-weighted high-intensity areas. We analyzed the relation between the extent of brain stem Wallerian degeneration and activities of daily living (ADL) after supratentorial hemorrhagic stroke. Twenty-six patients with supratentorial hemorrhage were examined on the coronal T2-weighted image of the pons 3 months or later after stroke, and the percentage of Wallerian degeneration in the pons was calculated. The patients were divided into three groups. In group A (n = 6), MR films were taken 3 to 6 months from the onset, and the ADL assessment was done within 2 months from the MRI. In group B (n = 11), MR films were taken 3 to 6 months from the onset, and the ADL assessment was done within 10 months from the MRI (mean, 15.5 months from the onset). In group C (n = 9), MR films were taken after 10 to 17 months (mean, 12.0 months) from the ictus, and the ADL assessment was done simultaneously. Barthel Index score was used for quantitative ADL assessment. All patients showed various degrees of pontine pyramidal tract Wallerian degeneration associated with capsular involvement by the hematoma. In group A, the percentage of degeneration did not correlate with the Barthel Index score (r = .2101, P = .6895). An inverse relation between percentage of degeneration and Barthel Index score was seen in groups B (r = .7354, P = .0099) and C (r = .888, P = .0014). In groups B and C, Wallerian degeneration was higher in patients with Barthel scores less than 60 (P = .005). The extent of pontine Wallerian degeneration on MRI 3 months or later after the stroke correlated with the patient's Barthel Index score 1 year after the stroke.