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1.
Prostate Cancer Prostatic Dis ; 20(4): 418-423, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28653675

RESUMO

BACKGROUND: Obesity, a cause of subclinical inflammation, is associated with increased risk of high-grade prostate cancer (PC) and poor outcomes. Whether inflammation occurs in periprostatic white adipose tissue (WAT), and contributes to the negative impact of obesity on PC aggressiveness, is unknown. METHODS: In a single-center, cross-sectional design, men with newly diagnosed PC undergoing radical prostatectomy were eligible for study participation. The primary objective was to examine the prevalence of periprostatic WAT inflammation defined by the presence of crown-like structures (CLS-P) as detected by CD68 immunohistochemistry. Secondary objectives were to explore the clinical and systemic correlates of periprostatic WAT inflammation. Tumor characteristics and host factors including BMI, adipocyte diameter, and circulating levels of lipids, adipokines, and other metabolic factors were measured. Wilcoxon rank-sum, Chi-square, or Fisher's exact tests, and generalized linear regression were used to examine the association between WAT inflammation and tumor and host characteristics. RESULTS: Periprostatic fat was collected from 169 men (median age 62 years; median BMI 28.3). Periprostatic WAT inflammation was identified in 49.7% of patients and associated with higher BMI (P=0.02), larger adipocyte size (P=0.004) and Gleason grade groups IV/V tumors (P=0.02). The relationship between WAT inflammation and high Gleason grade remained significant after adjusting for BMI (P=0.04). WAT inflammation correlated with higher circulating levels of insulin, triglycerides, and leptin/adiponectin ratio, and lower high density lipoprotein cholesterol, compared to those without WAT inflammation (P's <0.05). CONCLUSION: Periprostatic WAT inflammation is common in this cohort of men with PC and is associated with high-grade PC.


Assuntos
Tecido Adiposo Branco/patologia , Inflamação/patologia , Obesidade/patologia , Neoplasias da Próstata/patologia , Tecido Adiposo Branco/metabolismo , Idoso , Índice de Massa Corporal , Humanos , Inflamação/complicações , Inflamação/metabolismo , Inflamação/cirurgia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Obesidade/complicações , Obesidade/metabolismo , Obesidade/cirurgia , Próstata/metabolismo , Próstata/patologia , Próstata/cirurgia , Prostatectomia , Neoplasias da Próstata/complicações , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/cirurgia
2.
Prostate Cancer Prostatic Dis ; 20(1): 105-109, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27958385

RESUMO

BACKGROUND: A significant number of patients with minimal lymph node disease at radical prostatectomy (RP) and pelvic lymph node dissection (PLND) have better than expected long-term outcomes. We explored whether stratification by number of positive nodes enhances our institutional prediction model for biochemical recurrence after RP. METHODS: A total of 7789 patients underwent RP and pelvic lymph node dissection from 1995 to 2012 at a tertiary referral center. We compared two recurrence prediction models: one incorporated lymph node invasion and the other tracked the number of positive nodes. Existing and updated models' discrimination was assessed using Harrell's c-index and calibration. The 10-fold cross-validation was performed to correct for model overfitting. RESULTS: Of the 491 patients (6.3%) harboring nodal disease, 387 (5.0%) had 1-2 positive nodes and 104 (1.3%) had ⩾3 positive nodes. Data on number of positive nodes did not improve the c-index for the cohort as a whole. When we assessed discrimination for node-positive patients only, c-index for the model with number of positive nodes was 0.01 (95% confidence interval 0.001-0.024) higher than the model with lymph node invasion. Illustrative examples were provided by reclassification tables using number of positive lymph nodes. For instance, 40 of 7789 patients would be reclassified with a cutoff point of 50% for biochemical recurrence at 1 year, and 36 of 7789 patients would be reclassified with a cutoff point of 40% for biochemical recurrence at 10 years. CONCLUSIONS: Stratification by number of positive lymph nodes provided additional discriminative ability for evaluating risk in node-positive patients. Pending external validation, this model could be used for patient counseling and clinical trial stratification in this subpopulation.


Assuntos
Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/cirurgia , Idoso , Humanos , Estimativa de Kaplan-Meier , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Nomogramas , Período Pós-Operatório , Prognóstico , Modelos de Riscos Proporcionais , Prostatectomia , Neoplasias da Próstata/mortalidade
3.
Actas Urol Esp ; 40(7): 434-9, 2016 Sep.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27184342

RESUMO

BACKGROUND: Presence of lymph node metástasis (LNM) at salvage radical prostatectomy (sRP) is associated with poor outcome. Predictors of outcome in this context remain undetermined. ThE objective was to assess the role of number of positive lymph node on outcome of patients with LNM after sRP and for radio-recurrent prostate cancer. MATERIAL AND METHODS: We analyzed data from a consecutive cohort of 215 men treated with sRP at a single institution. We used univariate Cox proportional hazard regression models for biochemical recurrence (BCR) and metastatic outcomes, with prostate-specific antigen, Gleason score, extraprostatic extension, seminal vesicle invasion, time between radiation therapy and sRP, and number of positive nodes as predictors. RESULTS: Of the 47 patients with LNM, 37 developed BCR, 11 developed distant metastasis and 4 died with a median follow-up of 2.3 years for survivors. The risk of metastases increased with higher pre-operative PSA levels (HR 1.19 per 1ng/ml; 95% CI: 1.06-1.34; P=.003). The remaining predictors did not reach conventional levels of significance. However, removal of 3 or more positive lymph nodes demonstrated a positive association, as expected, with metastatic disease (HR 3.44; 95% CI: 0.91-13.05; P=.069) compared to one or 2 positive nodes. Similarly, the presence of extraprostatic extension, seminal vesicle invasion and Gleason grade greater than 7 also demonstrated a positive association with higher risk of metástasis, with hazard ratios of 3.97 (95% CI: 0.50, 31.4; P=.2), 3.72 (95% CI: 0.80-17.26; P=.1), and 1.45 (95% CI: 0.44-4.76; P=.5), respectively. CONCLUSIONS: In patients with LNM after sRP for radio-recurrent prostate cancer, the risk of distant metástasis is likely to be influenced by the number of positive nodes (3 or more), high preoperative PSA, Gleason grade and advanced pathologic stage. These results are consistent with the findings of number of nodes (1 to 2 vs. 3 or more nodes positive) as a prognostic indicator after primary radical prostatectomy and strengthen the plea for a revision of the nodal staging for prostate cancer.


Assuntos
Linfonodos/patologia , Recidiva Local de Neoplasia/patologia , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Idoso , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Terapia de Salvação , Resultado do Tratamento
4.
Prostate Cancer Prostatic Dis ; 18(1): 75-80, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25512262

RESUMO

BACKGROUND: The diffusion of minimally invasive radical prostatectomy (MIRP) in the United States may have led to adverse patient outcomes due to rapid surgeon adoption and collective inexperience. We hypothesized that throughout the early period of minimally invasive surgery, MIRP patients had inferior outcomes as compared with those who had open radical prostatectomy (ORP). METHODS: We used the Surveillance, Epidemiology and End RESULTS-Medicare dataset and identified men who had ORP and MIRP for prostate cancer from 2003-2009. Study endpoints were receipt of subsequent cancer treatment, and evidence of postoperative voiding dysfunction, erectile dysfunction (ED) and bladder outlet obstruction. We used proportional hazards regression to estimate the impact of surgical approach on each endpoint, and included an interaction term to test for modification of the effect of surgical approach by year of surgery. RESULTS: ORP (n=5362) and MIRP (n=1852) patients differed in their clinical and demographic characteristics. Controlling for patient characteristics and surgeon volume, there was no difference in subsequent cancer treatments (hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.76-1.05), although MIRP was associated with a higher risk of voiding dysfunction (HR 1.31, 95% CI 1.20-1.43) and ED (HR 1.43, 95% CI 1.31-1.56), but a lower risk of bladder outlet obstruction (HR 0.86, 95% CI 0.75-0.97). There was no interaction between approach and year for any outcome. When stratifying the analysis by year, MIRP consistently had higher rates of ED and voiding dysfunction with no substantial improvement over time. CONCLUSIONS: MIRP patients had adverse urinary and sexual outcomes throughout the diffusion of minimally invasive surgery. This may have been a result of the rapid adoption of robotic surgery with inadequate surgeon preparedness.


Assuntos
Prostatectomia/efeitos adversos , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/cirurgia , Idoso , Idoso de 80 Anos ou mais , Determinação de Ponto Final , Disfunção Erétil/epidemiologia , Disfunção Erétil/patologia , Humanos , Masculino , Complicações Pós-Operatórias , Neoplasias da Próstata/patologia , Resultado do Tratamento , Estados Unidos
5.
Br J Cancer ; 103(5): 708-14, 2010 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-20664589

RESUMO

BACKGROUND: Most men with elevated levels of prostate-specific antigen (PSA) do not have prostate cancer, leading to a large number of unnecessary biopsies. A statistical model based on a panel of four kallikreins has been shown to predict the outcome of a first prostate biopsy. In this study, we apply the model to an independent data set of men with previous negative biopsy but persistently elevated PSA. METHODS: The study cohort consisted of 925 men with a previous negative prostate biopsy and elevated PSA (>or=3 ng ml(-1)), with 110 prostate cancers detected (12%). A previously published statistical model was applied, with recalibration to reflect the lower positive biopsy rates on rebiopsy. RESULTS: The full-kallikrein panel had higher discriminative accuracy than PSA and DRE alone, with area under the curve (AUC) improving from 0.58 (95% confidence interval (CI): 0.52, 0.64) to 0.68 (95% CI: 0.62, 0.74), P<0.001, and high-grade cancer (Gleason >or=7) at biopsy with AUC improving from 0.76 (95% CI: 0.64, 0.89) to 0.87 (95% CI: 0.81, 0.94), P=0.003). Application of the panel to 1000 men with persistently elevated PSA after initial negative biopsy, at a 15% risk threshold would reduce the number of biopsies by 712; would miss (or delay) the diagnosis of 53 cancers, of which only 3 would be Gleason 7 and the rest Gleason 6 or less. CONCLUSIONS: Our data constitute an external validation of a previously published model. The four-kallikrein panel predicts the result of repeat prostate biopsy in men with elevated PSA while dramatically decreasing unnecessary biopsies.


Assuntos
Biópsia , Calicreínas/análise , Neoplasias da Próstata/diagnóstico , Detecção Precoce de Câncer , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Países Baixos , Antígeno Prostático Específico/sangue
6.
Br J Cancer ; 102(4): 678-84, 2010 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-20104229

RESUMO

BACKGROUND: The discovery of ERG/ETV1 gene rearrangements and PTEN gene loss warrants investigation in a mechanism-based prognostic classification of prostate cancer (PCa). The study objective was to evaluate the potential clinical significance and natural history of different disease categories by combining ERG/ETV1 gene rearrangements and PTEN gene loss status. METHODS: We utilised fluorescence in situ hybridisation (FISH) assays to detect PTEN gene loss and ERG/ETV1 gene rearrangements in 308 conservatively managed PCa patients with survival outcome data. RESULTS: ERG/ETV1 gene rearrangements alone and PTEN gene loss alone both failed to show a link to survival in multivariate analyses. However, there was a strong interaction between ERG/ETV1 gene rearrangements and PTEN gene loss (P<0.001). The largest subgroup of patients (54%), lacking both PTEN gene loss and ERG/ETV1 gene rearrangements comprised a 'good prognosis' population exhibiting favourable cancer-specific survival (85.5% alive at 11 years). The presence of PTEN gene loss in the absence of ERG/ETV1 gene rearrangements identified a patient population (6%) with poorer cancer-specific survival that was highly significant (HR=4.87, P<0.001 in multivariate analysis, 13.7% survival at 11 years) when compared with the 'good prognosis' group. ERG/ETV1 gene rearrangements and PTEN gene loss status should now prospectively be incorporated into a predictive model to establish whether predictive performance is improved. CONCLUSIONS: Our data suggest that FISH studies of PTEN gene loss and ERG/ETV1 gene rearrangements could be pursued for patient stratification, selection and hypothesis-generating subgroup analyses in future PCa clinical trials and potentially in patient management.


Assuntos
Carcinoma/mortalidade , Proteínas de Ligação a DNA/genética , PTEN Fosfo-Hidrolase/genética , Neoplasias da Próstata/mortalidade , Transativadores/genética , Fatores de Transcrição/genética , Idoso , Carcinoma/diagnóstico , Carcinoma/genética , Carcinoma/metabolismo , Causas de Morte , Estudos de Coortes , Análise Mutacional de DNA/métodos , Proteínas de Ligação a DNA/metabolismo , Loci Gênicos , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , PTEN Fosfo-Hidrolase/metabolismo , Prognóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Análise Serial de Tecidos , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Regulador Transcricional ERG
7.
Prostate ; 58(2): 103-8, 2004 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-14716735

RESUMO

BACKGROUND: High grade prostatic intraepithelial neoplasia (HGPIN) is a putative pre-malignant lesion of the prostate. While apolipoprotein-D (Apo-D), an androgen-regulated hydrophobic transporter protein, is expressed in prostate tumors, its expression in HGPIN is unknown. METHODS: Immunoreactivity for Apo-D and another androgen-regulated protein, prostate specific antigen (PSA), was investigated in 64 radical prostatectomy tissues by video image analysis. RESULTS: Eighty two percent of prostatectomy specimens demonstrated moderate to strong Apo-D immunoreactivity in areas of HGPIN. In comparison, weak Apo-D immunoreactivity was observed in non-malignant areas in only 24% of specimens. The median (range) percentage cellular area of HGPIN immunopositive for Apo-D (9.7%, 0-42.9), and the cellular concentration of Apo-D (MIOD 3.1, 0-13.3), were intermediate between that of normal (area 0%, 0-53.5%, MIOD 0, 0-12.6) and early stage prostate cancer tissues (area 29.2%, 0-90.8%, MIOD 6.7, 0-28.1). This increase in Apo-D expression from non-malignant, through HGPIN to prostate cancer was statistically significant (P < 0.001), and contrasted with the decrease observed in PSA staining between adjacent areas of normal glands, HGPIN, and cancer (P = 0.026). CONCLUSIONS: The presence of high levels of immunoreactive Apo-D in HGPIN and prostate cancer, but not in non-malignant epithelial cells, is consistent with HGPIN being an intermediate lesion in the transition to prostate cancer, and suggests that cellular Apo-D expression is a marker of malignant transformation of the prostate.


Assuntos
Apolipoproteínas/análise , Biomarcadores Tumorais/análise , Regulação Neoplásica da Expressão Gênica , Antígeno Prostático Específico/análise , Neoplasia Prostática Intraepitelial/genética , Neoplasia Prostática Intraepitelial/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Apolipoproteínas/biossíntese , Apolipoproteínas D , Transformação Celular Neoplásica , Humanos , Imunoensaio , Masculino , Prostatectomia , Neoplasia Prostática Intraepitelial/cirurgia , Neoplasias da Próstata/cirurgia , Gravação em Vídeo
8.
Urologe A ; 42(5): 685-92, 2003 May.
Artigo em Alemão | MEDLINE | ID: mdl-12750804

RESUMO

In patients suffering from prostate cancer, preoperative nomograms, which predict the risk of recurrence may provide a helpful tool in regard to the counselling and planning of an appropriate therapy. The best known nomograms were published by the Baylor College of Medicine, Houston and the Harvard Medical School, Boston. We investigated these nomograms derived in the U.S. when applied to German patients. Data from 1003 patients who underwent radical prostatectomy at the University-Hospital Hamburg were used for validation. Nomogram predictions of the probability for 2-years (Harvard nomogram) and 5-years (Kattan nomogram) freedom from PSA recurrence were compared with actual follow-up recurrence data using areas under the receiver-operating-characteristic curves (AUC). The recurrence free survival after 2 and 5 years was 78% and 58%, respectively. The AUC of the Harvard nomogram predicting 2-years probability of freedom from PSA recurrence was 0.80 vs. Kattan-Nomogram 5-years prediction of 0.83. Thereby, the Kattan nomogram showed a significant higher predictive accuracy (p=0.0274). For that reason preoperative nomograms derived in the U.S. can be applied to german patients. However, we would recommend the utilization of the Kattan nomogram due to its higher predictive accuracy.


Assuntos
Comparação Transcultural , Recidiva Local de Neoplasia/patologia , Neoplasias da Próstata/patologia , Biomarcadores Tumorais/sangue , Biópsia/estatística & dados numéricos , Intervalo Livre de Doença , Alemanha , Humanos , Masculino , Modelos Estatísticos , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias/estatística & dados numéricos , Próstata/patologia , Antígeno Prostático Específico/sangue , Prostatectomia/estatística & dados numéricos , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/cirurgia , Curva ROC , Valores de Referência , Reprodutibilidade dos Testes , Risco , Estados Unidos
9.
Urology ; 58(6): 983-7, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11744473

RESUMO

OBJECTIVES: To confirm the benefit of using an interposition sural nerve graft at the time of radical retropubic prostatectomy in an extended series of men with at least 1 year of follow-up. We previously reported the return of erectile function after resection of both cavernous nerves. METHODS: Twenty-eight potent men with clinically localized prostate cancer underwent radical retropubic prostatectomy with deliberate wide bilateral neurovascular bundle resection and the placement of bilateral nerve grafts. Erectile dysfunction questionnaires and patient interviews were completed at 6-month intervals. A minimum of 12 months of follow-up (mean 23 +/- 10 months) was obtained for 23 men (mean age 58 +/- 6 years). A control group of 12 men who underwent bilateral nerve resections, but declined nerve graft placement, was also followed up. RESULTS: Of the 23 men, 6 (26%) had spontaneous, medically unassisted erections sufficient for sexual intercourse with vaginal penetration. An additional 6 men (26%) described "40% to 60%" spontaneous erections (fullness, no rigidity, not able to penetrate). Ten men (43%) had intercourse with sildenafil. No demonstrable erections occurred before 5 months postoperatively. The greatest return of function thus far was observed at 18 months after surgery. CONCLUSIONS: This surgical technique continues to show promise as an advance in prostate cancer surgery. The results of this study demonstrated recovery of erectile function in men who underwent bilateral nerve graft placement during radical retropubic prostatectomy when both cavernous nerves were deliberately resected.


Assuntos
Ereção Peniana/fisiologia , Próstata/inervação , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Nervo Sural/transplante , Estudos de Casos e Controles , Coito , Denervação , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prostatectomia/efeitos adversos , Fatores de Tempo
10.
Am J Surg Pathol ; 25(11): 1429-32, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11684961

RESUMO

Pelvic lymph node metastases in prostate cancer (PCa) carry an ominous prognosis. Periprostatic/periseminal vesicle (PP/PSV) lymph nodes are present in some individuals, but their incidence and involvement by metastases are unknown. A total of 832 of 1233 (67.5%) patients who underwent radical retropubic prostatectomy for clinically localized PCa at the Methodist Hospital from 1983 to 1998 by one surgeon (P.T.S.) had whole-mount slides available for review. Of these, 92 (11.1%) had received preoperative therapy (radiation in 48 [5.8%], hormonal in 44 [5.3%]). Slides were examined with the naked eye by placing them on a white illuminated background, and any area suggestive of a lymph node in PP/PSV fat was confirmed microscopically and assessed for the presence of metastases. Thirty-seven of 832 patients (4.4%) had 39 PP/PSV lymph nodes-one bilateral, one with two ipsilateral lymph nodes, and the rest solitary. Sizes ranged from 0.7 to 4.5 mm (mean 1.8 mm). Distribution was 2 of 39 (5.1%) apical, 3 of 39 (7.7%) mid, 17 of 39 (43.6%) base, and 17 of 39 (43.6%) seminal vesicle. Five patients (0.6%) had metastatic PCa to the PP/PSV lymph nodes. All five patients were of advanced pathologic T stage [one pT3a (extraprostatic extension) and four pT3b (seminal vesicle invasion)]. Only two of those five (40%) had metastases (all ipsilateral) to pelvic lymph nodes. In three of five (60%) the metastases were isolated to the PP/PSV lymph nodes. Metastases were to the lymph nodes in the periseminal vesicle fat in four of five (80%) of the cases and in the fat surrounding the base of the prostate in one of five (20%). Four of five (80%) patients recurred. Histologic grade (Gleason score), tumor volume, and failure (recurrence) rates were significantly different between the five patients with metastases and the 32 patients without metastases to the PP/PSV lymph nodes (p <0.0001, p <0.0001, and p = 0.005, respectively). However, there was no evidence that an individual patient's probability of having a PP/PSV lymph node increased with resection of the neurovascular bundle (p = 0.7698). PP/PSV lymph nodes are uncommon, but based upon these limited data, it appears that patients with metastases limited to PP/PSV lymph nodes have a poor prognosis (similar to pelvic lymph node metastases) and should be included in the American Joint Committee on Cancer (AJCC) Staging Manual to indicate "N1" if positive for metastases.


Assuntos
Adenocarcinoma/secundário , Linfonodos/patologia , Próstata/patologia , Neoplasias da Próstata/patologia , Glândulas Seminais/patologia , Adenocarcinoma/terapia , Idoso , Terapia Combinada , Seguimentos , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Prostatectomia , Neoplasias da Próstata/terapia
12.
Urology ; 58(3): 393-9, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11549487

RESUMO

OBJECTIVES: To develop a prognostic nomogram to predict the freedom from recurrence for patients treated with permanent prostate brachytherapy for localized prostate cancer. METHODS: We performed a retrospective analysis of 920 patients treated with permanent prostate brachytherapy between 1992 and 2000. The clinical parameters included clinical stage, biopsy Gleason sum, pretreatment prostate-specific antigen (PSA) value, and administration of external beam radiation. Patients who received neoadjuvant androgen deprivation therapy were excluded. Failure was defined as any post-treatment administration of androgen deprivation, clinical relapse, or biochemical failure, defined as three PSA rises. Patients with fewer than three PSA rises were censored at the time of the first PSA rise. Data from two outside institutions served as validation. RESULTS: A nomogram that predicts the probability of remaining free from biochemical recurrence for 5 years after brachytherapy without adjuvant hormonal therapy was developed using Cox proportional hazards regression analysis. External validation revealed a concordance index of 0.61 to 0.64, and calibration of the nomogram suggested confidence limits of +5% to -30%. CONCLUSIONS: The pretreatment nomogram we developed may be useful to physicians and patients in estimating the probability of successful treatment 5 years after brachytherapy for clinically localized prostate cancer.


Assuntos
Adenocarcinoma/radioterapia , Braquiterapia , Recidiva Local de Neoplasia/diagnóstico , Neoplasias da Próstata/radioterapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Biópsia/estatística & dados numéricos , Estudos de Coortes , Intervalos de Confiança , Intervalo Livre de Doença , Seguimentos , Humanos , Masculino , Recidiva Local de Neoplasia/epidemiologia , Probabilidade , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Risco , Falha de Tratamento , Resultado do Tratamento
13.
Hum Pathol ; 32(8): 828-33, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11521227

RESUMO

We assessed whether the quantification of cancer invasion into the perineural space influences the prognosis of patients treated with radical prostatectomy. We conducted a retrospective study of clinical and pathologic features in 640 consecutive patients with clinical stage Tla-T3bNXM0 prostate cancer who were treated with radical retropubic prostatectomy by the same surgeon between 1989 and 1995. None had received preoperative hormonal therapy or radiotherapy. Detailed pathologic analysis, including the presence and maximum diameter of perineural invasion (PNI), was performed by 2 pathologists. Treatment failure was defined as either a serum prostate-specific antigen (PSA) level > 0.4 ng/mL and rising or initiation of adjuvant therapy. The median follow-up time was 48 months (range, 1 to 111 months). Overall, PNI was detected in 477 patients (75%). The progression-free 5-year probability rate after prostatectomy for patients with PNI was 70% +/- 3% compared with 94% +/- 2% for patients without PNI (P <.001). The mere presence of PNI was not an independent predictor of progression in a Cox proportional hazards analysis when the other established prognostic factors (serum PSA level, pathologic stage, surgical margin, and tumor volume) were considered. However, the increasing diameter of the largest focus of PNI was strongly associated with other established prognostic factors and the probability of progression after radical prostatectomy. Although little adverse effect in patients with PNI < 0.25 mm was seen 5 years after surgery, those with a PNI diameter of 0.25 to 0.5 mm were significantly (P <.001) less likely to remain free of progression; only 36% of those with PNI of 0.5 to 0.75 mm (P <.001) and 14% of those with PNI > or =0.75 mm (P =.002) were free of progression. In a Cox proportional hazard analysis, the PNI diameter was an independent predictor of prognosis. These results support that the measurement of the PNI diameter, easily recorded from prostatectomy specimens, could add important information to the prognosis of prostate cancer patients. Controversy regarding the significance of PNI may result from the lack of quantitative assessment of PNI in previous studies.


Assuntos
Adenocarcinoma/secundário , Nervos Periféricos/patologia , Neoplasias do Sistema Nervoso Periférico/secundário , Próstata/inervação , Neoplasias da Próstata/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Adulto , Idoso , Intervalo Livre de Doença , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias do Sistema Nervoso Periférico/mortalidade , Neoplasias do Sistema Nervoso Periférico/cirurgia , Modelos de Riscos Proporcionais , Prostatectomia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Glândulas Seminais/patologia , Taxa de Sobrevida
14.
Prostate ; 47(4): 269-75, 2001 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-11398174

RESUMO

BACKGROUND: Although prostate cancer is the most common incident cancer in men, not much is known about its etiology. We tested the hypothesis that expression levels of hMSH2 and hMLH1 in unaffected (normal) tissue play a role in the etiology of prostate cancer. METHODS: Total RNA was extracted from peripheral blood lymphocytes of subjects ascertained by a case-control study (70 patients and 97 age- and ethnicity-matched controls). A multiplex reverse transcription-polymerase chain reaction assay was used to simultaneously evaluate the relative expression of hMSH2 and hMLH1, using beta-actin as the internal control. RESULTS: The relative gene expression levels of hMSH2 and hMLH1 were significantly lower in cases than in controls (P < 0.05 for both genes). When compared with the highest tertile of the controls, low expression levels (the middle and lowest tertiles) of hMLH1 were associated with significantly increased risk of prostate cancer in a dose-response relationship (ORs = 2.68, and 4.31; 95% confidence interval = 1.00-7.23 and 1.64-11.30, respectively) after adjustment for age, ethnicity, smoking status, and family history of prostate cancer. CONCLUSIONS: These results suggest that reduced expression of hMLH1 in peripheral lymphocytes may be a risk factor for prostate cancer. However, it cannot be ruled out that the reduced expression we observed may be caused by the disease status. Our findings and the factors that may affect the expression of hMLH1 need further confirmation in larger prospective studies.


Assuntos
Adenocarcinoma/metabolismo , Reparo do DNA/genética , Proteínas de Ligação a DNA , Proteínas de Neoplasias/biossíntese , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Adaptadoras de Transdução de Sinal , Adenocarcinoma/sangue , Adenocarcinoma/genética , Idoso , Pareamento Incorreto de Bases , Proteínas de Transporte , Estudos de Casos e Controles , Di-Hidrotestosterona/sangue , Regulação Neoplásica da Expressão Gênica , Humanos , Linfócitos/metabolismo , Linfócitos/fisiologia , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS , Proteínas de Neoplasias/genética , Proteínas Nucleares , Projetos Piloto , Neoplasias da Próstata/sangue , Neoplasias da Próstata/genética , Proteínas Proto-Oncogênicas/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatísticas não Paramétricas , Testosterona/sangue
17.
Am J Surg Pathol ; 25(5): 657-60, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11342779

RESUMO

Gleason score (GS) is a powerful predictor of disease progression in men with prostate cancer (PCa). The majority of clinically localized prostate cancers, however, are moderately (GS5/6) or moderate to poorly (GS7) differentiated tumors with indeterminate prognosis. Differences in disease progression between patients with GS5/6 and GS7 tumors suggest the presence of any component of high-grade tumor (Gleason pattern [GP] 4/5) worsens prognosis markedly. Indeed, McNeal et al. have shown that quantification of GP4/5 provides prognostic information beyond the standard GS. Few investigators have analyzed whether primary and secondary GPs are important prognostically within GS7 PCa. All 823 whole-mount radical prostatectomy specimens with GS7 from a single surgeon (P.T.S.) were analyzed. Tumors were either 3+4 or 4+3, and primary GP was assigned by the same pathologist (T.M.W.). A total of 643 patients with 3+4 tumors and 180 patients with 4+3 tumors were studied. Statistical analysis using the log-rank test showed a significant difference in recurrence-free survival between patients with primary GP4 and those with GP3 (p <0.0001). However, in multivariate analysis with preoperative prostate-specific antigen, total tumor volume, surgical margin status, and the presence or absence of seminal vesicle involvement, extraprostatic extension, and lymph node metastasis, the primary GP did not retain independent significance (p = 0.0557). GS7 PCa is a heterogeneous group of tumors. In this cohort of men with GS7 tumors treated by radical retropubic prostatectomy, primary GP showed a significant correlation with other histologic and clinical predictors of disease progression; however, it was not independently predictive of disease progression in multivariate analysis (p = 0.76).


Assuntos
Adenocarcinoma/patologia , Neoplasias da Próstata/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Progressão da Doença , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Masculino , Análise Multivariada , Invasividade Neoplásica , Recidiva Local de Neoplasia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/cirurgia , Taxa de Sobrevida
18.
J Urol ; 165(5): 1562-8, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11342918

RESUMO

PURPOSE: Prediction is central to the management of prostate cancer. Nomograms are devices that make predictions. We organized many nomograms for prostate cancer. MATERIALS AND METHODS: Using MEDLINE a literature search was performed on prostate cancer nomograms from January 1966 to February 2000. We recorded input variables, prediction form, the number of patients used to develop the nomogram and the outcome being predicted. We also recorded the accuracy measures reported by the original authors and whether the nomograms have withstood validation. In addition, we noted whether the nomograms were proprietary or in the public domain. Each nomogram was classified into patient clinical disease state and the outcome being predicted. RESULTS: The literature search generated 42 published nomograms that may be applied to patients in various clinical stages of disease. Of the 42 nomograms only 18 had undergone validation, of which 2 partially failed. Few nomograms have been compared for predictive superiority and none appears to have been compared with clinical judgment alone. CONCLUSIONS: Patients with prostate cancer need accurate predictions. Prognostic nomograms are available for many clinical states and outcomes, and may provide the most accurate predictions currently available. Selection among them and progress in this field are hampered by the lack of comparisons for predictive accuracy.


Assuntos
Técnicas de Apoio para a Decisão , Neoplasias da Próstata/diagnóstico , Biópsia , Humanos , Masculino , Probabilidade , Prognóstico , Próstata/patologia , Antígeno Prostático Específico/análise , Neoplasias da Próstata/terapia , Sensibilidade e Especificidade
19.
J Urol ; 165(6 Pt 1): 1950-6, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11371887

RESUMO

PURPOSE: With the interposition of a sural nerve graft to replace resected cavernous nerves at radical retropubic prostatectomy, we have previously reported the return of effective erectile function. We determine the efficacy of this procedure in a series of men with at least 1-year followup. MATERIALS AND METHODS: A total of 12 potent men (mean age plus or minus standard deviation 57 +/- 6 years) with clinically localized prostate cancer underwent radical retropubic prostatectomy, with deliberate wide bilateral neurovascular bundle resection and placement of bilateral nerve grafts. A series of patient and partner erectile dysfunction questionnaires, and patient interviews were performed at 3, 6, 12 and 18 months postoperatively. Only results for those men with a followup of 12 months or greater (mean 16 +/- 4) are presented. A control group of 12 men who had undergone bilateral nerve resection but declined nerve graft placement, was also followed. RESULTS: Of the 12 men 4 (33%) had spontaneous medically unassisted erections sufficient for sexual intercourse with vaginal penetration. An additional 5 (42%) men describe "40 to 60%" spontaneous erections, with fullness, no rigidity and not able to penetrate. Overall, 9 (75%) men had return of erectile activity. No demonstrable erections occurred before 5 months postoperatively. The greatest return of function was observed at 14 to 18 months after surgery. CONCLUSIONS: This surgical technique has minimal morbidity and represents a significant advance in prostate cancer surgery in men requiring bilateral nerve resection. Our study clearly demonstrates recovery of erectile function in men who underwent bilateral nerve graft placement during radical retropubic prostatectomy when both cavernous nerves were deliberately resected.


Assuntos
Disfunção Erétil/prevenção & controle , Prostatectomia , Nervo Sural/transplante , Idoso , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
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