The impact of immunohistochemical expression of nitric oxide synthases on clinical and pathological features of renal cell carcinoma.

PURPOSE: To evaluate the immunohistochemical expression of nitric oxide synthase (NOS) types 1, 2, and 3 in intratumoral and non-neoplastic samples of renal cell carcinoma (RCC) and correlate it with the clinical and pathological features of this malignancy. METHODS: We analyzed 110 patients with RCC underwent radical nephrectomy (RN) or partial nephrectomy (PN) by streptavidin-biotin peroxidase method, tissue microarray, and digital microscopy. As endpoints, NOS expression was correlated with pathological features, overall survival (OS), and cancer-specific survival (CSS). RESULTS: Non-neoplastic samples had higher NOS3 and lower NOS 2 levels than RCC tissues. Greater expression of all NOS isoforms was associated with larger tumors. High NOS1 expression correlated with microscopic venous invasion (MVI) (p = 0.046) and lymph node metastases (p = 0.007). High NOS2 expression was linked to MVI, more RN performed, and male gender (p = 0.035, p = 0.003, and p = 0.027, respectively). High NOS3 expression correlated with lymph node metastases (p = 0.039), microlymphatic invasion (p = 0.029), invasion of the renal pelvis and ureter (p = 0.004), RN (p = 0.003), and shorter OS (58.1 vs. 79.4 % respectively, p = 0.033) by univariate analysis. DFS was not influenced by any NOS isoform. By multivariate analysis, the risk factors for death were TNM stages III and IV (hazard ratio [HR] = 4.5), high Fuhrman's grade (HR = 2.9), Karnofsky performance status ≤80 (HR = 2.5), progression (HR = 5.5), and recurrence (HR = 6.3). Stage III disease was an independent risk factor for recurrence (HR = 9.5). CONCLUSIONS: High NOS expression in RCC is associated with a poor prognosis and larger tumors. NOS3 influences OS by univariate analysis.

The use of the American Society of Anesthesiology Classification as a prognostic factor in patients with renal cell carcinoma.

OBJECTIVES: We analyzed whether the American Society of Anesthesiology (ASA) classification could be used as a prognostic factor in renal cell carcinoma. METHODS: ASA classification's impact on cancer-specific survival (CSS) and on overall survival in 145 patients submitted to radical or partial nephrectomy was evaluated, and was compared with clinicopathological variables. RESULTS: CSS was influenced by ASA in uni- and multivariate analyses. Five-year CSS was 95.7, 71.1 and 39.8% for ASA 1, ASA 2 and ASA 3, respectively (p = 0.007). The ASA classification influenced the overall survival too (p < 0.001). When 18 patients with metastases were excluded, the CSS was 95.7, 83.9 and 42.9% for ASA 1, ASA 2 and ASA 3, respectively (p = 0.001). ASA 3 patients had ten times more metastases than ASA1 patients and two times more than ASA 2 patients (p = 0.001). ASA 3 patients had fewer incidental tumors (p = 0.043) than ASA 2 and 3 patients. CONCLUSION: In this series, the ASA classification could be used as a prognostic factor in renal cell carcinoma.

Absence of TMPRSS2:ERG fusions and PTEN losses in prostate cancer is associated with a favorable outcome.

TMPRSS2:ERG gene fusions and PTEN deletions are the most common genomic aberrations in prostate cancer. Recent work has suggested that the TMPRSS2:ERG fusion is associated with a more aggressive phenotype. Similarly, PTEN deletion has been associated with biochemical recurrence and lymph node metastasis. To date, there has been no systematic analysis of the combined influence of genomic PTEN deletion with TMPRSS2:ERG gene fusions on clinical parameters of prostate cancer progression. We carried out a retrospective analysis of 125 prostate cancers with known clinical outcome using interphase fluorescence in situ hybridization to detect the relative prevalence of TMPRSS2:ERG rearrangements and/or PTEN genomic deletions. TMPRSS2:ERG rearrangement was found in 60 of 125 (48%) prostate cancers. Duplication of TMPRSS2:ERG fusion was observed in seven (6%) tumors. Gleason grade (P=0.0002)/score (P=0.001), median tumor volume (P=0.0024), preoperative PSA (P=0.001) and perineural invasion (P=0.0304) were significantly associated with biochemical recurrence by univariate analysis with TMPRSS2:ERG approaching significance (P=0.0523). By multivariate analysis, relevant factors associated with recurrence were Gleason scores 7 (P=0.001) and 8-10 (P=0.015), PTEN homozygous deletion (P=0.013) and concurrent TMPRSS2:ERG fusion and PTEN deletion (P=0.036). Kaplan-Meier analysis indicated that the presence of TMPRSS2:ERG fusion was marginally less favorable in comparison to no fusion. Duplication of fusion gene showed worse prognosis. It was possible to determine the relative frequencies of PTEN deletion and/or TMPRSS2:ERG fusions in 82 of 125 prostate cancers. With biochemical recurrence as an endpoint, the genomic biomarkers identified three patient groups: (1) 'poor genomic grade' characterized by both PTEN deletion and TMPRSS2:ERG fusions (23/82, 28%); (2) 'intermediate genomic grade' with either PTEN deletion or TMPRSS2:ERG fusion (35/82, 43%) and (3) 'favorable genomic grade' in which neither rearrangement was present (24/82, 29%). Kaplan-Meier and multivariate analysis indicate that TMPRSS2:ERG fusion and PTEN loss together are a predictor of earlier biochemical recurrence of disease.

Double-barreled wet colostomy is a safe option for simultaneous urinary and fecal diversion. Analysis of 56 procedures from a single institution.

BACKGROUND AND OBJECTIVES: Wide pelvic tumors need urinary and fecal diversion. We set out to assess the efficacy of the double-barreled wet colostomy (DBWC) in patients undergoing simultaneous double diversion. MATERIAL AND METHODS: We reviewed 56 consecutive patients submitted to surgery, divided into two groups: (1) total pelvic exenteration plus DBWC (n = 26); (2) DBWC without simultaneous pelvic resection (n = 30). Pelvic tumor recurrences accounted for most patients (n = 53), whereas the remaining three patients suffered from actinic pelvic complications. RESULTS: Surgical morbidity and mortality rates were 53.8% (14/26) and 11.5% (3/26) in Group 1, and 43.5% (13/30) and 3.3% (1/30) in Group 2, respectively. Only 2 patients out of 51 (3.9%) developed late postoperative urinary tract infection. Regression of the hydronephrosis was observed in 28 out of 33 assessable patients. Median survival in Groups 1 and 2 was 8.36 and 4.14 months, respectively. In the subgroup of patients submitted to curative surgery (n = 24), actuarial cancer-specific survival rate in 2 years was 58.78%. CONCLUSION: DBWC is a safe and efficient alternative for simultaneous urinary and fecal diversion, with low morbidity and mortality rates, improvement of renal insufficiency, and low risk of postoperative urinary tract infection.

Treatment of patients with superficial bladder cancer stratified by risk groups treated with lyophilized Moreau-Rio de Janeiro BCG strain.

INTRODUCTION: The Moreau-Rio de Janeiro BCG strain is considered the most effective to stimulate immunologic activity in mice. The objective of this prospective study was to evaluate BCG results for patients with superficial bladder cancer stratified by risk groups. MATERIAL AND METHODS: From April 1988 to May 2000, 100 patients were treated by transurethral resection for bladder tumor, followed by intravesical instillation of 40 mg BCG, with induction and maintenance cycles. Fisher exact test and Chi-square test, with 95% significance, were used to evaluate possible associations among variables. The Kaplan-Meier method was used to evaluate the disease-free interval and patients' survival, while log-rank test was used to compare the curves among the groups. RESULTS: The median follow-up was 69.3 months and varied from 10 to 153 months. Overall recurrence and progression rates were 55% and 13%, respectively. The medium time to recurrence was 9.4 months and to progression was 24.4 months. The cancer specific survive was 90%. Univariate analysis revealed that tumor recurrence was significantly associated with weekly BCG failure (p=0.011), multifocality (p=0.001), number of recurrences after primary therapy (p=0.001) and the need to Mitomycin C instillation (p=0.001). However, no variable was significantly associated with recurrence in multivariate analysis. There were significant associations, in univariate analysis, between disease progression and the following variables: tumor grade, weekly and 15-days BCG failure, both as first line and second line therapy, recurrence and need of Mitomycin C therapy. Independent variables to progression were 6.7 relative risk to weekly BCG failure, tumor grade and 15-days BCG (p= 0.08; CI=0.79-56.7), 2.4 (p= 0.11; CI=0.80-7.15) and 1.5 (p=0.23; CI=1.05-2.13), respectively. Patient stratification by risk groups were able to predict progression (p=0.045), but not recurrence (p=0.311). Disease progression rates were 3.2%, 12.2% e 25%, in low, intermediate and high risk groups, respectively. The BCG administration was well tolerated, and 21 patients (21%) didn't present any side effects. CONCLUSIONS: Intravesical instillation of BCG was overall well tolerated. Adjuvant BCG didn't decrease significantly recurrence rates, and 16% of the patients underwent alternative therapy with intravesical Mitomycin to prevent new recurrences. The risk group classification was able to select patients with high risk to progression. Tumor grade, BCG failure as first and second line therapies, were predictive factors of poor prognosis. BCG of Moreau-Rio de Janeiro strain was well tolerated, similar to other strains used in literature.

Emprego do samário 153-EDTMP no tratamento do adenocarcinoma de próstata avançado. Resultados preliminares / The use of samarium 153-EDTMP for treatment of advanced prostatic adenocarcinoma

Introduçäo: Os autores analisam os efeitos do emprego endovenoso do Samário 153-EDTMP no tratamento de 35 pacientes portadores de adenocarcinoma de próstata refratário à hormonioterapia com metástases ósseas dolorosas. Material e métodos: Entre novembro de 1995 e março de 1998, 35 pacientes com metástase óssea de adenocarcinoma de próstata näo responsivo ao tratamento hormonal foram submetidos à aplicaçäo endovenosa do Samário 153-EDTMP (1,0 a 1,5 mCi/Kg de peso), com finalidade antiálgica. Sessenta porcento dos pacientes tinham pelo menos 20 metástases ósseas, 30 porcento usaram morfina e 68,5 porcento já haviam sido irradiados. Foram avaliadas a resposta à dor, a mielotoxicidade e os níveis de PSA após a aplicaçäo. Resultados: Verificou-se resposta completa à dor em 8 (24,2 porcento) e resposta parcial em 14 pacientes (42,4 porcento) dentre 33 pacientes avaliáveis, totalizando-se 66,6 porcento de resposta global à dor. O tempo de duraçäo de resposta variou de 30 a 60 dias nos casos de resposta completa e entre 20 a 90 dias nos casos de resposta parcial. A ocorrência de toxicidade medular ocorreu em 17 de 23 casos avaliáveis sendo predominantemente através de leucopenia e plaquetopenia sempre de regressäo espontânea, sendo que em nenhum caso a toxicidade foi letal. A queda parcial de PSA após a aplicaçäo ocorreu em 3 e a progressäo em 19 de 22 casos avaliáveis. O seguimento dos pacientes variou entre 7 e 903 dias (média 190 dias), com sobrevida global de 51,1 porcento aos 6 meses e de 20,9 porcento ao final de um ano. A sobrevida mediana foi de 6,2 meses. Conclusöes: Os resultados sugerem que o Samário é uma alternativa segura no tratamento paliativo do câncer de próstata hormônio refratário

Atualizaçäo: complicaçöes actínicas do sistema genital e urinário / Atualization: actinics complications of genitourinary system

A radioterapia é empregada em várias neoplasias malignas pélvicas. Näo infreqüentemente, verifica-se complicaçöes actínicas em vários órgäos dos sistemas genital e urinário com intensidade variável. Nos casos mais graves, os pacientes mesmo com câncer controlado podem ter comprometidas de maneira significativa sua qualidade de vida e suas funçöes sexuais e reprodutivas. O risco da ocorrência de um segundo tumor primário, radioinduzido, deve ser lembrado. Os autores discutem de maneira individualizada essas complicaçöes, enfatizando aspectos de seu tratamento.

Linfadenectomia retroperitoneal para câncer do testículo / Retroperitoneal lymphadenectomy for malignant tumor of the testis

Säo apresentadas a técnica e a tática cirúrgica da linfadenectomia retroperitoneal, para as neoplasias malignas primárias do testículo, como usualmente säo feitas no Departamento de Cirurgia Pélvica do Hospital A. C. Camargo da Fundaçäo Antonio Prudente, em Säo Paulo

Implante ósseo liofilizado: estudo experimental em cobaias / Freezedried bone implant: experimental study in guinea-pigs

Os autores estudaram experimentalmente o implante ósseo liofilizado. Utilizaram 20 cobaios que receberam osso liofilizado, implantando-ono osso parietal esquerdo. Os animais foram sacrificados em lotes de 3 aos 15, 45, 90, 180, e 360 dias de pós-operatório e avaliados clínica, macroscópica, microscópica e radiologicamente. Infecçäo foi observada em 5 animais que evoluiram para óbito. No estudo radiológico aos 15 dias, os animais mostraram radiotransparência da área implantada. Aos 45, 90 e 180 dias houve evidentes sinais de tecido ósseo neoformado, estando aos 360 dias as áreas implantadas totalmente ocluídas por tecido radiopaco semelhante aos ossos receptores. Estes mesmos fatos foram comprovados na microscopia óptica