Long-term results of the implantation of the AMS 800 artificial sphincter for post-prostatectomy incontinence: a single-center experience

ABSTRACT Objectives Report the long-term outcomes of the AMS 800 artificial sphincer (AS) for the treatment post-prostatectomy incontinence (PPI) in a single center in Brazil. Materials and Methods Clinical data from patients who underwent the procedure were retrieved from the medical records of individuals with more than 1 year of follow-up from May 2001 to January 2016. Continence status (number of pads that was used), complications (erosion or extrusion, urethral atrophy, and infection), malfunctions, and need for secondary implantation were evaluated. The relationship between complications and prior or subsequent radiation therapy (RT) was also examined. Results From May 2001 to January 2016, 121 consecutive patients underwent AS implantation for PPI at an oncological referral center in Brazil. At the last visit, the AS remained implanted in 106 patients (87.6%), who reported adequate continence status (maximum of 1 pad/day). Eight-two subjects (67.8%) claimed not to be using pads on a regular basis at the final visit (completely dry). Revision occurred in 24 patients (19.8%). Radiation therapy (RT) for prostate cancer following radical prostatectomy was used in 47 patients before or after AS placement. Twelve patients with a history of RT had urethral erosion compared with 3 men without RT (p=0.004). Conclusion Considering our outcomes, we conclude that AS implantation yields satisfactory results for the treatment of PPI and should remain the standard procedure for these patients. Radiation therapy is a risk factor for complication.

Long-term results of the implantation of the AMS 800 artificial sphincter for post-prostatectomy incontinence: a single-center experience.

OBJECTIVES: Report the long-term outcomes of the AMS 800 artificial sphincer (AS) for the treatment post-prostatectomy incontinence (PPI) in a single center in Brazil. MATERIALS AND METHODS: Clinical data from patients who underwent the procedure were retrieved from the medical records of individuals with more than 1 year of follow-up from May 2001 to January 2016. Continence status (number of pads that was used), complications (erosion or extrusion, urethral atrophy, and infection), malfunctions, and need for secondary implantation were evaluated. The relationship between complications and prior or subsequent radiation therapy (RT) was also examined. RESULTS: From May 2001 to January 2016, 121 consecutive patients underwent AS implantation for PPI at an oncological referral center in Brazil. At the last visit, the AS remained implanted in 106 patients (87.6%), who reported adequate continence status (maximum of 1 pad/day). Eight-two subjects (67.8%) claimed not to be using pads on a regular basis at the final visit (completely dry). Revision occurred in 24 patients (19.8%).Radiation therapy (RT) for prostate cancer following radical prostatectomy was used in 47 patients before or after AS placement. Twelve patients with a history of RT had urethral erosion compared with 3 men without RT (p=0.004). CONCLUSION: Considering our outcomes, we conclude that AS implantation yields satisfactory results for the treatment of PPI and should remain the standard procedure for these patients. Radiation therapy is a risk factor for complication.

Análise da expressão imunoistoquímica da nucleofosmina, Ki67 e p53 como fatores prognósticos em câncer de pênis / Evaluation of prognostic value of the immunohistochemistry expression of the nucleophosmine, p53 and Ki67 in patients with penile carcinoma

O carcinoma epidermóide do pênis tem incidência significativa em países em desenvolvimento como o Brasil. O tratamento dos tumores invasivos consiste na ressecção da lesão primária e linfadenectomia bilateral, procedimento associado a alta taxa de morbidade. O estudo de fatores prognósticos do tumor primário pode ajudar na seleção dos pacientes candidatos às linfadenectomias. A expressão imunoistoquímica do ki-67, do p53 e da nucleofosmina (NPM) se associam a pior prognóstico em diversas neoplasias. Estudamos retrospectivamente 112 pacientes portadores de carcinoma epidermóide do pênis, submetidos a cirurgia do tumor primário no Departamento de Cirurgia Pélvica do AC Camargo Cancer Center. Os blocos de parafina foram revisados e submetidos a coloração imunoistoquímica para NPM, ki-67 e p53. A leitura foi realizada no dispositivo Aperio®. A imunorreatividade da NPM, Ki67 e p53 foi relacionada a fatores clínicos e patológicos: idade, estado civil, raça, tempo de evolução da doença, antecedentes venéreos, estadiamento clínico, espessura do tumor, grau de diferenciação, embolização linfovascular, estadiamento patológico, tipo de invasão. Analisamos quais fatores influenciaram o risco de metástases linfonodais e sobrevida global (SG) e livre de doença (SLD). Os testes estatísticos de associação utilizados foram o Qui-quadrado, teste de Fischer, a regressão logística múltipla. Na análise de sobrevida utilizamos o Kaplan e Meier, o Log-rank e o modelo de riscos proporcionais de cox. A imunorreatividade do p53 estava alta em 42,3% dos casos e se associou a maior ocorrência de recidivas, mas não a outras variáveis. A imunorreatividade do Ki67 estava alta em 89,1% dos casos e não se associou a nenhuma variável. A NPM apresentou imunoexpressão baixa em 50% dos casos e se associou a maiores estadios clínicos T e N e invasão de corpo cavernoso. A imunorreatividade do p53, da NPM e do Ki67 não se associaram a metástases linfonodais. A ocorrência de metástases linfonodais foi influenciada pelo estadiamento clínico N (p=0,001), grau de diferenciação (p=0,007), invasão vascular (p=0,004), invasão perineural (p<0,001), infiltração de corpos cavernosos (p=0,004), infiltração da uretra (p=0,013) e espessura tumoral (p=0,008). No modelo multivariado, estadiamento clínico N (RR=5,5); IC [1,4-20,8], infiltração de corpos cavernosos (RR=3,9); IC [1,2-12,3] e invasão perineural (RR=4,9); IC [1,5-16,2] foram fatores independentes de risco de metástases linfonodais. A SG ao final de 120 meses foi de 47,3% e foi influenciada por raça (p=0,009), recidivas (p=0,018), grau moderado e alto (p=0,031), infiltração de corpos cavernosos (p=0,037), invasão vascular (p=0,02), invasão perineural (p=0,030), espessura tumoral >5 mm (p=0,015) e metástases linfonodais (p=0,003). A imunoexpressão da NPM, do Ki67 e do p53 não influenciou a SG. Na análise multivariada, a invasão vascular (RR=1,9; IC [1,0-3,6]) se associou a menor SG. A SLD foi influenciada por infiltração de corpo cavernoso (p<0,001), infiltração da uretra (p=0,032), infiltração vascular (p<0,001), metástases linfonodais (p<0,001) e alta imunoexpressão do p53 (p=0,008). A imunorreatividade do Ki67 e da NPM não influenciaram a SLD. Na análise multivariada apenas a invasão de corpo cavernoso (RR=4,0; IC [1,4-11,3]) e a ocorrência de metástases linfonodais (RR=4,2;IC[1,4-13,1]) se associaram a menor SLD. Os resultados permitem concluir que a alta expressão do p53 se associou a pior SLD na análise univariada e a perda de expressão da NPM se associou a maiores estadios clínico e patológico

Penile carcinoma still has relevant incidence in developing countries like Brazil. The gold standard for the treatment of invasive lesions remains amputation followed by bilateral lymphadenectomy, procedures associated with high morbidity. The identification of prognostic factors could help to select the best candidates to lymphadenectomies. The immunoreactivity of p53, nucleophosmin (NPM) and ki67 has been associated with the prognosis of many tumors. A retrospective study of 112 patients with penile carcinoma submitted to amputation and lymphadenectomy at the Division of Urology of A.C.Camargo Cancer Center was undertaken to evaluate the prognostic value of immunoreactivity of p53, NPM and Ki67 in the primary tumor. The immunoreactivity of these proteins were correlated with the followed factors: age, race, marital status, time to diagnosis, venereal history, clinical stage, tumor thickness, histological grade, lymphovascular embolization, corpora cavernosa and urethra infiltration, pattern of invasion, lymph node metastasis, overall survival (OS) and disease free survival (DFS). The association among variables was done by the chi-square test and the survival analysis were performed with the Kaplan & Meier technique and the multi-factorial analysis by the Cox regression technique. The p53 immunoreactivity was high in 42,3% of the cases and was associated with high recurrence rates, but not with other variables. Ki67 immunoreactivity was high in 89,1% of the cases and was not associated with any variable. NPM immunostaining was considered low in 50% of the cases and was associated with higher clinical stages N and T and corpora cavernosa invasion, but not with other variables. There was no association between NPM, p53 and Ki67 immunostaining and lymph node metastasis. Clinical stage N (p=0,001), grade of differentiation (p=0,007), vascular invasion (p=0,004), perineural invasion (p<0,001), corpora cavernosa infiltration (p=0,004), urethral infiltration (p=0,013) and tumor thickness (p=0,008) were significant for the incidence of lymph node metastasis. The multivariate analysis revealed that clinical stage N (RR=5,5; CI [1,4-20,8]), corpora cavernosa infiltration (RR=3,9; CI [1,2-12,3]) and perineural invasion (RR=4,9; CI [1,5-16,2]) were significant for the incidence of lymph node metastasis. The OS at the end of 120 months was 47,3% and was influenced by race (p=0,009), recurrences (p=0,018), moderate or high pathologic grade (p=0,031), corpora cavernosa infiltration (p=0,037), lymphovascular embolization (p=0,02), perineural invasion (p=0,030), tumor thickness (p=0,015) and lymph node metastasis (p=0,03). There was no association between p53, NPM and Ki67 immunoreactivity and OS. Multivariate analysis revealed that vascular invasion (RR=1,9; CI [1,0-3,6]) influenced OS. DFS was influenced by corpora cavernosa infiltration (p<0,001), urethra infiltration (p=0,032), lymphovascular embolization (p<0,001), lymph node metastasis (p<0,001) and p53 immunostaining (p=0,008). NPM and Ki67 immunoreactivity did not influence DFS. Multivariate analysis revealed that corpora cavernosa infiltration (RR=4,0; CI [1,4-11,3]) and lymph node metastasis (RR=4,2; CI [1,4-13,1]) influenced DFS. These results showed that higher p53 expression was associated with a worst DFS at univariate analysis and the low NPM imunoexpression was associated with higher clinical and pathological stages

Do proliferating cell nuclear antigen and MIB-1/Ki-67 have prognostic value in penile squamous cell carcinoma?

OBJECTIVES: To evaluate the role of proliferating cell nuclear antigen (PCNA) and MIB-1/Ki-67 immunohistochemical expression in predicting lymph node metastasis and survival in primary penile squamous cell carcinoma. METHODS: We conducted a retrospective evaluation of 125 patients with penile squamous cell carcinoma submitted to primary tumor treatment, with information on lymph node status. Clinical and pathologic data for PCNA and MIB-1/Ki-67 expression in the primary tumor were analyzed. Correlations between these data and lymph node metastasis risk and survival were calculated. RESULTS: In univariate analysis, low MIB-1/Ki-67 expression, the presence of lymphovascular permeation, clinically positive lymph nodes, tumor thickness greater than 5 mm, and infiltration of cavernous bodies were correlated with lymph node metastasis. However, the independent factors for lymph node metastasis risk were PCNA and MIB-1/Ki-67 immunoreactivity, lymphovascular permeation, and N clinical stage. Independent variables for disease-free survival were urethra infiltration and the presence of lymph node metastasis. For death risk evaluation the independent variables were age, lymph node metastasis, and clinical stage. CONCLUSIONS: There was a correlation between PCNA and MIB1/Ki-67 immunohistochemical expression and the presence of lymph node metastasis. However, PCNA and MIB1/Ki-67 immunohistochemical expression did not have a relationship with survival and death risk.

The expression of metaloproteinases-2 and -9 is different according to the patterns of growth and invasion in squamous cell carcinoma of the penis.

Squamous cell carcinoma (SCC) of the penis is characterized by different patterns of growth and local invasion. The matrix metalloproteinases (MMPs) is a family of proteolytic enzymes that are involved in the degradation of extracellular matrix to allow the migration of tumor cells. The present study examined whether the expression of MMP-2 and -9 is correlated with the patterns of tumor growth and invasion in penile SCC. The expression of MMP-2 and -9 was examined immunohistochemically in samples of 115 patients. The cases were divided in three groups according to the patterns of growth and invasion: group 1, exophytic growth and pushing pattern of invasion; group 2, endophytic growth and invasion in large sheets of cells; and group 3, endophytic growth and invasion in small group or isolated cells. Tumors with MMP-2 and -9 overexpression are deeply invasive and present an invasion pattern of small groups of cells. Also, expression of MMP-2 changed from membrane to cytoplasm in invasive tumors, maybe representing activation of MMP-2. These findings allow us to conclude that the less differentiated tumors, which are more invasive and with a pattern of invasion in small group of cells, are associated with the overexpression of MMPs.

Front pattern of invasion in squamous cell carcinoma of the penis: new prognostic factor for predicting risk of lymph node metastases.

OBJECTIVES: Treatment of penile carcinoma is based on excision of the primary tumor and regional lymphadenectomies. Lymph node metastasis is the most important prognostic factor, yet it cannot be reliably evaluated by imaging studies or clinical examinations; thus, new prognostic factors such as the pattern of invasion must be investigated. METHODS: The data of 112 patients with penile carcinoma who underwent amputation and lymphadenectomy were analyzed. The clinicopathologic variables were studied, in addition to the front pattern of invasion according to the standards established by the modified criteria of Anneroth and Bryne first used as a part of a prognostic score in squamous cell carcinoma of the oral cavity. The pattern of invasion expresses the tumor-host tissue relationship, demonstrating the infiltrative tumor characteristics. This pattern was defined as infiltrating (invasion in blocks of small solid strands of cell tumors that broadly infiltrated the organ's stroma) and pushing infiltration (tumor cells have invaded large cell blocks with well-defined tumor-host interfaces). RESULTS: The variables that were significantly associated with the presence of lymph node metastases on univariate analysis were clinical N stage (P = 0.011), lymphatic permeation (P <0.001), venous embolization (P = 0.025), and the pattern of invasion (P <0.001). In the multivariate model, the lymphatic permeation, clinical N stage, and invasion type were independent risk factors for lymph node metastases. The follow-up varied from 0.1 to 452.8 months (mean 76.9, median 27.3). CONCLUSIONS: Lymphatic permeation, clinical N stage, and standard infiltrating invasion were independent prognostic variables for the risk of lymph node metastasis.

E-cadherin, MMP-2, and MMP-9 as prognostic markers in penile cancer: analysis of 125 patients.

OBJECTIVES: The treatment of choice for invasive penile carcinoma is amputation and lymphadenectomy. The latter is associated with a high morbidity rate. Analysis of new prognostic factors such as E-cadherin, matrix metalloproteinase (MMP)-2, and MMP-9 may help to select candidates for lymphadenectomy. METHODS: We assessed 125 patients with penile epidermoid carcinoma treated with amputation and bilateral lymphadenectomy. The following factors were analyzed: age, race, disease evolution time, venereal background, clinical and pathologic stage, tumor thickness, differentiation grade, venous and lymphatic embolization, koilocytosis, type of invasion, and E-cadherin, MMP-2, and MMP-9 immunoreactivity. The value of risk factors for lymph node metastases and specific survival was assessed. RESULTS: The mean follow-up was 76.5 months. Clinical N stage (P = 0.001), tumor thickness (P = 0.027), lymphatic permeation (P < 0.001), venous embolization (P = 0.002), corpus cavernosum infiltration (P = 0.002), and low E-cadherin expression (P = 0.032) significantly correlated with the presence of metastases. Independent risk factors for metastases were lymphatic permeation (relative risk [RR] = 5.99; 95% confidence interval [CI] 2.1 to 16.9) and clinical N stage (RR = 5.5; 95% CI = 1.9 to 16.7). Lymph node metastases (RR = 57.9; 95% CI = 7.4 to 453.9), urethral infiltration (RR = 3.5; 95% CI = 1.3 to 9.2), and MMP-9 immunoreactivity (RR = 3.2; 95% CI = 1.2 to 8.3) were considered independent risk factors for disease recurrence. CONCLUSIONS: On univariate analysis, low E-cadherin immunoreactivity was associated with a greater risk of lymph node metastases. High MMP-9 immunoreactivity was an independent risk factor for disease recurrence.