Antonio Augusto Ornellas

Surgical treatment of invasive squamous cell carcinoma of the penis : retrospective analysis of 350 cases

Between 1960 and 1987, 414 patients with invasive squamous cell carcinoma of the penis were referred to the Brazilian National Cancer Institute. Inguinal metastases were demonstrated by lymphadenectomy in 39% of the 23 patients with stage N0, 49% of 92 with stages N1 and N2, and 100% of 18 with stage N3 disease. We analyzed the followup of 350 patients who underwent surgical treatment. In 224 patients (64%) amputation or some form of penile surgery was done initially, while 102 (29%) underwent amputation and lymphadenectomy, and 24 (7%) underwent palliative surgery for advanced squamous cell carcinoma. The statistics revealed a better 5-year survival rate for the patients who underwent lymphadenectomy concomitantly with penile surgery compared to those who underwent delayed lymphadenectomy (p < 0.001). Patients in whom systematic lymphadenectomy was negative had a better prognosis than those with positive systematic lymphadenectomy results (p < 0.001). The latter patients had a better prognosis compared with those in whom delayed lymphadenectomy was positive (p = 0.0103). Patients with well and moderately differentiated carcinoma had a higher survival rate at 5 years than did those with poorly differentiated carcinoma (p < 0.001 and p = 0.003, respectively). All deaths from metastatic disease occurred within 24 months among the patients who underwent systematic lymphadenectomy and within 5 years after simple penile surgery. In the short term, surgical debulking combined with reconstruction techniques allowed for improved quality of life in patients with advanced local-regional disease.

Surgical treatment of invasive squamous cell carcinoma of the penis: Brazilian National Cancer Institute long-term experience.

We reviewed our long‐term experience with surgical treatment of patients with penile carcinoma.

Analyses of 200 Lymphadenectomies in Patients with Penile Carcinoma

From 1972 to 1987, 200 consecutive lymphadenectomies were performed in 112 patients with squamous cell carcinoma of the penis. A Gibson incision provided exposure of the iliac and inguinal lymph nodes with a low morbidity rate (5% flap necrosis, 15% wound infection, 16% lymphedema and 9% lymphocele). The controversy surrounding the necessity of iliac lymphadenectomy is discussed, since 305 iliac lymph nodes examined did not have metastatic invasion.

Prognostic factors in invasive squamous cell carcinoma of the penis: analysis of 196 patients treated at the Brazilian National Cancer Institute.

PURPOSE We evaluated the role of primary tumor histopathological features for predicting regional metastasis and the prognosis in patients with penile squamous cell carcinoma. MATERIALS AND METHODS From April 1996 to January 2007, 202 consecutive patients with penile carcinoma underwent surgical treatment at our institution. Of these patients 196 were studied to identify prognostic factors. All histological specimens were examined by the same pathologist. We considered certain histological parameters, including histological grade, invasion depth, lymphovascular embolization, perineural infiltration, infiltration of the corpus cavernosum or spongiosum, urethral infiltration and koilocytosis. RESULTS Variables significantly associated with regional metastasis on univariate analysis were stage stratification (p = 0.0338), histological grade (p = 0.0112), invasion depth (0.0114), lymphovascular embolization (p <0.0001), perineural infiltration (p = 0.0092), corpora cavernosa infiltration (p = 0.0005) and koilocytosis (p = 0.0013). In the multivariable model lymphovascular embolization and absent koilocytosis were independent risk factors for lymphatic metastasis (p = 0.001 and 0.009, respectively). We also found a better survival rate in patients with koilocytosis and without lymphovascular embolization (p = 0.001 and 0.005, respectively). CONCLUSIONS Lymphovascular embolization and absent koilocytosis were independent prognostic factors for the risk of lymphatic metastasis. Patients with koilocytosis and without lymphovascular embolization had better 5-year survival.

Verrucous Carcinoma of the Penis: Retrospective Analysis of 32 Cases

Between 1972 and 1987, 34 patients with verrucous carcinoma of the penis were referred to our national cancer institute. We analyzed retrospectively the followup of 32 patients treated by surgery, exclusive radiotherapy and neoadjuvant chemotherapy. No patient died or had recurrent verrucous penile carcinoma. Lymph nodes removed from 15 patients without previous treatment did not reveal metastatic invasion. Neoadjuvant chemotherapy allowed for more limited surgery in 3 of 6 patients treated.

Epidemiological aspects of penile cancer in Rio de Janeiro: evaluation of 230 cases

PURPOSE To determine epidemiological characteristics of penile cancer in Rio de Janeiro, its associated risk factors and clinical manifestations. PATIENTS AND METHODS Between 2002 and 2008 we evaluated 230 patients at three public institutions, considering age, ethnicity, birthplace, marital status, educational level, religion, tobacco smoking, presence of phimosis and practice of circumcision. RESULTS The ages ranged from 25 to 98 years, with an average of 58.35 years. Of the 230 patients, 167 (72.7%) were from the southeast region of Brazil (which includes Rio de Janeiro) and 45 (19.5%) were from the northeast of the country. Most patients were white (67.3%), married (58.6%), smokers (56.5%) and had not completed primary school (71.3%). The predominant religion was Catholic (74.8%). Of the 46 (20%) circumcised patients, only 1 (2.2%) had undergone neonatal circumcision. Grade I tumors were present in 87 (37.8%) of the patients, grade II in 131 (56.9%) and grade III in 12 (5.3%). Lymphovascular embolization was observed in 63 (27.3%) and koilocytosis in 124 (53.9%) patients. Of the total, 41.3% had corpora cavernosa or corpus spongiosum infiltration, and 40 (17.4%) had urethral invasion. Prophylactic lymphadenectomy was performed on 56 (36.1%), therapeutic lymphadenectomy on 84 (54.2%) and hygienic lymphadenectomy for advanced disease on 15 (9.7%) patients. The median time between the lesion onset and clinical diagnosis was 13.2 months. The mean follow up was 28.8 months. CONCLUSION Most of our patients were born in this state and had low socioeconomic status. Most of them were white men, married, smokers, uncircumcised, of the Catholic faith and in their sixties or older. Their disease was in most cases diagnosed only in the advanced stages.

Prevalence of human papillomavirus and Epstein-Barr virus DNA in penile cancer cases from Brazil

Penile cancer is a potentially mutilating disease. Although its occurrence is relatively rare worldwide, penile cancer rates can be high in developing countries. A few studies have been conducted on the involvement of human papillomavirus (HPV) in penile carcinoma, which have found HPV present in 30-70% of penile malignant lesions, with a higher prevalence of HPV 16 and 18. It has been assumed that cofactors, such as Epstein-Barr virus (EBV) infections, may play a role in the progression of penile neoplasia. The aim of this study was to determine HPV and EBV prevalence in 135 penile malignant lesions from Brazilian men through the use of MY09/11 polymerase chain reaction (PCR), type-specific PCR and restriction fragment length polymorphism analysis. HPV prevalence among the men tested was 60.7%. Of the men who tested positive, 27 presented with HPV 16 (29.7%), five with HPV 18 (5.5%), 21 with HPV 45 (23.1%) and nine with HPV 6 (9.9%). Seven mixed infections were detected (9.2%), while 11 cases remained untyped (13.4%). Regarding EBV positivity, 46.7% of the samples contained EBV DNA with EBV-1 as the most prevalent type (74.6%). More than 23% of the men were co-infected with both HPV and EBV, while 35% presented exclusively with HPV DNA and 20% presented only with EBV DNA. Penile carcinoma aetiology has not been fully elucidated and the role of HPV and EBV infections individually or synergistically is still controversial. Hence, more studies are needed to determine their possible role in carcinogenesis.

Renal Cell Carcinoma and Proteomics

Renal cell carcinoma (RCC) represents 3% of adult malignancies. About 30% of RCC patients develop metastatic disease. So far, drugs cannot significantly increase the survival of these patients. We present a recent review of proteomics and RCC. Proteomic technologies have been used in the research to discover new markers of RCC that might increase survival. Furthermore, newly discovered markers cannot increase patient survival, rather their prognostic value supporting therapeutic decisions or new agents targeted at these new markers. More research is required to develop proteomic technologies and biomarkers for identification and validation.

Proteomic analysis reveals differentially secreted proteins in the urine from patients with clear cell renal cell carcinoma

OBJECTIVE The aim of this study was to evaluate the differentially secreted protein profile in the urine from patients with clear cell renal cell carcinoma (ccRCC) using mass spectrometry-based methods. Urine composition can reflect kidney physiology and can be used to detect markers for renal diseases. Moreover, characterization of the secretome is likely to assist in the investigation of new drugs for biological targets and diagnose the ccRCC at an early stage. METHODS AND MATERIALS Urine samples from patients were divided according to Fuhrman degree (FI-IV), which was associated with the cellular differentiation as good prognosis (GP) and poor prognosis (PP). Healthy individuals were used as the control group (CG). We used both qualitative and quantitative mass spectrometry-based analyses that involved the following approaches: 1-dimensional gel electrophoresis combined with liquid chromatography mass spectrometry in tandem (1DE LC-MS/MS), in-solution digestion combined with label-free 1-dimensional LC-MS(E) (1D LC-MS(E)), and bidimensional gel electrophoresis combined with matrix-assisted laser desorption/ionization time of flight in tandem (2DE MALDI-TOF/TOF) or combined with LC-MS/MS. RESULTS All the strategies allowed the identification of 354 proteins from the CG, GP, and PP groups. Qualitative experiments using 1DE LC-MS/MS analysis detected different protein profiles, and 224 proteins were identified in all groups. The label-free MS(E) quantitative analysis identified 113 proteins and generated novel information on secreted protein profiles, including 49 up-secreted proteins in the urine from patients with ccRCC and 40 down-secreted proteins related to the CG. Proteins such as kininogen-1, uromodulin, apolipoprotein D, polyubiquitin, and CD59 glycoprotein were down secreted according to the groups CG>GP>PP. In contrast, apolipoprotein A, fibrinogen, and haptoglobin were up secreted in patient groups. The same expression profile observed for kininogen-1, apolipoprotein D, fibrinogen, and haptoglobin was corroborated by 2DE LC-MS/MS or 2DE MALDI-TOF/TOF analyses. These 2 strategies also showed 13 differentially secreted proteins among the 3 groups. CONCLUSIONS The proteins kininogen-1, apolipoprotein D, fibrinogen, and haptoglobin presented similar quantitative protein profiles according to MS(E) and 2DE approaches. The latter proteins were up secreted and the former ones were down-regulated. The strategies used proved to be valuable in identifying proteins that were differentially secreted in urine from patients with RCC.

Prognostic factors in renal cell carcinoma: analysis of 227 patients treated at the Brazilian National Cancer Institute

PURPOSE We evaluated the role of several prognostic factors in predicting death and/or progressive disease in patients with renal cell carcinoma. MATERIALS AND METHODS Between 2004 and 2010, 227 consecutive patients with renal cell carcinoma underwent radical nephrectomy at our Institute. All histological specimens were examined by the same pathologist. We considered certain histological parameters, including histological subtype, conventional Fuhrman grade, presence of sarcomatoid features, adrenal gland infiltration, invasion of the perinephric fat, vascular embolization, collecting system invasion, presence or absence of tumour necrosis (0 %, 1 % to 49 %, or 50 % or greater) and regional lymph node metastasis. RESULTS Variables significantly associated with death and/or progressive disease on univariate analysis were histological subtype (p = 0.006), Fuhrman grade (p < 0.0001), tumor necrosis (p = 0.009), perinephric fat invasion (p = 0.002), vascular embolization (p = 0.0002), presence of lymph node involvement (p < 0.002), tumor size (p = 0.0006), TNM stage (p < 0.00001) and presence of metastasis (p < 0.00001). In the multivariable model histological subtype, tumor necrosis, lymph node involvement and presence of metastasis were independent risk factors for disease-free survival (p = 0.011, 0.042, 0.025 and p < 0.0001, respectively). CONCLUSION Histological subtype, tumor necrosis, lymph node involvement and presence of metastasis proved to be independent prognostic factors for disease-free survival. Therefore, the presence and rate of tumor necrosis should always be informed by the pathologist and lymphadenectomy should be performed in all patients.