¿Son los criterios de vigilancia activa suficientes para predecir el cáncer de próstata de estadio avanzado? / Are active surveillance criteria sufficient for predicting advanced stage prostate cancer patients?

Objetivos: Examinar los resultados del tratamiento en pacientes con cáncer de próstata (CP) tratados con prostatectomía radical (PR) que podrían ser buenos candidatos para vigilancia activa (VA) y evaluar la confianza y fiabilidad de los criterios de VA para predecir la enfermedad en estadios avanzados (puntuación de Gleason en PR ≥ 7 o estadio patológico T3). Métodos: Entre 2005 y 2012 se examinaron los registros de 401 pacientes sometidos a PR con un diagnóstico de CP. De estos pacientes 173 resultaron ser candidatos para VA. Los criterios de inclusión fueron los siguientes: estadio clínico T2a o inferior, PSA < 10 ng/ml, 2 o menos núcleos afectados por cáncer, ningún núcleo con una afectación máxima por cáncer del 50% o más y ninguna puntuación de Gleason mayor de 3 en la muestra. Resultados: Los análisis univariantes revelaron que los pacientes con un estadio más avanzado de la enfermedad tenían una densidad del antígeno prostático específico (PSAD) más elevada, un mayor porcentaje máximo (% máx) de núcleos positivos y un mayor volumen tumoral en PR. En los análisis multivariantes la PSAD, el % máx de núcleos positivos y el volumen tumoral en PR eran factores estadísticamente significativos de enfermedad en estadios avanzados. Los análisis ROC revelaron que el volumen tumoral en PR es un buen test de la enfermedad en estadio avanzado. Conclusiones: Se debería considerar reducir los valores umbral de PSAD y % máx en núcleos positivos como criterios de inclusión para VA. Si se pudiera calcular el volumen tumoral antes de la PR podríamos minimizar los fracasos del tratamiento (exceso o falta de tratamiento) de CP. Quizás los nuevos protocolos de biopsias, los biomarcadores de tejidos y la tecnología de imágenes moleculares puedan perfeccionar los criterios para VA

Objectives: To examine the treatment outcomes of the prostate cancer (PCa) patients treated by radical prostatectomy (RP) who could be good candidates for active surveillance (AS) and test the confidence and reliability of the AS criteria for predicting advanced stage disease (RP Gleason score ≥7 or pathological stage T3). Methods: Between 2005 and 2012 the records of the 401 patients who underwent RP with a diagnosis of PCa were examined. Of these patients, 173 were found to be candidates of AS. The inclusion criteria were as follows; clinical stage T2a or less, PSA < 10 ng/ml, 2 or fewer cores involved with cancer, no single core with 50% or greater maximum involvement of cancer, and no Gleason grade greater than 3 in the specimen. Results: Univariate analyses revealed that patients with advanced stage disease have higher prostate specific antigen density (PSAD), higher maximum percent (max %) in positive cores and higher RP tumor volumes. In multivariate analyses PSAD, max % in positive cores and RP tumor volumes were statistically significant determinants for advanced stage disease. ROC analyses revealed that the RP tumor volume is a good test on advanced stage disease. Conclusions: Decreasing the cutoff values for PSAD and max% in positive cores should be considered for AS inclusion criteria. If we could calculate the tumor volume before RP, we can minimize the treatment failures (over or under treatment) of PCa. Perhaps new biopsy protocols, tissue biomarkers, and molecular imaging technology may refine AS criteria

Objectives: To examine the treatment outcomes of the prostate cancer (PCa) patients treated by radical prostatectomy (RP) who could be good candidates for active surveillance (AS) and test the confidence and reliability of the AS criteria for predicting advanced stage disease (RP Gleason score ≥7 or pathological stage T3). Methods: Between 2005 and 2012 the records of the 401 patients who underwent RP with a diagnosis of PCa were examined. Of these patients, 173 were found to be candidates of AS. The inclusion criteria were as follows; clinical stage T2a or less, PSA < 10 ng/ml, 2 or fewer cores involved with cancer, no single core with 50% or greater maximum involvement of cancer, and no Gleason grade greater than 3 in the specimen. Results: Univariate analyses revealed that patients with advanced stage disease have higher prostate specific antigen density (PSAD), higher maximum percent (max %) in positive cores and higher RP tumor volumes. In multivariate analyses PSAD, max % in positive cores and RP tumor volumes were statistically significant determinants for advanced stage disease. ROC analyses revealed that the RP tumor volume is a good test on advanced stage disease. Conclusions: Decreasing the cutoff values for PSAD and max% in positive cores should be considered for AS inclusion criteria. If we could calculate the tumor volume before RP, we can minimize the treatment failures (over or under treatment) of PCa. Perhaps new biopsy protocols, tissue biomarkers, and molecular imaging technology may refine AS criteria

Are active surveillance criteria sufficient for predicting advanced stage prostate cancer patients?

OBJECTIVES: To examine the treatment outcomes of the prostate cancer (PCa) patients treated by radical prostatectomy (RP) who could be good candidates for active surveillance (AS) and test the confidence and reliability of the AS criterias for predicting advanced stage disease (RP Gleason score≥7 or Pathological stage T3). METHODS: Between 2005 and 2012 the records of the 401 patients who underwent RP with a diagnosis of PCa were examined. Of these patients, 173 were found to be candidates of AS. The inclusion criteria were as follows; clinical stage T2a or less, PSA<10ng/ml, 2 or fewer cores involved with cancer, no single core with 50% or greater maximum involvement of cancer, and no Gleason grade greater than 3 in the specimen. RESULTS: Univariate analyzes revealed that patients with advanced stage disease have higher prostate specific antigen density (PSAD), higher maximum percent (max%) in positive cores and higher RP tumor volumes. In multivariate analyzes PSAD, max% in positive cores and RP tumor volumes were statistically significant determinants for advanced stage disease. ROC analyzes revealed that the RP tumor volume is a good test on advanced stage disease. CONCLUSIONS: Decreasing the cutoff values for PSAD and max% in positive cores should be considered for AS inclusion criteria. If we could calculate the tumor volume before RP, we can minimize the treatment failures (over or undertreatment) of PCa. Perhaps new biopsy protocols, tissue biomarkers, and molecular imaging technology may refine AS criteria.

Redo valve surgery with on-pump beating heart technique.

AIM: Reoperations have become of increasing frequency in the last four decades. Redo surgery is more complex than primary surgery and is associated with higher mortality and morbidity. We present our immediate and mid-term results of mitral and aortic prosthetic valve replacement undertaken with beating heart technique. METHODS: The prospective study included 26 consecutive redo valve surgery patients who underwent valve re-replacement. The operation was carried out on a beating heart using normothermic bypass without cross-clamping the aorta for mitral valve surgery and retrograde coronary sinus normothermic noncardioplegic blood perfusion during cross-clamping the aorta for aortic valve procedures. RESULTS: Twenty-six patients (mean age 50+/-15 years) underwent reoperation with beating heart technique. Twenty (76.9%) mitral prosthetic replacements, 4 (15.4%) aortic prosthetic replacements, and 2 (7.7%) double valve replacements were achieved. Fourteen patients (53.8%) were operated for prosthetic valve dysfunction. Eighteen patients (69.2%) were in NYHA class III or IV preoperatively. Mean bypass time was 85+/-30 min. Mean duration of ventilation was 13.6+/-6 h, mean intensive unit stay was 2.8+/-6.4 days, and mean hospital stay was 8.3+/-7.2 days. Two (7.7%) patients required high dose inotropic support and in one patient (3.8%) intra-aortic balloon support was required. Pulmonary complication occurred in 1 patient (3.8%), low cardiac output in 1 patient (3.8%), and re-exploration for bleeding in 2 patients (7.7%). Operative mortality was not observed. CONCLUSION: Normothermic on-pump beating heart valve replacement offers a safe alternative to cardioplegic arrest in high-risk group. Complication rates are low and perioperative mortality is lower than with conventional surgery. Beating heart technique has the advantage of maintaining physiologic condition of the heart throughout the procedure.

A new technique of myocardial protection during aortic root replacement: antegrade/retrograde coronary perfusion.

Aortic root surgery has traditionally been performed with an arrested and cooled heart using cardioplegia. A new technique of myocardial protection was utilized in the treatment of ascending aortic aneurysm with severe aortic valve regurgitation requiring aortic root replacement with the Cabrol technique. Retrograde and antegrade perfusion of the heart with blood allowed the surgical operation to be performed safely while the heart was beating and eliminated the ischemic reperfusion injury which occurs during cardioplegic arrest and reinstitution of blood perfusion after removal of the aortic cross-clamping required in traditional techniques.

Prognostic significance of nuclear morphometry in renal cell carcinoma.

OBJECTIVE: To assess nuclear morphometry as a predictor of prognosis in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: The study included 65 consecutive patients with RCC who underwent radical nephrectomy and were followed up for a median (range) of 80 (27-138) months. Nuclear morphometry was assessed using a computer-assisted image analysis system on histological sections and characterized by five nuclear variables (area, perimeter, major and minor diameter, and form factor). From the patients' records and pathology specimens, the clinicopathological prognostic variables (histological type, Fuhrman grade and pathological stage) were recorded. The proliferative activity was assessed using immunohistochemical staining with Ki-67 antibody. RESULTS: Higher values of mean nuclear area, perimeter, and major and minor diameter were significantly related to higher nuclear grade, proliferative activity and advanced tumour stage. They were significant predictors of disease progression and survival, together with grade, stage, sarcomatoid histology and proliferative activity. Of all significant prognostic factors predicting progression-free survival, only stage was independent (T4 vs T1, hazard ratio 6.55, 95% CI 1.63-26.13, P=0.008). CONCLUSION: Although the significance of these preliminary results must not be overstated, nuclear morphometry might provide significant prognostic information in predicting survival and tumours at high risk of progression in RCC.

Expression of pS2 protein and its relation with the Ki-67 proliferative indices and tumor recurrence in superficial bladder carcinomas.

OBJECTIVE: To investigate the expression and possible role of pS2 protein as a predictor of tumor recurrence in superficial transitional cell carcinoma of the bladder and to determine its relation with tumor stage, grade, size, number, recurrence and proliferative activity. METHODS: Paraffin sections of transurethral resection material from 80 patients with superficial transitional cell bladder carcinoma were stained with pS2 and Ki-67 antibodies using the standard streptavidin biotin immunoperoxidase method. Cytoplasmic pS2 staining was scored on a scale of 1-3 and the Ki-67-labelling index was determined as a percentage of positively staining tumor cells. RESULTS: An inverse relationship was found between pS2 expression and Ki-67 index (p<0.001). pS2 expression showed no relation with any clinicopathological prognostic parameters as well as the recurrence rate. The recurrence rate was only associated with increased tumor number (p = 0.05), while the time to first recurrence was significantly related to tumor size, proliferative activity and tumor grade (p = 0.04, p<0.001, and p = 0.03, respectively). On the other hand, higher tumor grade was correlated with increased tumor number, Ki-67 index and tumor stage (p = 0.016, p = 0.006, and p<0.001, respectively). CONCLUSION: pS2 expression is associated with a low proliferative potential of superficial transitional cell carcinoma of the bladder, while it does not seem to be related to the recurrence rate of the tumor and other prognostic factors. Tumor size and proliferative activity may aid in the estimation of the time to the first recurrence.

Does angiogenesis predict recurrence in superficial transitional cell carcinoma of the bladder?

OBJECTIVES: To investigate the role of angiogenesis in predicting tumor recurrence and its correlation with established clinicopathologic prognostic factors in superficial transitional cell carcinoma of the bladder. METHODS: The paraffin sections of 80 superficial papillary transitional cell bladder carcinoma specimens were stained with CD31 antibody to label the vascular endothelium using the standard streptavidin-biotin-immunoperoxidase method. The vascular surface density (VSD) equivalent to the vascular surface area per unit of tissue volume and number of vessels per square millimeter of stroma (NVES) were assessed by means of stereology, and these morphometric parameters of angiogenesis were statistically analyzed to interpret the relation to tumor recurrence in addition to tumor stage, grade, size, and number and the presence of carcinoma in situ. RESULTS: VSD and NVES values showed no statistically significant difference between pTa and pT1 tumors or patients with and without recurrence. In contrast, VSD and NVES values were found to increase in higher grade tumors (P = 0.019). VSD values were also higher in patients with coexisting carcinoma in situ in pTa tumors (P <0.001). Tumor number and size and recurrence number and time to the first recurrence did not correlate with any vascular parameters. CONCLUSIONS: Stereologic assessment of angiogenesis does not help to predict recurrence in superficial bladder cancer. Angiogenic parameters appeared to be well correlated with the conventional histologic grading system. Otherwise, the present study did not show any correlation of angiogenesis with any potential prognostic factors. This may be due to the diverse angiogenic pathways occurring in invasive and superficial tumors.

Proliferative activity, angiogenesis and nuclear morphometry in renal cell carcinoma.

BACKGROUND: Prognostic parameters other than tumor stage and grade are essential for renal cell carcinoma (RCC) patients. This study was undertaken to determine the usefulness of cellular proliferation, angiogenesis and nuclear morphometry in predicting the biological aggressiveness of RCC. METHODS: Surgical specimens of 70 patients with RCC were investigated by conventional histology, Ki-67 immunostaining and stereological assessment of angiogenesis and mean nuclear volume. RESULTS: There was no difference in disease-specific survival with respect to sex, age and histopathological type (except sarcomatoid and other types). The survival was significantly lower and the chance of metastases was higher in the group with higher proliferative activity (P=0.007). There was no relation between angiogenesis, mean nuclear volume, stage and survival. There was a significant relation between both Fuhrman and WHO grades, tumor stage and survival. Histopathological type, grade, angiogenesis and mean nuclear volume failed to predict recurrences and/or metastases. In multivariate analysis, only TNM stage and proliferative activity were found to be independent prognostic factors. CONCLUSIONS: In addition to tumor grade and stage, proliferative activity of a given RCC may have the potential to identify patients with an impaired prognosis.

Prognostic significance of microvascular invasion in localized renal cell carcinoma.

OBJECTIVES: The treatment of localized and even advanced renal cell carcinoma (RCC) is radical nephrectomy. However, 30% of these patients progress after radical nephrectomy. Prognostic factors are needed in order to determine the course of disease in patients undergoing radical nephrectomy. The aim of this study is to study the prognostic significance of microvascular invasion (MVI) in patients who had undergone radical nephrectomy for localized RCC. METHODS: Between June 1989 and February 1999, pathologic sections of the specimens from 41 patients without metastases, nodal involvement or macroscopic venous involvement were investigated for MVI. RESULTS: MVI was observed in 17% of the patients. MVI was related to the grade of the tumor and tumor size (p = 0.032, p = 0.017). In sarcomatoid-type RCC, MVI was more common than in other histologic types (p = 0.003). After a median follow-up of 48 months, the progression rate was 29% in patients with MVI and 17% without MVI (p = 0.001). Median progression time was 3 months in those with MVI and 41 months with no MVI (p = 0.01). The survival rate decreased from 85 to 70% in patients with MVI during a median follow-up of 48 months (p = 0.031). In multivariate analysis, MVI was not found to be an independent prognostic factor. CONCLUSION: Although MVI is closely related to progression and prognosis, in multivariate analysis it was not found to be an independent prognostic factor in localized RCC. We conclude that MVI should also be evaluated together with tumor grade in predicting the prognosis of patients with localized RCC.

Giant angiomyolipoma associated with marked pulmonary lesions suggesting lymphangioleiomyomatosis in a patient with tuberous sclerosis.

The association between Tuberous Sclerosis (TS) and Angiomyolipoma (AML) is well known. A patient with TS and giant AML mimicking Renal Cell Carcinoma (RCC), measuring 29 x 18 x 11 cm, weighing 4700 gr is presented. Imaging studies revealed coexistent pulmonary lymphangioleiomyomatosis and concurrent renal and pulmonary involvement is extremely rare in patients in TS. We believe that the growth potential of this hamartomatous lesion may reach to a life threatening size.

Comparison of microvascularization in diagnostic needle biopsies and radical prostatectomies in prostate carcinoma.

OBJECTIVES: Quantitation of microvessel density has been shown to predict tumor aggressiveness in prostate carcinoma (Pca). The correlation of estimated values of angiogenesis in needle biopsy and radical prostatectomy materials might show the efficiency of the diagnostic biopsy material to represent a good sample of the entire tumor. In this study, we assessed the correlation of microvascularization computed by morphometric methods in biopsy and radical operation materials. METHODS: Sections from diagnostic biopsy and radical prostatectomy materials of 23 patients with Pca were stained with factor- 8-associated antigen by immunohistochemistry and vascular surface density (VSD), microvessel numbers (NVES) and maximum microvessel number (NVES-MAX) were assessed by stereological methods. The microvascularization values in biopsy and radical operation materials were compared by Wilcoxon signed-ranks test for paired samples. RESULTS: No significant difference was observed between VSD and NVES values that were obtained from biopsy and radical operation materials of the same cases (p = 0.2478 and 0.3458, respectively). However, a significant difference was noted for NVES- MAX (p = 0.0004). CONCLUSION: We have shown, in a limited number of cases, that microvascularity prediction by stereological analysis using VSD and NVES in diagnostic needle biopsies correlates well with the radical operation specimens. Preoperative biopsies may predict overall tumor neovascularization characteristics that may have an impact on pathological stage and behavior.

Significance of serum laminin P1 values in patients with transitional cell carcinoma of the bladder.

OBJECTIVES: The goal of this study was to investigate the relation between serum laminin P1 expression and the grade, stage, size, and multiplicity of the tumors to elucidate the potential role of laminin as a diagnostic and prognostic factor in transitional cell carcinoma (TCC) of the bladder. METHODS: Serum concentration of laminin P1 was measured by radioimmunoassay in 38 patients with TCC of the bladder and compared with the serum laminin P1 values obtained from 34 healthy control subjects. Patients were grouped according to their tumor stage, grade, size, and multiplicity to compare the serum laminin P1 values. RESULTS: The mean serum laminin P1 level in the patient group was statistically higher than the controls (P = 1.3 x 10(-8); with the destruction of basement membrane (stages pT1 or greater), a significant increase in the serum value was observed (P = 0.00023). Laminin level was found to be positively related to the tumor size and number; however, no correlation was observed with the grade. In tumors invading the lamina propria and beyond, the sensitivity of laminin P1 was 78.9% and specificity was 97.1%. The positive and negative predictive values of laminin P1 were 93.7% and 89.5%, respectively. The patients whose serum laminin P1 levels were above the upper limit of normal (1.6863 U/mL) were found to have a higher recurrence rate (72%) than the patients who had lower serum values in the control cystoscopies performed 3 months after the first admission (P < 0.01). CONCLUSIONS: Serum laminin P1 seems to be a valuable adjunctive marker to predict tumor invasion and recurrence. This warrants further research.

Prostatic carcinoma presenting with painless parotid mass.

Metastasis of prostate cancer to the parotid gland is exceedingly rare, with only 4 cases reported in the literature. We present the case of an 83-year-old white man who had a painless parotid mass that was diagnosed as metastatic prostate cancer. Immunohistochemical staining with prostate-specific antigen was positive. This is the first case of prostate cancer presenting with a painless parotid mass. Prostate cancer can be metastatic to the head and neck region, and this should be kept in mind when treating patients with this disease.