Focalyx Dx, Bx, Tx et Apps: A novel contemporary fusion paradigm for the management of prostate cancer.

FocalyxTM conceived as a response to emerging evidence data across numerous cancer lesions that questions current standard treatment approaches that too often lead to detrimental quality of life yet delivering limited survival benefit, especially in-lieu of advances in imaging technology applicable to cancer patients. The Focalyx paradigm aims to control cancer with improvement in quality of life. We initially devised 5 milestones: 1- Consistently optimize Prostate MRI imaging using the novel published protocols adopted as guidelines by societies such as the European Society of Urology and Radiology; 2- Evaluate fusion platform software solutions that existed; 3- Determine best fusión platform for Focalyx on practicality, precision, and workflow premises; 4- Evaluate commercially available FDA approved ablative technologies to implement our treatment vision; 5- Design a treatment option that can be performed in the office setting under local anesthesia, which would not impact negatively QOL outcomes of Prostate Cancer patients and seamless constant nonintrusive practical patient-physician interaction by the Focalyx app that facilitates follow up and provides early warning signals shall any change in the disease dynamics emerge. Prostate cancer was identified as the pilot disease for Focalyx to deliver a "GPS" like solution for the prostate gland that destroys identifiable disease without adverse effects such as: cancer anxiety, urinary incontinence, loss of erections and ejaculation. Since September of 2013, over 300 men have been accrued in NCT02381990- clintrials.gov evaluating the feasibility of our solutions for imaging (FocalyxDx), Biopsy (FocalyxBx) and Treatment (FocalyxTx). In this review we detail the tools available to achieve the Focalyx paradigm for men with Prostate Cancer.

Laparoscopic radical prostatectomy: an evolution in surgery.

The late 1990s witnessed an unprecedented evolution in the surgical approaches to the prostate thru the eye of the laparoscope. Initially taken with doubt, laparoscopic radical prostatectomy (LRP) has gained tremendous popularity and widespread implementation at specialized centers worldwide becoming the standard in many of them. LRP represents a technically demanding laparoscopic procedure but it can be performed systematically with standard techniques. Obvious advantages are shorter convalescence and markedly lower operative blood loss without compromise of cancer control. Long-term functional and oncological results are maturing but early reports of positive surgical margin rates and freedom from prostate-specific antigen (PSA) recurrence rates after LRP are encouraging. Early quality of life results of postoperative urinary and sexual function appear similar to those in open surgical series. The real challenge for laparoscopic surgeons entails a paradigm swift, one that breaks off from the traditional and bias impetus, and tests the instruments, procedures, techniques differences and evaluates outcomes in a prospective controlled and randomized manner. If achieved, the laparoscopic movement may give rise to a generation of forward thinking surgeons generating a wealth of clinical evidence for their patients.

ÚItimos avances en la cirugía implante del peneano / Recent developments in penile implant surgery

A pesar de los múltiples tratamientos disponibles hoy para la disfunción eréctil , la prótesis peneana inflable multicompuesta de 3 piezas ha sobrevivido la prueba del tiempo, llegando a ser la modalidad con mayor tasa de éxito y de satisfacción por parte del paciente, debido tanto a la fiabilidad y calidad de la erección como a la consecución del estado de flacidez. En esta revisión, tras una breve visita a los orígenes históticos de la cirugía de la prótesis peneana, describimos meticulosamente comose implanta la prótesis y los pasos técnicos que permiten conseguir la operación con éxito. Finalmente, proporcionaremos algunas reflexiones sobre los últimos desarrollos en este campo, que incluyen los implantes de base estrecha, el reservorio valvular sin escape y los implantes cubiertos de antibiótico (AU)

How accurately does prostate biopsy Gleason score predict pathologic findings and disease free survival?

OBJECTIVE: Due to the significant impact on prognosis by subgrouping of prostatectomy Gleason scores < 7, 7, and > 7, we undertook this study to answer whether the biopsy Gleason score was as predictive of disease free survival and assess the correlation with the prostatectomy Gleason score in a modern prostatectomy series. METHODS: An analysis of 1,031 patients who underwent radical prostatectomy for clinically localized prostate cancer was performed. All data was prospectively collected. The Gleason score was categorized into 3 different groups (< 7, 7, and > 7) for biopsy and prostatectomy specimens. Disease free survival was then analyzed for each group. Discrepancies between scores and outcomes were evaluated. RESULTS: Accurate correlation was noted in 54.8, 66.8, and 47.4% of Gleason scores < 7, 7, and > 7, respectively. Overall accuracy was 58.3%. Both, biopsy and prostatectomy Gleason score correlated significantly with disease free survival (P = 0.001), furthermore the classification (Gleason scores < 7, 7 and > 7) was highly significant (P = 0.001). Patients with prostatectomy Gleason < 7 tumors had significant survival advantage over those with biopsy Gleason < 7, (P = 0.001). However, disease free survival was superior for patients with biopsy Gleason > 7 than those with prostatectomy Gleason > 7, (P = 0.02). The overall disease free survival was similar among the patients with Gleason score of 7 (P = 0.12). CONCLUSIONS: It appears that biopsy Gleason score, although oftentimes not correlating strongly with the prostatectomy Gleason score, is an important prognostic factor in prostate cancer. There are significant differences in disease free survival between biopsy and prostatectomy Gleason score categories.

Proliferation of prostate cancer cells in the bone marrow predicts recurrence in patients with localized prostate cancer.

BACKGROUND: Reverse-transcription polymerase chain reaction (RT-PCR) amplification of prostate specific antigen (PSA) mRNA has been used to detect the presence of prostate cancer cells in the peripheral blood and bone marrow of patients with clinically localized disease. Some studies have demonstrated a correlation between detection of PSA-mRNA and disease recurrence. However, many RT-PCR-positive patients remain disease-free. We propose that phenotypic characterization of individual micrometastatic cells may provide more prognostic information than mere detection of such cells. METHODS: We studied 58 patients undergoing radical prostatectomy for clinically localized disease whose bone marrow had been found to contain PSA-mRNA by RT-PCR. Immunohistochemical detection and phenotypic characterization of micrometastatic cells was performed using a two-color technique: cytokeratin antibody for detection and the MIB-1 antibody for proliferation. The clinical endpoint was disease recurrence. RESULTS: One or more micrometastatic cells were proliferating in 36.2% of the patients; the disease-free survival rate was 76.2% in this group. In contrast, in the patients with non-proliferating cells, 97.3% remained disease-free (P = 0.025). Multivariate analysis demonstrated that the presence of proliferating cells was the only preoperative variable that correlated with disease-free survival (P = 0.05). CONCLUSIONS: Determination of the phenotype of individual micrometastatic cells can contribute prognostic information above and beyond the mere determination of their presence or absence. Phenotypic characterization of individual micrometastatic cells may ultimately be used to select patients for systemic therapy given either alone or in combination with local therapy.

Structural alteration of p53 protein in patients with muscle invasive bladder transitional cell carcinoma.

PURPOSE: Recent data imply that 3-dimensional (D) p53 protein modeling provides more specific information on its function in patients with pancreatic adenocarcinoma. In addition to immunohistochemical and single strand conformational polymorphism analysis, we performed 3-D p53 protein modeling and correlated our results with the disease-free survival of patients with muscle invasive transitional cell carcinoma of the bladder who underwent surgery. MATERIALS AND METHODS: We identified 43 patients and analyzed p53 status in each by immunohistochemical testing, single strand conformational polymorphism and DNA sequencing with 3-D protein modeling. Median followup was 38 months (range 4 to 92). The results of each analysis were compared and correlated with cancer specific survival. Statistical analysis was performed using the log rank test on Kaplan-Meier survival curves. RESULTS: The population included 30 men and 13 women 35 to 84 years old (median age 65). Nuclear over expression of p53 protein was observed in 26 of the 43 cases (60%). Lymph node involvement did not correlate with p53 over expression. Significantly more patients with lymph node metastasis died of cancer. Median survival in the 26 patients with p53 over expression was 28 months versus 57 in those with negative staining (p = 0.25). Mutation analysis by single strand conformational polymorphism revealed no abnormality in 24 patients (56%) with a median survival of 28 months, whereas we noted abnormal mutational analysis in 19 (44%) with a median survival of 38 months (p = 0.33). Of 19 single strand conformational polymorphism positive cases DNA sequencing showed mutation near the DNA binding site in 10 (53%), mutation away from the site in 6 (32%) and no mutation in 3 (17%). No survival difference was detected in cases with mutation away and near the DNA binding site, respectively (p = 0.69). CONCLUSIONS: In this group of patients treated with radical cystectomy for muscle invasive bladder transitional cell carcinoma, analysis of p53 protein and the p53 gene by immunohistochemical testing, single strand conformational polymorphism and mutational analysis did not correlate with cancer specific survival.

Her-2/neu overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic significance and comparative analysis in primary and metastatic tumors.

PURPOSE: The prognostic significance of Her-2/neu overexpression in muscle-invasive urothelial carcinoma of the bladder is largely unknown. Accurate determination of Her-2/neu overexpression may have therapeutic importance. EXPERIMENTAL DESIGN: Eighty consecutive cases of muscle-invasive urothelial carcinoma of the bladder treated by radical cystectomy with available follow-up were analyzed. In each case, one representative section was stained with anti-Her-2/neu. Staining was graded as 1 = faint/equivocal, 2 = moderate, and 3 = strong and was considered positive if > or =2. In those cases with a metastasis, the stain was also performed in the metastatic tumor. Results were correlated with survival. RESULTS: Twenty-two (28%) cases were considered Her-2/neu-positive in the primary tumor, and 17 of 32 (53%) were considered Her-2/neu-positive in the lymph node metastasis. Median survival for Her-2/neu-positive primary tumors was 33 months, compared with 50 months for Her-2/neu-negative cases (P = 0.46). Similarly, Her-2/neu overexpression in the lymph node metastasis did not predict survival. Sixty metastatic urothelial carcinomas were further studied by comparing Her-2/neu expression in the primary tumor with that of the lymph node and/or distant metastasis. Forty-five percent of Her-2/neu-negative primary tumors had a Her-2/neu-positive lymph node metastasis, whereas only one case (8%) of Her-2/neu-positive primary tumors was Her-2/neu-negative in the lymph node metastasis (P = 0.009). Similarly, 67% of Her-2/neu-negative primary tumors had a Her-2/neu-positive distant metastasis, whereas no Her-2/neu-positive primary tumor was negative in the metastasis (P = 0.429). CONCLUSIONS: Her-2/neu overexpression in primary or metastatic tumor did not predict survival in this cohort of muscle-invasive tumors. Overexpression in the primary tumors consistently predicts overexpression in a distant or regional metastasis. However, some Her-2/neu-negative primary tumors may show overexpression in their corresponding metastasis. Her-2/neu analysis in a metastasis may be necessary to accurately determine Her-2/neu status in metastatic bladder urothelial carcinoma.

Impact of preoperative serum PSA level from 0 to 10 ng/ml on pathological findings and disease-free survival after radical prostatectomy.

BACKGROUND: To determine the impact of various preoperative serum prostate specific antigen (PSA) levels in the range from 0.1 to 10 ng/ml on pathological stage and disease-free survival after radical prostatectomy. METHODS: We selected a cohort of 585 patients who underwent radical prostatectomy between 1991-1996 for clinically localized prostate cancer and presented with preoperative serum PSA levels from 0.1 to 10 ng/ml. RESULTS: Pathological organ-confined disease was present in 57.6% of patients. The rate of organ-confined disease decreased from an average of 85% for patients with a PSA value < 2 ng/ml, to 46.8% for patients with a PSA value > 7 ng/ml. We found statistically significant correlations between preoperative serum PSA level and overall pathological stage (P = 0.001), pathologically organ-confined disease (P = 0.001), margin positive rates (P = 0.001), extra prostatic extension (P = 0.001), and seminal vesicle invasion (P = 0.001). The overall disease-free survival rate was 87%, with a median follow up of 42.4 months. Disease free survival was significantly better for patients with PSA up to 4 ng/ml (P = 0.005). CONCLUSIONS: Our data suggests that PSA detection programs should strive to detect prostate cancer in men before the PSA level rises above 7 ng/ml. In addition, since patients with a PSA level < 4 ng/ml had better disease-free survival rates than those with a PSA level between 4.1-10 ng/ml, eliminating an arbitrary cutoff of 4 ng/ml, may lead to improved disease-free survival.

Matrix metalloproteinase-9 expression in bladder washes from bladder cancer patients predicts pathological stage and grade.

The matrix metalloproteinases (MMPs), in particular the gelatinases (MMP-2 and MMP-9) have been associated with tumor cell invasion and metastasis in many human cancers. Here we examined the expression of proMMP-2 (gelatinase A) and proMMP-9 (gelatinase B) proteins in the cellular component of bladder washes obtained from 65 patients. Twenty-six patients had active bladder cancer, 24 had a history of bladder cancer but no evidence of active disease at the time of cystoscopy (recurrence-free), and 15 patients had lesions other than bladder cancer (controls). The results were correlated with the cytological findings of the bladder wash and the histopathological results of the tumor resection when performed. In patients with active transitional cell carcinoma of the bladder, 71 and 38% had expression and overexpression of the latent form of MMP-9 (proMMP-9), respectively. In contrast, neither latent nor active MMP-2 could be detected in any of the samples examined, regardless of tumor status. Overexpression of proMMP-9 correlated with higher grade (P = 0.003) and pathological stage (P = 0.04) of disease in the active bladder cancer group. No significant gelatinase expression was detected in the recurrence-free and control cases. Compared with urine cytology, proMMP-9 expression had an overall higher sensitivity for bladder cancer identification (71 versus 54%, P = 0.11). Detection of proMMP-9 in bladder washes may be a novel approach for the identification of patients with more aggressive forms of bladder cancer.

Limited role of radionuclide bone scintigraphy in patients with prostate specific antigen elevations after radical prostatectomy.

PURPOSE: Bone scintigrams of patients with increasing serum prostate specific antigen (PSA) after radical prostatectomy are only rarely positive. We identify clinical parameters that would improve our ability to select patients for this imaging study. MATERIALS AND METHODS: We reviewed all bone scintigrams done at our institution between 1991 and 1996 in patients with persistently increasing serum PSA after radical prostatectomy. What prompted the clinician to obtain the bone scintigram was trigger PSA (tPSA). The rate of increase in PSA to tPSA was measured by tPSA/time from radical prostatectomy (slope 1) and tPSA/time from last undetectable PSA (slope 2). These parameters were evaluated together with standard clinicopathological data in univariate and multivariate analyses to determine the ability to predict the bone scintigram result. RESULTS: In univariate analysis tPSA (p = 0.003), slope 1 (p = 0.005) and slope 2 (p = 0.004) were useful in predicting the bone scintigram result but pathological stage, Gleason score, preoperative PSA and time to recurrence were not. In multivariate analysis the single most useful parameter in predicting the bone scintigram result was tPSA (p = 0.01). Based on a logistic regression model the probability of a positive bone scintigram was less than 5% until tPSA increased to 40 to 45 ng./ml. CONCLUSIONS: In patients with increasing serum PSA after radical prostatectomy current serum PSA is the best predictor of the bone scintigram result. Furthermore, there is limited usefulness of bone scintigraphy until PSA increases above 30 to 40 ng./ml.

Outcome analysis of penile implant surgery after external beam radiation for prostate cancer.

PURPOSE: We evaluated the success and possible complication rates of penile implant surgery in patients who underwent external beam radiation therapy for prostate cancer. MATERIALS AND METHODS: We reviewed the charts of 43 patients who underwent penile implant surgery after radiation therapy for prostate cancer. The type, dose and volume of radiation were assessed. The types of surgical approach and prosthesis as well as complications were recorded. A total of 34 patients was alive and traceable, and 9 were untraceable (7 dead and 2 missing). The 34 traceable patients were interviewed personally or by telephone to evaluate the function of and satisfaction with the penile implant. Followup of the 9 untraceable patients was assessed through a chart review. RESULTS: A total of 35 patients (81%) received definitive radiation therapy to the prostate and seminal vesicles, and 8 (19%) underwent radical retropubic prostatectomy followed by radiation therapy to the prostatic bed. Mean age at implant surgery was 67 years (range 36 to 83). In the 43 men 46 procedures were done and mean followup was 40 months. None of the patients in this series had infection or erosion. Of the men 24 (71%) use the prosthesis at least once weekly or more for sexual intercourse, 6 (17%) use it twice monthly, 4 (12%) are not sexually active despite a functioning implant, 2 are not sexually active because of a lack of sexual partners, and 2 are not satisfied with the implant and would not recommend this device. Discomfort from the penile implant was reported by 2 patients, although they currently use the implant for intercourse at least twice weekly. CONCLUSIONS: Penile prosthesis surgery can be safely and effectively performed after radiation therapy with minimal intraoperative and postoperative complications, and an excellent patient satisfaction rate.

Histopathological changes in the testes of prepubertal male rats after chronic administration of cocaine.

PURPOSE: This study was conducted to evaluate histopathologic findings in the testes of prepubertal male rats after long-term cocaine exposure. METHODS: At 25 days of age, male Sprague-Dawley rats were administered cocaine hydrochloride daily (15 mg/kg body weight corresponding to an average single dose for a heavy cocaine user). The treatment was continued for 100 days when all the rats were sacrificed. Morphological analysis of the testes were assessed by qualitative and quantitative histological means. RESULTS: In all the groups, a minimum of 5 to 10 representative seminiferous tubules were examined. The mean diameter of the seminiferous tubules was less in the treated group than in their respective controls (p < 0.05). The thickness of the germinal epithelium was much reduced in the cocaine-treated groups when compared with their controls (p < 0.05). The number of degenerating germ cells was greater in the treated group than in the controls. There was evidence of failure to release the mature spermatids in the treated groups. There was no evidence of sloughed Sertoli cells or germ cells in the tubular lumen or the epididymis. CONCLUSION: There were distinct histopathological changes noted after chronic administration of cocaine. These changes are characteristic of toxic effects on the testes, but the exact mechanism is not clear. Further studies are underway in our laboratory to delineate the exact mechanism of action by cocaine on the testes.

Estado actual de la investigacion psiquiatrica. / Actual status of psychiatric research

Se ha realizado una revision del estado actual de la investigacion psiquiatrica en Venezuela; un estudio por muestreo demuestra la carencia de unidades, divisiones o departamentos de investigacion; que muy pocas investigaciones han sido llevadas a cabo y estas no tienen lineamientos especificos. El soporte financiero es muy dificil de obtener por lo que debieron crearse organizaciones para recabar fondos Este trabajo fue escrito durante el primer semestre de 1982 y fue parte de la Sesion Plenaria Principal de la Asamblea Anual de la Federacion Medica Venezolana