Gil Raviv

Possible Mechanisms of Action of Transurethral Needle Ablation of the Prostate on Benign Prostatic Hyperplasia Symptoms: A Neurohistochemical Study

PURPOSE Transurethral needle ablation of benign prostatic hypertrophy (BPH) is a rapid, anesthesia-free outpatient procedure using low level radiofrequency energy that produces coagulative necrosis lesions at temperatures of approximately 100C. Clinically, significant improvement in objective and subjective parameters has been observed in BPH patients. Transurethral needle ablation has also been shown to be effective in relieving urinary retention. However, the precise mechanism of action of this procedure remains to be clarified. Ablation could produce its action on the dynamic component of the infravesical outlet obstruction. We analyzed the possible effects of transurethral needle ablation on the intraprostatic innervation. MATERIALS AND METHODS Histological sections from 10 open prostatectomy specimens (BPH) recovered 1 to 46 days after transurethral needle ablation were stained with hematoxylin and eosin and an immunohistochemical technique, using antibodies against S100 proteins and nonspecific enolase as specific nerve markers, and against anti-prostate specific antigen and anti-desmin for glandular and muscle cells, respectively. We used 5 BPH specimens as controls. RESULTS Microscopic examination of the treated areas showed necrotic lesions affecting epithelial and smooth muscle cells in the transition zone at a depth of 0.3 to 1.0 cm, from the preserved urethra. Nerve fibers in the control specimens and untreated prostatic areas were predominant in the urethral submucosal layer and in the stroma surrounding the epithelial nodules. No staining of any axon or isolated nerve cell was observed in any specimen treated by transurethral needle ablation, and there was a sharp and clear delineation between treated and untreated areas. CONCLUSIONS Our study demonstrated severe thermal damage to intraprostatic nerve fibers caused by transurethral needle ablation. A long-term denervation of alpha-receptors and/or sensory nerves could explain the clinical effects of transurethral needle ablation of the prostate. Theoretically, the best location to produce necrotic lesions should include submucosal and subcapsular nerve endings. Differences in the distribution of the adrenoreceptors and morphometry of the prostate transition zone could partly explain differences in clinical outcome observed after transurethral needle ablation of the prostate.

Prostatic intraepithelial neoplasia: Influence of clinical and pathological data on the detection of prostate cancer

PURPOSE We attempted to characterize patients diagnosed with prostatic intraepithelial neoplasia without concurrent cancer on biopsy who had prostate cancer on subsequent biopsy. MATERIALS AND METHODS The records of 93 patients with low and high grade prostatic intraepithelial neoplasia without concurrent cancer on initial biopsy were analyzed. The relationships among prostatic intraepithelial neoplasia grades, patient age, digital rectal examination, serum prostate specific antigen (PSA), transrectal ultrasound appearance and final pathological results were investigated. RESULTS Subsequent carcinoma was found on repeat biopsy in 13.3% of patients with low grade and 47.9% with high grade prostatic intraepithelial neoplasia (p < 0.001). In the former group digital rectal examination, patient age, serum PSA and transrectal ultrasound were not predictive of cancer. Transrectal ultrasound appearance, digital rectal examination and serum PSA were statistically different between high grade prostatic intraepithelial neoplasia with and without subsequent cancer (p < 0.001, p = 0.008 and p = 0.016, respectively, univariate analysis). On multivariate analysis of patients with high grade prostatic intraepithelial neoplasia only digital rectal examination and PSA were predictive of subsequent carcinoma. CONCLUSIONS High grade prostatic intraepithelial neoplasia is a strong predictor of subsequent cancer, especially in men with abnormal digital rectal examination and elevated serum PSA. Patients with high grade prostatic intraepithelial neoplasia should undergo repeat biopsy to exclude cancer. Further investigations are needed to optimize the treatment of patients with low grade prostatic intraepithelial neoplasia.

The impact of tumor size on clinical outcome in patients with localized renal cell carcinoma treated by radical nephrectomy

PURPOSE We investigated the influence of tumor size on clinical outcome in patients with localized renal cell carcinoma treated with radical nephrectomy. MATERIALS AND METHODS We reviewed retrospectively the records of 54 patients with pathological T1, T2 renal cell carcinoma for age, sex, histological grade, cell type, architecture, deoxyribonucleic acid ploidy pattern, nuclear morphometry and vimentin expression. Variables found to predict outcome were correlated with tumor size, which was further tested for its prognostic value. RESULTS The best predictors of prognosis were grade, ploidy pattern, nuclear morphometry and vimentin expression. Small (less than 5 cm.) and large (larger than 5 cm.) tumors had similar distribution of prognostic variable subgroups. No differences in progression rate or survival were noted between the tumor size categories. CONCLUSIONS These results suggest that small renal tumors may follow unfavorable courses and require aggressive treatment.

Do prostate specific antigen and prostate specific antigen density enhance the detection of prostate carcinoma after initial diagnosis of prostatic intraepithelial neoplasia without concurrent carcinoma

Prostatic intraepithelial neoplasia (PIN) is considered to be a precursor of prostate carcinoma in which serum levels of prostate specific antigen (PSA) have been correlated with PIN grades. The aim of this study was to determine whether PSA and prostate specific antigen density (PSAD), obtained at the time of initial diagnosis of PIN without concurrent carcinoma, can be used as predictive factors to discriminate patients with subsequent cancer on repeat biopsy.

Objective measurement of the different collagen types in the corpus cavernosum of potent and impotent men: an immunohistochemical staining with computerized-image analysis

SummaryQuantitative measurements of the collagen types (I, III, and IV) in the corpora cavernosa of potent and impotent men were carried out to investigate whether quantitative immunohistochemistry might contribute additional information as to the cause of erectile dysfunction. The study group consisted of 22 men with various etiologies of impotence and 4 normal, potent men. The quantitative immunohistochemistry measurements were performed by means of a cell-image processor. Three variables for each of the three types of collagen were studied, namely, the mean optical density (MOD), which relates to histochemical staining intensity; the labeling index (LI), which is positively related to the percentage of immunostaining; and the quick score (QS) index, which takes into account both LI and MOD values. None of the quantitative parameters taken individually (monovariate statistical analyses) made it possible to obtain any statistically significant difference between the types of collagen of the group under study. The mean QS value recorded for collagen type IV was significantly lower than that noted for collagen type I in the psychogenic (P = 0.019), arteriogenic (P = 0.012), and venogenic (P = 0.001) groups, whereas the MOD value was significantly lower in the normal (P = 0.043), arteriogenic (P = 0.013), and venogenic (P = 0.001) groups but not in the psychogenic group. The mean MOD of collagen type III was intermediate between that of the other types. In contrast, the mean LI value recorded for collagen type IV was significantly lower only in the venogenic (P = 0.032) and psychogenic (P = 0.049) groups as compared with the other groups. No objective qualitative change in the collagen types was observed that could be correlated to the etiology of erectile dysfunction. The significant difference seen in the quantitative parameters with regard to collagen type IV and the observed increase in the type I/III collagen ratio might attest to the notion that the response of the erectile tissue to ischemia is similar to that of other organs. The net effect of these changes is a restricted capacity for corporal expansion and alteration of the veno-occlusive mechanism.

Clinical prognostic criteria for later diagnosis of prostate carcinoma in patients with initial isolated prostatic intraepithelial neoplasia

Prostatic intraepithelial neoplasia (PIN) is considered as a precursor of prostate cancer and is frequently associated with it. Diagnosis of PIN on a prostate needle biopsy without associated carcinoma is a difficult problem since high-grade PIN does not necessarily mean that prostate cancer is always present and low-grade PIN is associated with cancer as well. Definition of parameters predictive of the later finding of prostate cancer on repeat biopsy in patients with PIN is of evident interest and we have reviewed our experience and recent data from the literature on this topic. High grade is a strong predictor of later cancer found on repeat biopsy (50-100%) and in these patients, serum prostate-specific antigen (PSA), digital rectal examination and transrectal ultrasound are predictors of later cancer found on repeat biopsy. High-grade PIN is, however, frequently associated with later cancer whatever PSA, even when < or = ng/ml. Low-grade PIN seems to behave like BPH since the incidence of later cancer is extremely low when PSA is < 4 ng/ml and is high when PSA > 10 ng/ml. Patients with high-grade PIN should systematically be rebiopsied after 3-6 months to exclude cancer because they are likely to have undiagnosed cancer. Patients with low-grade PIN and low PSA seem to have a low risk of later cancer found on repeat biopsy. Patients with low-grade PIN and high serum PSA should have repeat biopsies because the incidence of subsequent cancer is high and comparable to high-grade PIN. Further investigations are needed to optimize the management of patients with low-grade PIN and intermediate PSA level.

Correlation of nocturnal penile tumescence monitoring, duplex ultrasonography and infusion cavernosometry for the diagnosis of erectile dysfunction

PURPOSE Nocturnal penile tumescence monitoring was compared to penile duplex ultrasonography and pharmaco-infusion cavernosometry in 50 cases of erectile dysfunction. MATERIALS AND METHODS Nocturnal penile tumescence was evaluated in all patients as normal or abnormal according to standard general criteria. The results were compared to penile duplex ultrasonography parameters (peak systolic velocity, normal greater than 35 cm. per second, and diastolic velocity, normal less than 5 cm. per second), and to the flow rate needed to maintain erection (normal less than 15 ml. per minute) with pharmaco-infusion cavernosometry. RESULTS Of the 50 patients 26 had normal nocturnal penile tumescence, including 25 (96%) with normal penile velocity, 18 (69%) with normal penile diastolic velocity and 22 (85%) with normal flow to maintain erection. On the other hand, 24 men had abnormal nocturnal penile tumescence of whom 7 (29%) had abnormal penile blood flow velocity, 17 (71%) had abnormal diastolic flow velocity and 18 (75%) had high flow rate to maintain erection. CONCLUSIONS Normal nocturnal penile tumescence appears to correlate well with normal systolic blood velocity and cavernosometry but poorly with diastolic blood velocity. On the other hand, a low correlation exists between abnormal nocturnal penile tumescence and abnormal diastolic blood flow or abnormal cavernosometry. Furthermore, no correlation exists between abnormal nocturnal penile tumescence and abnormal systolic blood flow. According to this observation we presume that nocturnal penile tumescence, penile duplex and infusion cavernosometry should be performed to achieve a reasonably accurate diagnosis.

CORPOREAL VENO-OCCLUSIVE DYSFUNCTION: A DISTAL ARTERIAL PATHOLOGY?

PURPOSE Alteration of intracavernous smooth muscle cells has been demonstrated in patients with pure venous leakage. This modification seems correlated with reduction of intracavernous oxygen tension. However, Doppler imaging of the cavernous arteries in these patients is normal. To understand the ischemic factor we studied the endothelium of the terminal arteries with computerized image analysis and immunohistochemical staining with 2 types of lectin in patients with venous leakage and those with normal erections. Lectins are glycoproteins that can be used as histological markers to monitor functional and pathological changes. MATERIALS AND METHODS Four patients 44 to 59 years old with normal erections who were operated on for penile cancer and 11 patients 27 to 62 years old with pure venous leakage (flow to maintain erection greater than 15 ml. per minute and cavernous flow velocity greater than 35 cm. per second) were included in the study. Immunohistochemical staining with 2 lectins, wheat germ agglutinin and Ulex europeaus agglutinin I, was performed and analyzed with computerized image analysis. The labeling index which relates to the percentage of staining indicates the distribution of the endothelial cells, and mean optical density which relates to the staining intensity indicates the function of these cells. RESULTS Mean labeling index values for the 2 lectins were similar in both groups (p >0.05). Mean optical density values for the 2 lectins were significantly greater for the patients with normal erections (p <0.01). Therefore, the distribution of the endothelial cells was the same while their function was different in patients with corporeal veno-occlusive dysfunction. CONCLUSIONS Staining with wheat germ agglutinin and Ulex europeaus agglutinin I lectin types allowed us to detect alteration in the glyco-histochemistry of the endothelial cells of the small arteries, and venous leakage could be the first step in vasculogenic impotence.

Role of Transrectal Ultrasonography in the Evaluation of Azoospermic Men With Low-Volume Ejaculate

Objective. The purpose of this prospective study was to evaluate the incidence of distal ejaculatory system defects with transrectal ultrasonography (TRUS) among patients evaluated for azoospermia. Methods. Forty‐two patients with low‐volume ejaculate and azoospermia were evaluated by physical examination, serum follicle‐stimulating hormone and luteinizing hormone level determination, karyotyping, selective screening for cystic fibrosis mutations, and TRUS. Results. On physical examination, in 29 patients (69%), either 1 (12 patients) or both (17 patients) of the vasa deferentia could not be palpated. In the group of 17 patients with bilateral involvement of the vasa deferentia, the ultrasonographic imaging universally showed bilateral absence or hypoplasia of the seminal vesicles with bilateral agenesis of the vasa deferentia and nonvisualization of both ejaculatory ducts. In the patients with a unilateral abnormality on physical examination, the ultrasonographic imaging showed absence of the ipsilateral seminal vesicle in 7 patients and the hypoplastic seminal vesicle in 5. In the group of 13 patients with normal physical examination findings, a variety of obstructive causes were diagnosed by TRUS examination. Conclusions. According to this study, TRUS appears to be a sensitive method for evaluating the anatomy of the distal ejaculatory system. Its safety and low costs make it a good alternative to the other invasive and expensive methods.

Lectin-induced alterations on the proliferation of three human prostatic cancer cell lines

SummaryWhile lectins are known to influence the cell growth of several types of normal and neoplastic tissues, their roles in the case of prostatic cancer cells remain relatively unexplored. In the present work, we report thein vitro influence of five lectins, namely peanut (PNA), wheat germ (WGA), Concanavalin A (Con A),Griffonia simplicifolia (GSA-IA4), andPhaseolus vulgaris (PHA-L) agglutinins, on the cell proliferation of one androgen-sensitive (LNCaP) and two androgen-insensitive (PC-3 and DU 145) human prostatic cancer cell lines cultured in either 10% or 1% fetal bovine serum (FBS)-supplemented media. The cell proliferation was assessed by means of the colorimetric 3-(4,5-dimethythiazol-2-yle)2,5-diphenyltetrazolium bromide. (MTT) assay. Four lectin concentrations were tested (i.e., 0.1, 1, 10, and 100 μg/ml) at five experimental states (i.e., 2, 3, 5, 7, and 9 d following the addition of each lectin to the culture media). Our results demonstrated that the five lectins under study had a globally significant dose-dependent toxic effect on prostatic cancer cell proliferation. Nevertheless, low doses of GSA-IA4 and PHA-L significantly (P<0.05 toP<0.001) increased the cell proliferation of confluent PC-3 cells. Increasing the FBS from 1% to 10% in the culture media significantly antagonized lectin-induced toxicity in the three prostatic cell lines. In conclusion, the present data strongly suggest that some lectins might influence the proliferation of prostatic carcinoma cells. In addition, because lectins are present in our diet, and are able to pass into the systemic circulation and thus reach the prostate, the present results suggest that some lectins might exert an influence on prostate cancer growth under clinical conditions.