Alessandro Bertaccini

Role of contrast enhanced ultrasound in acute scrotal diseases

ObjectiveTo evaluate the efficacy of contrast-enhanced ultrasound (CEUS) in patients with acute scrotal pain not defined at ultrasound (US) with colour Doppler .MethodsCEUS was carried out in 50 patients with acute scrotal pain or scrotal trauma showing testicular lesion of undefined nature at US. The accuracy of US and CEUS findings versus definitive diagnosis (surgery or follow-up) was calculated.ResultsTwenty-three patients had a final diagnosis of testicular tumour, three abscess, eight focal infarction, seven trauma, three testicular torsion, one haematoma. Five patients were negative. Thirty-five patients were operated (23 testicular tumours, six trauma, three testicular torsion, one abscess, one focal infarction, and one haematoma) and 15 underwent medical treatment or were discharged. US provided a definitive diagnosis in 34/50 as compared to the 48/50 patients diagnosed at CEUS. Sensitivity and specificity were 76% and 45% for US and 96% and 100% for CEUS respectively.ConclusionsCEUS was more accurate in the final diagnosis compared to US, potentially reducing the need for further imaging. In particular CEUS can be proposed in emergency in cases where US diagnosis remains inconclusive, namely in infarction, and trauma, when testicular torsion cannot be ruled out, and in identifying testicular mass.

Symptoms, Bothersomeness and Quality of Life in Patients with LUTS Suggestive of BPH

The QUIBUS study is the largest investigation ever performed in Italy with an extensive use of the ICS-BPH questionnaire. The internal consistency of each of its three domains was high for ICS-Male (Cronbach’s alpha = 0.83 and 0.89 for symptoms and bother, respectively) and lower for ICS-Sex (Cronbach’s alpha = 0.63 and 0.75, see a following paper of this issue) and ICS-QoL (Cronbach’s alpha = 0.53), as previously reported in the validation study of this tool. Voiding symptoms were more frequently reported, with reduced urinary stream, terminal dribble and incomplete bladder emptying as the most frequently represented. The first storage symptom in the ranking by frequency was ‘rush to toilet’ (70% of the population), in 7th position; however, the relevant bother was among the highest reported. Items related to urinary incontinence appeared, when present, highly bothersome (87–92% of patients), even though exhibited by a minority of the population (5–34%). The mean (±SD) IPSS, calculated on 970 patients, was 15 (±7). Two major discrepancies were found in the comparison between IPSS and ICS-Male. First, terminal dribble, which is not considered in the IPSS, is often reported in the ICS-Male. Second, some storage symptoms (nocturia and day-time frequency) are less frequently reported in the ICS-Male than in the IPSS, while being, in general, highly bothersome. As regards QoL, 95% of subjects declared that they would not be completely happy to spend the rest of their life with their actual symptoms (ICS-QoL item 33) and 79% that BPH influences their life from ‘a little’ to ‘a lot’ (ICS-QoL item 30). The mean (±SD) IPSS-QoL single question score was 3.0 ± 1.4 (n = 970), and the frequency distribution of scores was equivalent to the one detected by the corresponding question of ICS-QoL (item 33). SF-36, a disease-independent questionnaire about QoL, after a 1-year follow-up is expected to clarify which among the IPSS and ICS-BPH items better describe the impact of BPH on QoL.

Accuracy of MRI/MRSI-based transrectal ultrasound biopsy in peripheral and transition zones of the prostate gland in patients with prior negative biopsy

The purpose of the study was to evaluate the accuracy of transrectal ultrasound biopsy (TRUS‐biopsy) performed on regions with abnormal MRI and/or MRSI for both the transition (TZ) and the peripheral (PZ) zones in patients with suspected prostate cancer with prior negative biopsy, and to analyze the relationship between MRSI and histopathological findings. MRI and MRSI were performed in 54 patients (mean age: 63.9 years, mean PSA value: 11.4 ng/mL) and the ability of MRI/MRSI‐directed TRUS biopsy was evaluated. A three‐point score system was used for both techniques to distinguish healthy from malignant regions. Descriptive statistics and ROC analyses were performed to evaluate the accuracy and the best cut‐off in the three‐point score system. Twenty‐two out of 54 patients presented cancer at MRI/MRSI‐directed TRUS biopsy, nine presented cancer only in PZ, eight both in PZ and TZ, and five exclusively in TZ. On a patient basis the highest accuracy was obtained by assigning malignancy on a positive finding with MRSI and MRI even though it was not significantly greater than that obtained using MRI alone (area under the ROC curve, AUC: 0.723 vs 0.676). On a regional (n = 648) basis the best accuracy was also obtained by considering positive both MRSI and MRI for PZ (0.768) and TZ (0.822). MRSI was false positive in 11.9% of the regions. Twenty‐eight percent of cores with prostatitis were false positive findings on MRSI, whereas only 2.7% of benign prostatic hyperplasia was false positive. In conclusion, the accuracy of MRI/MRSI‐directed biopsies in localization of prostate cancer is good in patient (0.723) and region analyses (0.768). The combination of both MRI and MRSI results makes TRUS‐biopsy more accurate, particularly in the TZ (0.822) for patients with prior negative biopsies. Histopathological analysis showed that the main limitation of MRSI is the percentage of false positive findings due to prostatitis. Copyright

VASOACTIVE COCKTAILS FOR ERECTILE DYSFUNCTION: CHEMICAL STABILITY OF PGE1, PARAVERINE AND PHENTOLAMINE

PURPOSE Vasoactive cocktails are widely used in diagnosing and treating erectile dysfunction, especially in poor responders to prostaglandin E1 (PGE1). However, very little information as to their chemical interactions and stability is available, despite the huge amount of published work regarding their clinical efficacy. Obviously, medical and legal problems are involved. MATERIALS AND METHODS We analyzed four kinds of vasoactive cocktails, composed of papaverine, phentolamine and PGE1 in different combinations, using High Performance Liquid Chromatography analysis after 5 to 60 days of storage at temperatures between 2 and 8C. SPSS MANOVA analysis and a t-test for paired samples were used for statistical purposes. RESULTS Papaverine and phentolamine concentrations showed no significant variations during the 2 month study, ranging from a minimum of 96.75+/-1.20 to a maximum of 103.00+/-0.20% of the starting values. In the same period, PGE1 showed an accelerated degradation profile, reaching concentration values, after 60 days, of 76.00+/-2.28% and 70.20+/-2.02% when added to phentolamine or papaverine respectively and 70.00+/-2.40% with both. CONCLUSIONS Papaverine and phentolamine are characterized by chemical stability when blended together or with PGE1. Papaverine and/or phentolamine increase the naturally occurring degradation of PGE1 in physiological solution. This effect is most evident in the first 10 days. Papaverine has the greatest deteriorating effect on PGE1. A safe and proper use of these cocktails should take into account the variations of PGE1 concentration.

Telomerase Activity in Touch–Imprint Cell Preparations from Fresh Prostate Needle Biopsy Specimens

Objective: To evaluate whether it is possible to detect telomerase activity in cells exfoliated from prostate biopsies immediately before fixation. Methods: A total of 115 transrectal biopsies of prostate tissue from 49 patients were touch–imprinted on an RNase–free microscope slide and then fixed. Touch imprints were immediately frozen and used to extract telomerase. Telomerase activity was determined by a telomeric repeat amplification protocol (TRAP) using a PCR–ELISA method. Inflammation and epithelial cells in each biopsy were quantitated by image cytometry. Results: A total of 90/115 extracts had a proteic content suitable for analysis. Telomerase activity was detected in 18/26 (70%) carcinomas, 2/9 (22%) low–grade prostatic intraepithelial neoplasia (PIN) lesions, and 1/3 (33%) high–grade PIN lesions. In 4 of 7 patients with telomerase–positive tumors, telomerase activity was also found in a distant site devoid of morphologically detectable cancer cells. Telomerase activity was detected in touch imprints from fragments with less than 1 mm2 of epithelial tissue, and was not associated with the extent of inflammation. Conclusions: From the technical stand point, the touch–imprint method may provide a useful adjunct for telomerase detection in prostate biopsies. With this procedure the bioptic fragment is left intact for histological examination. Diagnostically, the presence of telomerase activity in sites distant from the original tumor might suggest the presence of tumor cells that are morphologically undetectable.

Soluble E-cadherin and IL-6 serum levels in patients affected by prostate cancer before and after prostatectomy

Prostate specific antigen (PSA) is still the best available tumour marker in prostate cancer (PCa), but presents some limits. Therefore, there is a need for novel markers in the detection and management of PCa. The 80-kDa soluble form of E-cadherin (sE-cad) and the cytokine IL-6 are being discussed as supplemental serum markers for PCa. In this study, sE-cad and IL-6 serum levels were determined in patients with pathological localized or locally advanced PCa without any previous treatment. These patients underwent radical retropubic prostatectomy (RRP) in accordance with the EAU Guidelines on Prostate Cancer. The molecules were determined via immunoenzymatic assays in samples collected before and after surgery. Statistical analysis was performed by Students t-test and Pearsons correlation test. sE-cad levels were 6.0 ± 2.7 and 4.6 ± 2.3 µg/ml, before and after RRP, respectively. A highly statistically significant decrease in sE-cad concentrations after RRP was observed (p<0.0001), in 50/61 patients (82%). sE-cad levels before and after surgery were correlated (Pearsons correlation coefficient, r=0.6993, p<0.0001). sE-cad values detected after surgery were higher in patients with PSA levels >10 ng/ml (p<0.05). sE-cad levels before RRP were significantly higher in patients with G3 tumours compared to those with G2 tumours (p<0.02). Finally, sE-cad concentrations both before and after surgery were higher in tumours with Gleason score =7 compared to those with Gleason score <7 (p<0.002 and p<0.05, respectively). Preliminary data from 20 patients indicated a statistically significant increase in IL-6 levels after RRP (11.2 vs. 7.2 pg/ml, p<0.001). This is the first study on the reduction in sE-cad levels after RRP in PCa patients. Moreover, it shows that preoperative sE-cad concentrations are higher in patients with less differentiated PCa. Promising findings of this pilot study may lead to investigation of sE-cad in a larger study with follow-up.

Stability study of prostaglandin E1(PGE1) in physiological solutions by liquid chromatography (HPLC)

Abstract The stability of prostaglandin E 1 (PGE 1 ) in physiological solution for the treatment of erectile dysfunctions was investigated by liquid chromatography (HPLC). Two different HPLC procedures were used; the first included a pre-chromatographic derivatization of PGE 1 with 2-bromoacetyl-6-methoxynaphthalene followed by fluorescence detection ( λ exc = 300 nm; λ em = 460 nm), and the other was based on direct UV detection (205 nm) of the underivatized drug. The results showed that PGE 1 physiological solutions can be conveniently stored at 2–8°C; under these conditions about 85% of the initial concentration remained at 90 days, while at ambient temperature rapid degradation of the drug was observed.

Influence of bicalutamide with or without tamoxifen or anastrozole on insulin-like growth factor 1 and binding proteins in prostate cancer patients.

BACKGROUND There is growing evidence that IGF-1 and binding proteins may be involved in prostate cancer promotion and progression. PATIENTS AND METHODS IGF-1 and binding proteins (IGFBP-1 and 3) serum levels were measured at baseline and after 3 and 6 months of treatment in a selected group of patients with prostate cancer who were randomly assigned to treatment with bicalutamide, bicalutamide plus anastrozole or bicalutamide plus tamoxifen in a comparative study investigating the role of pharmacological medication in the development of bicalutamide-induced gynecomastia. RESULTS Bicalutamide monotherapy does not appear to alter the IGF-1/IGFBP system. In fact, the increase in IGF-1 levels induced by this treatment was paralleled by comparable increases in binding protein (IGFBP-3). No major changes from baseline up to month 6 either in IGF-1 or in IGFBP-1 and 3 were observed in the bicalutamide plus anastrozole arm. The addition of tamoxifen to bicalutamide produced a sharp decrease in IGF-1 levels (p<0.001) coupled with an increase in both IGFBP-1 (p=0.001) and, to a lesser extent, IGFBP-3 (p=0.5). CONCLUSIONS The concurrent administration of tamoxifen and bicalutamide reduces the synthesis and bioavailability of IGF-1. Moreover, increased binding protein levels might exert antiproliferative and proapoptotic effects on prostate cancer cells, independently of the IGF-1/IGF receptor-mediated survival system. Both effects might have a synergistic inhibitory influence on prostate cancer growth.

The Role of TRUS Prostate Biopsy Quantitative Histology in Predicting the Risk of Extraprostatic Disease

Abstract Objectives: In the era of prostate-specific antigen (PSA), extended core biopsy schemes are widely adopted with an increased detection rate of stage T1c prostate cancer. As regards extraprostatic disease, the low predictive value of traditional prognostic factors, such as Gleason score (Gs) and PSA levels in this group of patients means that prostate biopsy quantitative histology plays a major role in the risk assessment of extraprostatic involvement. Methods: Literature on prostate biopsy was reviewed and a selection of articles made. Keywords used for the Medline search included: prostate cancer, biopsy, staging and prognosis. Results: Over the last few years, an increasing number of investigators have shown that number and percentage of positive cores, percentage of tumor involvement, maximum percentage of tumor involvement on the cores most strongly involved and tumor location, are considered the most predictive pathological parameters for adverse final pathological results. However, they are somewhat limited in terms of predicting the pathological stage of the disease on an individual basis. Conclusions: Nowadays, several quantitative histological parameters have been evidenced as good indicators for an extraprostatic spread of the tumor and positive surgical margins after radical prostatectomy. However, it is difficult for a single parameter in systematic biopsies to predict pathological stage and final outcome. Only the inclusion of some measure of neoplastic extension on the biopsies in models for the preoperative prediction of pathological stage will tell us what the definitive role of quantitative prostate biopsy is in assessing the risk of extraprostatic extension.

Biopsying prostate gland: telomerase evaluation

In eukaryocyte cells the DNA polymerase is not able to terminate the duplication of the DNA for the entire length of the chromatid ®lament. Chromosomes terminate with sequences of repetitive bases, called telomeres, which do not codify for mRNA. When telomeres shorten below a critical threshold, signals of damage to the DNA are sent which stop cell division. In embryonic and adult staminal cells the enzyme telomerase maintains telomere length at the end of DNA-duplication cycles. Telomerase is absent in most differentiated cells, but may become re-activated in many cancers. Prostate carcinomas usually show short telomeres and active telomerase. According to a recent study, 92% of prostate carcinomas showed evidence of telomerase activity, as did most PINs (73%), particularly if adjacent to neoplasia. Telomerasic activity is not usually found in non-malignant prostatic tissues, suggesting that the search for telomerase activity may improve the procedure of diagnosis in biopsies.