Investigation of Clinically Significant Molecular Aberrations in Patients with Prostate Cancer: Implications for Personalized Treatment, Prognosis and Genetic Testing.

The data on tumor molecular profiling of European patients with prostate cancer is limited. Our aim was to evaluate the prevalence and prognostic and predictive values of gene alterations in unselected patients with prostate cancer. The presence of gene alterations was assessed in patients with histologically confirmed prostate cancer using the ForeSENTIA® Prostate panel (Medicover Genetics), targeting 36 clinically relevant genes and microsatellite instability testing. The primary endpoint was the prevalence of gene alterations in homologous recombination repair (HRR) genes. Overall, 196 patients with prostate cancer were evaluated (median age 72.2 years, metastatic disease in 141 (71.9%) patients). Gene alterations were identified in 120 (61%) patients, while alteration in HRR genes were identified in 34 (17.3%) patients. The most commonly mutated HRR genes were ATM (17, 8.7%), BRCA2 (9, 4.6%) and BRCA1 (4, 2%). The presence of HRR gene alterations was not associated with advanced stage (p = 0.21), age at diagnosis (p = 0.28), Gleason score (p = 0.17) or overall survival (HR 0.72; 95% CI: 0.41-1.26; p = 0.251). We identified clinically relevant somatic gene alterations in European patients with prostate cancer. These molecular alterations have prognostic significance and therapeutic implications and/or may trigger genetic testing in selected patients. In the era of precision medicine, prospective research on the predictive role of these alterations for innovative treatments or their combinations is warranted.

Clopidogrel Therapy in Patients with Cardiovascular Disease Undergoing Transurethral Resection of the Prostate: A Step Towards Individualization.

OBJECTIVES: The objective of this study was to test platelet function pre- and peri-operatively in clopidogrel-treated patients undergoing transurethral resection of the prostate. METHODS: This was a pilot study involving 20 male patients treated with clopidogrel (75 mg/day) for the secondary prevention of cardiovascular disease and scheduled for elective transurethral resection of the prostate. Platelet function testing with light transmittance aggregometry in platelet-rich plasma of four samples (T0, T1, T2, and T3 drawn on the same day, 3 and 7 days of clopidogrel cessation and 24-h post-operatively, respectively) was performed and evaluated in each patient. P-selectin membrane expression was evaluated using monoclonal antibodies. RESULTS: The platelet response to adenosine diphosphate 5 µΜ and 20 µΜ at T0 were 42 ± 15 and 60 ± 14%, respectively. After discontinuation of clopidogrel, corresponding maximum aggregation values at T1 were 60 ± 16 and 74 ± 14%, and increased to 69 ± 16 and 79 ± 18% at T2. No significant difference in platelet aggregation values were noted between T1 and T2, while similar aggregation values were recorded at T3. CONCLUSIONS: Our findings indicate that in patients undergoing transurethral resection of the prostate, platelet activation is similar 3 and 7 days from clopidogrel cessation. These results may be of relevance in subjects at increased thrombotic risk prior to a surgical procedure carrying a high-bleeding risk.

Magnetic resonance diffusion tensor imaging of the testis: Preliminary observations.

INTRODUCTION: To evaluate the feasibility of testis diffusion tensor imaging (DTI), to determine normative apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values and to assess the efficacy of DTI in characterizing testicular pathology. MATERIALS AND METHODS: Fifty-six men underwent MRI of the scrotum, including DTI. Parametric and non-parametric statistical tests were used to compare the ADC and FA between the cranial, middle and lower thirds of normal testis and between the bilateral testicular thirds. Comparison between the ADC and FA of normal testis, malignant and benign testicular lesions was performed. RESULTS: No significant differences of the ADC and FA in normal testis between the cranial, middle and lower thirds and between the bilateral testicular thirds were found. ADC was significantly lower in malignancies compared to normal testis (P=0.006) and benign testicular lesions (P=0.006). FA was significantly higher both in malignancies (P=0.001) and benign lesions (P<0.001) compared to normal testis. FA in malignancies did not differ from FA in benign lesions (P=0.221) CONCLUSIONS: This study shows the feasibility of testis DTI. Both ADC and FA significantly differ between testicular lesions and normal testis, although FA did not show an incremental diagnostic value compared to ADC in lesion differentiation.

Microvascular density and immunohistochemical expression of VEGF, VEGFR-1 and VEGFR-2 in benign prostatic hyperplasia, high-grade prostate intraepithelial neoplasia and prostate cancer.

INTRODUCTION: The aim of our study was to determine and compare angiogenesis in benign prostatic hyperplasia (BPH), high-grade prostate intraepithelial neoplasia (HGPIN) and prostate cancer (Pca). Moreover, we evaluated its role as a prognostic factor for Pca. MATERIAL AND METHODS: We examined 39, 12 and 51 samples of BPH, HGPIN and Pca, respectively. Immunohistochemical methods were applied in order to evaluate the expression of VEGF and its receptors (VEGFR-1, VEGFR-2), while microvascular density (MVD) was determined using CD105. In Pca samples, we recorded stage, differentiation, perineural invasion, adjuvant radiotherapy and their correlation with angiogenesis. RESULTS: 225 The expression of VEGF, VEGFR-1 and VEGFR-2 was significantly higher in Pca than compared to BPH (p <0.001, p <0.001 and p <0.001, respectively) and HGPIN (p <0.001, p <0.001 and p = 0.04, respectively), while there was no difference between BPH and HGPIN. MVD was higher in Pca compared to BPH (p <0.001) and HGPIN (p <0.01), while there was no difference between BPH and HGPIN. VEGF expression and MVD were significantly greater in Pca samples with poor differentiation (p = 0.044 and p = 0.038, respectively) and perineural invasion (p <0.001 and p = 0.019, respectively), while overexpression of VEGF was associated with advanced pathological stage (p = 0.047). CONCLUSIONS: Angiogenesis is more prominent in Pca than in BPH and HGPIN, while there is no difference between BPH and HGPIN. Pharmaceutical inhibition of angiogenesis could be a valuable therapeutic option for Pca in the near future.

Magnetic resonance imaging findings of cellular angiofibroma of the tunica vaginalis of the testis: a case report.

BACKGROUND: Cellular angiofibroma represents a rare mesenchymal tumor typically involving the inguinoscrotal area in middle-aged men. Although the origin of this benign tumor is unknown, it is histologically classified as an angiomyxoid tumor. Cellular angiofibroma is characterized by a diversity of pathological and imaging features. An accurate preoperative diagnosis is challenging. Magnetic resonance imaging examination of the scrotum has been reported as a valuable adjunct modality in the investigation of scrotal pathology. The technique by providing both structural and functional information is useful in the differentiation between extratesticular and intratesticular diseases and in the preoperative characterization of the histologic nature of various scrotal lesions. There are few reports in the English literature addressing the magnetic resonance imaging findings of cellular angiofibroma of the scrotum and no reports on functional magnetic resonance imaging data. Here we present the first case of a cellular angiofibroma arising from the tunica vaginalis of the testis and we discuss the value of a multiparametric magnetic resonance protocol, including diffusion-weighted imaging, magnetization transfer imaging and dynamic contrast-enhanced magnetic resonance imaging in the preoperative diagnosis of this rare neoplasm. CASE PRESENTATION: A 47-year Greek man presented with a painless left scrotal swelling, which had gradually enlarged during the last 6 months. Magnetic resonance imaging of his scrotum displayed a left paratesticular mass, in close proximity to the tunica vaginalis, with heterogeneous high signal intensity on T2-weighted images and no areas of restricted diffusion. The tumor was hypointense on magnetization transfer images, suggestive for the presence of macromolecules. On dynamic contrast-enhanced magnetic resonance imaging the mass showed intense heterogeneous enhancement with a type II curve. Magnetic resonance imaging findings were strongly suggestive of a benign paratesticular tumor, which was confirmed on pathology following lesion excision. CONCLUSIONS: Magnetic resonance imaging of the scrotum by combining conventional and functional magnetic resonance data provides useful diagnostic information in the preoperative characterization of scrotal masses. A possible diagnosis of a benign paratesticular tumor based on magnetic resonance imaging features may improve patient care and decrease the number of unnecessary radical surgical explorations.

MR imaging of scrotum.

Magnetic resonance (MR) imaging of the scrotum has been used as a valuable supplemental diagnostic modality in evaluating scrotal pathology, mostly recommended in cases of inconclusive sonographic findings. Because of the advantages of the technique, MR imaging of the scrotum may provide valuable information in the detection and characterization of various scrotal diseases. The technique may accurately differentiate intratesticular from extratesticular mass lesions and provide important information in the preoperative characterization of the histologic nature of scrotal masses. An accurate estimation of the local extent of testicular carcinomas in patients for whom testis-sparing surgery is planned is possible.

Apparent diffusion coefficient values of normal testis and variations with age.

The usefulness of diffusion-weighted magnetic resonance imaging (DWI) in the evaluation of scrotal pathology has recently been reported. A standard reference of normal testicular apparent diffusion coefficient (ADC) values and their variations with age is necessary when interpreting normal testicular anatomy and pathology. We evaluated 147 normal testes using DWI, including 71 testes from 53 men aged 20-39 years (group 1), 67 testes from 42 men aged 40-69 years (group 2) and nine testes from six men older than 70 years (group 3). DWI was performed along the axial plane, using a single shot, multislice spin-echo planar diffusion pulse sequence and b-values of 0 and 900 s mm-2 . The mean and standard deviation of the ADC values of normal testicular parenchyma were calculated for each age group separately. Analysis of variance (ANOVA) followed by post hoc analysis (Dunnett T3) was used for statistical purposes. The ADC values (× 10-3 mm 2 s-1 ) of normal testicular tissue were different among age groups (group 1: 1.08 ± 0.13; group 2: 1.15 ± 0.15 and group 3: 1.31 ± 0.22). ANOVA revealed differences in mean ADC among age groups (F = 11.391, P < 0.001). Post hoc analysis showed differences between groups 1 and 2 (P = 0.008) and between groups 1 and 3 (P = 0.043), but not between groups 2 and 3 (P = 0.197). Our findings suggest that ADC values of normal testicular tissue increase with advancing age.

Dynamic contrast-enhanced subtraction MRI for characterizing intratesticular mass lesions.

OBJECTIVE: The objective of our study was to analyze the enhancement patterns of various intratesticular mass lesions at dynamic contrast-enhanced subtraction MRI and assess the value of the technique in distinguishing between benign and malignant lesions. MATERIALS AND METHODS: We retrospectively evaluated the records and images of 44 consecutive men (11 benign and 16 malignant intratesticular lesions) who presented to the department of urology with a variety of clinical symptoms and were referred for imaging. Dynamic contrast-enhanced subtraction MRI was performed using a 3D fast-field echo sequence after the administration of paramagnetic contrast medium. Patients were divided into three groups according to the final diagnosis: benign intratesticular lesions, malignant intratesticular lesions, and normal testes. The patterns of contrast enhancement of both the normal testes and the intratesticular lesions were evaluated. Time-signal intensity plots were created and classified according to shape: Type I presented a linear increase of contrast enhancement throughout the examination, type II showed an initial upstroke followed by either a plateau or a gradual increase in the late contrast-enhanced phase, and type III presented an initial upstroke followed by gradual washout of the contrast medium. The relative percentages of peak height, maximum time, and mean slope were also calculated. RESULTS: Normal testes enhanced homogeneously with a type I curve. Most benign intratesticular lesions showed inhomogeneous or homogeneous contrast enhancement and a type II curve. Testicular carcinomas showed heterogeneous contrast enhancement with a type III curve. The relative percentages of maximum time to peak proved the most important discriminating factor in differentiating malignant from benign intratesticular masses (p < 0.001). CONCLUSION: Dynamic contrast-enhanced MRI may be used to distinguish between benign and malignant intratesticular mass lesions.

Diffusion-weighted MR imaging of normal and abnormal scrotum: preliminary results.

Magnetic resonance (MR) imaging of the scrotum represents an important supplemental diagnostic tool in the evaluation of scrotal diseases. Diffusion-weighted (DW) MR imaging is a developing technique, proved to improve tissue characterization. We evaluated the feasibility and diagnostic performance of DW MR imaging in the detection and characterization of scrotal lesions. We retrospectively evaluated 31 scrotal lesions (23 intratesticular and 8 extratesticular) in 26 men. All MR examinations were performed on a 1.5-T unit, using a pelvic-phased array coil. DW sequences were obtained using a single shot, multislice spin echo planar diffusion pulse sequence and a b factor of 0 and 900 s mm(-2). The DW MR characteristics and the apparent diffusion coefficient (ADC) values of normal scrotal contents and scrotal diseases were evaluated. Comparison between the ADC values of normal scrotum, benign lesions and scrotal malignancies was performed. The accuracy of conventional sequences, DW images alone and DW imaging combined with conventional images in differentiating benign from malignant scrotal lesions was calculated. The ADC values of testicular malignancies were different from those of normal testis and benign intratesticular lesions, and the ADC values of benign extratesticular lesions from those of normal epididymis (P<0.05). The overall accuracy of conventional imaging, DW imaging alone and DW MR combined with conventional sequences in the characterization of intratesticular lesions was 91%, 87% and 100%, respectively. Our findings suggest that DW MR imaging and ADC values may provide valuable information in the diagnosis and characterization of scrotal diseases.

Penis auto-amputation and chasm of the lower abdominal wall due to advanced penile carcinoma: a case report.

INTRODUCTION: Penile cancer is uncommon. When penile cancer is left untreated, at an advanced stage it can have tragic consequences for the patient. CASE PRESENTATION: Our case report does not concern a new manifestation of penile cancer, but an interesting presentation with clinical significance that emphasizes the need to diagnose and treat penile cancer early. It is an unusual case of a neglected penile cancer in a 57-year-old Greek man that led to auto-amputation of the penis and a large chasm in the lower abdominal wall. The clinical staging was T4N3M0 and our patient was treated with a bilateral cutaneous ureterostomy, chemotherapy and radiotherapy. Our patient died 18 months after his first admission in our clinic. CONCLUSIONS: Emphasis must be placed on early diagnosis and treatment of penile cancer, so further development of the disease can be prevented.

Conventional and diffusion-weighted magnetic resonance imaging findings of benign fibromatous paratesticular tumor: a case report.

INTRODUCTION: The vast majority of paratesticular masses are benign. Magnetic resonance imaging of the scrotum may provide valuable information in the pre-operative work-up of scrotal masses, by allowing the precise localization of the lesion and helping in characterizing its nature. Diffusion-weighted magnetic resonance imaging is an evolving technique that can be used to improve tissue characterization, when interpreted with the findings of conventional magnetic resonance sequences. We present the case of an adenomatoid tumor of the tunica albuginea, with abundant fibrosis evaluated by magnetic resonance imaging of the scrotum, including both conventional and diffusion-weighted sequences. To the best of our knowledge, there are very few reports in the English literature regarding the magnetic resonance imaging features of this rare benign paratesticular tumor and no report on the diffusion-weighted magnetic resonance findings. We discuss the value of magnetic resonance imaging in the pre-operative diagnosis of benign fibromatous paratesticular tumors and differential diagnosis. CASE PRESENTATION: A 45-year-old Caucasian man was referred to us with a palpable left scrotal mass. Magnetic resonance imaging of his scrotum revealed the presence of a multilobular left paratesticular mass, mainly detected with very low signal intensity on T2-weighted images and restricted diffusion on apparent diffusion coefficient maps. These findings were suggestive of a fibrous component, and were confirmed on histology following lesion excision. CONCLUSION: Magnetic resonance imaging of the scrotum, by using both conventional and diffusion-weighted sequences, could have a potential role in the evaluation of scrotal masses.

Disposable pipette extraction for gas chromatographic determination of codeine, morphine, and 6-monoacetylmorphine in vitreous humor.

The availability of a sensitive and rapid analytical method for the determination of opiates, and other substances of forensic interest, in a variety of biological specimens is of utmost importance to forensic laboratories. Solid-phase extraction is very popular in the pre-treatment of forensic samples. Nevertheless, a new approach, disposable pipette extraction (DPX), is gaining increasing interest in sample preparation. DPX has already been applied to the analysis of drugs of abuse in common biological matrices, such as urine and blood, but has not yet been evaluated on alternative biological samples, such as vitreous humor. The objective of this study was to evaluate the applicability of DPX on the analysis of opiates in vitreous humor. The currently developed method is fast, reliable, and easy to perform. The sensitivity, precision, and accuracy are satisfactory. Recoveries obtained are within the range of 72-91%, whereas the sample volume of vitreous humor required is only 100 µL.

Development and validation of a direct headspace GC-FID method for the determination of sevoflurane, desflurane and other volatile compounds of forensic interest in biological fluids: application on clinical and post-mortem samples.

A simple and reliable headspace GC-flame ionization detection (HS-GC-FID) method has been developed and validated for the simultaneous determination of seven volatile compounds of forensic interest: sevoflurane, desflurane, ethanol, methanol, 1-propanol, acetone and acetaldehyde. All seven compounds including acetonitrile (internal standard) eluted within 10 min and were well resolved with no endogenous interference. Good linearity was observed in the range of 1-12 mg/dL for both anesthetics and 2.5-40 mg/dL for the other five analytes. The method showed good precision, sensitivity and repeatability. Most of the analytes remained stable during the storage of samples at 4°C. Desflurane and acetone degraded (>10%), when the samples remained on the autosampler for more than 2 and 3 h, respectively. The method was finally applied on clinical and post-mortem blood and urine samples. The clinical samples were collected both from patients who underwent surgery, as well as from the occupationally exposed medical and nursing staff of the university hospital, working in the operating rooms. The hospital staff samples were found negative for all compounds, while the patients' samples were found positive for the anesthetic administered to the patient. The post-mortem blood samples were found positive for ethanol and acetaldehyde.

MRI in the characterization and local staging of testicular neoplasms.

OBJECTIVE: The purpose of this study was to assess the role of MRI in the preoperative characterization and local staging of testicular neoplasms. SUBJECTS AND METHODS: MRI was performed on 33 patients referred because a testicular mass had been detected clinically and sonographically. Both T1- and T2-weighted sequences were performed with a 1.5-T MRI unit. Gadolinium chelate was administered IV in all cases. We recorded the presence of a lesion and whether the histologic diagnosis of testicular malignancy could have been predicted on the basis of MRI features. For testicular neoplasms, local extension of disease was studied. The MRI findings were correlated with the surgical and histopathologic results. RESULTS: Histologic examination revealed 36 intratesticular lesions, 28 (78%) of which were malignant and eight benign. Thirteen malignant testicular tumors (46%) were confined within the testis, 12 (43%) had invaded the testicular tunicae or epididymis, and three (11%) had invaded the spermatic cord. The sensitivity and specificity of MRI in differentiating benign from malignant intratesticular lesions were 100% (95% CI, 87.9-100%) and 87.5% (95% CI, 52.9-97.7%). The rate of correspondence between MRI and histologic diagnosis in the local staging of testicular tumors was 92.8% (26/28). CONCLUSION: MRI is a good diagnostic tool for the evaluation of testicular disease. It is highly accurate in the preoperative characterization and local staging of testicular neoplasms.

Antidepressant drugs for chronic urological pelvic pain: an evidence-based review.

The use of antidepressant drugs for the management of chronic pelvic pain has been supported in the past. This study aimed to evaluate the available evidence for the efficacy and acceptability of antidepressant drugs in the management of urological chronic pelvic pain. Studies were selected through a comprehensive literature search. We included all types of study designs due to the limited evidence. Studies were classified into levels of evidence according to their design. Ten studies were included with a total of 360 patients. Amitriptyline, sertraline, duloxetine, nortriptyline, and citalopram are the antidepressants that have been reported in the literature. Only four randomized controlled trials (RCTs) were identified (two for amitriptyline and two for sertraline) with mixed results. We conclude that the use of antidepressants for the management of chronic urological pelvic pain is not adequately supported by methodologically sound RCTs. From the existing studies amitriptyline may be effective in interstitial cystitis but publication bias should be considered as an alternative explanation. All drugs were generally well tolerated with no serious events reported.

Fibroepithelial polyp of distal ureter with periodic prolapse into bladder.

Ureteric fibroepithelial polyp is a rare disease; it is of mesodermal origin and exhibits benign characteristics. Hydronephrosis occurs in rare cases, and it is generally accepted that it may result in an obstruction without causing alterations of renal function. In many cases it is difficult to differentiate from transitional cell carcinomas. Nowadays, endoscopic evaluation is the means of treatment and management. In our case study we report a patient with a long fibroepithelial polyp of the distal ureter prolapsing into the bladder in a periodic pattern. Cystoscopy revealed that movement of the polyp was moving forward and backward in the right ureteric orifice. Cold-cut biopsy established the diagnosis. The patient underwent ureteroscopic excision and remains asymptomatic a year later.

16-MDCT cystoscopy in the evaluation of neoplasms of the urinary bladder.

OBJECTIVE: The purpose of this study was to evaluate the utility of 16-MDCT cystoscopy in the detection of urinary bladder neoplasms in a high-risk population. SUBJECTS AND METHODS: Fifty patients who presented with hematuria and a recent diagnosis or a history of bladder carcinoma underwent CT cystoscopy. All patients were examined in the supine and prone positions after bladder distention with room air. A detector configuration of 16 x 0.75 mm and a pitch of 1.2 was used. Virtual images were obtained with volume-rendered algorithms. Transverse tomographic slices, multiplanar reformatted images, and virtual images were prospectively evaluated separately and in combination. Conventional cystoscopy was considered the standard of reference for assessing the efficacy of MDCT cystoscopy in the detection of urinary bladder tumors. RESULTS: Fifty-five (96%) of 57 urinary bladder lesions recognized at conventional cystoscopy were detected with MDCT cystoscopy. The size of the lesions ranged from 0.3 to 9.7 cm in diameter, including 18 lesions with a diameter of 0.5 cm or less. Transverse, multiplanar reformatted, and virtual images proved complementary for lesion detection. CONCLUSION: MDCT cystoscopy is an accurate technique for the detection of urinary bladder neoplasms in patients at high risk, yielding satisfactory results in the identification of lesions smaller than 0.5 cm.

Penile erection during transurethral surgery.

Intraoperative penile erection during endoscopic surgery, although an infrequent occurrence, is a troublesome complication and a challenge to the urologist. It is difficult to perform the procedure during penile erection, because various complications may occur. The etiology is unclear, and a number of pharmacological remedies have been discussed in the literature. Herein, we describe the treatment and outcomes for 3 patients with intraoperative penile erection and provide a brief review of the associated literature. Intraoperative penile erection is a rare event during transurethral procedures, with a frequency of approximately 0.1% in our institution. To our knowledge, no generally accepted protocols for the prevention or treatment of this phenomenon have been reported in the literature. We recommend intracorporeal injection of 250 microg of phenylephrine: detumescence occurred rapidly in all patients after a single injection. The mode of administration is simple, and no complications have been reported.