External validation of a nomogram for outcome prediction in management of medium-sized (1-2 cm) kidney stones.

BACKGROUND: Stone nomogram by Micali et al., able topredict treatment failure of shock-wave lithotripsy (SWL), retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PNL) in the management of single 1-2 cm renal stones, was developed on 2605 patients and showed a high predictive accuracy, with an area under ROC curve of 0.793 at internal validation. The aim of the present study is to externally validate the model to assess whether it displayed a satisfactory predictive performance if applied to different populations. METHODS: External validation was retrospectively performed on 3025 patients who underwent an active stone treatment from December 2010 to June 2021 in 26 centers from four countries (Italy, USA, Spain, Argentina). Collected variables included: age, gender, previous renal surgery, preoperative urine culture, hydronephrosis, stone side, site, density, skin-to-stone distance. Treatment failure was the defined outcome (residual fragments >4 mm at three months CT-scan). RESULTS: Model discrimination in external validation datasets showed an area under ROC curve of 0.66 (95% 0.59-0.68) with adequate calibration. The retrospective fashion of the study and the lack of generalizability of the tool towards populations from Asia, Africa or Oceania represent limitations of the current analysis. CONCLUSIONS: According to the current findings, Micali's nomogram can be used for treatment prediction after SWL, RIRS and PNL; however, a lower discrimination performance than the one at internal validation should be acknowledged, reflecting geographical, temporal and domain limitation of external validation studies. Further prospective evaluation is required to refine and improve the nomogram findings and to validate its clinical value.

Office-based management of Non-Muscle Invasive Bladder Cancer (NMIBC): A position paper on current state of the art and future perspectives.

To the Editor, Bladder cancer is one of the most common cancers in humans, representing the 7th and 17th type of neoplasm in both genders. Its incidence and mortality are quite heterogeneous in different countries and are due to different risk factors, quality and prevalence of healthcare and the possibility of early diagnosis and treatment of the tumor and its potential recurrences [...].

Risk Related to Increasing Indications for Retrograde Intrarenal Surgery.

Cite this article as: Mantica G, Ambrosini F, Malinaric R, Calarco A, Terrone C. Risk related to increasing indications for retrograde intrarenal surgery (RIRS). Urol Res Pract. 2024;50(1):66-67.

New minimally invasive solutions for Benign Prostatic Obstruction (BPO) management: A position paper from the UrOP (Urologi Ospedalità Gestione Privata).

To the Editor, In recent years, alternative solutions have been proposed to obtain effective results comparable to TURP, which is currently considered the gold standard, and laser vapo-enucleation techniques (1, 2), but with the possibility of maintaining sexual functions. In recent years there has been a growing trend towards ejaculation preservation. Although the results of TURP (3), and most laser enucleation techniques are undoubted in the Benign Prostatic Hyperplasia (BPH) and Lower Urinary Tract Symptoms (LUTS) management, they often lack in the preservation of ejaculation. All the alternative recently proposed interventions (Rezum, AquaBeam, Urolift, TPLA, i-TIND, LEST) are procedures considered by some authors to be promising in both managing BPO and preserving sexual functions. However, all these methods are limited by a lack of long-term follow-up that would evaluate the efficacy over time, possible complications related to the method and the correct patient selection for a specific method. The aim of this letter is to summarize the available evidence and provide clinicians with practical recommendations on the use of the brand new minimally invasive techniques for the management of BPO. [...].

Uncommon Haemorrhagic Cystitis of Infectious Origin: A Narrative Review for Urologists.

Purpose: Haemorrhagic cystitis may be due to different etiologies with infectious diseases representing an insidious cause to diagnose. The aim of this narrative review is to provide a comprehensive overview of less common but difficult-to-diagnose causes of infectious haemorrhagic cystitis of bacterial, mycobacterial, and parasitic origin, Moreover, we highlight possible diagnostic tools and currently available treatment options in order to give an updated tool for urologists to use in daily practice. Patients and Methods: The search engine PubMed was used to select peer-reviewed articles published from 1/Jan/2010 to 31/Aug/2022. Results: Bacteria, fungal, TB and schistosomiasis are uncommon causes of haemorrhagic cystitis burdened by high morbidity, especially if not promptly diagnosed. Conclusion: Because haemorrhagic cystitis ranges in severity from mild dysuria associated with pelvic discomfort to severe life-threatening haemorrhage, punctual diagnosis, and immediate treatment are essential to avoid further complications.

The Impact of Ethnicity and Age on Distribution of Metastases in Patients with Upper Tract Urothelial Carcinoma: Analysis of SEER Data.

Upper tract urothelial carcinoma (UTUC) constitutes a rare and aggressive entity accounting for 5% to 10% of all urothelial tumors. The importance of stratification and disparities according to ethnicity and age has never been tested in a sufficiently large sample of patients with metastatic UTUC (mUTUC). We conducted this study to address this void, and we hypothesized that the distribution of metastases may vary according to age and ethnicity. Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2016), we identified 1115 patients with mUTUC. The chi-square and t-test tests were used to examine statistical significance in terms of proportions and mean differences. A total of 925 (83.0%) patients were Caucasians, while 190 (17.0%) were African Americans. Among both ethnicities, lungs were the most common metastatic site (39.1% vs. 48.9%). Brain metastases were infrequent among both ethnicities (1.2 vs. 2.6%; p = 0.13). The trends in the lung metastases decreased with age from 42.3% to 36.6% (p = 0.010) among Caucasians, whereas they increased among African Americans from 34.0% to 51.7% (p = 0.04). Overall, 32.8% of Caucasians and 40.5% of African Americans exhibited more than one metastatic site. Among Caucasians, increasing age was associated with lower rates of having multiple metastatic sites (from 34.3% to 30.2%) (p = 0.004). According to our multivariable analyses, younger age was associated with an increased risk of lung (OR: 1.29, 95% CI 1.04-1.71; p = 0.045) and bone metastases (OR: 1.34, 95% CI 1.07-1.79; p = 0.046). Racial differences exist in the distribution of mUTUC metastasis and vary according to age. Our findings may also be considered in the design of randomized trials.

TULA DUAL: Trans Urethral Laser Ablation of recurrent bladder tumors in outpatient setting.

To the Editor, Bladder cancer (BCa) is the second most common cancer in urological clinical practice, after prostate adenocarcinoma. Usually occurs in patients between 60 and 70 years old, three times more frequently in men than women. About 75% of bladder cancer are pTa or pT1, even more frequently considering a population younger than 40 years old. Early detection is of paramount importance since allows to find tumors when they are still superficial and therefore with a better prognosis.

External validation of Resorlu-Unsal stone score in predicting outcomes after retrograde intrarenal surgery. Experience from a single institution.

OBJECTIVE: Pre-operative assessment of renal stones is essential in selecting treatment options and achieving high success rates for retrograde intrarenal surgery (RIRS). Several nephrolithometric scoring systems have been developed using pre-operative clinical data and stone characteristics. Resorlu-Unsal stone score (RUSS) is composed of four different parameters, and each of them adds 1 point to the final score. One point is added in patients with stone size > 20 mm, lower calyceal stones and infundibulo-pelvic angle < 45°, stone number > 1, and abnormal anatomy, respec-tively. RUSS categorizes patients into four distinct groups and aims to predict stone-free rates (SFR) after RIRS. We externally validated RUSS and evaluated its predictive accuracy. MATERIALS AND METHODS: We performed a retrospective analysis of patients who underwent RIRS for renal stones between January 2020 and December 2021. Patient age, pre-operative hydronephrosis, stone size, stone density as Hounsfield Unit (HU), operative time and RUSS were investigated as potential preoperative predictive factors for stone-free status. RUSS was applied to all patients, and the nomogram was externally vali-dated. Area under the curve (AUC) was used for clinical validity assessment. RESULTS: The present study included a total of 79 patients. Mean patient age was 55.1 ± 15.4 years with a mean stone size was 14.2 ± 4.4 mm. Overall, 62/79 (78.4%) patients were stone free after the initial treatment. After applying RUSS, 36 (45.6%), 29 (36.7%), 10 (12.6%), and 4 (5.1%) patients had a score of 0, 1, 2, and 3, respectively. On multivariate logistic regression RUSS (OR = 0.220; 95%CI: 0.086-0.567; p = 0.002) was identified as the only predictor of postoperative stone-free status. CONCLUSIONS: RUSS is a user-friendly scoring system that may predict postoperative stone-free rate after RIRS with great effi-cacy and accuracy.

An original mininvasive corporoplasty technique for penile curvature without circumcision.

OBJECTIVE: We describe an original minimally invasive penile plication technique with scrotal or infrapubic access, not requiring circumcision, for penile curvature of different severity and types. This technique can be used to correct both congenital and acquired curvatures, mono or bidirectional deformities. MATERIALS AND METHODS: Between 2012 and 2018 we treated 134 patients suffering from congenital curvature (33) and acquired curvature from Peyronie's disease (101). The average curvature was 62.2° (± 30.4°). Preoperative evaluation included prostaglandin E1 injection with photographic documentation and measurement of penile angulation, administration of IIEF- 15, vasoactive penile Doppler ultrasound, analysis of thermal and vibratory sensitivity with Genito-Sensory-Analyzer (GSA) and assessment of nocturnal penile stiffness with Rigiscan, performed twice, for a detailed evaluation of patient's erectile function. Scrotal access was performed in patients with dorsal and/or lateral penile curvature; the infrapubic access was performed in patients with ventral curvature. After preparation and incision of Colles' fascia, penis was partially degloved and an original plication technique called "binary corporoplasty" was performed at the site or sites established at preoperative assessment, with non-resorbable synthetic multifilament (Premicron®) suture. RESULTS: Complete correction of penile curvature was achieved in 96.8 % of patients. No major complications were reported, and no patients suffered worsening in erectile function or in penile sensitivity. The average shortening of convex side was 1.65 cm (± 0.7 cm) and all patients report easy intercourse after correction. The average time of surgery was 46 minutes (± 11 min) and all procedures were performed as a day-hospital or ambulatory settings, with local anesthesia and light sedation. Overall satisfaction rate is 96%. CONCLUSIONS: This is a simple and rapid technique that perfectly corrects even the most severe and complex penile curvatures. In comparison to traditional techniques, such as Nesbit procedure, this technique is associated with low morbidity, a very low recurrence rate and a great aesthetic results. Aesthetic and functional patients' satisfaction was excellent.

Penile lenghthening original technique using a pubo-cavernous spacer. Long term results from a series of over 200 patients.

INTRODUCTION: We report our long experience in the surgical treatment of patients requesting penile lengthening by suspensory ligament release and placement of a custom-made soft silicone pubo-cavernous spacer. The aim was to show that with this surgical technique the results obtained are maintained over time. It is crucial to achieve postoperative satisfaction of these patients who show fragility and self-esteem problems. METHODS: From 1999 to 2020, we treated 245 patients with congenital or acquired penile brevity. We carefully analysed the preoperative and postoperative (at 6, 12, 24 and 48 months) penile size of the patients to evaluate whether this technique could allow the long-term maintenance of aesthetic results. We also assessed preoperative erectile function and we focused on the psychological aspects to avoid surgery in patients with dysmorphophobia. This original technique involves the section of the suspensory ligament and the implantation of a silicone spacer between the pubic symphysis and the corpora cavernosa. This spacer is conformed to the patient anatomy and maintains the relationship between the anatomical structures unchanged over time. Sexual self-esteem and patient satisfaction were assessed with the APPSSI questionnaire. RESULTS: The mean increase in penile length was about 2.5 cm in flaccid state and 1.9 cm in stretched state. There were no injuries of the neurovascular bundle or urethra, and no erectile dysfunction was noted. These results persisted at 6, 12, 24 and 48 months without significant differences. Over 80% of patients stated that they were completely satisfied with the results obtained. This satisfaction remained stable along follow up. CONCLUSION: The section of the suspensory ligament and the implant of the soft silicone spacer provide real penis elongation with satisfactory results that persist over time. This technique avoids the frequent complication of short-term shortening due to the scar adhesions of the edges of the dissected ligament. The high aesthetic satisfaction of patients is stable at controls at 6, 12, 24 and 48 months.

Endoscopic laser en bloc removal of bladder tumor. Surgical radicality and improvement of the pathological diagnostic accuracy.

INTRODUCTION: Bladder cancer is one of the most common tumors among the general population. The first surgical approach to the tumor is often the transurethral resection with monopolar or bipolar loop. Recently, laser energy has become an alternative for resection of small bladder tumor, because it allows to obtain high quality samples with the "en bloc" technique. Our study aims to show the results of endoscopic diode laser treatment of bladder tumor up to three centimeters in maximum diameter. MATERIALS AND METHODS: 189 patients underwent "en bloc" resection with diode dual length laser (980 nm-1470 nm). Follow up was over 12 months. Patients age range was from 45 to 75 years. Maximum diameter of the lesions was 3.0 cm. For each patient, a cold forceps biopsy sample was performed. RESULTS: All samples collected presented detrusorial layer. Pathological exam showed: 28 (14.8%) Ta, G1-G2; 7 (3.7%) T3, G2-G3; 14 (7.4%) T1, G2-G3 and 140 ( 74.1%) Ta, G2-G3. No complications occurred during or after surgery. At a median follow-up period of 6 months, we had no recurrence in the previous site of tumor. In the follow up at 3/6/12 months in 4 cases we had recurrence in different sites of bladder wall. CONCLUSIONS: Laser "en bloc" resection is an effective, feasible, and safe treatment for bladder tumor. It could be a valid alternative to monopolar and bipolar resection in small bladder cancer treatment.

The active guidewire technique versus standard technique as different way to approach ureteral endoscopic stone treatment.

BACKGROUND: One of the greatest challenges in semi-rigid ureteroscopies, for both stones and tumors, is the control of endoscopic vision and the maintenance of low intracavitary liquid pressure. We present a comparison between two operative techniques: in the first method an ordinary guide wire (diameter 0.032'') is used for the procedure; in the second one a 5 Fr ureteral catheter replaces the guidewire (we called it "Active guidewire") Methods We compared 50 semirigid ureteroscopies (sURS) performed using the active guidewire with another 50 procedures conducted with a classic guidewire. We evaluated the difference in operating times, quality of endoscopic vision, periprocedural infections rate and stone-free rate. RESULTS: The use of active guidewire has considerably reduced the standardized operating times per unit stone-volume by about 39%. Vision quality has improved considerably thanks to the continuous flow in-and-out. Consequently, periprocedural infections decreased (3% vs 30%) and the stone-free rate rose from 86% to 92%. DISCUSSION AND CONCLUSIONS: Employing an "active guidewire" instead of the standard guidewire, the risk of complications related to high pressures and operating time is considerably lower, as well as better treatment quality thanks to the cleaner vision. This technique has proven to be safe as well as easy to apply, and in our belief is to be preferred whenever the ureter accepts without forcing, both the presence of the catheter and the semi-rigid 7 F ureteroscope.

[Brachytherapy in men with prostate cancer: update on indications and outcomes]. / Brachiterapia nel trattamento del carcinoma prostatico: indicazioni ed efficacia.

Brachytherapy (BT), using either a low-dose-rate (LDR) or mostly high-dose-rate (HDR) technique, is the device able to deliver the highest dose-rate in the most conformal way. It is used as monotherapy or in combination with external beam radiotherapy (EBRT). LDR-BT is mostly used as monotherapy; HDR-BT is combined with EBRT ± adjuvant hormone therapy. In patients with low-risk disease and in selected intermediate-risk patients, LDR-BT ensures long-term good disease control rates and HDR-BT can show similar results, even if with shorter follow-up. In patients with intermediate/high risk disease the combination therapy (EBRT + HDR-BT) shows better oncological outcomes compared to EBRT monotherapy, even if the role of adjuvant hormone therapy is still unclear. Literature shows variable efficacy of BT in case of local recurrence after EBRT and radical prostatectomy even if few cases have been reported with short follow-up. Side effects are acceptable (urogenital toxicity, urinary incontinence, sexual function) and comparable with the other treatment modalities. So far, randomized controlled trials comparing the different treatment modalities are necessary to clarify indications and real efficacy.

High-intensity focused ultrasound in prostate cancer: today's outcomes and tomorrow's perspectives.

High-intensity focused ultrasound (HIFU) is a minimally invasive therapy applied for prostate cancer that capitalizes on the coagulation necrosis that occurs at temperatures greater than 60°C. Owing to a lack of long-term follow-up data the procedure is still considered experimental treatment. As primary therapy, HIFU is indicated in patients aged ≥70 years with clinical organ-confined disease, although it has also been used, with encouraging results, as first line salvage therapy after definitive treatment, and in locally advanced (T3-4) and non-metastatic hormone-resistant prostate cancer. Morbidity associated with this treatment method appears to be low and includes urinary retention (1-9%), urethral stricture (4-14%), incontinence (1-15%), erectile dysfunction (13-53%) and rectourethral fistulae (0-3%). The risk of complications increases with repeated treatments. A few studies have recently been published on HIFU as focal therapy. HIFU technology can be enhanced using means such as ultrasound microbubble contrast agents for assessment of therapy efficacy, magnetic resonance imaging to guide the enhancement of heat rate, and localized drug and gene delivery.

Role of SOCS3 evaluated by immunohistochemical analysis in a cohort of patients affected by prostate cancer: preliminary results.

BACKGROUND: Chronic inflammation may play a role in prostate carcinogenesis. Molecular alterations of the Suppressor of Cytokine Signaling (SOCS)-3 can contribute to explain the pleiotropic role of interleukin (IL)-6 in this type of cancer. Recently, the methylation of SOCS3 gene has been demonstrated to cause the non-expression of the protein, being involved in the pathogenesis of prostate cancer (PC) and identifying a subset of aggressive tumors. We evaluated the expression of SOCS3 protein in patients (pt) with bioptically-diagnosed PC by immunohistochemical analysis, which is easier to perform, cheaper and more reproducible compared to DNA analysis. METHODS: We analyzed the protein expression of SOCS3 by immunohistochemistry in 44 patients (pt) with PC diagnosed after biopsy. Slides were incubated with monoclonal antibody SOCS3 (1E4, 1.5 µg/mL; Abnova, Taiwan). The SOCS3 staining intensity was evaluated by two pathologists (FP and LML) in three different ways: positive (+), negative (-) and weak (+/-). Colonic mucosa was used as positive control. 36/44 patients underwent radical prostatectomy (RP). RESULTS: Biopsy Gleason score (Gs) was: <7 in 8 pt, 7 in 33 pt (3 + 4 pattern in 21 pt, 4 + 3 pattern in 12 pt), >7 in 3 pt. 8/8 (100%) pt with Gs <7 and 7/33 (21%) with Gs 7 were SOCS+. 15/33 (45%) pt with Gs 7 and 3/3 (100%) pt with Gs >7 were negative. In 11/33 pt (33%) Gs 7 a weak intensity was found so they were classified as SOCS3 +/-.25/36 (69%) patients who underwent RP were SOCS3- (15 pt with Gs 7(3 + 4), 7 pt with Gs 7(4 + 3), 3 pt with Gs 8) and 11/36 (30%) SOCS3+ (8 pt with Gs 6 and 3 pt with Gs 7(3 + 4)) (Tab 2). 12/25 (48%) SOCS3- pt had an organ-confined disease (≤pT2), whereas 13/25 (52%) had an extra prostatic neoplasm (5 pT3a (one was N+), 6 pT3b, 1 pT4). All SOCS3+ patients (8/8 (100%)) had an organ-confined disease. 3/3 (100%) SOCS3+/- pt had an extra prostatic neoplasm (>pT2). CONCLUSIONS: SOCS3- pt turned out to have a more aggressive disease compared with SOCS3+. In particular, also SOCS3+/- patients seemed to have an aggressive behavior. The non-expression of SOCS3 protein may identify PC with more aggressive behavior and can be evaluated with immunohystochemical analysis, which is a relatively easy and cheap procedure in clinical practice. These results, if confirmed by a wider population and a longer follow-up, may encourage the research on the use of this molecular family as a prognostic marker and a target for therapy with demethylating agents.

Microbiological follow-up of nosocomial infections in a single urological center.

BACKGROUND: To analyze data from the cultural examinations of different biological fluids, obtained from urologic patients from January 2007 to April 2010, in order to describe the incidence of infections in our setting. METHODS: In the period of reference a urine culture was carried out for every patient admitted, in case of suspected urinary tract infection, a blood culture in case of suspected sepsis, and a wound culture in case of wound infection. RESULTS: In the period of investigation 321 patients developed some kind of infection: 589 positive isolations obtained from cultural examinations have been diagnosed in urine (63%), blood (6%), surgical wound (6%), venous central catheter (7%) and other sites (18%) (tip of ureteral and bladder catheters). The most commonly isolated pathogenic agent for all the sites of infection has been Escherichia coli (22.5%). In urine, the most frequently isolated species have been Escherichia coli (27.8%), Enterococcus (12.5%), and Candida spp (9.3%). Escherichia coli (22.9%), Pseudomonas (5.7%), and Staphylococcus aureus (3.5%) were the most frequently found pathogenic agents responsible for sepsis, compared to others. In the period of investigation we have recorded 35 episodes of sepsis. CONCLUSIONS: Empiric antibiotic therapy is frequent in cases of clinical evidence of infection, before the identification of the causative microorganism is available; therefore, it is important to know which are the bacterial species mainly responsible for these specific infections. We need continuous surveillance of infections and the improvement in the use of antibiotic therapy in order to limit the antimicrobial resistance.

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 Student's t-test and Pearson's 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 (Pearson's 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.

Imaging in prostate cancer staging: present role and future perspectives.

Despite recent improvements in detection and treatment, prostate cancer continues to be the most common malignancy and the second leading cause of cancer-related mortality. Thus, although survival rate continues to improve, prostate cancer remains a compelling medical health problem. The major goal of prostate cancer imaging in the next decade will be more accurate disease characterization through the synthesis of anatomic, functional, and molecular imaging information in order to plan the most appropriate therapeutic strategy. No consensus exists regarding the use of imaging for evaluating primary prostate cancer. However, conventional and functional imaging are expanding their role in detection and local staging and, moreover, functional imaging is becoming of great importance in oncologic management and monitoring of therapy response. This review presents a multidisciplinary perspective on the role of conventional and functional imaging methods in prostate cancer staging.

Imaging in prostate cancer diagnosis: present role and future perspectives.

Prostate cancer (PCa) remains a major health concern for the male population. Detection and primary diagnosis of PCa are based on digital rectal examination, serum prostate-specific antigen levels, and transrectal ultrasound (TRUS)-guided random biopsy. Moreover, the gold standard for detecting PCa, systematic biopsy, lacks sensitivity as well as grading accuracy. This review summarizes recent developments of ultrasonography modalities and functional magnetic resonance imaging (MRI) in the diagnosis of PCa. A comparison between the different methods is presented, including their clinical value and usefulness. It is concluded that innovative ultrasound techniques (including ultrasound contrast agents, 3-D and 4-D sonography, elastography and harmonic sonography) promise benefits in comparison to standard TRUS to accurately diagnose PCa. Promising advances have been made in the detection of PCa with multiparametric MRI. The combination of conventional and functional MRI techniques (including diffusion-weighted imaging, dynamic contrast-enhanced MRI, and MR spectroscopy) can provide information for differentiating PCa from noncancerous tissue and can be used for MRI-guided biopsies, especially in patients with persistent elevation of serum prostate-specific antigen and previous negative TRUS-guided biopsies. However, functional MRI technique and MRI-guided biopsy remain expensive and complex tools presenting inherent challenges.

Epigenetic silencing of SOCS3 identifies a subset of prostate cancer with an aggressive behavior.

BACKGROUND: Chronic inflammation and subsequent tissutal alterations may play a key role in prostate carcinogenesis. In this way, molecular alterations of the suppressor of cytokine signaling 3 (SOCS3), one of the most important inhibitory molecule of inflammatory signal transduction circuitries, could contribute to explain the pleiotropic role of interleukin-6 (IL-6) in this type of cancer. METHODS: We analyzed the methylation status and mRNA expression of SOCS3 in 20 benign prostate hyperplasias (BPH) and in 51 prostate cancer specimens. We analyzed the SOCS3 methylation status using methylation-specific PCR. Hypermethylation was confirmed by sequencing after subcloning. Epigenetic silencing of this gene was also demonstrated by real-time PCR and by immunohistochemistry. Results and correlation with clinical data were statistically analyzed. RESULTS: We found that the promoter of SOCS3 was methylated in 39.2% of prostate cancer. On the contrary, all BPH and normal controls had an unmethylated pattern. Real-time analysis showed that in methylated cases SOCS3 mRNA expression was reduced by three and four folds as compared to BPH and unmethylated cases, respectively. Interestingly, SOCS3 mRNA level was higher in unmethylated prostate cancer than in BPH. The immunohistochemical staining analysis for SOCS 3 confirmed mRNA results. Moreover, methylation of SOCS3 promoter significantly associated with intermediate-high grade Gleason score (P = 0.0007) and with an unfavorable clinical outcome (P = 0.0019). CONCLUSIONS: Our data suggest that SOCS3 hypermethylation may be involved in the pathogenesis of prostate cancer and could identify a tumor subset with an aggressive behavior.