Paraoxonase-2 shRNA-mediated gene silencing suppresses proliferation and migration, while promotes chemosensitivity in clear cell renal cell carcinoma cell lines.

Clear cell renal cell carcinoma (ccRCC) represents the most common subtype of renal tumor. Despite recent advances in identifying novel target molecules, the prognosis of patients with ccRCC continues to be poor, mainly due to the lack of sensitivity to chemo- and radiotherapy and because of one-third of renal cell carcinoma patients displays metastatic disease at diagnosis. Thus, identifying new molecules for early detection and for developing effective targeted therapies is mandatory. In this work, we focused on paraoxonase-2 (PON2), an intracellular membrane-bound enzyme ubiquitously expressed in human tissues, whose upregulation has been reported in a variety of malignancies, thus suggesting its possible role in cancer cell survival and proliferation. To investigate PON2 involvement in tumor cell metabolism, human ccRCC cell lines were transfected with plasmid vectors coding short harpin RNAs targeting PON2 transcript and the impact of PON2 silencing on cell viability, migration, and response to chemotherapeutic treatment was then explored. Our results showed that PON2 downregulation was able to trigger a decrease in proliferation and migration of ccRCC cells, as well as an enhancement of cell sensitivity to chemotherapy. Thus, taken together, data reported in this study suggest that the enzyme may represent an interesting therapeutic target for ccRCC.

Comparison of Perioperative, Functional, and Oncologic Outcomes of Open vs. Robot-Assisted Off-Clamp Partial Nephrectomy: A Propensity Scored Match Analysis.

Off-clamp partial nephrectomy represents one of the latest developments in nephron-sparing surgery, with the goal of preserving renal function and reducing ischemia time. The aim of this study was to evaluate and compare the functional, oncologic, and perioperative outcomes between off-clamp robot-assisted partial nephrectomy (off-C RAPN) and off-clamp open partial nephrectomy (off-C OPN) through a propensity score-matched (PSM) analysis. A 1:1 PSM analysis was used to balance variables potentially affecting postoperative outcomes. To report surgical quality, 1 year trifecta was used. Univariable Cox regression analysis was performed to identify predictors of trifecta achievement. The Kaplan-Meier method was used to compare cancer-specific survival (CSS), overall survival (OS), disease-free survival (DFS), and metastasis-free survival (MFS) probabilities between groups. Overall, 542 patients were included. After PSM analysis, two homogeneous cohorts of 147 patients were obtained. The off-C RAPN cohort experienced shorter length of stay (LoS) (3.4 days vs. 5.4 days; p < 0.001), increased likelihoods of achieving 1 year trifecta (89.8% vs. 80.3%; p = 0.03), lower postoperative Clavien-Dindo ≤ 2 complications (1.3% vs. 18.3%, p < 0.001), and lower postoperative transfusion rates (3.4% vs. 12.2%, p = 0.008). At univariable analysis, the surgical approach (off-C RAPN vs. off-C OPN, OR 2.22, 95% CI 1.09-4.46, p = 0.02) was the only predictor of 1 year trifecta achievement. At Kaplan-Meier analysis, no differences were observed between the two groups in terms of OS (log-rank p = 0.451), CSS (log-rank p = 0.476), DFS (log-rank p = 0.678), and MFS (log-rank p = 0.226). Comparing RAPN and OPN in a purely off-clamp scenario, the minimally invasive approach proved to be a feasible and safe surgical approach, with a significantly lower LoS and minor rate of postoperative complications and transfusions as a result of improved surgical quality expressed by higher 1 year trifecta achievement.

Does Alexis Wound Protector/Retractor Reduce the Risk of Surgical Site Infections After Open Radical Cystectomy for Bladder Cancer? Results From a Single Center, Comparative Study.

OBJECTIVE: To assess if Alexis dual-ring wound protector/retractor reduced the incidence of superficial and deep incisional infection following open radical cystectomy (ORC). METHODS: Since January 2020, all procedures were performed using the Alexis retractor. We retrospectively reviewed our ORC database and compared patients who were operated on with Alexis with the same number of consecutive patients operated with a stainless steel retractor in the previous period. Data are presented as median and (interquartile range). RESULTS: Seventy-four patients underwent RC with Alexis (group 1) and 74 with stainless steel retractor (group 2). Median age was 73.0(13) in group 1, 73.5(14) in group 2 (P = .338). There were 59(79.7%) men in both groups. The groups were comparable in terms of comorbidities, body mass index, American Society of Anesthesiology score, and neoadjuvant chemotherapy rate. There was no statistically significant difference in type of lymph node dissection and urinary diversion, total surgical time. Postoperative stay was shorter in group 1 [8(4) days vs 9(4) in group 2, P = .012]. Group 2 had a significantly higher rate of both superficial (8.1% vs 18.9%, P = .045) and deep incisional infection (2.7% vs 14.9%, P = .009). At multivariable analysis, body mass index (OR 1.129 95% CI 1.162-1.283, P = .043) was significantly associated with higher odds of superficial incisional infection. The use of Alexis was significantly associated with lower odds of having both superficial (OR 0.274 95%CI 0.033-0.781, P = .023) and deep incisional infection (OR 0.159 95% CI 0.034-0.745, P = .020). CONCLUSION: The use of Alexis significantly reduces the rate of superficial and deep incisional infection following ORC.

Recent Advances in the Management of Clear Cell Renal Cell Carcinoma: Novel Biomarkers and Targeted Therapies.

Renal cell carcinoma (RCC) belongs to a heterogenous cancer group arising from renal tubular epithelial cells. Among RCC subtypes, clear cell renal cell carcinoma (ccRCC) is the most common variant, characterized by high aggressiveness, invasiveness and metastatic potential, features that lead to poor prognosis and high mortality rate. In addition, diagnosis of kidney cancer is incidental in the majority of cases, and this results in a late diagnosis, when the stage of the disease is advanced and the tumor has already metastasized. Furthermore, ccRCC treatment is complicated by its strong resistance to chemo- and radiotherapy. Therefore, there is active ongoing research focused on identifying novel biomarkers which could be useful for assessing a better prognosis, as well as new molecules which could be used for targeted therapy. In this light, several novel targeted therapies have been shown to be effective in prolonging the overall survival of ccRCC patients. Thus, the aim of this review is to analyze the actual state-of-the-art on ccRCC diagnosis, prognosis and therapeutic options, while also reporting the recent advances in novel biomarker discoveries, which could be exploited for a better prognosis or for targeted therapy.

Simultaneous Inguinal Hernia Repair with Monofilament Polypropylene Mesh during Robot-Assisted Radical Prostatectomy: Results from a Single Institute Series.

Background and Objectives: Inguinal hernia (IH) is a usual finding in men with prostate cancer (PCa) due to their similar risk factors, such as age, gender, and smoking. This study aims to present a single institution's experience with simultaneous IH repair (IHR) and robotic-assisted radical prostatectomy (RARP). Materials and Methods: We retrospectively reviewed 452 patients who underwent RARP between January 2018 and December 2020. A total of 73 patients had a concomitant IHR with a monofilament polypropylene mesh. Patients with bowel in the hernia sac or recurrent hernia were excluded. Results: The median age and the American Society of Anesthesiologists (ASA) score were 67 years (inter-quartile range (IQR) 56-77) and 2 (IQR 1-3), respectively. The median prostate volume and preoperative prostate-specific antigen (PSA) were 38 mL (IQR 25.0-75.2) and 7.8 ng/mL (IQR 2.6-23.0), respectively. The surgery was successfully performed in all cases. The median overall and IHR operative time were 190.0 (IQR 140.0-230.0) and 32.5 (IQR 14.0-40.0) minutes, respectively. The median estimated blood loss and length of hospital stay were 100 mL (IQR 10-170) and 3 days (IQR 2-4), respectively. Only five (6.8%) minor complications occurred after surgery. At the 24-month follow-up, no cases of mesh infection, seroma formation, or groin pain were recorded. Conclusions: This study confirmed the safety and efficacy of performing simultaneous RARP and IHR.

The pathway of isolated seminal vesicle invasion has a different impact on biochemical recurrence after radical prostatectomy and pelvic lymphadenectomy.

OBJECTIVE: Prostate cancer with seminal vesicle invasion (SVI) has been considered an aggressive cancer. To evaluate the prognostic significance of different patterns of isolated SVI in patients undergoing radical prostatectomy (RP) and pelvic lymphadenectomy. METHODS AND MATERIALS: We retrospectively analyzed all patients who underwent RP between 2007 and 2019. Inclusion criteria were localized prostate adenocarcinoma, SVI at RP, at least 24-months follow-up, and no adjuvant treatment. Patterns of SVI were following Ohori's classification: type 1: direct spread along the ejaculatory duct from inside; type 2: seminal vesicle invasion outside the prostate, through the capsule; type 3: the presence of cancer island(s) in the seminal vesicle with no continuity from the primary tumor (discontinuous metastases). Patients with type 3 SVI (isolated or in association) were included in the same group. Biochemical recurrence (BCR) was defined as any postoperative PSA ≥0.2 ng/ml. A logistic regression analysis was performed to assess predictors of BCR. Time to BCR was investigated using the Kaplan-Meier analysis with the log-rank test. RESULTS: Sixty-one out of 1,356 patients were included. Median age was 67(7.2) years. Median PSA was 9.4(8.92) ng/ml. Mean follow-up was 85.28 ± 45.27 months. BCR occurred in 28(45.9%) patients. Logistic regression showed that a positive surgical margin (OR 19.964, 95%CI:1.172-29.322, P = 0.038) was predictor of BCR. Kaplan-Meier analysis demonstrated that patients with pattern 3 had a significantly shorter time to BCR compared to other groups (log-rank, P = 0.016). The estimated time to BCR was 48.7 months in type 3, 60.9 months in pattern 1 + 2, 74.8, and 100.8 months in isolated patterns 1 and 2, respectively. In patients with negative surgical margins, pattern 3 confirmed a shorter time to BCR compared to other types of invasions, with an estimated time to BCR of 30.8 months. CONCLUSIONS: Patients with type 3 SVI demonstrated a shorter time to BCR compared to other patterns.

The influence of lead exposure on male semen parameters: A systematic review and meta-analysis.

Lead (Pb) is a metal with a widespread diffusion in the environment. Pb tends to accumulate in the human body and, as a consequence, semen alterations can be present in exposed workers or general population. The aim of the present study is to evaluate the effect on semen parameters among healthy men exposed to environmental or occupational Pb. A systematic literature search was performed on November 12th, 2022, through MEDLINE via PubMed, Scopus, and Embase. Observational studies comparing semen parameters in men exposed to Pb and those not exposed were included. Sperm parameters were pooled using the Cochran-Mantel-Haenszel Method with a random effect model. The weighted mean difference (WMD) was used as a summary measure. Statistical significance was set at p-value 0.05. Ten papers were included. Pb exposure was associated with a significant reduction in semen volume (WMD -0.76 ml.95% CI -1.47, -0.05, p = 0.04), sperm concentration (WMD -0.63 ×106/ml 95% CI -1.15, -0.12, p = 0.02), total sperm count (WMD -1.94 ×106 95% CI -3. 77, -0.11, p = 0.04), sperm vitality (WMD -2.18% 95% CI -3.92, -0.45, p = 0.01), and total sperm motility (WMD -1.31% 95% CI -2.33, -0.30, p = 0.01). No difference was found in sperm normal morphology, progressive motility, and seminal viscosity. This review demonstrated the negative effect of Pb exposure on most of semen parameters. Given the diffuse exposure to this metal of the general population, public health concerns should be considered and exposed workers should be assessed to evaluate their semen.

Do Hounsfield Units have any significance in predicting intra- and postoperative outcomes in retrograde intrarenal surgery using Holmium and Thulium fiber laser? Results from the FLEXible ureteroscopy Outcomes Registry (FLEXOR).

PURPOSE: To evaluate outcomes of flexible ureteroscopy for renal stones by comparing hard versus soft stones based on their attenuation on computed tomography (Hounsfield Units-HU). METHODS: Patients were divided into two groups according to the type of laser employed [Holmium:YAG (HL) or Thulium fiber laser (TFL)]. Residual fragments (RF) were defined as > 2 mm. Multivariable logistic regression analysis was performed to evaluate factors associated with RF and RF needing further intervention. RESULTS: 4208 patients from 20 centers were included. In whole series, age, recurrent stones, stone size, lower pole stones (LPS), and multiple stones were predictors of RF at multivariable analysis and LPS and stone size with RF requiring further treatment. HU and TFL were associated with lesser RF and RF requiring an additional treatment. In HU < 1000 stones, recurrent stones, stone size, and LPS were predictors of RF at multivariable analysis, whereas TFL was less likely associated with RF. Recurrent stones, stone size, and multiple stones were predictors of RF requiring further treatment, while LPS and TFL were associated with lesser RF requiring further treatment. In HU ≥ 1000 stones, age, stone size, multiple stones, and LPS were predictors of RF at multivariable analysis, while TFL was less likely associated with RF. Stone size and LPS were predictors of RF requiring further treatment, whereas TFL was associated with RF requiring further treatment. CONCLUSION: Stone size, LPS, and use of HL are predictors of RF after RIRS for intrarenal stones regardless of stone density. HU should be considered an important parameter in predicting SFR.

An Update of In Vivo Application of Artificial Intelligence and Robotics for Percutaneous Nephrolithotripsy: Results from a Systematic Review.

PURPOSE OF REVIEW: Kidney puncture is a key step in percutaneous nephrolithotomy (PCNL). Ultrasound/fluoroscopic-guided access to the collecting systems is commonly used in PCNL. Performing a puncture is often challenging in kidneys with congenital malformations or complex staghorn stones. We aim to perform a systematic review to examine data on in vivo applications, outcomes, and limitations of using artificial intelligence and robotics for access in PCNL. RECENT FINDINGS: The literature search was performed on November 2, 2022, using Embase, PubMed, and Google Scholar. Twelve studies were included. 3D in PCNL is useful for image reconstruction but also in 3D printing with definite benefits seen in improving anatomical spatial understanding for preoperative and intraoperative planning. 3D model printing and virtual and mixed reality allow for an enhanced training experience and easier access which seems to translate into a shorter learning curve and better stone-free rate compared to standard puncture. Robotic access improves the accuracy of the puncture for ultrasound- and fluoroscopic-guided access in both supine and prone positions. The potential advantage robotics are using artificial intelligence to do remote access, reduced number of needle punctures, and less radiation exposure during renal access. Artificial intelligence, virtual and mixed reality, and robotics may play a key role in improving PCNL surgery by enhancing all aspects of a successful intervention from entry to exit. There is a gradual adoption of this newer technology into clinical practice but is yet limited to centers with access and the ability to afford this.

Efficacy of 1-Year Cavacurmin® Therapy in Reducing Prostate Growth in Men Suffering from Lower Urinary Tract Symptoms.

We aim to assess the effect of Cavacurmin® on prostate volume (PV), lower urinary tract symptoms (LUTS) and micturition parameters in men after 1 year of therapy. From September 2020 to October 2021, data from 20 men with LUTS/benign prostatic hyperplasia and PV ≥40 mL who were on therapy with α1-adrenoceptor antagonists plus Cavacurmin® were retrospectively compared with 20 men on only α1-adrenoceptor antagonists. Patients were evaluated at baseline and after 1 year using the International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA), maximum urinary flow (Qmax) and PV. A Mann-Whitney U-test and Chi-square were used to assess the difference between the two groups. A comparison of paired data was performed with the Wilcoxon signed-rank test. Statistical significance was set at p-value < 0.05. There was no statistically significant difference in baseline characteristics between the two groups. At the 1-year follow-up, PV [55.0 (15.0) vs. 62.5 (18.0) mL, p = 0.04)], PSA [2.5 (1.5) ng/mL vs. 3.05 (2.7) vs. p = 0.009] and IPSS [13.5 (3.75) vs. 18 (9.25) p = 0.009] were significantly lower in the Cavacurmin® group. Qmax was significantly higher in the Cavacurmin® group [15.85 (2.9) vs. 14.5 (4.2), p = 0.022]. PV was reduced to 2 (5.75) mL in the Cavacurmin® group from baseline, while it increased to 12 (6.75) mL in the α1-adrenoceptor antagonists group (p < 0.001). PSA decreased in the Cavacurmin® group [-0.45 (0.55) ng/mL], whereas it increased in the α1-adrenoceptor antagonists group [0.5 (0.30) ng/mL, p < 0.001]. In conclusion, one-year Cavacurmin® therapy was able to block prostate growth with a concomitant decrease in PSA value from baseline. The association of Cavacurmin® with α1-adrenoceptor antagonists had a more beneficial effect compared to patients on α1-adrenoceptor antagonists alone but this needs further larger studies to be confirmed, particularly in the long-term.

Case report: A hybrid technique for a safe nephrectomy in a giant kidney angiomyolipoma.

Background: Giant angiomyolipoma is usually associated with genetic syndromes and complications (spontaneous rupture and bleeding, hematuria, hypertension) and mass-related symptoms (flank and abdominal pain). Case presentation: We present a case of a 20-year-old woman suffering from tuberous sclerosis who was referred to our hospital with a giant angiomyolipoma causing abdominal pain. A contrast-enhanced computed tomography showed a left angiomyolipoma, measuring 28 cm × 17 cm × 27 cm. After a multidisciplinary team discussion, the patient was submitted for a nephrectomy. Percutaneous temporary occlusion of the main renal artery was achieved through an endovascular balloon catheter. Through the balloon catheter guidewire, 2,500 IU of heparin was infused to reduce the risk of tumor vein thrombosis and venous embolism. This allowed a safe kidney manipulation through a left thoracoabdominal approach. The postoperative course was uneventful. Pathology showed a 40 cm × 30 cm × 9 cm and 10 kg AML. One year after surgery, the patient is on follow-up, and her estimated glomerular filtration is 120.5 ml/min/1.73 m2. Conclusion: The present case showed that the endovascular control of the main renal artery could be considered a useful approach to safely managing huge renal masses when renal hilar control is expected to be very difficult.

Is spinal anesthesia a safe alternative for retrograde intrarenal surgery for stone disease in daily practice?

OBJECTIVES: Retrograde intrarenal surgery (RIRS) is commonly performed under general anesthesia (GA) because renal mobility during breathing may affect lithotripsy. However, spinal anesthesia (SA) is adopted in clinical practice due to clinical conditions that contraindicate GA. We aimed to compare results of RIRS for stones performed under GA compared to SA regarding stone-free rate (SFR) status and postoperative complications in a consecutive single-center series. METHODS: We retrospectively reviewed all patients who underwent RIRS for stones between 2017 and 2020. INCLUSION CRITERIA: age ≥ 18 years, renal stone burden deemed suitable for RIRS with a stone diameter ≤ 20 mm. EXCLUSION CRITERIA: stones >20 mm, urinary tract infection, bilateral surgery, second-look procedures, unmodifiable bleeding diathesis, <5mm asymptomatic lower calyx stones. SFR was defined as no residual fragment >3 mm at 6-12 weeks follow-up. The choice of anesthesia was a shared decision between anesthesiologists and patient preference. RESULTS: 230 patients were included in the analysis. Mean age was 57.50±13.73 years. 33% of stones were located in the pelvis. 28.7% of patients had multiple stones. Mean cumulative stone diameter was 16.60±6.54 mm. 63% of patients underwent RIRS under SA. There were no significant differences between the two groups in terms of preoperative characteristics, except for comor-bidity, significantly higher in the GA group. Mean time of operating room occupation was longer in the GA group (81.58±35.37 minutes) than in the SA group (72.85±25.91 minutes,p=0.033). Length of stay was shorter in the SA group (mean 2.2±1.66 days vs 3.46±5.88 in GA,p=0.019). Logistic regression showed that multiple stones in the collecting system were associated with residual fragments (HR 0.386, 95%CI 0.151-0.991,p=0.04). There were no statistically significant differences in overall and high-grade complications, and in SFR between SA (75.9%) and GA groups (70.6%,p=0.317). CONCLUSION: SA does not affect SFR and postoperative complications in patients who underwent RIRS in daily practice.

Concomitant robot-assisted laparoscopic surgeries for upper and lower urinary tract malignancies: a comprehensive literature review.

Worldwide, we have witnessed an expansion of robot-assisted laparoscopic surgery (RALS) and thanks to the global adoption of high-resolution diagnostic imaging technologies, an increased incidence of newly diagnosed prostatic, renal and bladder cancers has been recorded with concurrent second primary urological cancer diagnoses increasing by 1.5%. Diverse authors have reported their findings concerning synchronous multi-visceral malignances robotic treatment within the scientific literature. The aim of this study is to comprehensively review all reported articles describing concurrent upper and lower RALS using a singular robotic port scheme within the same intervention for renal malignances and concomitant prostatic or bladder cancers. To the best of our knowledge and vigorous literature search, this is the first study that comprehensively evaluates and reports all combined upper and lower urinary tract surgeries published so far. In carefully selected patients, thanks to multidisciplinary preoperative assessment and surgical planning a combined robotic approach can reduce the morbidity, complications, hospital admissions and the overall length of hospitalization.

The Utility of Nicotinamide N-Methyltransferase as a Potential Biomarker to Predict the Oncological Outcomes for Urological Cancers: An Update.

Nicotinamide N-methyltransferase (NNMT) catalyzes the N-methylation reaction of nicotinamide, using S-adenosyl-L-methionine as the methyl donor. Enzyme overexpression has been described in many non-neoplastic diseases, as well as in a wide range of solid malignancies. This review aims to report and discuss evidence available in scientific literature, dealing with NNMT expression and the potential involvement in main urologic neoplasms, namely, renal, bladder and prostate cancers. Data illustrated in the cited studies clearly demonstrated NNMT upregulation (pathological vs. normal tissue) in association with these aforementioned tumors. In addition to this, enzyme levels were also found to correlate with key prognostic parameters and patient survival. Interestingly, NNMT overexpression also emerged in peripheral body fluids, such as blood and urine, thus leading to candidate the enzyme as promising biomarker for the early and non-invasive detection of these cancers. Examined results undoubtedly showed NNMT as having the capacity to promote cell proliferation, migration and invasiveness, as well as its potential participation in fundamental events highlighting cancer progression, metastasis and resistance to chemo- and radiotherapy. In the light of this evidence, it is reasonable to attribute to NNMT a promising role as a potential biomarker for the diagnosis and prognosis of urologic neoplasms, as well as a molecular target for effective anti-cancer treatment.

Robot-assisted segmental ureterectomy with psoas hitch ureteral reimplantation: Oncological, functional and perioperative outcomes of case series of a single centre.

INTRODUCTION: According to the Urology guidelines, in selected cases of distal upper tract urothelial carcinoma (UTUC) segmental ureterectomy (SU) can be offered. There is no consensus in the surgical technique of preference. Robot-assisted SU could be an option to overcome all the limitations of open and laparoscopic techniques. We describe our first experience of robot assisted SU with psoas hitch ureteral reimplantation (RAPHUR). MATERIALS AND METHODS: 11 patients underwent RAPHUR for distal UTUC between 2013 and 2017 in a single centre. Pre-, intra-, and postoperative outcomes were assessed. Conventional imaging was performed after 1, 3, 6 months and 1 year from surgery as follow up protocol. We retrospectively evaluated the technical feasibility, oncological and functional outcomes. RESULTS: Median age was 71 years (57-91). The median length of the ureteral defect was 23 mm (10-40). Median preoperative creatinine level was 1.22 mg/dl (0.7-1.85) and median eGFR was 57.5 ml/min/1.73m2 (31-80). Five (45.5%) patients were symptomatic and 7 (63.6%) had hydronephrosis. Median operative time was 185 min (120-240), with a median blood loss of 100 ml (50-300). No case required conversion to open surgery. Overall, only 1 (9%) patient developed Clavien Dindo ≥ 3 postoperative complications. Average hospital stay was 7 (2-9) days. Mean postoperative creatinine was 1.05 mg/dl (0.8-1.85) and mean postoperative eGFR was 72 (36-83). During a median follow up time of 25.5 months (12-53), 4 (36.4%) patients experienced recurrence of urothelial cancer at conventional imaging follow up and 2 (18.2%) died due to its progression. CONCLUSIONS: In our initial experience RAPHUR can be proposed to selected cases of distal ureteral carcinoma with optimal perioperative and functional outcomes. However, cancer control may be undermined compared to nephroureterectomy. Thus, further prospective studies are needed to confirm our findings.

Unusual clinical scenarios in Urology and Andrology.

This collection includes some unusual cases and how they were diagnosed and treated. Case 1: A case of a patient with primary hyperthyroidism presenting with a submucosal ureteral stone after endoscopic lithotripsy was described. After multiple endoscopic treatment, the stone was successfully removed by open ureterolithotomy recovering ureteral patency and normal renal function. Case 2: A case of burned-out testicular cancer with atypical lymphatic spread (stage II A) was presented. After right orchiectomy and complete remission of tumor markers, due to atypical metastases location and uncertain histology, the patient was treated with systemic therapy based on bleomycin, etoposide and cisplatin (PEB). At re-staging after chemotherapy computed tomography showed reduction of all node metastases and an observation protocol was proposed. Case 3: A patient was readmitted to hospital after 12 days from an uneventful Robot-Assisted Radical Prostatectomy (RARP) for prostate cancer due to lower abdominal pain plus abdominal distension, nausea and constipation not responsive to medical therapy. Computed Tomography showed colon and small bowel dilatation without any evidence of anatomical or mechanical obstruction. Laparoscopic abdominal exploration confirmed bowel distension without evidence of obstructing lesions. Ogilvie's Syndrome or acute colonic pseudo-obstruction (ACPO) was diagnosed. The patient fully recovered and was discharged six days after the procedure. Case 4: A case of recurrent Acute Idiopathic Scrotal Edema (AISE) was diagnosed on clinical signs together with the decisive help of pathognomonic ultrasound findings as the "fountain sign". Case 5: Small bilateral testicular nodules were diagnosed in a 30-years old patient undergoing scrotal ultrasound in follow up of acute lymphoblastic leukemia. Ultrasound guided testis sparing surgery was performed demonstrating Leydig cell tumors.

Bladder Cancer Chemosensitivity is Affected by Paraoxonase-2 Expression.

The goal of the current study was to identify potential roles of paraoxonase-2 in bladder carcinogenesis. T24 bladder cancer cells were transfected with plasmids inducing paraoxonase-2 silencing or overexpression. Upon the selection of clones stably down- or upregulating paraoxonase-2, cell proliferation, migration, and the production of reactive oxygen species were evaluated, before and after treatment with cisplatin and gemcitabine, used alone or in combination. The activity levels of both caspase-3 and caspase-8 were also analyzed. shRNA-mediated gene silencing and the overexpression of paraoxonase-2 revealed that the enzyme was able to promote both the proliferation and migration of T24 cells. Moreover, the knockdown of paraoxonase-2 was significantly associated with a reduced cell viability of T24 cells treated with chemotherapeutic drugs and led to both an increase of reactive oxygen species production and caspase-3 and caspase-8 activation. Conversely, under treatment with anti-neoplastic compounds, a higher proliferative capacity was found in T24 cells overexpressing paraoxonase-2 compared with controls. In addition, upon enzyme upregulation, both the production of reactive oxygen species and activation of caspase-3 and caspase-8 were reduced. Although further analyses will be required to fully understand the involvement of paraoxonase-2 in bladder tumorigenesis and in mechanisms leading to the development of chemoresistance, the data reported in this study seem to demonstrate that the enzyme could exert a great impact on tumor progression and susceptibility to chemotherapy, thus suggesting paraoxonase-2 as a novel and interesting molecular target for effective bladder cancer treatment.

Involvement of transforming growth factor beta 1 in the transcriptional regulation of nicotinamide N-methyltransferase in clear cell renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common tumor of the kidney and its major histologic subtype is clear cell RCC (ccRCC). About 30% of diagnosed ccRCCs already have metastasis. Traditionally, localized ccRCC is treated with nephrectomy but the relapse rate is 30%. Thus, the discovery of effective biomarkers for early detection, as well as the identification of new targets for molecular-based therapy of ccRCC are urgently required. In this study, we focused on molecules that could modulate the trascription of the enzyme nicotinamide N-methyltransferase (NNMT) that is known to be up-regulated in ccRCC. Signal transducer and activator of transcription 3 (STAT3), interleukin 6 (IL-6), hepatocyte nuclear factor 1 beta (HNF-1ß) and transforming growth factor beta 1 (TGF-ß1) expression levels were determined in tumor and non tumor samples obtained from 30 patients with ccRCC, using Real-Time PCR. Results obtained showed that TGF-ß1 is significantly (p<0.05) overexpressed in tumor compared with normal tissue samples of ccRCC patients. Conversely, we did not find any statistically significant difference concerning STAT3, IL-6, HNF-1ß gene expression levels. TGF-ß1 up-regulation could be responsible for the high levels of NNMT observed in ccRCC. Targeting TGF-ß1 could improve the outcome of ccRCC patients due to its role in epithelial-mesenchymal transition (EMT), that is known to be associated with a worse overall survival (OS) in this neoplasm.

Evaluating the predictive accuracy and the clinical benefit of a nomogram aimed to predict survival in node-positive prostate cancer patients: External validation on a multi-institutional database.

OBJECTIVES: To assess the predictive accuracy and the clinical value of a recent nomogram predicting cancer-specific mortality-free survival after surgery in pN1 prostate cancer patients through an external validation. METHODS: We evaluated 518 prostate cancer patients treated with radical prostatectomy and pelvic lymph node dissection with evidence of nodal metastases at final pathology, at 10 tertiary centers. External validation was carried out using regression coefficients of the previously published nomogram. The performance characteristics of the model were assessed by quantifying predictive accuracy, according to the area under the curve in the receiver operating characteristic curve and model calibration. Furthermore, we systematically analyzed the specificity, sensitivity, positive predictive value and negative predictive value for each nomogram-derived probability cut-off. Finally, we implemented decision curve analysis, in order to quantify the nomogram's clinical value in routine practice. RESULTS: External validation showed inferior predictive accuracy as referred to in the internal validation (65.8% vs 83.3%, respectively). The discrimination (area under the curve) of the multivariable model was 66.7% (95% CI 60.1-73.0%) by testing with receiver operating characteristic curve analysis. The calibration plot showed an overestimation throughout the range of predicted cancer-specific mortality-free survival rates probabilities. However, in decision curve analysis, the nomogram's use showed a net benefit when compared with the scenarios of treating all patients or none. CONCLUSIONS: In an external setting, the nomogram showed inferior predictive accuracy and suboptimal calibration characteristics as compared to that reported in the original population. However, decision curve analysis showed a clinical net benefit, suggesting a clinical implication to correctly manage pN1 prostate cancer patients after surgery.