Activation of the kynurenine pathway predicts poor outcome in patients with clear cell renal cell carcinoma.

OBJECTIVE: To investigate the expression of the kynurenine (KYN) pathway components and the prognostic role of the KYN-to-tryptophan ratio (KTR) in a cohort of patients with clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: The expression of KYN pathway components was investigated by tissue microarray-based immunohistochemistry, indirect immunofluorescence, and confocal microscopy analysis in 100 ccRCC cases and 30 normal renal samples. The role of this pathway in sustaining cancer cell proliferation, migration, and chemoresistance was evaluated. In addition, tryptophan and KYN concentrations and their ratio were measured in serum of 195 patients with ccRCC using a sandwich enzyme-linked immunosorbent assay. The role of KTR as a prognostic factor for ccRCC cancer-specific survival (CSS) and progression-free survival (PFS) was assessed. RESULTS: Tissue microarray-based immunohistochemistry and indirect immunofluorescence staining showed an increased signal for KYN pathway components in ccRCC. Kaplan-Meier curves showed significant differences in CSS and PFS among groups of patients with high vs. low KTR. In particular, patients with high KTR values had a 5-year survival rate of 76.9% as compared with 92.3% for subjects with low levels (P  < 0.0001). Similar findings were observed for PFS (72.8% vs. 96.8% at 5y). At multivariate analysis, KTR was an independent adverse prognostic factor for CSS (hazard ratio  = 1.24, P  =  0.001), and PFS (hazard ratio  =  1.14, P  =  0.001). CONCLUSIONS: The involvement of the KYN pathway enzymes and catabolites in ccRCC occurs via both immune and nonimmune mechanisms. Our data suggest that KTR could serve as a marker of ccRCC aggressiveness and as a prognostic factor for CSS and PFS.

A Challenging Surgical Approach to Locally Advanced Primary Urethral Carcinoma: A Case Report and Literature Review.

Primary urethral carcinoma (PUC) is a rare and aggressive cancer, often underdetected and consequently unsatisfactorily treated. We report a case of advanced PUC, surgically treated with combined approaches.A 47-year-old man underwent transurethral resection of a urethral lesion with histological evidence of a poorly differentiated squamous cancer of the bulbomembranous urethra. Computed tomography (CT) and bone scans excluded metastatic spread of the disease but showed involvement of both corpora cavernosa (cT3N0M0). A radical surgical approach was advised, but the patient refused this and opted for chemotherapy. After 17 months the patient was referred to our department due to the evidence of a fistula in the scrotal area. CT scan showed bilateral metastatic disease in the inguinal, external iliac, and obturator lymph nodes as well as the involvement of both corpora cavernosa. Additionally, a fistula originating from the right corpus cavernosum extended to the scrotal skin. At this stage, the patient accepted the surgical treatment, consisting of different phases. Phase I: Radical extraperitoneal cystoprostatectomy with iliac-obturator lymph nodes dissection. Phase II: Creation of a urinary diversion through a Bricker ileal conduit. Phase III: Repositioning of the patient in lithotomic position for an overturned Y skin incision, total penectomy, fistula excision, and "en bloc" removal of surgical specimens including the bladder, through the perineal breach. Phase IV: Right inguinal lymphadenectomy.The procedure lasted 9-and-a-half hours, was complication-free, and intraoperative blood loss was 600 mL. The patient was discharged 8 days after surgery. Pathological examination documented a T4N2M0 tumor. The clinical situation was stable during the first 3 months postoperatively but then metastatic spread occurred, not responsive to adjuvant chemotherapy, which led to the patient's death 6 months after surgery.Patients with advanced stage tumors of the bulbomembranous urethra should be managed with radical surgery including the corporas up to the ischiatic tuberosity attachment, and membranous urethra in continuity with the prostate and bladder. Neo-adjuvant treatment may be advisable with the aim of improving the poor prognosis, even if the efficacy is not certain while it can delay the radical treatment of the disease.

Experience of percutaneous access under ultrasound guidance in renal transplant patients with allograft lithiasis.

OBJECTIVE: Urolithiasis of the transplanted kidney has an incidence of 0.2 to 1.7%, it increases the risk of infection in immunosuppressed patients and it can lead to ureteral obstruction that is often associated with deterioration of renal function. Urolithiasis of the transplanted kidney has different characteristics compared to the native kidney, due to the absence of innervation, which does not lead to colic pain. Percutaneous approach is an optimal choice in transplant patients. MATERIAL AND METHODS: Here we report our experience in two cadaveric transplant patients with urolithiasis. The first case was a patient of 68 years with a 20 mm stone located in the transplanted kidney pelvis and another smaller in a lower calyx. The second case was a patient of 65 years with a 15 mm stone in the distal part of the transplanted ureter. In both cases the patients were asymptomatic, but they had a reduction in urine output associated with worsening of the transplanted kidney function. The diagnosis was performed in both cases with ultrasound study, showing a severe hydronephrosis and it was confirmed by computed tomography scan. In both cases, we performed a Percutaneous Nephrolithotomy (PCNL). Access was made after targeting the stone, through a lower pole puncture under ultrasound guidance. The first case was treated with pneumatic and laser energy, breaking stones through a nephroscope. In the second case we performed a laser lithotripsy of the ureteral stone, using a flexible videoureteroscope. At the end of both procedures a Double-J stent and a 14 Fr Malecot nephrostomy were positioned, that were removed at 6 weeks and 10 days, respectively. RESULTS: Both patients achieved a resolution of the worsening of renal function, recovering the spontaneous diuresis. The surgical procedure using ultrasound guidance was safe and allowed quick access to the renal pelvis. Both patients experienced no bleeding or infection during hospitalization. CONCLUSIONS: Percutaneous Nephrolithotomy (PCNL) is an established safe and effective surgical treatment option for larger renal calculi in renal allografts. The ultrasound guided access to the transplanted kidney in percutaneous treatment of urolithiasis is useful and fast, minimizing patient exposure to ionizing radiation.

Renal Cell Carcinoma: A Study through NMR-Based Metabolomics Combined with Transcriptomics.

Renal cell carcinoma (RCC) is a heterogeneous cancer often showing late symptoms. Until now, some candidate protein markers have been proposed for its diagnosis. Metabolomics approaches have been applied, predominantly using Mass Spectrometry (MS), while Nuclear Magnetic Resonance (NMR)-based studies remain limited. There is no study about RCC integrating NMR-based metabolomics with transcriptomics. In this work, ¹H-NMR spectroscopy combined with multivariate statistics was applied on urine samples, collected from 40 patients with clear cell RCC (ccRCC) before nephrectomy and 29 healthy controls; nine out of 40 patients also provided samples one-month after nephrectomy. We observed increases of creatine, alanine, lactate and pyruvate, and decreases of hippurate, citrate, and betaine in all ccRCC patients. A network analysis connected most of these metabolites with glomerular injury, renal inflammation and renal necrosis/cell death. Interestingly, intersecting metabolites with transcriptomic data from CD133+/CD24+ tumoral renal stem cells isolated from ccRCC patients, we found that both genes and metabolites differentially regulated in ccRCC patients belonged to HIF-α signaling, methionine and choline degradation, and acetyl-CoA biosynthesis. Moreover, when comparing urinary metabolome of ccRCC patients after nephrectomy, some processes, such as the glomerular injury, renal hypertrophy, renal necrosis/cell death and renal proliferation, were no more represented.

Increased Expression of the Autocrine Motility Factor is Associated With Poor Prognosis in Patients With Clear Cell-Renal Cell Carcinoma.

Glucose-6-phosphate isomerase (GPI), also known as phosphoglucose isomerase, was initially identified as the second glycolytic enzyme that catalyzes the interconversion of glucose-6-phosphate to fructose-6-phosphate. Later studies demonstrated that GPI was the same as the autocrine motility factor (AMF), and that it mediates its biological effects through the interaction with its surface receptor (AMFR/gp78). In this study, we assessed the role of GPI/AMF as a prognostic factor for clear cell renal cell carcinoma (ccRCC) cancer-specific (CSS) and progression-free survival (PFS). In addition, we evaluated the expression and localization of GPI/AMF and AMFR, using tissue microarray-based immunohistochemistry (TMA-IHC), indirect immunofluorescence (IF), and confocal microscopy analysis.Primary renal tumor and nonneoplastic tissues were collected from 180 patients who underwent nephrectomy for ccRCC. TMA-IHC and IF staining showed an increased signal for both GPI and AMFR in cancer cells, and their colocalization on plasma membrane. Kaplan-Meier curves showed significant differences in CSS and PFS among groups of patients with high versus low GPI expression. In particular, patients with high tissue levels of GPI had a 5-year survival rate of 58.8%, as compared to 92.1% for subjects with low levels (P < 0.0001). Similar findings were observed for PFS (56.8% vs 93.3% at 5 years). At multivariate analysis, GPI was an independent adverse prognostic factor for CSS (HR = 1.26; P = 0.001), and PFS (HR = 1.16; P = 0.01).In conclusion, our data suggest that GPI could serve as a marker of ccRCC aggressiveness and a prognostic factor for CSS and PFS.

Metabolomic profiling for the identification of novel diagnostic markers in prostate cancer.

Metabolomic profiling offers a powerful methodology for understanding the perturbations of biochemical systems occurring during a disease process. During neoplastic transformation, prostate cells undergo metabolic reprogramming to satisfy the demands of growth and proliferation. An early event in prostate cell transformation is the loss of capacity to accumulate zinc. This change is associated with a higher energy efficiency and increased lipid biosynthesis for cellular proliferation, membrane formation and cell signaling. Moreover, recent studies have shown that sarcosine, an N-methyl derivative of glycine, was significantly increased during disease progression from normal to localized to metastatic prostate cancer. Mapping the metabolomic profiles to their respective biochemical pathways showed an upregulation of androgen-induced protein synthesis, an increased amino acid metabolism and a perturbation of nitrogen breakdown pathways, along with high total choline-containing compounds and phosphocholine levels. In this review, the role of emerging biomarkers is summarized, based on the current understanding of the prostate cancer metabolome.

Practical recommendations for performing ultrasound scanning in the urological and andrological fields.

AIM: US scanning has been defined as the urologist's stethoscope. These recommendations have been drawn up with the aim of ensuring minimum standards of excellence for ultrasound imaging in urological and andrological practice. A series of essential recommendations are made, to be followed during ultrasound investigations in kidney, prostate, bladder, scrotal and penile diseases. METHODS: Members of the Imaging Working Group of the Italian Society of Urology (SIU) in collaboration with the Italian Society of Ultrasound in Urology, Andrology and Nephrology (SIEUN) identified expert Urologists, Andrologists, Nephrologists and Radiologists. The recommendations are based on review of the literature, previously published recommendations, books and the opinions of the experts. The final document was reviewed by national experts, including members of the Italian Society of Radiology. RESULTS: Recommendations are listed in 5 chapters, focused on: kidney, bladder, prostate and seminal vesicles, scrotum and testis, penis, including penile echo-doppler. In each chapter clear definitions are made of: indications, technological standards of the devices, the method of performance of the investigation. The findings to be reported are described and discussed, and examples of final reports for each organ are included. In the tables, the ultrasound features of the principal male uro-genital diseases are summarized. Diagnostic accuracy and second level investigations are considered. CONCLUSIONS: Ultrasound is an integral part of the diagnosis and follow-up of diseases of the urinary system and male genitals in patients of all ages, in both the hospital and outpatient setting. These recommendations are dedicated to enhancing communication and evidence-based medicine in an inter- and multi-disciplinary approach. The ability to perform and interpret ultrasound imaging correctly has become an integral part of clinical practice in uro-andrology, but intra and inter-observer variability is a well known limitation. These recommendations will help to improve reliability and reproducibility in uro-andrological ultrasound scanning.

Impact of donor-recipient gender on kidney graft and patient survival: short- and long-term outcomes.

PURPOSE: Donor and recipient gender influence on post-transplant kidney and patient survival is still controversial, and the literature data do not present unanimous conclusions. The aim of this study was to evaluate the effect of gender disparities between donor and recipient in 963 kidney transplants performed at our center from January 2000 to December 2010. METHODS: The patients were subdivided into four groups according to recipient and donor gender: male donor-to-male recipient (MDMR; n = 305), male donor-to-female recipient (MDFR; n = 203), female donor-to-female recipient (FDFR; n = 206), and female donor-to-male recipient (FDMR; n = 249). Independent sample's t test and one-way ANOVA were used for statistical analyses. Graft and patient survival were calculated by the Kaplan-Meier method and compared using the log rank test. RESULTS: There were no statistically significant differences between the groups with regard to age, cold ischemia time, delayed graft function, primary non-function, and episodes of acute and chronic rejection. Moreover, no difference in either graft (p = 0.92) or patient (p = 0.41) survival at 1, 3, and 5 years was observed. However, female recipients had significantly lower serum creatinine values and higher estimated GFR, particularly if they received a male donor kidney, and these findings were stable up to 3-year post-transplantation. CONCLUSIONS: No impact of gender on short- or long-term graft and patient survival was observed in deceased kidney transplantation. However, we report a lower creatinine level in the male donors to female recipients group as compared with other recipient-donor gender combinations, although this difference loses statistical significance after the third-year post-transplantation.

Predictive value of resistive index in graft survival after kidney transplant.

INTRODUCTION: The intrarenal resistance index (RI) is a calculated parameter for the assessment of the status of the graft during the follow-up ultrasound of the transplanted kidney. Currently it is still unclear the predictive value of RI, also in function of the time. MATERIALS AND METHODS: We retrospectively investigated the correlation between the RI and the graft survival (GS) and the overall survival (OS) after transplantation. We evaluated 268 patients transplanted between 2003 and 2011, the mean followup was 73 months (12-136). The RI was evaluated at 8 days, 6 months, 1 year and 3 years. The ROC analysis was used to calculate the predictive value of RI and the Kaplan Mayer curves was used to evaluated the OS and PS. RESULTS: The ROC analysis, correlated to the GS, identified a value of RI equal to 0.75 as a cut-off. All patients was stratified according to the RI at 8 days (RI ≤ 0,75: 212 vs RI > 0.75: 56), at 6 months (RI ≤ 0.75: 237 vs RI > 0.75: 31), at 1 year (RI ≤ 0.75: 229 vs RI > 0.75: 39) and at 3 years (RI ≤ 0.75: 224 vs RI > 0.75: 44). The RI showed statistically significant differences between the two groups in favor of those who had an RI ≤ 0.75 only at 8 days and at 6 moths (p = 0.0078 and p = 0.02 to 8 days to 6 months) on the GS. On the contrary, we observed that the RI estimated at 1 year and 3 years has not correlated with the GS. The same RI cut-off was correlate with PS after transplantation. We observed that there are no correlations between the RI and OS. CONCLUSIONS: The RI proved to be a good prognostic factor on survival organ when it was evaluated in the first months of follow- up after transplantation. This parameter does not appear, however, correlate with OS of the transplanted subject.

Burned-out in a mixed germ cell tumor of the testis: the problem of pT0. Case report.

Germ cell tumors constitute the majority of all testicular tumors, which are relatively rare overall and are mainly encountered in young adults and teenagers. The term 'burned-out' germ cell tumor refers to the presence of a metastatic germ cell tumor with histological regression of the primary testicular lesion. Clinical examination of the testes and scrotal sonography is the initial diagnosis of such neoplasms. We report an unusual case of a burned-out testicular tumor with metastases to retroperitoneal lymphnodes in an asymptomatic patient with right testicular hypoechoic nodule associated with multiple calcifications of the testicular parenchyma.

Spondin-2, a secreted extracellular matrix protein, is a novel diagnostic biomarker for prostate cancer.

PURPOSE: SPON2 belongs to the F-spondin family of secreted extracellular matrix proteins. It is deregulated in some tumors, including prostate cancer. In this prospective study we assessed the role of serum SPON2 as a biomarker for prostate cancer diagnosis as well as any association between SPON2 levels and clinicopathological features. We also compared the diagnostic performance of this biomarker to that of serum sarcosine, and percent free-to-total and total prostate specific antigen. MATERIALS AND METHODS: SPON2 was measured using a sandwich enzyme linked immunosorbent assay in serum samples from 286 patients with prostate cancer and 68 with no evidence of malignancy, as confirmed by 10 to 12-core ultrasound guided prostate biopsy. Nonparametric statistical tests and ROC analysis were done to assess the diagnostic performance of SPON2 vs the other biomarkers. RESULTS: Median serum SPON2 was significantly higher in patients with prostate cancer than in those with no evidence of malignancy (77.5 vs 23.6 ng/ml, p<0.0001). ROC analysis showed a higher predictive value of SPON2 (AUC 0.952) than of serum sarcosine (AUC 0.674), percent free-to-total prostate specific antigen (AUC 0.806) and total prostate specific antigen (AUC 0.561). Moreover, patients with low grade prostate cancer had higher median SPON2 levels (p=0.001). Spearman rank correlation confirmed a negative association with Gleason score (rs=-0.29, p=0.0005). CONCLUSIONS: We found evidence that SPON2 levels were significantly higher in patients with prostate cancer than in healthy individuals. Moreover, this biomarker had better diagnostic performance than serum sarcosine, and percent free-to-total and total prostate specific antigen. This greater accuracy was also present in a subset of patients with normal prostate specific antigen.

Ultrasonographic findings in dual kidney transplantation.

INTRODUCTION: Organ shortage has led to using grafts from expanded criteria donors (ECD). Double kidney transplantation is an accepted strategy to increase the donor pool, using organs from an ECD which are not acceptable for single kidney transplantation (SKT). Aim of this retrospective study was to analyse the role of colour Doppler ultrasound (CDUS) in the diagnosis of major surgical complications in DKT, performed with unilateral or bilateral placement. MATERIALS AND METHODS: From 2000 to 2011 we performed 54 DKT. Unilateral placement of both kidneys was done in 26 patients and bilateral DKT in 28, through two separate Gibson incisions (18) or one midline incision (10). Each patient underwent at least 3 CDUS before hospital discharge. The main surgical complications, discovered initially thanks to ultrasound (US), were hydronephrosis from ureteral obstruction, lymphocele and deep venous thrombosis (DVT). RESULTS: Mean follow-up was 42.7 months. Good postoperative renalfunction was demonstrated in 25 patients (46.3%), while delayed graft function occurred in 29 (53.7%). US showed ureteral obstruction requiring surgery in 5 unilateral DKT while no patient subjected to bilateral DKT developed severe hydronephrosis. Lymphoocele, surgically drained, was demonstrated in 6 bilateral DKT with a midline incision, 2 bilateral DKT with two separate incisions and 3 unilateral DKT. CDUS also enabled diagnosis of 2 cases of DVT in ipsilateral DKTs. CONCLUSIONS: CDUS provides useful information in patients with DKT, allowing the detection of clinically unsuspected unilateral diseases. US study of our patients demonstrated that unilateral DKTs are more susceptible to the development of DVT and ureteral stricture, while the incidence of voluminous lymphocele is more frequent in bilateral DKT through a single midline incision. In this scenario, all patients undergoing DKT should be carefully monitored by US after surgery.

Value of the resistive index in patient and graft survival after kidney transplant.

INTRODUCTION: The resistive index (RI) obtained by performing doppler sonography is a hemodynamic index commonly used to measure flow resistance within an organ to assess if there is a vascular disease associated with that organ. It is a well-known predictor of kidney transplant outcome. The purpose of this study was to analyze the impact of RI values on patient and graft survival, as well as kidney graft function during 5-year follow-up. MATERIALS AND METHODS: We retrospectively investigated 761 kidney transplant recipients from cadaveric donors performed between 1998 to 2011. RI was measured at hospital discharge after the kidney transplant. All the patients were divided into tertiles, according to the baseline RI value (group 1: RI < 0.70, group 2: RI between 0.70 and 0.79 and group 3: RI > 0.80). RESULTS: Patients with a low RI (<0.70) showed the lowest incidence of delayed graft function (DGF) compared to the other two groups (20.2% vs. 32.2% vs. 33%). Recipients with low RI values displayed significantly better creatinine clearance (70 vs. 55 vs 35 ml/min, respectively) than those with medium or high RI values at 5-year follow-up. Kaplan-Meier estimates of cumulative graft survival were significantly worse in patients who had a RI of 0.70 or more than in patients with a RI of less than 0.70 (p = 0.02). Cumulative patient survival showed the same behavior (0.01) CONCLUSIONS: Low RI values measured in segmental arteries in the very early post-transplant period predict better kidney graft function and reduce the risk of all-cause graft loss, including patient death in a 5-year follow-up period.

Ureteral strictures after kidney transplantation: risk factors.

INTRODUCTION: Ureteral obstruction is one of the most commonly reported urological complications after kidney transplantation often occurring within the first 3 months after surgery. Ischemia is the most frequent cause of ureteral stenosis and is the result of excessive hilar dissection and a poor anastomotic technique. Aim of this study was to identify the main risk factors for ureteral stenosis after kidney transplantation from cadaveric donors and to assess their impact on both graft survival and patient. MATERIALS AND METHODS: We retrospectively investigated 761 kidney transplants from cadaveric donors performed between 1998 to 2011. In all the patients, the ureteroneocystostomy was stented with a double J stent 4.7Ch x 12 cm held in place for an average time of 4-6 weeks post-operatively. Each patient underwent at least 3 ultrasound scans during hospital stay and subsequently during follow-up. All patients with severe hydronephrosis were followed by sequential renal scintigraphy with MAG3 and diuretic stimulus. RESULTS: After a mean follow-up of 60.1 (+/- 38.5) months, severe ureteral stenosis was discovered in 21 patients (2.76%), with exclusive involvement of the vesicoureteral junction. No statistically significant correlation was found with donor age and the incidence of delayed graft function, whereas a significant correlation between ureteral obstruction and unilateral placement of both grafts in dual kidney transplantation (DKT) (p < 0.001) was found. These patients had a longer mean hospital stay than the control group, but there was no influence on survival of the organ or patient. CONCLUSIONS: ureteral obstruction after renal transplantation often features subtle and late symptoms. Early ultrasound monitoring is therefore essential and in the presence of severe hydronephrosis, scintigraphic confirmation of the obstruction. In fact. early resolution of the stenosis appears to provide optimal graft and patient survival.

High energy microwave thermotherapy for symptomatic benign prostatic enlargment: predictive parameters of long term outcome.

OBJECTIVES: High-energy transurethral microwave thermotherapy (HE-TUMT) has become one of the most preferred minimally invasive procedure for the treatment of benign prostatic enlargement (BPE). In this study we report the long term results in a subset of patients treated with the 30-minute high energy protocol. PATIENTS AND METHODS: A total of 135 patients were treated with TUMT Prostasoft 3.5. The International Prostate Symptom Score (IPSS), Madsen Symptom Score (MSS), Quality of Life (QoL) score, peak urinary flow rate (Qmax) and post-voiding residual urine volume (PVR) were assessed at baseline and at 12, 24, 36, 48 and 60 months after treatment. RESULTS: The mean follow-up period was 46.1 months. The mean IPSS at baseline was 17.8 and decreased to 5.6 at 60 months (p < 0.001). The MSS decreased from 12.6 at baseline to 4.3 at 5 years (p < 0.0001). The QoL score improved from 4.1 to 2.2 at 5 years (p < 0.001). The mean Qmax value at baseline was 9.4 ml/sec and it improved to 15.7 ml/sec at 60 months (p = 0.001), whereas PVR decreased from 97 to 24 ml at 5 years (p = 0.001). Retreatment was required for 47 patients (34.8%). Univariate and multivariate analysis showed that the only baseline parameters able to predict the long-term efficacy were a IPSS <18 and a Qm, > 10 ml/sec (p = 0.04). CONCLUSIONS: These data shows a high response rate obtained with 30-minute TUMT protocol and a durability of response up to 5 years after treatment, making this procedure a safe and effective alternative to TURP in selected patients.

Role of imaging and biopsy to assess local recurrence after definitive treatment for prostate carcinoma (surgery, radiotherapy, cryotherapy, HIFU).

PURPOSE: Defining the site of recurrent disease early after definitive treatment for a localized prostate cancer is a critical issue as it may greatly influence the subsequent therapeutic strategy or patient management. METHODS: A systematic review of the literature was performed by searching Medline from January 1995 up to January 2011. Electronic searches were limited to the English language, and the keywords prostate cancer, radiotherapy [RT], high intensity focused ultrasound [HIFU], cryotherapy [CRIO], transrectal ultrasound [TRUS], magnetic resonance [MRI], PET/TC, and prostate biopsy were used. RESULTS: Despite the fact that diagnosis of a local recurrence is based on PSA values and kinetics, imaging by means of different techniques may be a prerequisite for effective disease management. Unfortunately, prostate cancer local recurrences are very difficult to detect by TRUS and conventional imaging that have shown limited accuracy at least at early stages. On the contrary, functional and molecular imaging such as dynamic contrast-enhanced MRI (DCE-MRI), and diffusion-weighted imaging (DWI), offers the possibility of imaging molecular or cellular processes of individual tumors. Recently, PET/CT, using 11C-choline, 18F-fluorocholine or 11C-acetate has been successfully proposed in detecting local recurrences as well as distant metastases. Nevertheless, in controversial cases, it is necessary to perform a biopsy of the prostatic fossa or a biopsy of the prostate to assess the presence of a local recurrence under guidance of MRI or TRUS findings. CONCLUSION: It is likely that imaging will be extensively used in the future to detect and localize prostate cancer local recurrences before salvage treatment.

T helper 1, 2 and 17 cell subsets in renal transplant patients with delayed graft function.

Ischemia-reperfusion injury (IRI) in kidney transplantation is the major cause of delayed graft function (DGF), an event associated with an increased risk of acute rejection. The aim of this study was to evaluate T helper (Th) cell phenotype in renal transplants with DGF. T-bet (Th1), GATA-3 (Th2) and IL-17 (Th17) protein expression was investigated in pretransplant biopsies, DGF and acute tubular damage (ATD) caused by calcineurin-inhibitor toxicity. Intracytofluorimetric analysis of IFN-γ, IL-4 and IL-17 was performed to analyze Th1, Th2 and Th17 responses in peripheral blood mononuclear cells of recipients with early graft function (EGF) and DGF, before (T0) and 24 h after transplantation (T24). In pretransplant biopsies, T-bet(+) , GATA-3(+) and IL-17(+) cells were barely detectable. In DGF, T-bet(+) and IL-17(+) cells were significantly increased compared with pretransplant and ATD. More than 90% of T-bet(+) and less then 5% of IL-17(+) cells were CD4(+) . GATA-3(+) cells were increased to a lower extent. T-bet(+) /GATA-3(+) cell ratio was significantly higher in DGF. Peripheral CD4(+) IFN-γ/IL-4 ratio was significantly decreased in DGF, while CD4(+) /IL-17(+) cells did not differ between T0 and T24 in DGF. Our data suggest that DGF is characterized by a prevalent Th1 phenotype within the graft. This event might represent a link between DGF and acute rejection.

Transperitoneal deviceless hand-assisted laparoscopic living donor nephrectomy: an alternative technique for kidney recovery.

PURPOSE: Deviceless hand-assisted laparoscopic living donor nephrectomy is an alternative surgical technique that relies on the classic laparoscopic approach, supported by insertion of the surgeon's hand during kidney recovery without the need to use any device because of the sealing effect of the particular wall incision. PATIENTS AND METHODS: From 2006 to 2008, deviceless hand-assisted laparoscopic living donor nephrectomy was performed in 25 patients (M/F = 7/18; mean age = 53 years; range = 30-68). One right nephrectomy was performed. We made a lateral paramedian incision. No sealing device is required in our technique because the pneumoperitoneum is maintained by the sealing effect of two complexes: the peritoneum/deep rectus abdominis muscle fascia and muscle itself/lateral edge of the double fascial incision. These structures clench around the surgeon's wrist, preventing leakage of CO2. After dissection, the kidney is removed through the hand port without an endobag. RESULTS: Mean surgical time was 105 minutes (range = 60-150), estimated blood loss was 50 to 200 mL, and mean warm ischemia time was 3.5 minutes (range = 2-11). Mean hospital stay was 4 days (range = 3-6). One uncontrollable hemorrhage due to a renal vein lesion required conversion to open surgery. As to graft function, recipient serum creatinine on day 7 ranged from 0.8 to 2.6 mg/dL. CONCLUSIONS: The ability to better control bleeding by manual compression, as well as the advantages related to decreased donor morbidity, shorter hospital stay, cost saving, and excellent graft function, make this deviceless technique a good option for kidney recovery.

Therapeutic targeting of classical and lectin pathways of complement protects from ischemia-reperfusion-induced renal damage.

Ischemia-reperfusion injury is the major cause of delayed graft function in transplanted kidneys, an early event significantly affecting long-term graft function and survival. Several studies in rodents suggest that the alternative pathway of the complement system plays a pivotal role in renal ischemia-reperfusion injury. However, limited information is currently available from humans and larger animals. Here we demonstrated that 30 minutes of ischemia resulted in the induction of C4d/C1q, C4d/MLB, and MBL/MASP-2 deposits in a swine model of ischemia-reperfusion injury. The infusion of C1-inhibitor led to a significant reduction in peritubular capillary and glomerular C4d and C5b-9 deposition. Moreover, complement-inhibiting treatment significantly reduced the numbers of infiltrating CD163(+), SWC3a(+), CD4a(+), and CD8a(+) cells. C1-inhibitor administration led to significant inhibition of tubular damage and tubular epithelial cells apoptosis. Interestingly, we report that focal C4d-deposition colocalizes with C1q and MBL at the peritubular and glomerular capillary levels also in patients with delayed graft function. In conclusion, we demonstrated the activation and a pathogenic role of classical and lectin pathways of complement in a swine model of ischemia-reperfusion-induced renal damage. Therefore, inhibition of these two pathways might represent a novel therapeutic approach in the prevention of delayed graft function in kidney transplant recipients.

Penile prostheses.

Penile prosthesis implantation is recognized as a valid option to obtain an artificial erection satisfactory for sexual intercourse in those patients in which a pharmacological approach is contraindicated or ineffective. Penile prostheses are subbject to continuous development and they are achieving ever better mechanical reliability and safety. The devices are divided into two general types: semirigid (malleable and mechanical) and inflatables. The AMS® (American Medical Systems) and Coloplast Ltd® produce the majority of inflatable and semirigid devices.Malleable and mechanical prostheses have the disadvantage that the penis is always erect although it can be orientated in different ways, while the advantages are ease of use and the need for a simpler surgical procedure compared with inflatable prostheses. Three-component prostheses are more sophisticated than semirigid devices. The advantages of these devices are that the prosthesis feels softer than semirigid or two-piece devices when deflated, with a better cosmetic result, and it ensures a more natural erection than others kinds of prosthesis. The disadvantages are the possibility of malfunction and the need for a more complicated surgical technique. Implantation of a penile prosthesis can be performed in a short surgical time under locoregional anaesthesia, and for this reason hospitalization is usually brief and the patient can be discharged 2 days after the operation if complications are not evident. Patient and partner satisfaction reflect the quality and the effectiveness of this treatment. Even though the results are positive in the vast majority of patients, the possibility of several complications makes penile prosthesis implantation a delicate kind of surgery. Complications can happen when the operation is carried out, in the peri-operative and in the postoperative period, and include infections, erosions of the prosthesis and mechanical failure in case of inflatable prosthesis. Penile prostheses available on the market have improved the success of this kind of surgery, thanks to the introduction of new materials and designs.