Carlo Bettocchi - Academia.edu (original) (raw)

Papers by Carlo Bettocchi

Research paper thumbnail of A prospective study on patient's erectile function following transrectal ultrasound guided prostate biopsy

Archivio italiano di urologia, andrologia: organo ufficiale [di] Società italiana di ecografia urologica e nefrologica / Associazione ricerche in urologia

This study is intended to assess variation of sexual function in 222 patient at different treatme... more This study is intended to assess variation of sexual function in 222 patient at different treatment stages of prostate cancer with the aid of a validated questionnaire in comparison with patients diagnosed with a benign lesion. The questionnaire covers the period before carrying out prostate biopsy, the disclosure of histological examination, and the recovery period. 240 patients who were to undergo trans-rectal ultrasound guided prostate biopsy due to suspected prostate cancer were consecutively and prospectively studied between January 2008 and January 2009. Patients were asked to complete an IIEF-15 questionnaire to assess sexual function during the initial consultation (T0), generally whilst they waited to be called forward for an ECG or to provide blood samples. The same questionnaire was re-administered 30 days following disclosure of results (T30) and, in all cases of confirmed malignancy, at pre-surgical admission (T pre-op). In this study we examined results on perceived se...

Research paper thumbnail of 397 DIABETES MELLITUS IS A RISK FACTOR FOR RECURRENCE AND MORTALITY IN PATIENTS WITH RENAL CELL CARCINOMA

European Urology Supplements, 2011

Eur Urol Suppl 2011;10(2):139 classified as low RS showed better PFS than patients with tumors wi... more Eur Urol Suppl 2011;10(2):139 classified as low RS showed better PFS than patients with tumors with high RS (88.9% vs 63.9%, P=0.0488). Conclusions: CDK1 specific activity of tumors and the CDK2 specific activity are both associated with recurrence and prognosis. Analysis of cyclin-dependent kinase activity in the clinical setting could be a powerful approach for predicting cancer recurrence and prognosis in RCC after surgery and has potential for use as a routine laboratory test.

Research paper thumbnail of 633 SERUM SARCOSINE INCREASES THE ACCURACY OF PROSTATE CANCER DETECTION IN LOW RANGE PSA

European Urology Supplements, 2011

Research paper thumbnail of Androgen deprivation therapy regulation of beta1C integrin expression in prostate cancer

Oncology Reports

The beta1C integrin is an alternatively spliced variant of the beta1 integrin subfamily that at v... more The beta1C integrin is an alternatively spliced variant of the beta1 integrin subfamily that at variance with its wild-type counterpart, i.e., the beta1A integrin, inhibits cell proliferation in prostate cancer cells. We have recently shown that transcriptional, translational and post-translational processes contribute to the selective loss of beta1C integrin during prostate malignant transformation. Here, we investigated whether androgen deprivation therapy (ADT) may affect beta1C mRNA expression in prostate cancer. Neoplastic prostates were obtained from patients undergoing radical prostatectomy who had received neoadjuvant ADT. The beta1C mRNA level was measured by Northern hybridization experiments and compared to normal prostates obtained from patients who underwent radical cystoprostatectomy for bladder cancer. Furthermore, the beta1C integrin gene transcriptional activity was measured by nuclear Run-on assays. We found an increase of beta1C mRNA expression (208+/-11%; p<0....

Research paper thumbnail of Metabolomic profile of glycolysis and the pentose phosphate pathway identifies the central role of glucose-6-phosphate dehydrogenase in clear cell-renal cell carcinoma

Oncotarget, Jan 14, 2015

The analysis of cancer metabolome has shown that proliferating tumor cells require a large quanti... more The analysis of cancer metabolome has shown that proliferating tumor cells require a large quantities of different nutrients in order to support their high rate of proliferation. In this study we analyzed the metabolic profile of glycolysis and the pentose phosphate pathway (PPP) in human clear cell-renal cell carcinoma (ccRCC) and evaluate the role of these pathways in sustaining cell proliferation, maintenance of NADPH levels, and production of reactive oxygen species (ROS). Metabolomic analysis showed a clear signature of increased glucose uptake and utilization in ccRCC tumor samples. Elevated levels of glucose-6-phosphate dehydrogenase (G6PDH) in association with higher levels of PPP-derived metabolites, suggested a prominent role of this pathway in RCC-associated metabolic alterations. G6PDH inhibition, caused a significant decrease in cancer cell survival, a decrease in NADPH levels, and an increased production of ROS, suggesting that the PPP plays an important role in the re...

Research paper thumbnail of Obesity in kidney transplantation affects renal function but not graft and patient survival

Transplantation proceedings

The number of overweight and obese patients undergoing renal transplantation has increased dramat... more The number of overweight and obese patients undergoing renal transplantation has increased dramatically over the past two decades. Studies on graft survival and posttransplantation complications have often yielded conflicting results. Some authors have reported similar results for graft and patient survivals between obese and normal weight patients, but with a marginally increased rate of postoperative complications. In contrast, other reports note higher percentage of graft losses as well as increased mortality. In our study, we analyzed early- and long-term outcomes among obese versus nonobese kidney transplant recipients. Between January 2000 and December 2008, we performed 563 cadaveric kidney transplantations. Recipients were classified in 1 of 5 groups based on their body mass index (BMI) at the time of transplantation: group A (n = 68; BMI < 18.5); group B (n = 310; 18.6 < BMI < 24.9); group C (n = 143; 25 < BMI < 29.9); group D (n = 32; 30 < BMI < 34.9);...

Research paper thumbnail of Long term results (4 years) of high-energy transurethral microwave

European Urology Supplements, 2003

Research paper thumbnail of Penile prostheses

Therapeutic advances in urology, 2010

Penile prosthesis implantation is recognized as a valid option to obtain an artificial erection s... more 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 device...

Research paper thumbnail of CTR2 identifies a population of cancer cells with stem cell-like features in patients with clear cell renal cell carcinoma

The Journal of urology, 2014

In clear cell renal cell carcinoma tissue samples we identified and characterized a population of... more In clear cell renal cell carcinoma tissue samples we identified and characterized a population of renal cell carcinoma derived CD133+/CD24+ cancer cells. We studied differences between these cells and their nonneoplastic counterpart, tubular adult renal progenitor cells. CD133+/CD24+ renal cell carcinoma derived cells were isolated from 40 patients. The mesenchymal phenotype and stemness proteomic profile of these renal cell carcinoma derived cells were characterized. Colony forming efficiency and self-renewal ability were tested by limiting dilution. Tumorigenic properties were evaluated in vitro by soft agar assay. The angiogenic response was evaluated in vivo by the chorioallantoic membrane angiogenic assay. Microarray analysis was performed on 6 tubular adult renal progenitor cell and 6 renal cell carcinoma derived cell clones. Membrane protein expression was evaluated by flow cytometry and immunofluorescence staining. CD133+/CD24+ cells were isolated from normal and tumor kidne...

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

Archivio italiano di urologia, andrologia : organo ufficiale [di] Società italiana di ecografia urologica e nefrologica / Associazione ricerche in urologia, 2014

Germ cell tumors constitute the majority of all testicular tumors, which are relatively rare over... more 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.

Research paper thumbnail of Testicular granulosa cell tumor of adult type: A new case and a review of the literature

Urologic Oncology: Seminars and Original Investigations, 2007

Testicular granulosa cell tumor of the adult type is a very rare tumor, and, to date and our know... more Testicular granulosa cell tumor of the adult type is a very rare tumor, and, to date and our knowledge, only 23 cases of this rare testicular tumor have been reported in the literature, 5 of which developed metastases. We report a case of granulosa cell tumor of adult type in a 45-year-old man with a 15-year history of a painless increasing right testicular volume who underwent radical orchiectomy. The patient is disease-free after a 2-year follow-up, without any adjuvant therapy. Our case and a review of the literature indicate that this type of tumor is a rare, slow-growing neoplasm. Because distant metastases may occur late in the clinical course, long-term follow-up of these patients is recommended.

Research paper thumbnail of Impact of donor–recipient gender on kidney graft and patient survival: short- and long-term outcomes

World Journal of Urology, 2013

Purpose Donor and recipient gender influence on posttransplant kidney and patient survival is sti... more Purpose Donor and recipient gender influence on posttransplant 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-tomale recipient (M D M R ; n = 305), male donor-to-female recipient (M D F R ; n = 203), female donor-to-female recipient (F D F R ; n = 206), and female donor-to-male recipient (F D M R ; 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 posttransplantation.

Research paper thumbnail of Current insights in renal cell cancer pathology

Urologic Oncology: Seminars and Original Investigations, 2008

In recent years molecular biologists and pathologists have described new entities of renal cell c... more In recent years molecular biologists and pathologists have described new entities of renal cell cancer (RCC) with a totally different morphology and biology among the histotypes of renal carcinoma, but always referring to the same renal cancer disease. The evidence of a distinct biological behavior and long-term prognosis among these makes the correct pathological diagnosis of renal cancer critically important for the clinician. Advances in understanding of the pathogenesis, behavior, and importance of prognostic factors for RCC have paved the way for a revision of its classification and staging. We reviewed the role of histological classification, microscopic tumor necrosis, microscopic venous invasion, lymph node involvement and, particularly, pathological stage. In our series of patients who underwent renal surgery for neoplasm, a retrospective study established the predictive role of tumor size on recurrence rate, compared with other known prognostic factors, and we conclude that histological grade, pathological stage and tumor size remain relevant prognosticators in early stage RCC patients. In order to optimize the management of patients with RCC it is necessary to develop an interdisciplinary approach (surgeon, radiologist, pathologist, oncologist) and find new prognostic parameters at molecular and cellular levels. Many efforts are ongoing to integrate molecular data (from tissue microarrays) and clinical data (traditional prognosticators) into a molecular integrated staging system. In the postgenomic era, new tumor-associated antigens and molecules can be identified at the protein level using proteomics, providing a major opportunity for screening and finding novel targets that are the basis of new emerging therapies for RCC.

Research paper thumbnail of Extended Criteria Donor Kidney Transplantation: Comparative Outcome Analysis Between Single versus Double Kidney Transplantation at 5 Years

Transplantation Proceedings, 2010

Introduction. Dual kidney transplantation (DKT), using extended criteria donor (ECD) grafts not s... more Introduction. Dual kidney transplantation (DKT), using extended criteria donor (ECD) grafts not suitable for single kidney transplantation (SKT), has been suggested to expand the kidney donor pool. Herein, we reviewed the long-term outcomes of DKT to assess its results versus a control group of 179 ECD SKTs. The allocation policy was based on a Remuzzi score obtained from a pretransplant biopsy. Materials and methods. We analyzed SKT in 179 (31.8%) and DKT in 41 (7.3%) of 563 cadaveric transplants from 2000 to 2008. Patients with DKT versus SKT showed mean recipient ages of 54 versus 51 years. We performed 17 ipsilateral and 24 bilateral DKT. The mean score was 2.78 for SKT and 4.3/4.6 for DKT. Results. Delayed graft function requiring dialysis occurred in 23 (56.1%) DKT and 70 (39.1%) SKT recipients. Primary nonfunction was observed in 1 (2.4%) DKT and 7 (3.9%) SKT recipients respectively. One DKT patient underwent monolateral transplantectomy. In the DKT versus SKT group, patient survivals were 92% versus 95%, 89% versus 93%, and 89 versus 91% at 12, 36, and 60 months, respectively (P ϭ .3). Graft survivals were 100% versus 94%, 95% versus 90%, and 89% versus 78% at 12, 36, and 60 months, respectively (P Ͻ .001). We observed a lower incidence of chronic allograft nephropathy (P ϭ .01) and a higher incidence of surgical adverse events (P ϭ .04) in DKT. Conclusions. ECD graft survival using DKT provided better results compared with SKT, despite the use of organs from higher-risk donors. At 5 years follow-up, DKT was a safe strategy to face the organ shortage. To optimize the use of available kidneys, the criteria for DKT require further refinement and standardization. Preimplantation evaluation must maximize transplant success and protect recipients from receiving organs at increased risk of premature failure.

Research paper thumbnail of Rapamycin Inhibits PAI-1 Expression and Reduces Interstitial Fibrosis and Glomerulosclerosis in Chronic Allograft Nephropathy

Transplantation, 2008

Background. Chronic allograft nephropathy (CAN) is characterized by deposition of extracellular m... more Background. Chronic allograft nephropathy (CAN) is characterized by deposition of extracellular matrix (ECM) in all renal compartments. PAI-1 seems to play a pivotal role in ECM turnover in CAN. Rapamycin has been shown to improve long-term graft survival in patients with CAN. The aim of the study was to evaluate the molecular mechanisms underlying the beneficial effects of rapamycin on CAN progression at glomerular and tubulointerstitial level. Methods. After a biopsy-proven CAN diagnosis (T0), 18 patients on calcineurin inhibitors (CNI) were randomly assigned in a 2:1 ratio to continue CNI (6 patients) or to receive rapamycin (RAPA; 12 patients). After 2 years of treatment (T24), all patients underwent a second renal biopsy. Morphometric analysis was conducted at T0 and at T24. PAI-1 expression was evaluated at T0 and T24 by immunohistochemistry. We evaluated the effect of rapamycin on PAI-1 gene expression in cultured proximal tubular cells incubated with CD40L or thrombin, two potential CAN pathogenic mediators. Results.The RAPA group showed a significant regression of glomerulosclerotic lesions and only a 26% increase in interstitial fibrosis after 2 years compared to baseline, whereas the CNI group showed progression of glomerulosclerosis and 112% increase in fibrosis. Glomerular and tubulointerstitial PAI-1 expression was reduced compared to the baseline in the RAPA group, while they were unchanged in the CNI group. In vitro data showed that rapamycin significantly reduced PAI-1 gene expression induced by both CD40L and thrombin in proximal tubular epithelial cells. Conclusions. These data suggest that rapamycin may modulate ECM deposition in CAN reducing PAI-1 expression.

Research paper thumbnail of Tunica Albuginea Plication for the Correction of Penile Curvature

Scandinavian Journal of Urology and Nephrology, 2002

To evaluate the efficacy of tunica albuginea plication (TAP) in the correction of congenital and ... more To evaluate the efficacy of tunica albuginea plication (TAP) in the correction of congenital and acquired penile curvatures and determine key points for a successful outcome of this procedure. From December 1995 to January 2001, 40 patients with penile curvature (10 congenital and 30 secondary to Peyronie&#39;s disease) underwent surgical correction by TAP. Indications were difficult or impossible penetration, normal erectile function, stable disease. For TAP we used non-absorbable inverted stitches tied with the assistant pushing down the tunica albuginea with a mosquito clamp to create an adequate groove for the knot. The results were evaluated subjectively and objectively. At mean follow-up of 30 months, full subjective and objective success (straight penis, mild shortening, normal erection, penetration and sensation) was achieved in 37 (92.5%) patients. Objective but not subjective success was achieved in 2 patients (5%), 1 complaining of psychogenic erectile dysfunction and the other of excessive penile shortening. There was only one failure, namely persistent glans numbness due to damage of the non-mobilized neurovascular bundle. TAP is a simple and effective method for the correction of congenital and acquired penile curvatures. Key points for successful outcome are adequate preoperative evaluation and counselling, careful preparation of tunica albuginea, mobilization of urethra or neurovascular bundle when needed, use of inverted stitches carefully buried, objective postoperative evaluation with a pharmacological erection test.

Research paper thumbnail of CONCEPTION FOLLOWING PENILE RECONSTRUCTION

Plastic & Reconstructive Surgery, 1999

Research paper thumbnail of Ejaculatory disorders: pathophysiology and management

Nature Clinical Practice Urology, 2008

Ejaculatory dysfunction (EjD) is one of the most common male sexual disorders, yet EjD is still f... more Ejaculatory dysfunction (EjD) is one of the most common male sexual disorders, yet EjD is still frequently misdiagnosed or overlooked as a result of numerous patient and physician barriers. The wide spectrum of EjD ranges from premature or rapid ejaculation, through delayed ejaculation, to a complete inability to ejaculate--otherwise known as anejaculation--and includes retrograde ejaculation and painful ejaculation. Conventional algorithms for managing ejaculatory disorders are based either on an organic or psychogenic etiology, with the latter more traditionally considered the main cause. This paper reviews physiopathological, diagnostic and therapeutic aspects of ejaculation disorders, with a particular focus on the most prevalent disorder, premature ejaculation.

Research paper thumbnail of Flexible-Dose Vardenafil in a Community-Based Population of Men Affected by Erectile Dysfunction: A 12-Week Open-Label, Multicenter Trial

The Journal of Sexual Medicine, 2005

To evaluate the efficacy, safety, and tolerability of a flexible-dose regimen of vardenafil in a ... more To evaluate the efficacy, safety, and tolerability of a flexible-dose regimen of vardenafil in a community-based population of men with erectile dysfunction (ED). This was a 12-week, open-label, flexible-dose, multicenter study of unselected men with ED of diverse origins and severity. Unlike previous studies, prostatectomy-induced ED and previous unresponsiveness to sildenafil were not exclusion criteria. After 4 weeks of treatment with 10 mg of vardenafil, the dose could be continued or titrated to 5 mg or 20 mg, depending on efficacy and tolerability. After 8 weeks, another dose change was possible. Efficacy was assessed with International Index of Erectile Function erectile function (IIEF-EF) domain scores, diary questions of the Sexual Encounter Profile (SEP), and a global assessment question (GAQ) about erection improvement during the previous 4 weeks. Safety was evaluated in 497 patients, and 480 were suitable for intention-to-treat analysis. After 12 weeks of treatment, the mean per patient rate of successful intercourse, defined by an affirmative response to SEP questions 1-3, was 72%, and was related to age and ED duration. The overall success rate increased from 66% at week 4 to 77% at week 12. The mean IIEF-EF domain score of the whole population increased from 17.2 (baseline) to 24.4 (endpoint). At week 12, the best scores were obtained by patients taking 5 mg and 10 mg. At week 12, GAQ scores showed improved erection in 97.4%, 94.8%, and 78.8% of patients in the 5 mg, 10 mg, and 20 mg group, respectively. Safety was excellent: no serious drug-related event was reported, and only 2.2% of patients discontinued treatment because of side-effects. Vardenafil was effective and well tolerated in this community-based ED population that is truly representative of the general ED population. Dose titration meets the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s needs and optimizes clinical outcome.

Research paper thumbnail of Plexiform Neurofibroma of the Penis Associated with Erectile Dysfunction due to Arterial Steeling

The Journal of Sexual Medicine, 2007

Solitary involvement of the genitourinary tract by Von Recklinghousen disease (VRD) is extremely ... more Solitary involvement of the genitourinary tract by Von Recklinghousen disease (VRD) is extremely rare. Aims. This report documents the management of a case of a plexiform neurofibroma on the penile shaft associated with erectile dysfunction. The literature surrounding VRD and its effects on the genital area was also investigated. Methods. After a complete preoperative investigation of the nature of the mass and of the erectile dysfunction, the neurofibroma was completely excised with preservation of the neurovascular bundle. Results. At 6-months postoperative follow-up, there was no sign of tumor recurrence and the glans sensation was maintained. The erectile dysfunction persisted postoperatively and failed to respond to medical treatment.

Research paper thumbnail of A prospective study on patient's erectile function following transrectal ultrasound guided prostate biopsy

Archivio italiano di urologia, andrologia: organo ufficiale [di] Società italiana di ecografia urologica e nefrologica / Associazione ricerche in urologia

This study is intended to assess variation of sexual function in 222 patient at different treatme... more This study is intended to assess variation of sexual function in 222 patient at different treatment stages of prostate cancer with the aid of a validated questionnaire in comparison with patients diagnosed with a benign lesion. The questionnaire covers the period before carrying out prostate biopsy, the disclosure of histological examination, and the recovery period. 240 patients who were to undergo trans-rectal ultrasound guided prostate biopsy due to suspected prostate cancer were consecutively and prospectively studied between January 2008 and January 2009. Patients were asked to complete an IIEF-15 questionnaire to assess sexual function during the initial consultation (T0), generally whilst they waited to be called forward for an ECG or to provide blood samples. The same questionnaire was re-administered 30 days following disclosure of results (T30) and, in all cases of confirmed malignancy, at pre-surgical admission (T pre-op). In this study we examined results on perceived se...

Research paper thumbnail of 397 DIABETES MELLITUS IS A RISK FACTOR FOR RECURRENCE AND MORTALITY IN PATIENTS WITH RENAL CELL CARCINOMA

European Urology Supplements, 2011

Eur Urol Suppl 2011;10(2):139 classified as low RS showed better PFS than patients with tumors wi... more Eur Urol Suppl 2011;10(2):139 classified as low RS showed better PFS than patients with tumors with high RS (88.9% vs 63.9%, P=0.0488). Conclusions: CDK1 specific activity of tumors and the CDK2 specific activity are both associated with recurrence and prognosis. Analysis of cyclin-dependent kinase activity in the clinical setting could be a powerful approach for predicting cancer recurrence and prognosis in RCC after surgery and has potential for use as a routine laboratory test.

Research paper thumbnail of 633 SERUM SARCOSINE INCREASES THE ACCURACY OF PROSTATE CANCER DETECTION IN LOW RANGE PSA

European Urology Supplements, 2011

Research paper thumbnail of Androgen deprivation therapy regulation of beta1C integrin expression in prostate cancer

Oncology Reports

The beta1C integrin is an alternatively spliced variant of the beta1 integrin subfamily that at v... more The beta1C integrin is an alternatively spliced variant of the beta1 integrin subfamily that at variance with its wild-type counterpart, i.e., the beta1A integrin, inhibits cell proliferation in prostate cancer cells. We have recently shown that transcriptional, translational and post-translational processes contribute to the selective loss of beta1C integrin during prostate malignant transformation. Here, we investigated whether androgen deprivation therapy (ADT) may affect beta1C mRNA expression in prostate cancer. Neoplastic prostates were obtained from patients undergoing radical prostatectomy who had received neoadjuvant ADT. The beta1C mRNA level was measured by Northern hybridization experiments and compared to normal prostates obtained from patients who underwent radical cystoprostatectomy for bladder cancer. Furthermore, the beta1C integrin gene transcriptional activity was measured by nuclear Run-on assays. We found an increase of beta1C mRNA expression (208+/-11%; p<0....

Research paper thumbnail of Metabolomic profile of glycolysis and the pentose phosphate pathway identifies the central role of glucose-6-phosphate dehydrogenase in clear cell-renal cell carcinoma

Oncotarget, Jan 14, 2015

The analysis of cancer metabolome has shown that proliferating tumor cells require a large quanti... more The analysis of cancer metabolome has shown that proliferating tumor cells require a large quantities of different nutrients in order to support their high rate of proliferation. In this study we analyzed the metabolic profile of glycolysis and the pentose phosphate pathway (PPP) in human clear cell-renal cell carcinoma (ccRCC) and evaluate the role of these pathways in sustaining cell proliferation, maintenance of NADPH levels, and production of reactive oxygen species (ROS). Metabolomic analysis showed a clear signature of increased glucose uptake and utilization in ccRCC tumor samples. Elevated levels of glucose-6-phosphate dehydrogenase (G6PDH) in association with higher levels of PPP-derived metabolites, suggested a prominent role of this pathway in RCC-associated metabolic alterations. G6PDH inhibition, caused a significant decrease in cancer cell survival, a decrease in NADPH levels, and an increased production of ROS, suggesting that the PPP plays an important role in the re...

Research paper thumbnail of Obesity in kidney transplantation affects renal function but not graft and patient survival

Transplantation proceedings

The number of overweight and obese patients undergoing renal transplantation has increased dramat... more The number of overweight and obese patients undergoing renal transplantation has increased dramatically over the past two decades. Studies on graft survival and posttransplantation complications have often yielded conflicting results. Some authors have reported similar results for graft and patient survivals between obese and normal weight patients, but with a marginally increased rate of postoperative complications. In contrast, other reports note higher percentage of graft losses as well as increased mortality. In our study, we analyzed early- and long-term outcomes among obese versus nonobese kidney transplant recipients. Between January 2000 and December 2008, we performed 563 cadaveric kidney transplantations. Recipients were classified in 1 of 5 groups based on their body mass index (BMI) at the time of transplantation: group A (n = 68; BMI < 18.5); group B (n = 310; 18.6 < BMI < 24.9); group C (n = 143; 25 < BMI < 29.9); group D (n = 32; 30 < BMI < 34.9);...

Research paper thumbnail of Long term results (4 years) of high-energy transurethral microwave

European Urology Supplements, 2003

Research paper thumbnail of Penile prostheses

Therapeutic advances in urology, 2010

Penile prosthesis implantation is recognized as a valid option to obtain an artificial erection s... more 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 device...

Research paper thumbnail of CTR2 identifies a population of cancer cells with stem cell-like features in patients with clear cell renal cell carcinoma

The Journal of urology, 2014

In clear cell renal cell carcinoma tissue samples we identified and characterized a population of... more In clear cell renal cell carcinoma tissue samples we identified and characterized a population of renal cell carcinoma derived CD133+/CD24+ cancer cells. We studied differences between these cells and their nonneoplastic counterpart, tubular adult renal progenitor cells. CD133+/CD24+ renal cell carcinoma derived cells were isolated from 40 patients. The mesenchymal phenotype and stemness proteomic profile of these renal cell carcinoma derived cells were characterized. Colony forming efficiency and self-renewal ability were tested by limiting dilution. Tumorigenic properties were evaluated in vitro by soft agar assay. The angiogenic response was evaluated in vivo by the chorioallantoic membrane angiogenic assay. Microarray analysis was performed on 6 tubular adult renal progenitor cell and 6 renal cell carcinoma derived cell clones. Membrane protein expression was evaluated by flow cytometry and immunofluorescence staining. CD133+/CD24+ cells were isolated from normal and tumor kidne...

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

Archivio italiano di urologia, andrologia : organo ufficiale [di] Società italiana di ecografia urologica e nefrologica / Associazione ricerche in urologia, 2014

Germ cell tumors constitute the majority of all testicular tumors, which are relatively rare over... more 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.

Research paper thumbnail of Testicular granulosa cell tumor of adult type: A new case and a review of the literature

Urologic Oncology: Seminars and Original Investigations, 2007

Testicular granulosa cell tumor of the adult type is a very rare tumor, and, to date and our know... more Testicular granulosa cell tumor of the adult type is a very rare tumor, and, to date and our knowledge, only 23 cases of this rare testicular tumor have been reported in the literature, 5 of which developed metastases. We report a case of granulosa cell tumor of adult type in a 45-year-old man with a 15-year history of a painless increasing right testicular volume who underwent radical orchiectomy. The patient is disease-free after a 2-year follow-up, without any adjuvant therapy. Our case and a review of the literature indicate that this type of tumor is a rare, slow-growing neoplasm. Because distant metastases may occur late in the clinical course, long-term follow-up of these patients is recommended.

Research paper thumbnail of Impact of donor–recipient gender on kidney graft and patient survival: short- and long-term outcomes

World Journal of Urology, 2013

Purpose Donor and recipient gender influence on posttransplant kidney and patient survival is sti... more Purpose Donor and recipient gender influence on posttransplant 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-tomale recipient (M D M R ; n = 305), male donor-to-female recipient (M D F R ; n = 203), female donor-to-female recipient (F D F R ; n = 206), and female donor-to-male recipient (F D M R ; 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 posttransplantation.

Research paper thumbnail of Current insights in renal cell cancer pathology

Urologic Oncology: Seminars and Original Investigations, 2008

In recent years molecular biologists and pathologists have described new entities of renal cell c... more In recent years molecular biologists and pathologists have described new entities of renal cell cancer (RCC) with a totally different morphology and biology among the histotypes of renal carcinoma, but always referring to the same renal cancer disease. The evidence of a distinct biological behavior and long-term prognosis among these makes the correct pathological diagnosis of renal cancer critically important for the clinician. Advances in understanding of the pathogenesis, behavior, and importance of prognostic factors for RCC have paved the way for a revision of its classification and staging. We reviewed the role of histological classification, microscopic tumor necrosis, microscopic venous invasion, lymph node involvement and, particularly, pathological stage. In our series of patients who underwent renal surgery for neoplasm, a retrospective study established the predictive role of tumor size on recurrence rate, compared with other known prognostic factors, and we conclude that histological grade, pathological stage and tumor size remain relevant prognosticators in early stage RCC patients. In order to optimize the management of patients with RCC it is necessary to develop an interdisciplinary approach (surgeon, radiologist, pathologist, oncologist) and find new prognostic parameters at molecular and cellular levels. Many efforts are ongoing to integrate molecular data (from tissue microarrays) and clinical data (traditional prognosticators) into a molecular integrated staging system. In the postgenomic era, new tumor-associated antigens and molecules can be identified at the protein level using proteomics, providing a major opportunity for screening and finding novel targets that are the basis of new emerging therapies for RCC.

Research paper thumbnail of Extended Criteria Donor Kidney Transplantation: Comparative Outcome Analysis Between Single versus Double Kidney Transplantation at 5 Years

Transplantation Proceedings, 2010

Introduction. Dual kidney transplantation (DKT), using extended criteria donor (ECD) grafts not s... more Introduction. Dual kidney transplantation (DKT), using extended criteria donor (ECD) grafts not suitable for single kidney transplantation (SKT), has been suggested to expand the kidney donor pool. Herein, we reviewed the long-term outcomes of DKT to assess its results versus a control group of 179 ECD SKTs. The allocation policy was based on a Remuzzi score obtained from a pretransplant biopsy. Materials and methods. We analyzed SKT in 179 (31.8%) and DKT in 41 (7.3%) of 563 cadaveric transplants from 2000 to 2008. Patients with DKT versus SKT showed mean recipient ages of 54 versus 51 years. We performed 17 ipsilateral and 24 bilateral DKT. The mean score was 2.78 for SKT and 4.3/4.6 for DKT. Results. Delayed graft function requiring dialysis occurred in 23 (56.1%) DKT and 70 (39.1%) SKT recipients. Primary nonfunction was observed in 1 (2.4%) DKT and 7 (3.9%) SKT recipients respectively. One DKT patient underwent monolateral transplantectomy. In the DKT versus SKT group, patient survivals were 92% versus 95%, 89% versus 93%, and 89 versus 91% at 12, 36, and 60 months, respectively (P ϭ .3). Graft survivals were 100% versus 94%, 95% versus 90%, and 89% versus 78% at 12, 36, and 60 months, respectively (P Ͻ .001). We observed a lower incidence of chronic allograft nephropathy (P ϭ .01) and a higher incidence of surgical adverse events (P ϭ .04) in DKT. Conclusions. ECD graft survival using DKT provided better results compared with SKT, despite the use of organs from higher-risk donors. At 5 years follow-up, DKT was a safe strategy to face the organ shortage. To optimize the use of available kidneys, the criteria for DKT require further refinement and standardization. Preimplantation evaluation must maximize transplant success and protect recipients from receiving organs at increased risk of premature failure.

Research paper thumbnail of Rapamycin Inhibits PAI-1 Expression and Reduces Interstitial Fibrosis and Glomerulosclerosis in Chronic Allograft Nephropathy

Transplantation, 2008

Background. Chronic allograft nephropathy (CAN) is characterized by deposition of extracellular m... more Background. Chronic allograft nephropathy (CAN) is characterized by deposition of extracellular matrix (ECM) in all renal compartments. PAI-1 seems to play a pivotal role in ECM turnover in CAN. Rapamycin has been shown to improve long-term graft survival in patients with CAN. The aim of the study was to evaluate the molecular mechanisms underlying the beneficial effects of rapamycin on CAN progression at glomerular and tubulointerstitial level. Methods. After a biopsy-proven CAN diagnosis (T0), 18 patients on calcineurin inhibitors (CNI) were randomly assigned in a 2:1 ratio to continue CNI (6 patients) or to receive rapamycin (RAPA; 12 patients). After 2 years of treatment (T24), all patients underwent a second renal biopsy. Morphometric analysis was conducted at T0 and at T24. PAI-1 expression was evaluated at T0 and T24 by immunohistochemistry. We evaluated the effect of rapamycin on PAI-1 gene expression in cultured proximal tubular cells incubated with CD40L or thrombin, two potential CAN pathogenic mediators. Results.The RAPA group showed a significant regression of glomerulosclerotic lesions and only a 26% increase in interstitial fibrosis after 2 years compared to baseline, whereas the CNI group showed progression of glomerulosclerosis and 112% increase in fibrosis. Glomerular and tubulointerstitial PAI-1 expression was reduced compared to the baseline in the RAPA group, while they were unchanged in the CNI group. In vitro data showed that rapamycin significantly reduced PAI-1 gene expression induced by both CD40L and thrombin in proximal tubular epithelial cells. Conclusions. These data suggest that rapamycin may modulate ECM deposition in CAN reducing PAI-1 expression.

Research paper thumbnail of Tunica Albuginea Plication for the Correction of Penile Curvature

Scandinavian Journal of Urology and Nephrology, 2002

To evaluate the efficacy of tunica albuginea plication (TAP) in the correction of congenital and ... more To evaluate the efficacy of tunica albuginea plication (TAP) in the correction of congenital and acquired penile curvatures and determine key points for a successful outcome of this procedure. From December 1995 to January 2001, 40 patients with penile curvature (10 congenital and 30 secondary to Peyronie&#39;s disease) underwent surgical correction by TAP. Indications were difficult or impossible penetration, normal erectile function, stable disease. For TAP we used non-absorbable inverted stitches tied with the assistant pushing down the tunica albuginea with a mosquito clamp to create an adequate groove for the knot. The results were evaluated subjectively and objectively. At mean follow-up of 30 months, full subjective and objective success (straight penis, mild shortening, normal erection, penetration and sensation) was achieved in 37 (92.5%) patients. Objective but not subjective success was achieved in 2 patients (5%), 1 complaining of psychogenic erectile dysfunction and the other of excessive penile shortening. There was only one failure, namely persistent glans numbness due to damage of the non-mobilized neurovascular bundle. TAP is a simple and effective method for the correction of congenital and acquired penile curvatures. Key points for successful outcome are adequate preoperative evaluation and counselling, careful preparation of tunica albuginea, mobilization of urethra or neurovascular bundle when needed, use of inverted stitches carefully buried, objective postoperative evaluation with a pharmacological erection test.

Research paper thumbnail of CONCEPTION FOLLOWING PENILE RECONSTRUCTION

Plastic & Reconstructive Surgery, 1999

Research paper thumbnail of Ejaculatory disorders: pathophysiology and management

Nature Clinical Practice Urology, 2008

Ejaculatory dysfunction (EjD) is one of the most common male sexual disorders, yet EjD is still f... more Ejaculatory dysfunction (EjD) is one of the most common male sexual disorders, yet EjD is still frequently misdiagnosed or overlooked as a result of numerous patient and physician barriers. The wide spectrum of EjD ranges from premature or rapid ejaculation, through delayed ejaculation, to a complete inability to ejaculate--otherwise known as anejaculation--and includes retrograde ejaculation and painful ejaculation. Conventional algorithms for managing ejaculatory disorders are based either on an organic or psychogenic etiology, with the latter more traditionally considered the main cause. This paper reviews physiopathological, diagnostic and therapeutic aspects of ejaculation disorders, with a particular focus on the most prevalent disorder, premature ejaculation.

Research paper thumbnail of Flexible-Dose Vardenafil in a Community-Based Population of Men Affected by Erectile Dysfunction: A 12-Week Open-Label, Multicenter Trial

The Journal of Sexual Medicine, 2005

To evaluate the efficacy, safety, and tolerability of a flexible-dose regimen of vardenafil in a ... more To evaluate the efficacy, safety, and tolerability of a flexible-dose regimen of vardenafil in a community-based population of men with erectile dysfunction (ED). This was a 12-week, open-label, flexible-dose, multicenter study of unselected men with ED of diverse origins and severity. Unlike previous studies, prostatectomy-induced ED and previous unresponsiveness to sildenafil were not exclusion criteria. After 4 weeks of treatment with 10 mg of vardenafil, the dose could be continued or titrated to 5 mg or 20 mg, depending on efficacy and tolerability. After 8 weeks, another dose change was possible. Efficacy was assessed with International Index of Erectile Function erectile function (IIEF-EF) domain scores, diary questions of the Sexual Encounter Profile (SEP), and a global assessment question (GAQ) about erection improvement during the previous 4 weeks. Safety was evaluated in 497 patients, and 480 were suitable for intention-to-treat analysis. After 12 weeks of treatment, the mean per patient rate of successful intercourse, defined by an affirmative response to SEP questions 1-3, was 72%, and was related to age and ED duration. The overall success rate increased from 66% at week 4 to 77% at week 12. The mean IIEF-EF domain score of the whole population increased from 17.2 (baseline) to 24.4 (endpoint). At week 12, the best scores were obtained by patients taking 5 mg and 10 mg. At week 12, GAQ scores showed improved erection in 97.4%, 94.8%, and 78.8% of patients in the 5 mg, 10 mg, and 20 mg group, respectively. Safety was excellent: no serious drug-related event was reported, and only 2.2% of patients discontinued treatment because of side-effects. Vardenafil was effective and well tolerated in this community-based ED population that is truly representative of the general ED population. Dose titration meets the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s needs and optimizes clinical outcome.

Research paper thumbnail of Plexiform Neurofibroma of the Penis Associated with Erectile Dysfunction due to Arterial Steeling

The Journal of Sexual Medicine, 2007

Solitary involvement of the genitourinary tract by Von Recklinghousen disease (VRD) is extremely ... more Solitary involvement of the genitourinary tract by Von Recklinghousen disease (VRD) is extremely rare. Aims. This report documents the management of a case of a plexiform neurofibroma on the penile shaft associated with erectile dysfunction. The literature surrounding VRD and its effects on the genital area was also investigated. Methods. After a complete preoperative investigation of the nature of the mass and of the erectile dysfunction, the neurofibroma was completely excised with preservation of the neurovascular bundle. Results. At 6-months postoperative follow-up, there was no sign of tumor recurrence and the glans sensation was maintained. The erectile dysfunction persisted postoperatively and failed to respond to medical treatment.