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

T cells and 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

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

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

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

Long-Term Neuropsychological Outcome in Preterm Twins

Few long-term studies have yet described neuropsychological outcome in preterm twins. Our aim was to assess, by long-term evaluation, neuropsychological outcome in preterm twins in order to define a correct follow-up program. Our study was a cohort one, with an index and a comparison group. Neonatal medical records of all preterm newborns admitted to our centre between 1991 and 1997 were reviewed and selected patients were recalled. The sample population included two matched groups of children aged 6—12 years, 86 twins and 86 singletons, submitted to paediatric, neurological, psychological, and ophthalmological examinations. Inclusion criteria were twin pregnancy and gestational age 27—36 weeks for index group; same gestational age, but single pregnancy, for the comparison group. All children underwent paediatric and neuropsychiatric examinations, cognitive assessment, and psychological evaluation by standardized tests for screening of learning specific disorders and language difficulties, and finally, ophthalmological examination. In order to study their role in predicting neuropsychological outcome, we examined some perinatal prognostic factors by statistical analysis. Unfavourable neuropsychological outcome was observed in 55/172 (32%) children, with different prevalence in the two groups, 42/172 (24%) in twins and 13/172 (8%) in singletons. Statistical analysis performed for examined prognostic factors showed significant differences in neuropsychological outcome with regard only to gestational age < 32 weeks, low birth weight, intraventricular haemorrhage, and periventricular leukomalacia. The incidence of neuropsychological diseases in the two groups showed significant difference about language and learning difficulties. Our data suggest that preterm twins represent a particular high-risk category of premature babies, mostly regarding the risk of so-called “minimal brain dysfunction”, so a careful follow-up is recommended

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

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 &gt; 0.75: 56), at 6 months (RI ≤ 0.75: 237 vs RI &gt; 0.75: 31), at 1 year (RI ≤ 0.75: 229 vs RI &gt; 0.75: 39) and at 3 years (RI ≤ 0.75: 224 vs RI &gt; 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