A right colon pouch with a novel efferent channel concept: long-term results of the Turin pouch.

PURPOSE: To report stoma stenosis rates and efferent channel (EC) complications at long term follow-up for Turin pouch (TP). METHODS: This is a retrospective analysis of the prospectively maintained database of patients who underwent TP between March 2006 and May 2018. The TP is a U-shaped right colon pouch. The EC was conceived by the tubularization of 5 cm of the colon wall with the use of a stapler and sutured to the skin (EC-cutaneostomy). The ureters are sutured separately to the last 10 cm of ileum before the ileocecal valve. In literature, catheterization problems have been described on average in 20.3% of patients and stoma stenosis in 19.5% of the patients with flap valve systems. RESULTS: Thirty-eight consecutive patients underwent a TP procedure. The median age was 55 years (IQR: 52-60). Median operative time was 201 min (IQR: 170-210), median reconstructive time was 61 min (IQR: 55-65) and the blood loss was 244 ml (IQR: 150-300) and 4 patients (10.5%) needed blood transfusions. The median follow-up was 52 months (IQR: 37-92). Complete 24h continence was achieved in 34 (89%) patients. Seven (18.4%) patients reported difficulties in EC catheterization and 4 (10.5%) patients had stoma stenosis. This study is limited by the relatively small number of patients. CONCLUSION: In relation to similar systems, the TP seems to offer comparatively good functional results but EC and stoma complications were lower than other pouch variants in literature.

A multicentric study on accurate grading of prostate cancer with systematic and MRI/US fusion targeted biopsies: comparison with final histopathology after radical prostatectomy.

OBJECTIVE: To evaluate the accuracy in histologic grading of MRI/US image fusion biopsy by comparing histopathology between systematic biopsies (SB), targeted biopsies (TB) and the combination of both (SB + TB) with the final histopathologic outcomes of radical prostatectomy specimens. MATERIALS AND METHODS: Retrospective, multicentric study of 443 patients who underwent SB and TB using MRI/US fusion technique (Urostation® and Trinity®) prior to radical prostatectomy between 2010 and 2017. Cochran's Q test and McNemar test were conducted as a post hoc test. Uni-multivariable analyses were performed on several clinic-pathological variables to analyze factors predicting histopathological concordance for targeted biopsies. RESULTS: Concordance in ISUP (International Society of Urological Pathology) grade between SB, TB and SB + TB with final histopathology was 49.4%, 51.2%, and 63.2% for overall prostate cancer and 41.2%, 48.3%, and 56.7% for significant prostate cancer (ISUP grade ≥ 2), respectively. Significant difference in terms of concordance, downgrading and upgrading was found between SB and TB (ISUP grade ≥ 2 only), SB and SB + TB, TB and SB + TB (overall ISUP grade and ISUP grade ≥ 2) (p < 0.001). Total number of cores and previous biopsies were significant independent predictive factors for concordance with TB technique. CONCLUSION: In this retrospective study, combination of SB and TB significantly increased concordance with final histopathology despite a limited additional number of cores needed.

Adjuvant chemotherapy with cisplatin and gemcitabine versus chemotherapy at relapse in patients with muscle-invasive bladder cancer submitted to radical cystectomy: an Italian, multicenter, randomized phase III trial.

BACKGROUND: The purpose of the study was to evaluate the benefit of adjuvant chemotherapy (AC) versus surgery alone in patients with muscle-invasive bladder cancer (MIBC). PATIENTS AND METHODS: One hundred and ninety-four patients with pT2G3, pT3-4, N0-2 transitional cell bladder carcinoma were randomly allocated to control (92 patients) or to four courses of AC (102 patients). These latter patients were further randomly assigned to receive gemcitabine 1000 mg/m(2) days 1, 8 and 15 and cisplatin 70 mg/m(2) day 2 or gemcitabine as above plus cisplatin 70 mg/m(2) day 15, every 28 days. RESULTS: At a median follow-up of 35 months, the 5-year overall survival (OS) was 48.5%, with no difference between the two arms [P = 0.24, hazard ratio (HR) 1.29, 95% confidence interval (CI) 0.84-1.99]. Mortality hazard was significantly correlated with Nodes (N) and Tumor (T) stage. The control and AC arms had comparable disease-free survival (42.3% and 37.2%, respectively; P = 0.70, HR 1.08, 95% CI 0.73-1.59). Only 62% of patients received the planned cycles. A significant higher incidence of thrombocytopenia was observed in patients receiving cisplatin on day 2 (P = 0.006). A similar global quality of life was observed in the two arms. CONCLUSION: The study was underpowered to demonstrate that AC with cisplatin and gemcitabine improves OS and disease-free survival in patients with MIBC.

Pressure blades and total cutting edge: an experiment in lithic technology.

Pressure techniques were used to remove 83 blades from a preformed obsidian core weighing 820 grams, yielding 17.32 meters of acute cutting edge. The blades represented 91 percent of the original weight (2.1 centimeters of acute cutting edge per gram of original material), thus demonstrating the efficiency of the pressure-blade techniques for the production of acute cutting edges.

Elastic fusion biopsy versus systematic biopsy for prostate cancer detection: Results of a multicentric study on 1,119 patients. / Evaluación de la biopsia de fusión elástica vs. biopsia sistemática para la detección del cáncer de próstata: resultados de un estudio multicéntrico en 1.119 pacientes.

OBJECTIVES: To assess the accuracy of targeted and systematic biopsies for the detection of prostate cancer (PCa) and clinically significant PCa (csPCa) in the everyday practice, evaluating the need for additional systematic biopsies at the time of targeted biopsy. PATIENTS AND METHODS: From our multicentric database gathering data on 2,115 patients who underwent fusion biopsy with Koelis™ system between 2010 and 2017, we selected 1,119 patients who received targeted biopsies (a median of 3 for each target), followed by systematic sampling of the prostate (12 to 14 cores). Overall and clinically significant cancer detection rate (CDR) of Koelis™ fusion biopsies were assessed, comparing target and systematic biopsies. Secondary endpoint was the identification of predictors of PCa detection. RESULTS: The CDR of targeted biopsies only was 48% for all cancers and 33% for csPCa. The performance of additional, systematic prostate sampling improved the CDR of 15% for all cancers and of 12% for csPCa. PCa was detected in 35%, 69%, and 92% of patients with lesions scored as PI-RADS 3, 4 and 5, respectively. Elevated PI-RADS score and positive digital rectal examination were predictors of PCa, whereas biopsy-naïve status was associated with csPCa. CONCLUSION: In the everyday practice target biopsy with Koelis™ achieves a good CDR for all PCa and csPCa, which is significantly improved by subsequent systematic sampling of the prostate. The outstanding outcomes of fusion biopsy are confirmed also in biopsy-naïve patients. Elevated PI-RADS score and positive digital rectal examination are strongly associated with presence of PCa.

C-Met/miR-130b axis as novel mechanism and biomarker for castration resistance state acquisition.

Although a significant subset of prostate tumors remain indolent during the entire life, the advanced forms are still one of the leading cause of cancer-related death. There are not reliable markers distinguishing indolent from aggressive forms. Here we highlighted a new molecular circuitry involving microRNA and coding genes promoting cancer progression and castration resistance. Our preclinical and clinical data demonstrated that c-Met activation increases miR-130b levels, inhibits androgen receptor expression, promotes cancer spreading and resistance to hormone ablation therapy. The relevance of these findings was confirmed on patients' samples and by in silico analysis on an independent patient cohort from Taylor's platform. Data suggest c-Met/miR-130b axis as a new prognostic marker for patients' risk assessment and as an indicator of therapy resistance. Our results propose new biomarkers for therapy decision-making in all phases of the pathology. Data may help identify high-risk patients to be treated with adjuvant therapy together with alternative cure for castration-resistant forms while facilitating the identification of possible patients candidates for anti-Met therapy. In addition, we demonstrated that it is possible to evaluate Met/miR-130b axis expression in exosomes isolated from peripheral blood of surgery candidates and advanced patients offering a new non-invasive tool for active surveillance and therapy monitoring.

Stapled orthotopic ileal neobladder after radical cystectomy for bladder cancer: Functional results and complications over a 20-year period.

AIMS: To present the long term-results and complications of a large series of stapled ileal orthotopic neobladders. MATERIALS AND METHODS: From 1992 to 2012 we performed 606 radical cystectomies with stapled orthotopic neobladder substitution in male patients. The median patient age was 65 years (interquartile range [IQR]: 58-71). RESULTS: Median operative time was 205 min (IQR: 180-225). The overall survival rates at 5, 10, 15, and 20 yr were 68% (336 of 494), 55% (207 of 376), 38% (98 of 259), and 23% (14 of 62), respectively, and the disease specific survival rates were 75% (371 of 494), 59% (222 of 376), 50% (130 of 259), and 35% (22 of 62), respectively. After a median follow-up of 81 months (IQR: 30-144), a total of 147 early (less than 90 days) complications (38 diversion related, 109 diversion unrelated) occurred in 144 patients (24%); 163 late complications (141 diversion related, 22 diversion unrelated) affected 141 patients (23%). At 60 months, daytime and nighttime continence was complete in 96% and 72% of cases, respectively. Urodynamic studies showed that maximum capacity, residual volume, maximum flow rate, pressure at maximum capacity, and maximum outlet closure pressure were not statistically different at 12 and 60 months postoperatively. CONCLUSIONS: The use of a stapler when performing orthotopic neobladders significantly reduces the operating time, and offers good functional results with acceptable complication rates. Our results could encourage the use of a stapler when performing an ileal neobladder during laparoscopic and robotic radical cystectomies.

A microRNA code for prostate cancer metastasis.

Although the development of bone metastasis is a major detrimental event in prostate cancer, the molecular mechanisms responsible for bone homing and destruction remain largely unknown. Here we show that loss of miR-15 and miR-16 in cooperation with increased miR-21 expression promote prostate cancer spreading and bone lesions. This combination of microRNA endows bone-metastatic potential to prostate cancer cells. Concomitant loss of miR-15/miR-16 and gain of miR-21 aberrantly activate TGF-ß and Hedgehog signaling, that mediate local invasion, distant bone marrow colonization and osteolysis by prostate cancer cells. These findings establish a new molecular circuitry for prostate cancer metastasis that was validated in patients' cohorts. Our data indicate a network of biomarkers and druggable pathways to improve patient treatment.

Trends in the use of partial nephrectomy for cT1 renal tumors: Analysis of a 10-yr European multicenter dataset.

AIM: Although extensively addressed in US registries, the utilization rate of Partial Nephrectomy has been poorly addressed in European settings. Our aim is to evaluate the impact of hospital volume on the use of PN for cT1 renal tumors. METHODS: 2526 patients with cT1N0M0 renal tumors treated with either PN or radical nephrectomy at 10 European centres in the last decade were included in the analysis. Joinpoint regression analysis was used to identify significant changes over time in linear slope of the trend for each center. The correlation between yearly caseload and the slopes was assessed with the non-parametric Spearman test. Coincident pairwise tests and regression analyses were used to generate and compare the trends of high-volume (HV), mid-volume (MV) and low-volume (LV) groups. RESULTS: Yearly caseload was significantly associated with increased use of PN (R = 0.69, p = 0.028). The utilization rate of PN was stable at LV centres (p = 0.67, p = 0.7, p = 0.76, for cT1, cT1a, and cT1b tumors, respectively), while increased significantly at MV (p = 0.002, 0.0005 and 0.007, respectively) and HV centers (all p < 0.0001). Regression analysis confirmed the trends for HV and MV as significantly different from those observed in LV centres (all p ≤ 0.002) and highlighted significant differences also between MV and HV centres (all p ≤ 0.03). CONCLUSIONS: We confirmed the association between caseload and the use of PN for cT1 tumors. Our findings suggest that a minimum caseload might turn the tide also in LV centres while a selective referral to HV centers for cT1b tumors should be considered.

Inhibitory effect of nicotinamide on in vitro and in vivo production of tumor necrosis factor-alpha.

Nicotinamide, a pellagra-preventive factor, has multiple functions such as inhibition of poly-ADP-ribose synthetase, inhibition of inducible nitric oxide synthase, free radical scavenging and suppression of major histocompatibility complex class II expression and ICAM-1 expression on endothelial cells. In addition to these, we have found an inhibitory effect of nicotinamide on production of tumor necrosis factor-alpha (TNF-alpha) in vitro and in vivo. Lipopolysaccharide (LPS)-induced in vitro TNF-alpha production by human peripheral blood mononuclear cells, measured by enzyme-linked immunosorbent assay (ELISA), was significantly inhibited with more than 1 x 10(-3) mol/l of nicotinamide, while interleukin-1-beta was not inhibited and interleukin-6 was slightly inhibited even with 10(-2) mol/l. Oral administration of nicotinamide with more than 62.5 mg/kg also significantly inhibited LPS-induced serum TNF-alpha production measured by ELISA and bioassay in Balb/c mice. Thus, nicotinamide has an inhibitory effect on TNF-alpha production that may be beneficial to TNF-alpha-mediated diseases.

Effects of complete androgen blockade for 12 and 24 weeks on the pathological stage and resection margin status of prostate cancer.

AIMS: To compare the pathological stage and surgical margin status in patients undergoing either immediate radical prostatectomy or 12 and 24 weeks of neoadjuvant hormonal treatment (NHT) in a prospective, randomised study. METHODS: Whole mount sections of 393 radical prostatectomy specimens were evaluated: 128 patients had immediate surgery, 143 were treated for 12 weeks and 122 for 24 weeks with complete androgen blockade. RESULTS: Histopathology revealed organ confined tumours in 40.4% of patients with clinical stage B disease in the immediate surgery group, whereas 12 and 24 weeks of NHT increased the number of organ confined tumours to 54.6% and 64.8%, respectively. Among patients with clinical stage C tumours, pathological staging found organ confined disease in 10.4%, 31.4%, and 61.2% in the immediate surgery, 12 weeks of NHT, and 24 weeks of NHT groups, respectively. Preoperative NHT caused a significant decrease in positive margins both in patients with clinical stage B and C disease. The extent of margin involvement was not influenced by preoperative treatment. CONCLUSIONS: Neoadjuvant androgenic suppression is effective in reducing both the pathological stage and the positive margin rate in patients with stage B and C prostatic cancer undergoing radical surgery. Some beneficial effects are evident in those patients treated for 24 weeks, and it is reasonable to assume that the optimal duration of NHT is longer than three months.

Determination of nitric oxide by bromate oxidation of the nitrosyl ethylenediaminetetra-acetatoiron(II) complex.

A new spectrophotometric method for nitric oxide is proposed, based on formation of the nitrosyl-ethylenediaminetetra-acetatoiron(II) complex [Fe(II)NO-edta] by absorption of NO in Fe(II)edta solution and spectrophotometric determination of the NO(-)(2) produced by oxidation of the Fe(II)NO-edta complex by potassium bromate. The oxidation is easily performed completely and the absorption efficiency for 10.1-102.0 ppm NO (flow-rate, 100 ml/min) is nearly 100%. The detection limit is about 3 ppm for a sampling absorption time of 30 min.

[Nephrogenic adenoma of the bladder associated with urinary tuberculosis. Case report]. / L'adenoma nefrogenico della vescica associato a tubercolosi urinaria. Contributo casisitico.

Nephrogenic adenoma is an uncommon benign lesion of the urinary tract, that histologically is characterised by glandular-like aspects resembling the distal part of the nephron. It is usually associated with antecedent inflammation, surgical procedures or other injuries. Personal experience with one additional case nephrogenic adenoma of the bladder in a patient with urinary tract tuberculosis is presented.

Simple circular odor chart for characterization of trace amounts of odorants discharged from thirteen odor sources.

A simple circular odor chart is proposed for the explanation of the relationship between sensory responses (to odor quality and intensity) to odors and chemical analysis data of the odorants responsible for each odor discharged from thirteen odor sources. The odorants were classified into eight odorant groups and were analyzed by a systematic gas chromatographic (GC) technique. The characterization of the trace amounts of the odorants was carried out by using the values of a new proposed unit (pOU) based on the ratio of detected concentration to recognition threshold value. The calculated pOU values of the eight groups were plotted in circular charts. It was found that the shape and size of each circular odor chart represent the quality and the intensity of each odor.

[Transurethral needle ablation (TUNA) of the prostate: preliminary results]. / Ablazione transuretrale di prostata con aghi (TUNA): risultati preliminari.

A multicentric prospective study was designed in Italy to verify the efficacy and the safety of TUNA-BPH patients treatment. The study is co-ordinate by Progress in Urology Association was started in January 1994. Thirty five patients were treated (Mean age 68.4 +/- 4.1 aa). All patients were selected and evaluated to respect the recommendations of the International Consensus Committee (Paris 1993). The procedure was performed with lidocaine 2.5% urethral gel, oral intake of 10 mg of diazepam and steroidal antiphlogistic drugs 1 hour before treatment. Maximal number of prostatic lesions were 6; in 2 BPH initial cases were done 2 lesions alone. The treatment was interrupted at the third lesion in 2 patients because uncomfortable. Hematuria was observed in all patients, but it was resolved within 12 hours. Irritative symptoms were referred by 10 patients (28.6%) and they spontaneously were insignificant within 24 hours. One patient had an acute prostatitis. In 15 patients (42.6%) was necessary to put a suprapubic cystostomy, but all except one voided within 36 hours. We noted narrow connection between prostatic lesions number and urinary acute retention after TUNA. The average follow-up is 3.2 months (range 0.5-6). At the follow-up urine culture was always negative and PSA values increased in the first month. The value of PSA was always higher than pre-treatment, but from 1 month to 3 months progressively reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Benefits and shortcomings of superselective transarterial embolization of renal tumors before zero ischemia laparoscopic partial nephrectomy.

AIMS: To report feasibility, safety and effectiveness of "zero-ischemia" laparoscopic partial nephrectomy (LPN) following preoperative superselective transarterial embolization (STE) for clinical T1 renal tumors. METHODS: We retrospectively reviewed perioperative data of 23 consecutive patients, who underwent STE prior LPN between March 2010 and November 2012 for incidental clinical T1 renal mass. STE was performed by two experienced radiologists the day before surgery. Surgical procedures were performed in extended flank position, transperitoneally, by a single surgeon. RESULTS: Mean patients age was 68 years (range 56-74), mean tumor size was 3.5 cm (range 2.2-6.3 cm). STE was successfully completed in 16 patients 12-15 h before surgery. In 4 cases STE failed to provide a complete occlusion of all feeding arteries, while in 3 cases the ischemic area was larger than expected. LPN was successfully completed in all patients but one where open conversion was necessary; a "zero-ischemia" approach was performed in 19/23 patients (82.6%) while hilar clamp was necessary in 4 cases, with a mean warm-ischemia time of 14.8 min (range 5-22). Mean operative time was 123 min (range 115-130) and mean intraoperative blood loss was 250 mL (range 20-450). No patient experienced postoperative acute renal failure and no patient developed new onset IV stage chronic kidney disease at 1-yr follow-up. CONCLUSIONS: STE is a viable option to perform "zero-ischemia" LPN at beginning of learning curve; however, hilar clamp was necessary to achieve a relatively blood-less field in 17.4% of cases.

BTG2 loss and miR-21 upregulation contribute to prostate cell transformation by inducing luminal markers expression and epithelial-mesenchymal transition.

Prostate cancer is one of the leading causes of cancer-related death in men. Despite significant advances in prostate cancer diagnosis and management, the molecular events involved in the transformation of normal prostate cells into cancer cells have not been fully understood. It is generally accepted that prostate cancer derives from the basal compartment while expressing luminal markers. We investigated whether downregulation of the basal protein B-cell translocation gene 2 (BTG2) is implicated in prostate cancer transformation and progression. Here we show that BTG2 loss can shift normal prostate basal cells towards luminal markers expression, a phenotype also accompanied by the appearance of epithelial-mesenchymal transition (EMT) traits. We also show that the overexpression of microRNA (miR)-21 suppresses BTG2 levels and promotes the acquisition of luminal markers and EMT in prostate cells. Furthermore, by using an innovative lentiviral vector able to compete with endogenous mRNA through the overexpression of the 3'-untranslated region of BTG2, we demonstrate that in prostate tumor cells, the levels of luminal and EMT markers can be reduced by derepression of BTG2 from microRNA-mediated control. Finally, we show that the loss of BTG2 expression confers to non-tumorigenic prostate cells ability to grow in an orthotopic murine model, thus demonstrating the central role of BTG2 downregulaton in prostate cancer biology.

Control of tumor and microenvironment cross-talk by miR-15a and miR-16 in prostate cancer.

The interaction between cancer cells and microenvironment has a critical role in tumor development and progression. Although microRNAs regulate all the major biological mechanisms, their influence on tumor microenvironment is largely unexplored. Here, we investigate the role of microRNAs in the tumor-supportive capacity of stromal cells. We demonstrated that miR-15 and miR-16 are downregulated in fibroblasts surrounding the prostate tumors of the majority of 23 patients analyzed. Such downregulation of miR-15 and miR-16 in cancer-associated fibroblasts (CAFs) promoted tumor growth and progression through the reduced post-transcriptional repression of Fgf-2 and its receptor Fgfr1, which act on both stromal and tumor cells to enhance cancer cell survival, proliferation and migration. Moreover, reconstitution of miR-15 and miR-16 impaired considerably the tumor-supportive capability of stromal cells in vitro and in vivo. Our data suggest a molecular circuitry in which miR-15 and miR-16 and their correlated targets cooperate to promote tumor expansion and invasiveness through the concurrent activity on stromal and cancer cells, thus providing further support to the development of therapies aimed at reconstituting miR-15 and miR-16 in advanced prostate cancer.