26 research outputs found

    MYC is a metastasis gene for non-small-cell lung cancer.

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    Metastasis is a process by which cancer cells learn to form satellite tumors in distant organs and represents the principle cause of death of patients with solid tumors. NSCLC is the most lethal human cancer due to its high rate of metastasis. Lack of a suitable animal model has so far hampered analysis of metastatic progression. We have examined c-MYC for its ability to induce metastasis in a C-RAF-driven mouse model for non-small-cell lung cancer. c-MYC alone induced frank tumor growth only after long latency at which time secondary mutations in K-Ras or LKB1 were detected reminiscent of human NSCLC. Combination with C-RAF led to immediate acceleration of tumor growth, conversion to papillary epithelial cells and angiogenic switch induction. Moreover, addition of c-MYC was sufficient to induce macrometastasis in liver and lymph nodes with short latency associated with lineage switch events. Thus we have generated the first conditional model for metastasis of NSCLC and identified a gene, c-MYC that is able to orchestrate all steps of this process. Potential markers for detection of metastasis were identified and validated for diagnosis of human biopsies. These markers may represent targets for future therapeutic intervention as they include genes such as Gata4 that are exclusively expressed during lung development

    Embouchure Interaction Model for Brass Instruments

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    A common approach for simulating brass instrument sounds is that of a mass-spring system strongly coupled to an air tube resonator of a certain length. This approach, while yielding good quality timbre results for the synthesized audio, does not aid expressive sound synthesis. An improvement of this modeling design is proposed, which takes into account the independent movement of the embouchure and its influence on the sound. To achieve this interaction, vortex-induced vibration (VIV) is taken into account as an additional source of excitation for the mass-spring system. In addition to this, the model also simulates breath noise of a brass instrument player, which is dependent of the embouchure’s aperture dimensionality. The end result is a real-time VST application of a brass instrument with augmented embouchure interaction. The process loop of the VST is presented step-by-step and the application is evaluated both through informal listening and spectral measurements. From this evaluation, the model showcases a more varied and veridic timbre of brass sound, that supports a more expressive playing style

    Validation of the Italian version of wisconsin stone quality of life (WISQOL): a prospective Italian multicenter study

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    Urolithiasis is a worldwide spread condition that affects patients' Health-Related Quality of Life (HRQOL), which measurement is an important tool for routine clinical and research practice. Disease-specific HRQOL measures demonstrated to perform better in assessing the effects of specific conditions. A disease-specific questionnaire for kidney stones, the WISQOL, has been validated in different languages, but an Italian version is still missing. Our aim is to produce and validate the Italian version of WISQOL (IT-WISQOL). Patients undergoing any elective treatment for upper urinary tract stones were enrolled. A multi-step process with forward- and back-translation was used to translate WISQOL into Italian. Patients were evaluated within 15 days pre-operatively and then at 30-, 90 days post-operatively and administered both IT-WISQOL and SF-36v2. Post-operative data such as 30 days postoperative complications, late stone-related events, successful status, and stone complexity were collected. Cronbach's α was used to evaluate the internal consistency of IT-WISQOL, while Spearman's rho was used for item and inter-domain correlations and IT-WISQOL with SF-36v2 correlation. We found excellent internal consistency across all domains (α ≥ 0.88), particularly when the total score is considered (α = 0.960). Test-retest reliability showed excellent results for the total questionnaire (Pearson correlation value: 0.85). The Inter-domain association ranged from 0.497 to 0.786. Convergent validity was confirmed by a good correlation with subdomains of the SF-36v2 measures. IT-WISQOL is a reliable tool to measure HRQOL in stone patients. It shows analog characteristics if compared to English WISQOL

    Robotic revision of vesicourethral stricture after robot-assisted radical prostatectomy

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    Vesicourethral anastomotic stenosis is an uncom- mon complication following radical prostatectomy (RP). The incidence is 1–26% and after surgery most strictures occur within the first 6 months and are rare after 24 months. In 2007, the CAPSURE study, on 3310 men, found an incidence of vesico- urethral anastomotic stenosis in 8.4% of patients following RP. Nathan et al. reported an incidence rate between 22 and 26% in salvage RARP (robot- assisted radical prostatectomy) post radiotherapy or brachytherapy. The exact pathophysiology needs to be better defined. There are different factors in- volved: patient-related factors such as body mass index (BMI) and age; and technical factors such as number of surgical procedures performed by the surgeon, absence of mucosal eversion, poor vesico- urethral mucosal apposition, urinary extravasation, increased blood loss, ischemia of the bladder neck/ membranous urethra, or excessive narrowing of the urethral anastomosis at the time of the procedure. The first-line treatment of vesicourethral anasto- motic stenosis includes endoscopic dilation, inter- nal urethrotomy, and transurethral resection of the strictured fragment. Further treatment options are bladder neck reconstruction or urinary diversion. We present a case of robotic revision of urethro- vescical stricture in a 62-year-old man treated with robot-assisted radical prostatectomy for acinar adenocarcinoma of prostate International Society of Urological Pathology (ISUP) 2, pT2c R1. Oncological follow-up was negative. The last pros- tate-specific antigen (PSA) level was 0.03 ng/mL. The postoperative course was complicated by steno- sis of vesicourethral anastomosis. The patient underwent transurethral resection (TUR) of the stenotic vesicourethral anastomosis, followed by urethrotomy for stenosis 2 cm before anastomosis. During the urethrocystography, no micturition occurred, so it was necessary to posi- tion an epicystostomy. A standard transperitoneal robotic approach was planned to correct the vesicourethral anastomotic stenosis. After removing the suprapubic catheter, the first step was the dissection of the bladder from the walls of the pelvis, anteriorly and laterally, try- ing to identify the levator ani muscle and the cor- rect anatomy, which was very difficult due to fibro- sis and adhesions. We opened the cystotomy site close to the bladder neck to highlight the anatomy of the bladder neck and the bladder more clearly regarding the position of the urethral orifice. Then the next step was to reach the site of the blad- der neck and of the stenotic anastomosis location with white light from the cystoscope inserted from the urethra. The robot's light was reduced to see the light from the cystoscope: the diameter of the urethra was very nar- row even after these first incisions. The dissection of the stenotic fibrotic part of the anastomosis was not excessively close to the bladder trigone to avoid injury. The bladder neck was separated from the urethra to dissect this fibrotic tissue and then make the anas- tomosis on healthy, well-vascularized tissue, paying attention to the rectal wall posteriorly. The scar tissue was excised. We then inserted a 20 Fr silicone catheter on a wire. We developed a posterior plane between the bladder neck and the rectum in the pouch of Douglas, rejoin- ing the lateral and the anterior planes of the dissection started at the beginning of the surgery. We obtained an isolated bladder neck from the urethral stump gaining healthy tissue to redo the vesicourethral anastomosis. Performing the vesicourethral re-anastomosis is similar to the standard surgery, but the posterior reconstruction should lower the tension in the new anastomosis. When the stricture is too close to the ureteral ostia, postoperative edema could obliterate them. To avoid this, the placement of Bracci ure- teral catheters is needed and the ureteral orifices should be checked during surgery. The operative time was 150 minutes. The hospital stay was 3 days. The urethral catheter was kept indwelling for 12 days. At the removal of the urinary catheter, micturition resumed. Five months after surgery, urethrocystography demonstrated regular bladder walls, better bladder lumen expansion, and complete bladder emptying after micturition, with bladder neck within radio- logical limits

    Acute kidney injury strongly influences renal function after radical nephroureterectomy for upper tract urothelial carcinoma: A single-centre experience

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    The aim of our study was to investigate frequency and predictors both of postoperative acute kidney injury (AKI) and renal function decline in a population of consecutive upper tract urothelial carcinoma (UTUC) patients who underwent radical nephroureterectomy (RNU)

    Preoperative endogenous testosterone density predicts disease progression from localized impalpable prostate cancer presenting with PSA levels elevated up to 10 ng/mL

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    To investigate endogenous testosterone density (ETD) predicting disease progression from clinically localized impalpable prostate cancer (PCa) presenting with prostate-specific antigen (PSA) levels elevated up to 10 ng/mL and treated with radical prostatectomy

    Clinical implications of endogenous testosterone density on prostate cancer progression in patients with very favorable low and intermediate risk treated with radical prostatectomy

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    : We tested the association between endogenous testosterone density (ETD; the ratio between endogenous testosterone [ET] and prostate volume) and prostate cancer (PCa) aggressiveness in very favorable low- and intermediate-risk PCa patients who underwent radical prostatectomy (RP). Only patients with prostate-specific antigen (PSA) within 10 ng ml-1, clinical stage T1c, and International Society of Urological Pathology (ISUP) grade group 1 or 2 were included. Preoperative ET levels up to 350 ng dl-1 were classified as abnormal. Tumor quantitation density factors were evaluated as the ratio between percentage of biopsy-positive cores and prostate volume (biopsy-positive cores density, BPCD) and the ratio between percentage of cancer invasion at final pathology and prostate weight (tumor load density, TLD). Disease upgrading was coded as ISUP grade group >2, and progression as recurrence (biochemical and/or local and/or distant). Risk associations were evaluated by multivariable Cox and logistic regression models. Of 320 patients, 151 (47.2%) had intermediate-risk PCa. ET (median: 402.3 ng dl-1) resulted abnormal in 111 (34.7%) cases (median ETD: 9.8 ng dl-1 ml-1). Upgrading and progression occurred in 109 (34.1%) and 32 (10.6%) cases, respectively. Progression was predicted by ISUP grade group 2 (hazard ratio [HR]: 2.290; P = 0.029) and upgrading (HR: 3.098; P = 0.003), which was associated with ISUP grade group 2 (odds ratio [OR]: 1.785; P = 0.017) and TLD above the median (OR: 2.261; P = 0.001). After adjustment for PSA density and body mass index (BMI), ETD above the median was positively associated with BPCD (OR: 3.404; P < 0.001) and TLD (OR: 5.238; P < 0.001). Notably, subjects with abnormal ET were more likely to have higher BPCD (OR: 5.566; P = 0.002), as well as TLD (OR: 14.998; P = 0.016). Independently by routinely evaluated factors, as ETD increased, BPCD and TLD increased, but increments were higher for abnormal ET levels. In very favorable cohorts, ETD may further stratify the risk of aggressive PCa

    Advanced age portends poorer prognosis after radical prostatectomy: a single center experience

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    Introduction and objective Although advanced age doesn't seem to impair oncological outcomes after robot-assisted radical prostatectomy (RARP), elderly patients have increased rates of prostate cancer (PCa) related deaths due to a higher incidence of high-risk disease. The potential unfavorable impact of advanced age on oncological outcomes following RARP remains an unsettled issue. We aimed to evaluate the oncological outcome of PCa patients > 69 years old in a single tertiary center. Materials and methods 1143 patients with clinically localized PCa underwent RARP from January 2013 to October 2020. Analysis was performed on 901 patients with available follow-up. Patients >= 70 years old were considered elderly. Unfavorable pathology included ISUP grade group > 2, seminal vesicle, and pelvic lymph node invasion. Disease progression was defined as biochemical and/or local recurrence and/or distant metastases. Results 243 cases (27%) were classified as elderly patients (median age 72 years). Median (IQR) follow-up was 40.4 (38.7-42.2) months. Disease progression occurred in 159 cases (17.6%). Elderly patients were more likely to belong to EAU high-risk class, have unfavorable pathology, and experience disease progression after surgery (HR = 5.300; 95% CI 1.844-15.237; p = 0.002) compared to the younger patients. Conclusions Elderly patients eligible for RARP are more likely to belong to the EAU high-risk category and to have unfavorable pathology that are independent predictors of disease progression. Advanced age adversely impacts on oncological outcomes when evaluated inside these unfavorable categories. Accordingly, elderly patients belonging to the EAU high-risk should be counseled about the increased risk of disease progression after surgery

    Normal preoperative endogenous testosterone levels predict prostate cancer progression in elderly patients after radical prostatectomy

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    Background: The impact of senior age on prostate cancer (PCa) oncological outcomes following radical prostatectomy (RP) is controversial, and further clinical factors could help stratifying risk categories in these patients. Objective: We tested the association between endogenous testosterone (ET) and risk of PCa progression in elderly patients treated with RP. Design: Data from PCa patients treated with RP at a single tertiary referral center, between November 2014 and December 2019 with available follow-up, were retrospectively evaluated. Methods: Preoperative ET (classified as normal if >350 ng/dl) was measured for each patient. Patients were divided according to a cut-off age of 70 years. Unfavorable pathology consisted of International Society of Urologic Pathology (ISUP) grade group >2, seminal vesicle, and pelvic lymph node invasion. Cox regression models tested the association between clinical/pathological tumor features and risk of PCa progression in each age subgroup. Results: Of 651 included patients, 190 (29.2%) were elderly. Abnormal ET levels were detected in 195 (30.0%) cases. Compared with their younger counterparts, elderly patients were more likely to have pathological ISUP grade group >2 (49.0% versus 63.2%). Disease progression occurred in 108 (16.6%) cases with no statistically significant difference between age subgroups. Among the elderly, clinically progressing patients were more likely to have normal ET levels (77.4% versus 67.9%) and unfavorable tumor grades (90.3% versus 57.9%) than patients who did not progress. In multivariable Cox regression models, normal ET [hazard ratio (HR) = 3.29; 95% confidence interval (CI) = 1.27-8.55; p = 0.014] and pathological ISUP grade group >2 (HR = 5.62; 95% CI = 1.60-19.79; p = 0.007) were independent predictors of PCa progression. On clinical multivariable models, elderly patients were more likely to progress for normal ET levels (HR = 3.42; 95% CI = 1.34-8.70; p = 0.010), independently by belonging to high-risk category. Elderly patients with normal ET progressed more rapidly than those with abnormal ET. Conclusion: In elderly patients, normal preoperative ET independently predicted PCa progression. Elderly patients with normal ET progressed more rapidly than controls, suggesting that longer exposure time to high-grade tumors could adversely impact sequential cancer mutations, where normal ET is not anymore protective on disease progression
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