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BackgroundSalvage lymph node dissection (sLND) for nodal recurrence in prostate cancer (PCa) patients with biochemical recurrence (BCR) is still not recommended in current guidelines, because of the diagnostic inaccuracy of current conventional imaging. To assess the performance of [68Ga] Ga-prostate-specific membrane antigen conjugate 11 positron emission tomography (PSMA-PET) in detecting PCa lymph node metastasis using pathologic confirmation through sLND.MethodsLiterature search was conducted using the MEDLINE, SCOPUS, Web of Science, and Cochrane Library on November 11th, 2018 to identify the eligible studies. Studies were eligible if they investigated the diagnostic performance of PSMA-PET before sLND in PCa patients with BCR and reported the number of true positive, false positive, false negative, and true negative on a lesion-based and/or field-based analyses to compare with histopathologic findings in sLND specimens.ResultsFourteen studies published between 2015 and 2018 comprising 462 patients were selected in this systematic review and meta-analysis. The positive predictive value of PSMA-PET before sLND on a patient-based analysis ranged between 0.70 and 0.93. The pooled sensitivity using lesion-based and field-based analyses were 0.84 (95%CI: 0.61–0.95) and 0.82 (95%CI: 0.72–0.89), respectively. The pooled specificity using lesion-based and field-based analyses were 0.97 (95%CI: 0.95–0.99) and 0.95 (95%CI: 0.70–0.99), respectively. The diagnostic odds ratio using lesion-based and field-based analyses were 189 (95%CI: 39–920) and 82 (95%CI: 8–832), respectively.ConclusionsPSMA-PET before sLND provided highly accurate performance with clinically relevant high positive and negative predictive values for detecting lymph node disease in patients with BCR after local treatment with curative intent for PCa. PSMA-PET can identify the patients who are likely to benefit from sLND and possibly direct to lesion or region-based dissection.

BackgroundPreoperative blood-based inflammatory biomarkers have been suggested to improve staging and prognostication in patients with upper-tract urothelial carcinoma (UTUC). Neutrophil-to-lymphocyte ratio (NLR) is the most studied blood-based biomarker. NLR is an indicator of systemic inflammation and has been shown to be associated with a poor prognosis in various malignancies. The aim of this study was to analyze the current evidence regarding the prognostic significance of preoperative NLR in patients undergoing radical nephroureterectomy (RNU) for UTUC to assess its prognostic potential.Materials and methodsA systematic search of Web of Science, Medline/PubMed and Cochrane library was performed on the 1st of October, 2017. Studies were deemed eligible if they compared patients with high NLR before surgical treatment for UTUC to patients with low NLR to determine its predictive value for survival using multivariable logistic regression analysis. We performed a formal meta-analysis for cancer-specific survival (CSS), recurrence-free survival (RFS) and overall survival (OS).ResultsNine studies including a total of 4385 patients assessing the importance of NLR were included in this meta-analysis. The cut-off NLR varied in the eligible studies ranging from 2 to 3. Increased pretreatment NLR predicted OS (pooled HR 1.64 95% CI; 1.23–2.17), RFS (pooled HR 1.60 95% CI; 1.16–2.20) and CSS (pooled HR 1.73 95% CI; 1.23–2.44) in multivariable analyses.ConclusionIn this meta-analysis, preoperative blood-based NLR is associated with worse prognosis in patients who underwent RNU for UTUC. NLR could be used to improve clinical decision making regarding RNU vs. kidney-sparing surgery, extent of lymphadenectomy, perioperative systemic therapy and follow-up schedule.

PurposeThe accurate selection of patients who are most likely to benefit from neoadjuvant chemotherapy is an important challenge in oncology. Serum AGR has been found to be associated with oncological outcomes in various malignancies. We assessed the association of pre-therapy serum albumin-to-globulin ratio (AGR) with pathologic response and oncological outcomes in patients treated with neoadjuvant platin-based chemotherapy followed by radical nephroureterectomy (RNU) for clinically non-metastatic UTUC.MethodsWe retrospectively included all clinically non-metastatic patients from a multicentric database who had neoadjuvant platin-based chemotherapy and RNU for UTUC. After assessing the pretreatment AGR cut‐off value, we found 1.42 to have the maximum Youden index value. The overall population was therefore divided into two AGR groups using this cut‐off (low, < 1.42 vs high, ≥ 1.42). A logistic regression was performed to measure the association with pathologic response after NAC. Univariable and multivariable Cox regression analyses tested the association of AGR with OS and RFS.ResultsOf 172 patients, 58 (34%) patients had an AGR < 1.42. Median follow-up was 26 (IQR 11–56) months. In logistic regression, low AGR was not associated with pathologic response. On univariable analyses, pre-therapy serum AGR was neither associated with OS HR 1.15 (95% CI 0.77–1.74; p = 0.47) nor RFS HR 1.48 (95% CI 0.98–1.22; p = 0.06). These results remained true regardless of the response to NAC.ConclusionPre-therapy low serum AGR before NAC followed by RNU for clinically high-risk UTUC was not associated with pathological response or long-term oncological outcomes. Biomarkers that can complement clinical factors in UTUC are needed as clinical staging and risk stratification are still suboptimal leading to both over and under treatment despite the availability of effective therapies.

PurposeTo investigate the prognostic role of expression of urokinase-type plasminogen activator system members, such as urokinase-type activator (uPA), uPA-receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1), in patients treated with radical prostatectomy (RP) for prostate cancer (PCa).MethodsImmunohistochemical staining for uPA system was performed on a tissue microarray of specimens from 3121 patients who underwent RP. Cox regression analyses were performed to investigate the association of overexpression of these markers alone or in combination with biochemical recurrence (BCR). Decision curve analysis was used to assess the clinical impact of these markers.ResultsuPA, uPAR, and PAI-1 were overexpressed in 1012 (32.4%), 1271 (40.7%), and 1311 (42%) patients, respectively. uPA overexpression was associated with all clinicopathologic characteristics of biologically aggressive PCa. On multivariable analysis, uPA, uPAR, and PAI-1 overexpression were all three associated with BCR (HR: 1.75, p < 0.01, HR: 1.22, p = 0.01 and HR: 1.20, p = 0.03, respectively). Moreover, the probability of BCR increased incrementally with increasing cumulative number of overexpressed markers. Decision curve analysis showed that addition of uPA, uPAR, and PAI-1 resulted in a net benefit compared to a base model comparing standard clinicopathologic features across the entire threshold probability range. In subgroup analyses, overexpression of all three markers remained associated with BCR in patients with favorable pathologic characteristics.ConclusionOverexpression of uPA, uPAR, and PAI-1 in PCa tissue were each associated with worse BCR. Additionally, overexpression of all three markers is informative even in patients with favorable pathologic characteristics potentially helping clinical decision-making regarding adjuvant therapy and/or intensified follow-up.

ObjectivesTo evaluate the concordance rate of lymphovascular invasion (LVI) and variant histology (VH) of transurethral resection (TUR) with radical cystectomy (RC) specimens. Furthermore, to evaluate the value of LVI and VH at TUR for predicting non-organ confined (NOC) disease, lymph node metastasis, and survival outcomes.Patients and methodsTwo hundred and sixty-eight patients who underwent TUR and subsequent RC were reviewed. Logistic regression analyses were performed to evaluate the association of LVI and VH with NOC and lymph node metastasis at RC. Cox regression analyses were used to estimate recurrence-free survival (RFS) and cancer-specific survival (CSS).ResultsLVI and VH were detected in 13.8 and 11.2% of TUR specimens, and in 30.2 and 25.4% of RC specimens, respectively. The concordance rate between LVI and VH at TUR and subsequent RC was 69.8 and 83.6%, respectively. They were both associated with adverse pathological features such as lymph node metastasis and advanced stage. TUR LVI and VH were both independently associated with lymph node metastasis and TUR VH was independently associated with NOC. On univariable Cox regression analyses, TUR LVI was associated with RFS and CSS while TUR VH was only associated with RFS. Only TUR LVI was independently associated with RFS.ConclusionDetection of LVI is missed in a third of TUR specimens while VH seems more accurately identified. TUR LVI and VH are associated with more advanced disease and LVI predicts disease recurrence. Assessment and reporting of LVI and VH on TUR specimen are important for risk stratification and decision-making.

Purpose: To assess the rate and severity of functional outcomes after salvage therapy for radiation recurrent prostate cancer. Methods: This systematic review of the MEDLINE/PubMed database yielded 35 studies, evaluating salvage radical prostatectomy (RP), brachytherapy (BT), high-intensity focal ultrasound (HIFU) and cryotherapy (CT) after failure of primary radiation therapy. Data on pre- and post-salvage rates and severity of functional outcomes (urinary incontinence, erectile dysfunction, and lower urinary tract symptoms) were collected from each study. Results: The rates of severe urinary incontinence ranged from 28–88%, 4.5–42%, 0–6.5%, 2.4–8% post salvage RP, HIFU, CT and BT, respectively. The rates of erectile dysfunction were relatively high reaching as much as 90%, 94.6%, 100%, 62% following RP, HIFU, CT and BT, respectively. Nonetheless, the high pre-salvage rates of ED preclude accurate estimation of the effect of salvage therapy. There was an increase in the median IPSS following salvage HIFU, BT and CT ranging from 2.5–3.4, 3.5–12, and 2, respectively. Extended follow-up showed a return-to-baseline IPSS in a salvage BT study. The reported data suffer from selection, reporting, publication and period of study biases, making inter-study comparisons inappropriate. Conclusions: local salvage therapies for radiation recurrent PCa affect continence, lower urinary tract symptoms and sexual functions. The use of local salvage therapies may be warranted in the setting of local disease control, but each individual decision must be made with the informed patient in a shared decision working process.

Introduction To evaluate temporal trends in the delivery and extent of lymphadenectomy (LND) in radical nephroureterectomy (RNU) performed in upper tract urothelial carcinoma (UTUC) patients. Methods We evaluated a multi institutional collaborative database composed by 1512 consecutive patients diagnosed with UTUC treated with RNU between 1990 and 2016. Year of surgery were grouped in five periods: 1990–1996, 1997–2002, 2003–2007, 2008–2012 and 2013–2016. Data about LND were available for all patients and numbers of nodes removed and positive were reported by dedicate uropathologists. The Mann–Whitney and Chi square tests were used to compare the statistical significance of differences in medians and proportions, respectively. Results Five hundred forty-five patients (36.0%) received a concomitant LND while 967 (64.0%) did not; 41.9% of open RNU patients received a concomitant LND compared to 24.4% of laparoscopic RNU patients. The rate of concomitant LND increased with time in the overall, laparoscopic and open RNU patients (all p  < 0.03). Patients treated with open RNU also had an increasing likelihood to receive an adequate concomitant LND ( p  < 0.001) while those undergoing a laparoscopic approach did not ( p  = 0.1). Patients treated with concomitant LND had a median longer operative time of 20 min ( p  = 0.01). There were no differences in perioperative outcomes and complications between patients who received a concomitant LND and those who did not ( p  > 0.1). Conclusion Although an increased trend was observed, most patients treated with RNU did not receive LND. Surgeons using a laparoscopic RNU were less likely to perform a concomitant LND, and when done, they remove less nodes.

To investigate the impact of moderate wine consumption on the risk of prostate cancer (PCa). We focused on the differential effect of moderate consumption of red versus white wine. This study was a meta-analysis that includes data from case-control and cohort studies. A systematic search of Web of Science, Medline/PubMed, and Cochrane library was performed on December 1, 2017. Studies were deemed eligible if they assessed the risk of PCa due to red, white, or any wine using multivariable logistic regression analysis. We performed a formal meta-analysis for the risk of PCa according to moderate wine and wine type consumption (white or red). Heterogeneity between studies was assessed using Cochrane's Q test and statistics. Publication bias was assessed using Egger's regression test. A total of 930 abstracts and titles were initially identified. After removal of duplicates, reviews, and conference abstracts, 83 full-text original articles were screened. Seventeen studies (611,169 subjects) were included for final evaluation and fulfilled the inclusion criteria. In the case of moderate wine consumption: the pooled risk ratio (RR) for the risk of PCa was 0.98 (95% CI 0.92-1.05, =0.57) in the multivariable analysis. Moderate white wine consumption increased the risk of PCa with a pooled RR of 1.26 (95% CI 1.10-1.43, =0.001) in the multi-variable analysis. Meanwhile, moderate red wine consumption had a protective role reducing the risk by 12% (RR 0.88, 95% CI 0.78-0.999, =0.047) in the multivariable analysis that comprised 222,447 subjects. In this meta-analysis, moderate wine consumption did not impact the risk of PCa. Interestingly, regarding the type of wine, moderate consumption of white wine increased the risk of PCa, whereas moderate consumption of red wine had a protective effect. Further analyses are needed to assess the differential molecular effect of white and red wine conferring their impact on PCa risk.

Laser processing with ultra-short double pulses has gained attraction since the beginning of the 2000s. In the last decade, pulse bursts consisting of multiple pulses with a delay of several 10 ns and less found their way into the area of micromachining of metals, opening up completely new process regimes and allowing an increase in the structuring rates and surface quality of machined samples. Several physical effects such as shielding or re-deposition of material have led to a new understanding of the related machining strategies and processing regimes. Results of both experimental and numerical investigations are placed into context for different time scales during laser processing. This review is dedicated to the fundamental physical phenomena taking place during burst processing and their respective effects on machining results of metals in the ultra-short pulse regime for delays ranging from several 100 fs to several microseconds. Furthermore, technical applications based on these effects are reviewed.

The usage of pulse bursts allows increasing the throughput, which still represents a key factor for machining with ultra-short pulsed lasers. The influence of the number of pulses within a burst on the specific removal rate is investigated for copper and stainless steel. Furthermore, calorimetric measurements were performed to estimate the residual energy coefficient as well as the absorptance of machined surfaces for copper to explain the reduced specific removal rate for a 2-pulse burst and the similar or even higher rate for a 3-pulse burst compared to single pulse ablation. Based on the measurements, a description of the process using single pulses and pulse bursts with up to three pulses is presented.