BACKGROUND: The appropriate surveillance protocol after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) is still poorly addressed. OBJECTIVE: To evaluate the appropriate intensity and duration of oncologic surveillance following RNU, according to a prior history of bladder cancer (BCa). DESIGN, SETTING, AND PARTICIPANTS: We identified 1378 high-risk UTUC patients, according to the European Association of Urology (EAU) guidelines, from a prospectively maintained database involving eight European referral centers. Surveillance protocol was based on cystoscopies and cross-sectional imaging, as per the EAU guidelines. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: First, we evaluated the noncumulative risk of bladder and other-site recurrences (including distant metastasis and locoregional relapse) against the follow-up time points, as suggested by the current EAU guidelines. Second, in an effort to identify the time points when the risk of other-cause mortality (OCM) exceeded that of recurrence and follow-up might be discontinued, we relied on adjusted Weibull regression. RESULTS AND LIMITATIONS: The median follow-up was 4 yr. A total of 427 and 951 patients with and without a prior BCa history, respectively, were considered. At 5-yr, the time point after which cystoscopies should be performed semiannually, the bladder recurrence risk was 10%; at 4 yr, the bladder recurrence risk was 13%. At 2 yr, the time point after which imaging should be obtained semiannually, the nonbladder recurrence risk was 42% in case of nonprior BCa and 47% in case of prior BCa; at 4 yr, the nonbladder recurrence risk was 23%. Among patients without a prior BCa history, individuals younger than 60 yr should continue both cystoscopies and imaging beyond 10 yr from RNU, 70-79-yr-old patients should continue only imaging beyond 10 yr, while patients older than 80 yr might discontinue oncologic surveillance because of an increased risk of OCM. Limitations include the fact that patients were treated and surveilled over a relatively long period of time. CONCLUSIONS: We suggest intensifying the frequency of imaging to semiannual till the 4th year after RNU, the time point after which the risk of recurrence was almost halved. Cystoscopies could be obtained annually from the 4th year given a similar risk of recurrence at 4 and 5 yr after RNU. Oncologic surveillance could be discontinued in some cases in the absence of a prior BCa history. PATIENT SUMMARY: In this study, we propose a revision of the current guidelines regarding surveillance protocols following radical nephroureterectomy. We also evaluated whether oncologic surveillance for high-risk upper tract urothelial carcinoma could be discontinued and, if so, in what circumstances.

• MeSH
• karcinom z přechodných buněk * patologie   MeSH
• lidé MeSH
• lokální recidiva nádoru epidemiologie   chirurgie   MeSH
• nádory močového měchýře * epidemiologie   chirurgie   MeSH
• nádory močovodu * patologie   chirurgie   MeSH
• nefroureterektomie metody   MeSH
• retrospektivní studie MeSH
• ureter * patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: Presently, major guidelines do not provide specific recommendations on oncologic surveillance for patients who harbor variant histology (VH) bladder cancer (BCa) at radical cystectomy. We aimed to create a personalized followup scheme that dynamically weighs other cause mortality (OCM) vs the risk of recurrence for VH BCa, and to compare it with a similar one for pure urothelial carcinoma (pUC). MATERIALS AND METHODS: Within a multi-institutional registry, 528 and 1,894 patients with VH BCa and pUC, respectively, were identified. The Weibull regression was used to detect the time points after which the risk of OCM exceeded the risk of recurrence during followup. The risk of OCM over time was stratified based on age and comorbidities, and the risk of recurrence on pathological stage and recurrence site. RESULTS: Individuals with VH had a higher risk of recurrence (recurrence-free survival 30% vs 51% at 10 years, p <0.001) and shorter median time to recurrence (88 vs 123 months, p <0.01) relative to pUC. Among VH, micropapillary variant conferred the greatest risk of recurrence on the abdomen and lungs, and mixed variants carried the greatest risk of metastasizing to bones and other sites compared to pUC. Overall, surveillance should be continued for a longer time for individuals with VH BCa. Notably, patients younger than 60 years with VH and pT0/Ta/T1/N0 at radical cystectomy should continue oncologic surveillance after 10 years vs 6.5 years for pUC individuals. CONCLUSIONS: VH BCa is associated with greater recurrence risk than pUC. A followup scheme that is valid for pUC should not be applied to individuals with VH. Herein, we present a personalized approach for surveillance that may allow an improved shared decision.

• MeSH
• časové faktory MeSH
• cystektomie MeSH
• hodnocení rizik statistika a číselné údaje   MeSH
• karcinom z přechodných buněk diagnóza   mortalita   patologie   terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru diagnóza   epidemiologie   patologie   MeSH
• močový měchýř patologie   chirurgie   MeSH
• nádory močového měchýře diagnóza   mortalita   patologie   terapie   MeSH
• následné studie MeSH
• pozorné vyčkávání * MeSH
• přežití bez známek nemoci MeSH
• registrace statistika a číselné údaje   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• staging nádorů MeSH
• věkové faktory MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Radical nephroureterectomy (RNU) with the concomitant excision of the distal ureter and bladder cuff is the current standard of care for the treatment of muscle invasive and/or high-risk upper tract urothelial carcinoma (UTUC). In small uncontrolled studies, laparoscopic RNU has been suggested to be associated with better perioperative outcomes compared to open RNU. The aim of our study was to compare the perioperative oncological and functional outcomes of open RNU versus laparoscopic RNU after adjusting for preoperative baseline patient-related characteristics. METHODS: We evaluated a multi-institutional retrospective database composed by 1512 patients diagnosed with UTUC and treated with open or laparoscopic RNU between 1990 and 2016. Perioperative outcomes included operative time, blood loss, and length of hospital stay, as well as postoperative complications, readmission, reoperation, and mortality rates at 30 and 90 days from surgery. A 1:1 propensity score matching estimated using logistic regression with the teffects psmatch function of STATA 13® (caliper 0.2, no replacement; StataCorp LLC; College Station, TX, USA) was performed using preoperative parameters such as: age, gender, Body Mass Index (BMI), and American Society of Anesthesiologists (ASA) Score. RESULTS: Overall, 1007 (66.6%) patients were treated with open and 505 (33.4%) with laparoscopic RNU. Open RNU resulted into shorter median operative time (180 vs. 230 min, P<0.001) and longer median hospital stay (10 vs. 7 days, P<0.001) in comparison to laparoscopic RNU. No statistically significant difference was identified for the other variables of interest (all P>0.05). At multivariable linear regression after propensity score matching adjusted for lymph node dissection and year of surgery, laparoscopic RNU resulted in longer operative time (coefficient 43.6, 95% CI 27.9-59.3, P<0.001) and shorter hospital stay (coefficient -1.27, 95% CI -2.1 to -0.3, P=0.01) compared to open RNU, but the risk of other perioperative complications remained similar between the two treatments. CONCLUSIONS: Laparoscopic RNU is associated with shorter hospital stay, but longer operative time in comparison to open RNU. Otherwise, there were no differences in other perioperative outcomes between these surgical modalities even after propensity score matching. The choice to offer laparoscopic or open RNU in the treatment of UTUC should not be based on concerns of different safety outcomes.

• MeSH
• karcinom z přechodných buněk * MeSH
• laparoskopie * škodlivé účinky   metody   MeSH
• lidé MeSH
• nádory močového měchýře * chirurgie   MeSH
• nádory močovodu * MeSH
• nefroureterektomie metody   MeSH
• retrospektivní studie MeSH
• tendenční skóre MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: To investigate the function of a novel primate-specific long non-coding RNA (lncRNA), named FLANC, based on its genomic location (co-localised with a pyknon motif), and to characterise its potential as a biomarker and therapeutic target. DESIGN: FLANC expression was analysed in 349 tumours from four cohorts and correlated to clinical data. In a series of multiple in vitro and in vivo models and molecular analyses, we characterised the fundamental biological roles of this lncRNA. We further explored the therapeutic potential of targeting FLANC in a mouse model of colorectal cancer (CRC) metastases. RESULTS: FLANC, a primate-specific lncRNA feebly expressed in normal colon cells, was significantly upregulated in cancer cells compared with normal colon samples in two independent cohorts. High levels of FLANC were associated with poor survival in two additional independent CRC patient cohorts. Both in vitro and in vivo experiments demonstrated that the modulation of FLANC expression influenced cellular growth, apoptosis, migration, angiogenesis and metastases formation ability of CRC cells. In vivo pharmacological targeting of FLANC by administration of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine nanoparticles loaded with a specific small interfering RNA, induced significant decrease in metastases, without evident tissue toxicity or pro-inflammatory effects. Mechanistically, FLANC upregulated and prolonged the half-life of phosphorylated STAT3, inducing the overexpression of VEGFA, a key regulator of angiogenesis. CONCLUSIONS: Based on our findings, we discovered, FLANC as a novel primate-specific lncRNA that is highly upregulated in CRC cells and regulates metastases formation. Targeting primate-specific transcripts such as FLANC may represent a novel and low toxic therapeutic strategy for the treatment of patients.

• MeSH
• farmakogenomické testování MeSH
• genetická terapie MeSH
• genetické markery MeSH
• karcinogeneze * účinky léků   genetika   MeSH
• kolorektální nádory * genetika   terapie   MeSH
• lidé MeSH
• myši MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• objevování léků MeSH
• patologická angiogeneze * genetika   metabolismus   MeSH
• proliferace buněk * účinky léků   genetika   MeSH
• regulace genové exprese u nádorů MeSH
• RNA dlouhá nekódující * genetika   metabolismus   MeSH
• transkripční faktor STAT3 metabolismus   MeSH
• vaskulární endoteliální růstový faktor A metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

INTRODUCTION: The only phase III trial that evaluated the role of adjuvant chemotherapy following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) was terminated early. Thus, eventual overall survival (OS) surrogacy, as per Prentice, cannot be assessed in this setting. We aimed to identify an intermediate clinical endpoint (ICE) that could serve as an OS surrogate after RNU for UTUC. PATIENTS AND METHODS: We retrospectively analyzed 823 high-grade UTUC patients treated with RNU at 8 tertiary referral centers. We explored the role of any recurrence (aR), defined as recurrence in the urinary tract or in the resection bed as well the presence of distant metastasis (DM), defined as metastatic disease outside the urinary tract and regional lymph nodes, on OS through a time-varying Cox regression analyses fitted at the landmark points of 1, 2, 3, and 4 years from RNU. Models' discrimination was assessed using Harrell's c index, after internal validation. RESULTS: Median follow-up for survivors was 5.6 years (interquartile range: 2.0-8.8). Overall, 391 and 212 patients experienced aR and DM, respectively. In a time-varying model, aR and DM were predictors of OS: hazard ratio [HR]:1.20, 95% confidence interval [CI]: 1.13-1.28 (P < .001) and HR:1.26, 95% CI: 1.18-1.34 (P < .001), respectively. Progression to DM within 3 years from RNU was the most informative ICE for predicting OS (c index: 0.81; HR: 4.40; 95%CI: 2.45-7.92; P < .001), compared to DM within 1, 2, and 4 years (c indexes: 0.74, 0.76, and 0.78, respectively). Progression to DM within 3 years from RNU was further found superior for predicting OS compared to aR at any landmark points. CONCLUSIONS: Progression to DM within 3 years represents a potential OS surrogate for surgically-treated UTUC. This information could help in patient counseling, future study design and expedite results release of ongoing randomized controlled trials.

• MeSH
• adjuvantní chemoterapie MeSH
• karcinom z přechodných buněk * farmakoterapie   MeSH
• lidé MeSH
• nádory močového měchýře * chirurgie   MeSH
• nefroureterektomie MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Objectives: To compare oncological outcomes of open (ORNU) and laparoscopic radical nephroureterectomy (LRNU) after controlling for preoperative patient-derived factors. Patients and methods: We evaluated a multi-institutional collaborative database composed of 3984 patients diagnosed with upper tract urothelial carcinoma (UTUC) treated with RNU between 2006 and 2018. To adjust for potential selection bias, propensity score matching adjusted for age, gender and American society Anesthesiology (ASA) score was performed with one ORNU patient matched to one LRNU patient. Uni- and multivariable Cox regression evaluating the risk of overall recurrence, cancer-specific mortality (CSM) and overall mortality (OM) in the overall population and after propensity matching were performed. Results: In total, 3984 patients underwent RNU, of these 3227 (81%) patients were treated with ORNU and 757 (19%) patients with LRNU. Within a median follow-up of 62 months, 1276 recurrences, 844 CSMs and 1128 OMs were recorded. On multivariable analyses, the LRNU approach was associated with an increased risk of overall recurrence (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.03-1.54; P = 0.02), but on the other hand LRNU was associated with a protective effect on CSM (HR 0.74, 95% CI 0.56-0.98; P = 0.04). After propensity matching analyses adjusted for age, gender and ASA score, 757 patients treated with LRNU and 757 patients treated with ORNU were available for the analyses. On multivariable Cox regression, LRNU vs ORNU was not associated with any difference in overall recurrence (P = 0.08), CSM (P = 0.1) or OM (P = 0.9). Conclusion: Our present data suggest that even if the type of approach to RNU was associated with different survival outcomes considering the overall population, this difference vanished when adjusted for potential confounders in propensity matching analyses. Therefore, we found that LRNU is not inferior to the ORNU approach for the treatment of UTUC. Abbreviations: ASA: American Society of Anesthesiology; CIS: carcinoma in situ; CSM: cancer-specific mortality; HR: hazard ratio; IQR: interquartile range; LN: lymph node; LNI: lymph node invasion; LVI: lymphovascular invasion; OM: overall mortality; pT: pathological tumour stage; RCT: randomised controlled trial; (L)(O)RNU: (laparoscopic) (open) radical nephroureterectomy; UTUC: upper tract urothelial carcinoma.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: The preoperative lymph node (LN) staging of bladder cancer (BCa) addresses the subsequent therapeutic strategy and influences patient's prognosis. However, sparce evidence exists regarding the accuracy of conventional cross-sectional imaging, such as computed tomography or magnetic resonance imaging, in correctly detect LN status. We aimed to assess the diagnostic accuracy of conventional cross-sectional imaging in detecting preoperative LN involvement among BCa patients treated with radical cystectomy and pelvic lymph node dissection. METHODS: We retrospectively analyzed data of 1,104 patients who underwent preoperative LN staging with computed tomography or magnetic resonance imaging and subsequent radical cystectomy with pelvic lymph node dissection for BCa between 1997 and 2017 at three tertiary referral centers. Patients receiving neoadjuvant chemotherapy were excluded. We assessed the concordance between clinical (cN) and pathological LN (pN) status, defined as the accuracy of imaging in detecting LN involvement using pathological specimen as reference; concordance was expressed according to Cohen's kappa coefficient. Location-based sub-analyses were performed, distinguishing among external iliac, intern iliac, obturator, common iliac, presacral and paraaortic LNs. RESULTS: Among 870 cN0 patients, 68.9% were confirmed pN0 at pathological report; while among 234 cN+ patients, 50.5% were found with LN metastases at pathological specimen. Overall, conventional imaging showed slight concordance (64.9%) between cN and pN stages (sensitivity: 30%; specificity: 84%). At sub-analysis, no agreement between cN and pN status was found in each LN location, with the only exception of common iliac LNs with slight concordance (37.5%). Common iliac LNs achieved the highest sensitivity and positive likelihood ratio (15% and 2.4, respectively) compared to other LN locations. CONCLUSIONS: Overall, preoperative cross-sectional imaging exhibited a slight concordance between cN and pN status. Our location-based sub-analyses showed unsatisfactory results in each LN location- Thus, nomograms combining morphological patterns with serological and clinicopathological features are urgently required.

• MeSH
• cystektomie metody   MeSH
• lidé MeSH
• lymfadenektomie metody   MeSH
• lymfatické uzliny diagnostické zobrazování   patologie   chirurgie   MeSH
• nádory močového měchýře * diagnostické zobrazování   patologie   chirurgie   MeSH
• retrospektivní studie MeSH
• staging nádorů MeSH
• urologie * MeSH
• urologové MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

PURPOSE: To assess the impact of perioperative chemotherapy on survival in cN+ BCa patients and analyze it according to the pN status. METHODS: A retrospective analysis was conducted on 639 BCa patients with cTanyN1-3M0 BCa treated with radical cystectomy (RC) and bilateral lymph node dissection (LND) with or without perioperative chemotherapy in ten tertiary referral centers from 1990 to 2017. Selected cN+ patients received induction chemotherapy (IC), whereas adjuvant chemotherapy (ACT) was delivered to selected pN+ patients. Univariable and multivariable Cox regression analyses were used to predict overall mortality (OM) after surgery, adjusting for clinicopathological confounders. Kaplan-Meier analyses assessed OM according to the treatment modality. RESULTS: Overall, 356 (56%) patients were treated with surgery alone, 155 (24%) with IC followed by surgery, and 128 (20%) with ACT following surgery. Over a median follow-up of 25 months, 316 deaths were recorded. At univariable analysis, patients treated with IC and surgery had lower OM both considering cN+ [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.87, p = 0.004] and cN+pN- patients (HR 0.61, 95% CI 0.37-0.99, p = 0.05) compared to those treated with surgery alone. cN+pN+ patients treated with ACT experienced lower OM compared to those treated with IC or surgery alone at multivariable analysis (HR 0.40, 95% CI 0.22-0.74, p = 0.003). CONCLUSION: Patients with cTany cN+ cM0 BCa benefit more in terms of OS when treated with IC followed by RC + LND compared to RC + LND alone, regardless of LNMs at final histopathology examination. More data are needed to assess the role of ACT in the management of cN+ patients.

• MeSH
• adjuvantní chemoterapie MeSH
• cystektomie MeSH
• indukční chemoterapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfadenektomie MeSH
• lymfatické metastázy MeSH
• míra přežití MeSH
• nádory močového měchýře mortalita   patologie   terapie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

OBJECTIVE: To compare the accuracy in detecting variant histologies (VH) at transurethral resection of bladder (TURB) and radical cystectomy (RC) specimen among tertiary referral centres, in order to investigate potential reasons of discrepancies from the pathological point of view. PATIENTS AND METHODS: Clinical and histopathological data of TURB specimen and subsequent cystectomy specimen of 3,445 RC candidate patients have been retrospectively collected from 24 tertiary referral centres between 1980 and 2021. VH considered in the analysis were pure squamous cell carcinoma, urothelial carcinoma with squamous differentiation, pure adenocarcinoma, urothelial carcinoma with glandular differentiation, micropapillary bladder cancer (BCa), neuroendocrine BCa, and other variants. The degree of agreement between TURB and RC concerning the identification of VH was expressed as concordance, classified according to Cohen's kappa coefficient. RESULTS: A VH was reported in 17% of TURB specimens, 45% of which were not confirmed in RC. The lowest concordance rate was reported for micropapillary BCa with 11 out of 18 (61%) centres reporting no agreement, whereas neuroendocrine BCa achieved the highest concordance rate with only 3 centres (17%) reporting no agreement. Our results shows that even among centres with the advantage of a referent uropathologist the micropapillary variant is characterized by scarce accuracy between TURB and RC. Differences in TURB specimen acquisition by the urologist and in sampling methods among different centres are the main limitations of the study. CONCLUSIONS: Accuracy of TURB in detecting VH is poor for certain VH, in particular for micropapillary BCa, with evident variation among centres. Novel diagnostic tools are required to better identify these VH and drive patients toward a personalized treatment.

• MeSH
• cystektomie metody   MeSH
• karcinom z přechodných buněk * patologie   MeSH
• lidé MeSH
• močový měchýř patologie   MeSH
• nádory močového měchýře * diagnóza   farmakoterapie   chirurgie   MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• peniciliny terapeutické užití   MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Farmacie. Farmakologie
• NLK Obory
• farmacie a farmakologie
• terapie