PURPOSE: A re-transurethral resection of the bladder (re-TURB) is a well-established approach in managing non-muscle invasive bladder cancer (NMIBC) for various reasons: repeat-TURB is recommended for a macroscopically incomplete initial resection, restaging-TURB is required if the first resection was macroscopically complete but contained no detrusor muscle (DM) and second-TURB is advised for all completely resected T1-tumors with DM in the resection specimen. This study assessed the long-term outcomes after repeat-, second-, and restaging-TURB in T1-NMIBC patients. METHODS: Individual patient data with tumor characteristics of 1660 primary T1-patients (muscle-invasion at re-TURB omitted) diagnosed from 1990 to 2018 in 17 hospitals were analyzed. Time to recurrence, progression, death due to bladder cancer (BC), and all causes (OS) were visualized with cumulative incidence functions and analyzed by log-rank tests and multivariable Cox-regression models stratified by institution. RESULTS: Median follow-up was 45.3 (IQR 22.7-81.1) months. There were no differences in time to recurrence, progression, or OS between patients undergoing restaging (135 patients), second (644 patients), or repeat-TURB (84 patients), nor between patients who did or who did not undergo second or restaging-TURB. However, patients who underwent repeat-TURB had a shorter time to BC death compared to those who had second- or restaging-TURB (multivariable HR 3.58, P = 0.004). CONCLUSION: Prognosis did not significantly differ between patients who underwent restaging- or second-TURB. However, a worse prognosis in terms of death due to bladder cancer was found in patients who underwent repeat-TURB compared to second-TURB and restaging-TURB, highlighting the importance of separately evaluating different indications for re-TURB.
- MeSH
- cystektomie MeSH
- lidé MeSH
- močový měchýř chirurgie patologie MeSH
- nádory močového měchýře neinvadující svalovinu * MeSH
- nádory močového měchýře * chirurgie patologie MeSH
- prognóza MeSH
- staging nádorů MeSH
- urologické chirurgické výkony MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The tumoricidal complex alpha1-oleate targets bladder cancer cells, triggering rapid, apoptosis-like tumor cell death. Clinical effects of alpha1-oleate were recently observed in patients with non-muscle invasive bladder cancer (NMIBC), using a randomized, placebo-controlled study protocol. AIMS: To investigate if there are dose-dependent effects of alpha1-oleate. MATERIALS AND METHODS: Here, patients with NMIBC were treated by intravesical instillation of increasing concentrations of alpha1-oleate (1.7, 8.5, or 17 mM) and the treatment response was defined relative to a placebo group. RESULTS: Strong, dose-dependent anti-tumor effects were detected in alpha1-oleate treated patients for a combination of molecular and clinical indicators; a complete or partial response was detected in 88% of tumors treated with 8.5 mM compared to 47% of tumors treated with 1.7 mM of alpha1-oleate. Uptake of alpha1-oleate by the tumor triggered rapid shedding of tumor cells into the urine and cell death by an apoptosis-like mechanism. RNA sequencing of tissue biopsies confirmed the activation of apoptotic cell death and strong inhibition of cancer gene networks, including bladder cancer related genes. Drug-related side effects were not recorded, except for local irritation at the site of instillation. DISCUSSION AND CONCLUSIONS: These dose-dependent anti-tumor effects of alpha1-oleate are promising and support the potential of alpha1-oleate treatment in patients with NMIBC.
- MeSH
- antitumorózní látky terapeutické užití MeSH
- aplikace intravezikální MeSH
- apoptóza účinky léků MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory močového měchýře * farmakoterapie patologie genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: The molecular content of urine is defined by filtration in the kidneys and by local release from tissues lining the urinary tract. Pathological processes and different therapies change the molecular composition of urine and a variety of markers have been analyzed in patients with bladder cancer. The response to BCG immunotherapy and chemotherapy has been extensively studied and elevated urine concentrations of IL-1RA, IFN-α, IFN-γ TNF-α, and IL-17 have been associated with improved outcome. METHODS: In this study, the host response to intravesical alpha 1-oleate treatment was characterized in patients with non-muscle invasive bladder cancer by proteomic and transcriptomic analysis. RESULTS: Proteomic profiling detected a significant increase in multiple cytokines in the treatment group compared to placebo. The innate immune response was strongly activated, including IL-1RA and pro-inflammatory cytokines in the IL-1 family (IL-1α, IL-1β, IL-33), chemokines (MIP-1α, IL-8), and interferons (IFN-α2, IFN-γ). Adaptive immune mediators included IL-12, Granzyme B, CD40, PD-L1, and IL-17D, suggesting broad effects of alpha 1-oleate treatment on the tumor tissues. CONCLUSIONS: The cytokine response profile in alpha 1-oleate treated patients was similar to that reported in BCG treated patients, suggesting a significant overlap. A reduction in protein levels at the end of treatment coincided with inhibition of cancer-related gene expression in tissue biopsies, consistent with a positive treatment effect. Thus, in addition to killing tumor cells and inducing cell detachment, alpha 1-oleate is shown to activate a broad immune response with a protective potential.
- MeSH
- antagonista receptoru pro interleukin 1 terapeutické užití MeSH
- BCG vakcína * terapeutické užití MeSH
- cytokiny MeSH
- imunita MeSH
- interferon alfa farmakologie terapeutické užití MeSH
- kyselina olejová MeSH
- lidé MeSH
- nádory močového měchýře * patologie MeSH
- proteomika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
AIM: Intravesical thermochemotherapy, also known as HIVEC (Hyperthermic Intra-VEsical Chemotherapy), represents an alternative adjuvant topical treatment for non-muscle-invasive urothelial bladder cancer (NMIBC). High-risk (HR) and very HR tumors carry a substantial risk of recurrence and progression. In this study, we present our own results using HIVEC as an alternative to unavailable Bacillus Calmette-Guérin (BCG) vaccine in the treatment of such groups of patients. METHODS: During the period of November 2014-June 2022, a total of 47 patients with HR and very HR NMIBC underwent treatment with HIVEC after transurethral resection. They were given an induction of 6 instillations with/without a maintenance. The aim was to evaluate the time to recurrence, event-free survival (recurrence or progression), as measured by Kaplan-Meier analysis, the effect of maintenance treatment and other factors on survival (log-rank test and multivariable Cox regression analysis), and complications. RESULTS: The median follow-up for patients who did not experience an event was 32 months. The median time to HR (high grade and/or T1 tumor) recurrence in those who recurred was 15 months. The survival rate without HR recurrence at 12, 24, and 48 months was 84, 70, and 59%, respectively. Progression was detected in 10.6% of patients, which translated to 89% of patients living without progression after 24 months. Maintenance treatment (defined as more than six instillations) and presence of CIS significantly correlated with risk of HR recurrence (Hazard ratio 0.34 and 3.12, respectively). One female patient underwent salvage cystectomy due to contractory bladder, and 19.1% of patients experienced transient lower urinary tract symptoms. CONCLUSION: Based on our experience, HIVEC represents an adequate and safe alternative treatment for HR and very HR NMIBC in situations where BCG is not available or radical cystectomy is not an option for the patient. However, high-quality data from prospective randomized studies are still lacking, and thus, thermochemotherapy should still be regarded as an experimental treatment modality.
- MeSH
- aplikace intravezikální MeSH
- hodnocení rizik MeSH
- indukovaná hypertermie * MeSH
- invazivní růst nádoru * MeSH
- karcinom z přechodných buněk terapie patologie farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory močového měchýře * terapie patologie farmakoterapie MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: Patients with resected localized clear-cell renal cell carcinoma (ccRCC) remain at variable risk of recurrence. Incorporation of biomarkers may refine risk prediction and inform adjuvant treatment decisions. We explored the role of tumor genomics in this setting, leveraging the largest cohort to date of localized ccRCC tissues subjected to targeted gene sequencing. EXPERIMENTAL DESIGN: The somatic mutation status of 12 genes was determined in 943 ccRCC cases from a multinational cohort of patients, and associations to outcomes were examined in a Discovery (n = 469) and Validation (n = 474) framework. RESULTS: Tumors containing a von-Hippel Lindau (VHL) mutation alone were associated with significantly improved outcomes in comparison with tumors containing a VHL plus additional mutations. Within the Discovery cohort, those with VHL+0, VHL+1, VHL+2, and VHL+≥3 tumors had disease-free survival (DFS) rates of 90.8%, 80.1%, 68.2%, and 50.7% respectively, at 5 years. This trend was replicated in the Validation cohort. Notably, these genomically defined groups were independent of tumor mutational burden. Amongst patients eligible for adjuvant therapy, those with a VHL+0 tumor (29%) had a 5-year DFS rate of 79.3% and could, therefore, potentially be spared further treatment. Conversely, patients with VHL+2 and VHL+≥3 tumors (32%) had equivalent DFS rates of 45.6% and 35.3%, respectively, and should be prioritized for adjuvant therapy. CONCLUSIONS: Genomic characterization of ccRCC identified biologically distinct groups of patients with divergent relapse rates. These groups account for the ∼80% of cases with VHL mutations and could be used to personalize adjuvant treatment discussions with patients as well as inform future adjuvant trial design.
Dinh PT, Brisuda A. Raritní trombóza plexu pampiniformis u covid-19 pozitivního pacienta - kazuistika. V tomto článku prezentujeme 48letého anamnesticky velmi rizikového pacienta, který je na Urologické klinice Fakultní Nemocnice Motol sledován pro recidivující oboustranné epididymitidy následované raritními trombózami plexu pampiniformis. Poslední příhodě zároveň předcházelo infekční onemocnění covid-19, u kterého je známé mimo jiné i zvýšené riziko trombofilních stavů.
Dinh PT, Brisuda A. A rare pampiniform plexus thrombosis in a COVID-19 patient - case report. In this case report, we present a 48-year-old patient with several comorbidities who was seen under follow at the Department of Urology Motol University Hospital for recurrent bilateral epididymitis followed by rare pampiniform plexus thrombosis. The viral disease COVID-19, which is known to increase the likelihood of thrombophilic conditions, occurred prior to this presentation.
- Klíčová slova
- trombóza plexu pampiniformis, akutní skrotální příhody,
- MeSH
- COVID-19 * komplikace MeSH
- epididymitida diagnóza terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- trombóza diagnóza etiologie terapie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND: Ta grade 3 (G3) non-muscle-invasive bladder cancer (NMIBC) is a relatively rare diagnosis with an ambiguous character owing to the presence of an aggressive G3 component together with the lower malignant potential of the Ta component. The European Association of Urology (EAU) NMIBC guidelines recently changed the risk stratification for Ta G3 from high risk to intermediate, high, or very high risk. However, prognostic studies on Ta G3 carcinomas are limited and inconclusive. OBJECTIVE: To evaluate the prognostic value of categorizing Ta G3 compared to Ta G2 and T1 G3 carcinomas. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for 5170 primary Ta-T1 bladder tumors from 17 hospitals were analyzed. Transurethral resection of the tumor was performed between 1990 and 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time to recurrence and time to progression were analyzed using cumulative incidence functions, log-rank tests, and multivariable Cox-regression models with interaction terms stratified by institution. RESULTS AND LIMITATIONS: Ta G3 represented 7.5% (387/5170) of Ta-T1 carcinomas of which 42% were classified as intermediate risk. Time to recurrence did not differ between Ta G3 and Ta G2 (p = 0.9) or T1 G3 (p = 0.4). Progression at 5 yr occurred for 3.6% (95% confidence interval [CI] 2.7-4.8%) of Ta G2, 13% (95% CI 9.3-17%) of Ta G3, and 20% (95% CI 17-23%) of T1 G3 carcinomas. Time to progression for Ta G3 was shorter than for Ta G2 (p < 0.001) and longer than for T1 G3 (p = 0.002). Patients with Ta G3 NMIBC with concomitant carcinoma in situ (CIS) had worse prognosis and a similar time to progression as for patients with T1 G3 NMIBC with CIS (p = 0.5). Multivariable analyses for recurrence and progression showed similar results. CONCLUSIONS: The prognosis of Ta G3 tumors in terms of progression appears to be in between that of Ta G2 and T1 G3. However, patients with Ta G3 NMIBC with concomitant CIS have worse prognosis that is comparable to that of T1 G3 with CIS. Our results support the recent EAU NMIBC guideline changes for more refined risk stratification of Ta G3 tumors because many of these patients have better prognosis than previously thought. PATIENT SUMMARY: We used data from 17 centers in Europe and Canada to assess the prognosis for patients with stage Ta grade 3 (G3) non-muscle-invasive bladder cancer (NMIBC). Time to cancer progression for Ta G3 cancer differed from both Ta G2 and T1 G3 tumors. Our results support the recent change in the European Association of Urology guidelines for more refined risk stratification of Ta G3 NMIBC because many patients with this tumor have better prognosis than previously thought.
- MeSH
- karcinom * diagnóza patologie MeSH
- lidé MeSH
- močový měchýř patologie MeSH
- nádory močového měchýře * diagnóza terapie patologie MeSH
- prognóza MeSH
- staging nádorů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE OF REVIEW: Transurethral resection of bladder cancer (TURBT) is in its standard form an inherently imperfect technique. Fluorescence-guided photodynamic diagnosis (PDD) represents one way to improve the outcome by enhancing tumour detection. Fluorescence has been used in connection with bladder cancer since the 1970s, with a number of studies being published since then. However, the method is still not recommended as a standard part of TURBT mainly because of the limited level of evidence of concerned studies, questionable cost-effectiveness and even contradictory results. The review lists the latest articles covering this topic. RECENT FINDINGS: Several recently published meta-analyses reviewed a series of randomized controlled trials (RCTs) concerning PDD assisted TURBT. Results were generally supporting the positive effect on reduction of recurrence rate. However, the mentioned meta-analyses are overlapping in terms of reviewed RCT that provide only a low level of evidence according to a recent Cochrane review. Supposed limitations of PDD (timing of the procedure, low specificity) and possible solutions are also covered. SUMMARY: Most of the published data confirmed reduced early recurrence rate after PDD assisted TURBT comparing to standard TURBT. Its impact on late recurrence rate, progression rate or cost-effectiveness has not been sufficiently demonstrated.
- MeSH
- cystektomie metody MeSH
- fluorescence MeSH
- fotosenzibilizující látky * MeSH
- lidé MeSH
- lokální recidiva nádoru epidemiologie prevence a kontrola patologie MeSH
- nádory močového měchýře * patologie MeSH
- transuretrální resekce močového měchýře MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: The pathological existence and clinical consequence of stage T1 grade 1 (T1G1) bladder cancer are the subject of debate. Even though the diagnosis of T1G1 is controversial, several reports have consistently found a prevalence of 2-6% G1 in their T1 series. However, it remains unclear if T1G1 carcinomas have added value as a separate category to predict prognosis within the non-muscle-invasive bladder cancer (NMIBC) spectrum. OBJECTIVE: To evaluate the prognostic value of T1G1 carcinomas compared to TaG1 and T1G2 carcinomas within the NMIBC spectrum. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for 5170 primary Ta and T1 bladder tumors from 17 hospitals in Europe and Canada were analyzed. Transurethral resection (TUR) was performed between 1990 and 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time to recurrence and progression were analyzed using cumulative incidence functions, log-rank tests, and multivariable Cox regression models stratified by institution. RESULTS AND LIMITATIONS: T1G1 represented 1.9% (99/5170) of all carcinomas and 5.3% (99/1859) of T1 carcinomas. According to primary TUR dates, the proportion of T1G1 varied between 0.9% and 3.5% per year, with similar percentages in the early and later calendar years. We found no difference in time to recurrence between T1G1 and TaG1 (p = 0.91) or between T1G1 and T1G2 (p = 0.30). Time to progression significantly differed between TaG1 and T1G1 (p < 0.001) but not between T1G1 and T1G2 (p = 0.30). Multivariable analyses for recurrence and progression showed similar results. CONCLUSIONS: The relative prevalence of T1G1 diagnosis was low and remained constant over the past three decades. Time to recurrence of T1G1 NMIBC was comparable to that for other stage/grade NMIBC combinations. Time to progression of T1G1 NMIBC was comparable to that for T1G2 but not for TaG1, suggesting that treatment and surveillance of T1G1 carcinomas should be more like the approaches for T1G2 NMIBC in accordance with the intermediate and/or high risk categories of the European Association of Urology NMIBC guidelines. PATIENT SUMMARY: Although rare, stage T1 grade 1 (T1G1) bladder cancer is still diagnosed in daily clinical practice. Using individual patient data from 17 centers in Europe and Canada, we found that time to progression of T1G1 cancer was comparable to that for T1G2 but not TaG1 cancer. Therefore, our results suggest that primary T1G1 bladder cancers should be managed with more aggressive treatment and more frequent follow-up than for low-risk bladder cancer.
- MeSH
- lidé MeSH
- nádory močového měchýře neinvadující svalovinu * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
Zhoubné novotvary močového měchýře představují v České republice nadále časté onkologické onemocnění. Ačkoliv se z histologického hlediska jedná ve více než 90 % případů o malignity uroteliálního původu, z hlediska biologického chování, a tedy i dalšího průběhu onemocnění, se naráží na značnou heterogenitu. U podskupiny pacientů s vysokým rizikem častých recidiv a, to především, s vysokým rizikem progrese do svalovinu invadujícího onemocnění (T2 a výše) je imperativem léčby adekvátní adjuvantní terapie. Tu nadále představuje BCG intravezikální imunoterapie. Jedná se o standardní léčbu s prokázaným efektem na četnost recidiv i na snížení rizika progrese onemocnění. V případě jejího selhání je doporučeným postupem radikální cystektomie. Vzhledem k rozsahu operace a z něj vyplývajících trvalých konsekvencí pro pacienta je vyvíjeno značné úsilí směrem k účinným měchýř zachovávajícím postupům. V článku jsou uvedeny hlavní směry, kterými je toto výzkumné úsilí vedeno.
Bladder neoplasms are still among the most common cancer types in the Czech Republic. Even though the majority (more than 90%) of bladder tumours are of urothelial origin, the group is vastly heterogeneous in terms of biological behaviour and thus also progression of the disease. Adequate adjuvant treatment is the cornerstone of the therapy in high-risk patients for disease recurrence, particularly those with a high risk of progression to a muscle-invasive disease (T2 and higher). Intravesical BCG immunotherapy still remains such a therapy. It is a standard therapy with well-established efficacy as regards the recurrence rate and a reduced risk of progression. Nevertheless, radical cystectomy is recommended in patients in whom this therapy fails. Considering the non-negligible morbidity and mortality associated with this type of surgery, intensive research efforts have been put forth to develop new bladder preserving strategies. This article outlines the main bladder preserving strategies that are currently explored.
- MeSH
- BCG vakcína terapeutické užití MeSH
- cystektomie MeSH
- invazivní růst nádoru MeSH
- lidé MeSH
- lokální recidiva nádoru chirurgie MeSH
- nádory močového měchýře * terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
