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BACKGROUND: The type of pneumonia that is caused by the new coronavirus (SARS-CoV-2) has spread across the world in a pandemic. It is not clear if COVID-19 patients have any lower urinary tract signs or symptoms. METHODS: The effect of COVID-19 on lower urinary tract function was studied in a prospective multi-centre, observational study including 238 patients who were admitted with symptoms caused by COVID-19 to the university hospital of Aachen in Germany and Tabriz in Iran. RESULTS: None of the patients reported to have any lower urinary tract symptoms. SARS-CoV-2 was found in the urine of 19% of the tested patients. The mortality rate in COVID-19 infected patients with microscopic haematuria together with white blood cells in their urine, was significantly increased from 48 to 61% in the Tabriz cohort (p-value = 0.03) and from 30 to 35% in the Aachen cohort (p-value =0.045). Furthermore, in the group of patients with SARS-CoV-2 urine PCR, the mortality rate rose from 30 to 58%. (p-value =0.039). CONCLUSION: Patients admitted with COVID-19 did not report to have any lower urinary tract symptoms, even those patient who had a positive Urine SARS-CoV-2 PCR. In addition, hematuria, WBC in urine as well as SARS- CoV-2 presence in urine, were found to be strong negative prognostic factors in admitted COVID-19 patients.
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COVID-19 , Sistema Urinário , Humanos , Pandemias , Estudos Prospectivos , SARS-CoV-2RESUMO
Histologically, bladder cancer is a heterogeneous group comprising urothelial carcinoma (UC), squamous cell carcinoma, adenocarcinomas (ACs), urachal carcinomas (UrCs), and small cell neuroendocrine carcinomas (SCCs). However, all bladder cancers have been treated so far uniformly, and targeted therapy options are still limited. Thus, we aimed to determine the protein expression/molecular status of commonly used cancer targets (programmed cell death 1 ligand 1 (PD-L1), mismatch repair (MMR), androgen and estrogen receptors (AR/ER), Nectin-4, tumor-associated calcium signal transducer 2 (Tacstd2, Trop-2), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and fibroblast growth factor receptor 3 (FGFR3)) to give first insights into whether patients with SCC, AC/UrCs, and squamous-differentiated carcinomas (Sq-BLCA) of the bladder could be eligible for targeted therapies. In addition, for MMR-deficient tumors, microsatellite instability was analyzed. We completed our own data with molecular data from The Cancer Genome Atlas (TCGA). We present ratios for each drug and cumulative ratios for multiple therapeutic options for each nonurothelial subtype. For example, 58.9% of SCC patients, 33.5% of AC/UrCs patients, and 79.3% of Sq-BLCA patients would be eligible for at least one of the analyzed targets. In conclusion, our findings hold promise for targeted therapeutic approaches in selected patients in the future, as various drugs could be applied according to the biomarker status.
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Terapia de Alvo Molecular/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Idoso , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/metabolismo , Reparo de Erro de Pareamento de DNA , Feminino , Humanos , Imuno-Histoquímica , Masculino , Instabilidade de Microssatélites , Terapia de Alvo Molecular/tendências , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologiaRESUMO
BACKGROUND: Immune checkpoint inhibitors (ICI) are an integral part of bladder cancer therapy, however, the relevance of ICI treatment for mixed and pure squamous cell carcinoma of the bladder remains poorly studied. Therefore, we analysed the expression of programmed death-ligand 1 (PD-L1) in urothelial carcinomas with squamous differentiation (UC/SCC) and pure squamous cell carcinoma (SCC) of the bladder and studied a UC/SCC patient with ICI therapy. METHODS: Tissue microarrays of 45 UC/SCC and 63 SCC samples were immunohistochemically stained with four anti-PD-L1 antibodies (28-8, 22C3, SP142 and SP263). PD-L1 expression was determined for tumour cells (TP-Score), immune cells (IC-Score) and combined (CPS, combined positive score). In addition, we present clinical and histological data of an UC/SCC patient with nivolumab therapy. RESULTS: Overall, positive PD-L1 staining ranged between 4.8 and 61.9% for IC and 0 and 51.2% for TC depending on the used antibody. There were no significant differences between UC/SCC and SCC. According to current FDA guidelines for example for first line therapy of urothelial cancer with pembrolizumab (CPS ≥ 10), a subset of SCC patients up to 20% would be eligible. Finally, our UC/SCC index patient revealed excellent therapy response regarding his lung metastasis. CONCLUSIONS: Our data reveal a PD-L1 expression in squamous differentiated carcinomas comparable with current data shown for urothelial tumours. In accordance with the encouraging clinical data of the index patient we suggest ICI treatment also for mixed and pure SCC of the urinary bladder.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Carcinoma de Células Escamosas/tratamento farmacológico , Nivolumabe/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/análise , Antígeno B7-H1/metabolismo , Carcinoma de Células Escamosas/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Análise Serial de Tecidos , Neoplasias da Bexiga Urinária/metabolismoRESUMO
Background: To evaluate predictive factors for survival outcomes after post-prostatectomy radiotherapy.Material and methods: In the years 2003-2008, 324 patients have received postoperative radiotherapy a median time of 14 months after radical prostatectomy. All patients have been treated up to 66.0-66.6 Gy in 1.8-2.0 Gy fractions. Predictive factors were analyzed at two stages, using a multivariable Cox regression analysis: (1) based on factors known before radiotherapy and (2) based on prostate-specific antigen response after radiotherapy.Results: Median follow-up after radiotherapy was 121 months. Prostate-specific antigen before radiotherapy, pN1 and Gleason score remained predictive factors for disease-free (hazard ratio, HR of 6.0, 2.3 and 2.5) and overall survival (HR of 2.8, 2.0 and 1.6) in multivariable analysis. Prostate-specific antigen levels increased despite radiotherapy in 27% of patients in the first six months. Failed response following salvage radiotherapy and prostate-specific antigen doubling time at the time of biochemical recurrence were predictive factors for disease-free (HR of 2.8 and 7.3; p < .01) and overall survival (HR of 2.2 and 2.6; p < .01).Conclusion: To reach the best survival outcomes following prostatectomy, salvage radiotherapy should be initiated early with low prostate-specific antigen levels, especially in patients with higher Gleason scores. Patients not responding to radiotherapy and/or patients with a short prostate-specific antigen doubling time after radiotherapy are candidates for early additional treatments.
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Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/radioterapia , Idoso , Intervalo Livre de Doença , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Radioterapia Adjuvante , Terapia de Salvação , Taxa de SobrevidaRESUMO
We present a case of a patient with a large, symptomatic abdominal tumour, which finally could be classified as a leiomyoma arising from the right seminal duct/seminal vesicle. In computed tomography (CT) scan, it appeared as a 7.5 × 6.5 cm solid, supravesical mass. A cystoscopy as well as bilateral retrograde studies was normal, a transrectal ultrasound-guided biopsy and an ultrasound-guided transabdominal biopsy of the mass were inconclusive. Subsequently, we performed a tumour extirpation through a lower midline laparotomy. Histological examination showed a leiomyoma arising from the right seminal duct or seminal vesicle. In this article, we discuss clinical presentation, findings on imaging and management of this rare benign tumour and review the relevant literature where only 13 similar cases could be identified.
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Neoplasias dos Genitais Masculinos/diagnóstico por imagem , Leiomioma/diagnóstico por imagem , Glândulas Seminais/diagnóstico por imagem , Adulto , Neoplasias dos Genitais Masculinos/patologia , Neoplasias dos Genitais Masculinos/cirurgia , Humanos , Leiomioma/patologia , Leiomioma/cirurgia , Masculino , Glândulas Seminais/patologia , Glândulas Seminais/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , UltrassonografiaRESUMO
PURPOSE: To analyze clinical results and quality of life of patients with localized prostate cancer after irradiation of the prostate with an 18F-choline-PET/CT-based simultaneous integrated boost (SIB) in comparison to a control group without SIB. METHODS: A total of 134 patients underwent intensity-modulated radiotherapy from 2007-2010. All patients received a total dose of 76â¯Gy with 2â¯Gy fractions to the prostate; 67 patients received an additional SIB of 80â¯Gy. The median follow-up was 65 months. Quality of life was evaluated with the EPIC (Expanded Prostate Cancer Index Composite) questionnaire. RESULTS: Baseline characteristics were similar in both groups (prostate-specific antigen 11â¯ng/ml vs. 8â¯ng/ml, pâ¯= 0.20, Gleason score <6 in 36% vs. 46%, pâ¯= 0.22, with vs. without SIB). No prostate cancer-related death was observed. No significant difference of quality of life scores was found. The largest difference after 5-6 years in comparison to baseline was reported for sexual bother (mean 15 vs. 17 points with vs. without SIB). Mean urinary scores did not decrease. Bowel bother scores changes were larger in the SIB group (mean 5 vs. 2 points, dependent on SIB volume), with increased bowel problems (15 vs. 2% big/moderate problem with bowel movements, pâ¯= 0.03). However, a trend towards higher efficacy with SIB resulted (biochemical recurrence-free survival of 92% vs. 85%, pâ¯= 0.17). CONCLUSIONS: The first long-term analysis of patients treated with SIB based on molecular imaging with 18-F-choline-PET/CT showed an excellent biochemical recurrence-free survival, but a larger percentage of bowel problems in comparison to the control group.
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Colina/análogos & derivados , Imagem Molecular , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata/radioterapia , Dosagem Radioterapêutica , Radioterapia Guiada por Imagem/métodos , Radioterapia de Intensidade Modulada/métodos , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/diagnóstico por imagem , Qualidade de Vida , Planejamento da Radioterapia Assistida por Computador , Inquéritos e QuestionáriosRESUMO
Background: This study is aimed to analyze the effect of social distancing on functional outcomes (potency, continence recovery, and quality of life) on patients undergoing open radical prostatectomy (ORP) and robot-assisted radical prostatectomy (RARP) during the COVID-19 pandemic. Materials and methods: We retrospectively assessed functional outcomes of 55 consecutive patients who underwent radical prostatectomy during the COVID-19 pandemic (group A: 12 ORP and 15 RARP) and compared these data with patients from the previous year (group B: 13 ORP and 15 RARP). Propensity-score matching was performed to analyze variables associated with potency, continence recovery and compared between the groups at 1 and 3months. Results: Patients from group A were less interested in postsurgical rehabilitation compared to those from group B (95.7% vs. 56.2%, pâ=â0.042). Continence recovery among group B patients also tended to be higher for RARP (pâ=â0.06) and ORP (pâ=â0.08) at 1âmonth, although statistical significance was not reached. The cumulative continence recovery at 3âmonths among group B patients was higher and statistically significantly advantageous for RARP (pâ=â0.00) and ORP (pâ<â0.01). Potency rates among younger group B patients following bilateral nerve-sparing procedures were statistically significantly advantageous for RARP (pâ=â0.026) and ORP (pâ=â0.011). Conclusions: Our results highlight the large impact of the COVID-19 pandemic on functional outcomes following radical prostatectomy. Future design and planning of home-based models for improved post-operative care should consider this evidence.
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OBJECTIVE: To evaluate the efficacy and safety of desmopressin on frequency and urgency in female patients with overactive bladder (OAB) and nocturia. METHODS: A selective database search was conducted to validate the effectiveness of desmopressin in patients with OAB and nocturia. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were utilised. The meta-analysis included 378 women (five studies) with OAB. The clinical outcomes and adverse events were analysed. RESULTS: The treatment strategy of all the studies included can be divided into three categories: (1) The effect of desmopressin compared with baseline, (2) desmopressin compared with placebo, and (3) desmopressin and anticholinergic combination versus desmopressin monotherapy. There was a significant (50%) reduction in nocturia and urgency episodes after using desmopressin alone. Combined desmopressin and anticholinergic led to a decrease in the frequency of nocturia voids when only using anticholinergic (65% vs. 33.2%). The time increased in the middle to the first nightly voids in the combination arm (65.11 min; p=0.045). The mean incidence (standard deviation) of leak-free episodes was higher under desmopressin than under placebo in the first 4 h (62% [35%] vs. 48% [40%]) and in the first 8 h (55% [37%] vs. 40% [41%]). The safety profile was comparable between treatments. CONCLUSION: Available data indicate that desmopressin is efficacious in significantly reducing nighttime urine production, episodes of nocturia, and urgency episodes. The affectivity of the combination therapy was very high with least side effects for the treatment of OAB/nocturnal polyuria.
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BACKGROUND: A new method was developed based on the relative ranking of gene expression level, overcoming the flaw of the batch effect, and having reliable results in various studies. In the current study, we defined the two methylation sites as a pair. The methylation level in a specific sample was subject to pairwise comparison to calculate a score for each CpGs-pair. The score was defined as a CpGs-pair score. If the first immune-related CpG value was higher than the second one in a specific CpGs-pair, the output score of this immune-related CpGs-pair was 1; otherwise, the output score was 0. This study aimed to construct a new classification of Kidney Clear Cell Carcinoma (KIRC) based on DNA CpGs (methylation sites) pairs. METHODS: In this study, the biomarkers of 28 kinds of immune infiltration cells and corresponding methylation sites were acquired. The methylation data were compared between KIRC and normal tissue samples, and differentially methylated sites (DMSs) were obtained. Then, DNA CpGs-pairs were obtained according to the pairs of DMSs. In total, 441 DNA CpGs-pairs were utilized to construct a classification using unsupervised clustering analysis. We also analyzed the potential mechanism and therapy of different subtypes, and validated them in a testing set. RESULTS: The classification of KIRC contained three subgroups. The clinicopathological features were different across three subgroups. The distribution of immune cells, immune checkpoints and immune-related mechanisms were significantly different across the three clusters. The mutation and copy number variation (CNV) were also different. The clinicopathological features and potential mechanism in the testing dataset were consistent with those in the training set. CONCLUSIONS: Our findings provide a new accurate and stable classification for developing personalized treatments for the new specific subtypes.
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OBJECTIVE: To evaluate the safety and efficacy rate of polyvinylidene fluoride (PVDF) slings in the treatment of female stress urinary incontinence (SUI). MATERIAL AND METHODS: A prospective pilot study was conducted with women with SUI who underwent PVDF slings. Data regarding subjective (International Consultation on Incontinence Questionnaire - Urinary Incontinence [ICIQ-UI] and International Consultation on Incontinence Questionnaire - Overactive Bladder [ICIQ-OAB]) and objective (stress test and bladder diary) outcomes and complication rates were evaluated. Primary outcomes were objective (negative pad and stress test) and subjective (no leakage episodes) success after a median follow-up of 24 months. RESULTS: PVDF slings demonstrated a high level of satisfaction with objective cure (transobturator 90% compared with retropubic 100%, P = .90), urgency to urinate, frequency of de novo incontinence (transobturator 90% compared with retropubic 80%, P = .85), ability of physical and sexual activity (transobturator 90% compared with retropubic 100%, P = .90). The multivariate logistic regression model for satisfaction was associated with overall treatment success (odds ratio [OR] = 3.55, 95% confidence interval [CI] 2.32-6.1), greater reduction in ICIQ-UI (OR = 0.85; 95% CI 0.78-1.85) and ICIQ-OAB (OR =0.99; 95% CI 0.89-1.78). The total Female Sexual Function Index (FSFI) score for both groups was 19.3 ± 1.2 and 20.7 ± 1.8, statistically significant when compared with perioperative FSFI score 16.7 ± 1.1 and 17.6 ± 1.4 (P < .001). CONCLUSION: PVDF mid-urethral slings are safe with clinically efficacies at 3, 6, 12, and 24-month follow-up for the treatment of SUI. The high level of satisfaction seen after PVDF sling procedures is associated with objective improvement of SUI and fewer slings related complications. Further studies using larger sample sizes with longer and comparative clinical follow-up are required.
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BACKGROUND: SelectMDx is a urinary biomarker test for determining prostate cancer risk. AIM: In a group of patients with a biopsy proven prostate cancer (PCa) who had undergone a multi parametric Magnetic Resonance Imaging (mpMRI) and urinary biomarker test with SelectMDx, we studied the additive value of SelectMDx to mpMRI and correlated that to the radical prostatectomy histology. METHODS AND RESULTS: Thirty-nine consecutive patients with a positive prostate biopsy were included in the study. They all had mpMRI and SelectMDx and underwent a radical prostatectomy. Overall, the mpMRI showed a PIRADS ≤3 lesion in seven cases out of the 39 patients. Significant lesions (PIRADS ≥4) were found in 32 cases (82%), that is, in 17 cases a PIRADS 5 lesion and in 15 cases a PIRADS 4 lesion. The mpMRI missed significant PCa in seven cases (18%) who had a PIRADS ≤3 lesion but had a significant PCa on final histology after RP. In our study, the positive predictive values of mpMRI were 97% and that of the SelectMDx was 100%. CONCLUSION: In this real-life selected group of consecutive patients with a confirmed positive PCa biopsy and available mpMRI, the liquid biopsy test with SelectMDx, did not provide an additional information about the PCa clinical significance. The addition of SelectMDx was only found valuable in those patients who had a very high-risk PCa (ie, GS ≥8) who had a positive SelectMDx test outcome despite of a negative mpMRI outcome.
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Biomarcadores Tumorais/genética , Biópsia Líquida/métodos , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Prostatectomia/métodos , Neoplasias da Próstata/diagnóstico , Idoso , Biomarcadores Tumorais/urina , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/urinaRESUMO
Background: Scientific congresses are an important medium for presenting recent clinical findings. Publication of abstracts allows wider dissemination. Objectives: To determine the publication rates of prostate cancer abstracts presented at the annual congress of the European Association of Urology (EAU). Design, Setting, and Participants: All abstracts with the term prostate cancer or carcinoma presented at the congress of the European Association of Urology from 2015 to 2018 were analyzed. We captured their publication rate, journal impact factor and time to publication. Moreover, we formulated a scoring system to determine the grade of discrepancy between the conclusions mentioned in the congress abstract and published abstract. Results: A total of 834 abstracts presented at EAU annual meeting included prostate cancer or carcinoma in their title. We recorded a publication rate of 56.8% with 474 of the 834 abstracts being published with a mean time of 12.5 months. Conclusion: Approximately, 57% of the prostate cancer abstracts presented at the EAU congress are published in peer reviewed journals. This acceptance rate indicates the high distribution and dissemination of these abstracts.
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In the future, precision medicine with agents targeting specific genetic alterations will play an important role in bladder cancer. This includes both single genetic alterations (e.g. FGFR3) and gene panel analyses in patients with no further therapeutic options, rare cancer subtypes or unusual clinical courses. These molecular analyses can be carried out on formalin-fixed paraffin-embedded tumor samples and the results should be discussed in interdisciplinary molecular tumor boards in order to either recommend approved targeted therapies or suggest patients for molecular-based clinical trials, compassionate use programs or off-label use of drugs. The remuneration of molecular diagnostics is largely well-represented for the outpatient sector in Germany; however, the covering of treatment costs must currently be approved by the health insurances.
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Neoplasias da Bexiga Urinária , Testes Genéticos , Humanos , Mutação , Patologia Molecular , Medicina de Precisão , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/terapiaRESUMO
PURPOSE: Until recently, the urine of healthy individuals was assumed to be sterile. However, improvement of bacterial detection methods has debunked this assumption. Recent studies have shown that the bladder contains microbiomes, which are not detectable under standard conditions. In this review, we aimed to present an overview of the published literature regarding the relationship between urinary microbiota and functional disorders of the genitourinary system. METHODS: We searched Medline, PubMed, Embase, The Cochrane library and Scopus to identify RCTs published, with MeSH and free keywords including microbiota, bladder pain syndrome, prostatitis, kidney stone disease, and bladder cancer until September 2020. Randomized controlled trials investigating microbiome and lower urinary tract symptoms were included. Non-randomized trials, cross-over trials and pooled studies were excluded. The articles were critically appraised by two reviewers. CONCLUSION: The urine microbiome is a newly introduced concept, which has attracted the attention of medical researchers. Since its recent introduction, researchers have conducted many fruitful studies on this phenomenon, changing our perspective toward the role of bacteria in the urinary tract and our perception of the genitourinary system health. RESULT: A deeper understanding of the urinary microbiome can help us to develop more efficient methods for restoring the microbiota to a healthy composition and providing symptom relief. Modification of the urinary microbiome without antibiotic use can be a possible venue for future research.
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Doenças Urogenitais Femininas/urina , Doenças Urogenitais Masculinas/urina , Microbiota , Sistema Urogenital/microbiologia , Correlação de Dados , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Bladder cancer is highly related to immune cell infiltration. This study aimed to develop a new classification of BC molecular subtypes based on immune-cell-associated CpG sites. METHODS: The genes of 28 types of immune cells were obtained from previous studies. Then, methylation sites corresponding to immune-cell-associated genes were acquired. Differentially methylated sites (DMSs) were identified between normal samples and bladder cancer samples. Unsupervised clustering analysis of differentially methylated sites was performed to divide the sites into several subtypes. Then, the potential mechanism of different subtypes was explored. RESULTS: Bladder cancer patients were divided into three groups. The cluster 3 subtype had the best prognosis. Cluster 1 had the poorest prognosis. The distribution of immune cells, level of expression of checkpoints, stromal score, immune score, ESTIMATEScore, tumor purity, APC co_inhibition, APC co_stimulation, HLA, MHC class_I, Type I IFN Response, Type II IFN Response, and DNAss presented significant differences among the three subgroups. The distribution of genomic alterations was also different. CONCLUSIONS: The proposed classification was accurate and stable. BC patients could be divided into three subtypes based on the immune-cell-associated CpG sites. Specific biological signaling pathways, immune mechanisms, and genomic alterations were varied among the three subgroups. High-level immune infiltration was correlated with high-level methylation. The lower RNAss was associated with higher immune infiltration. The study of the intratumoral immune microenvironment may provide a new perspective for BC therapy.
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OBJECTIVE: To evaluate the current state, therapeutic benefit and safety of urethral injection of autologous stem cells for the treatment stress urinary incontinence (SUI). MATERIALS AND METHODS: A selective database search of PubMed, the Excerpta Medica dataBASE (EMBASE), Cochrane Library and Google Scholar was conducted to validate the effectiveness of stem cell-based therapy. The search included clinical trials published up until 4 January 2020, written in English, and included cohorts of women and men who had received stem cell-based therapy for SUI. The search used the following keywords in various combinations: 'stem cell therapy', 'cell-based therapy for SUI', 'regenerative medicine for SUI', and 'tissue engineering'. The success rates were assessed according to cough test, urodynamics, pad tests, and International Consultation on Incontinence Questionnaire-Urinary Incontinence. The primary endpoint was continence rate to measure objectively the effect of the treatment. RESULTS: We identified four clinical trials using local injections of adipose-derived stem cells (ADSCs), 11 trails with muscle-derived stem cells (MDSCs), and two trails with human umbilical cord blood stem cells (HUCBs) and total nucleated cells (TNCs). The median improvement rate of intrinsic sphincter deficiency after ADSCs, MDSCs, TNCs, HUCBs injections were 88%, 77%, 89%, 36% (improvement rate: 1-2 pads) at a mean (range) follow-up of 6 (1-72) months. The cell sources, methods of cell processing, cell number, and implantation techniques differed considerably between studies. Most of the periurethral injections were at the 3, 5, 7, and 9 o'clock positions and for submucosa were at the 4, 6, and 8 o'clock positions. No significant postoperative complications were reported. CONCLUSION: Despite many challenges in stem cell-based therapy for treating SUI, it appears to provide, in both male and female patients, acceptable functional results with minimal side-effects and complications. In the future, more clinical trials should be funded in order to optimise stem cell-based therapy and evaluate long-term outcomes. ABBREVIATIONS: ADSC: adipose-derived stem cell; BMSCs: bone marrow-derived mesenchymal stem cell; CLPP: cough leak-point pressure; FPL: functional profile length; HUCB: human umbilical cord blood stem cell; ICIQ-(QOL)(SF)(UI): International Consultation on Incontinence Questionnaire (Quality of life) (-Urinary incontinence Short Form) (-Urinary Incontinence); IIQ-7: Incontinence Impact Questionnaire-short form; I-QOL: Incontinence quality of life questionnaire; ISD: intrinsic urinary sphincter deficiency; MDSC: muscle-derived stem cell; MUCP: maximum urethral closure pressure; NR: not reported; Pdet-max: maximum detrusor pressure; PVR: post-void residual urine volume; Qmax: maximum urinary flow; QOL: quality of life; RP: radical prostatectomy; TNC: total nucleated cell; (S)UI: (stress) urinary incontinence; UDSCs: urine-derived stem cells; UTUS: upper tract ultrasonography; VLPP: Valsalva leak-point pressure.
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OBJECTIVE: To evaluate the complications and results of artificial urinary sphincter (AUS) implantation in women with stress urinary incontinence (SUI). METHODS: A selective database search using keywords (1990-2019) was conducted to validate the effectiveness of the AUS in women. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were utilised. The meta-analysis included 964 women (15 studies) with persistent SUI. The Newcastle-Ottawa score was used to determine the quality of the evidence in each study. The success rate and complications associated with the AUS were analysed. RESULTS: Meta-analysis of the published studies showed that complete continence was achieved at a mean rate of 79.6% (95% confidence interval [CI] 72.2-86.6%) and a significant improvement was achieved in 15% (95% CI 10-25%). The mean (range) follow-up was 22 (6-204) months. The mean number of patients per study was 68. The mean (range) explantation rate was 13 (0-44)%. Vaginal erosion occurred in a mean (range) of 9 (0-27)% and mechanical complications in 13 (0-47)%. Infections accounted for 7% of the complications. The total mean (range) revision rate of the implanted AUS was 15.42 (0-44)%. The mean (range) size of the cuff used was 6.7 (5-10) cm. CONCLUSION: Our present analysis showed that implantation of an AUS in women with severe UI is an effective treatment option after failure of first-line therapy. However, the currently available study population is too small to draw firm conclusions. ABBREVIATIONS: AMS: American Medical Systems; AUS: artificial urinary sphincter; EAU: European Association of Urology; LE: Level of Evidence; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; QoL: quality of life; SHELTER: Services and Health for Elderly in Long TERm care (study); SUI: (stress) urinary incontinence.
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Recent findings suggested a benefit of anti-EGFR therapy for basal-like muscle-invasive bladder cancer (MIBC). However, the impact on bladder cancer with substantial squamous differentiation (Sq-BLCA) and especially pure squamous cell carcinoma (SCC) remains unknown. Therefore, we comprehensively characterized pure and mixed Sq-BLCA (n = 125) on genetic and protein expression level, and performed functional pathway and drug-response analyses with cell line models and isolated primary SCC (p-SCC) cells of the human urinary bladder. We identified abundant EGFR expression in 95% of Sq-BLCA without evidence for activating EGFR mutations. Both SCaBER and p-SCC cells were sensitive to EGFR tyrosine kinase inhibitors (TKIs: erlotinib and gefitinib). Combined treatment with anti-EGFR TKIs and varying chemotherapeutics led to a concentration-dependent synergism in SCC cells according to the Chou-Talalay method. In addition, the siRNA knockdown of EGFR impaired SCaBER viability suggesting a putative "Achilles heel" of Sq-BLCA. The observed effects seem Sq-BLCA-specific since non-basal urothelial cancer cells were characterized by poor TKI sensitivity associated with a short-term feedback response potentially attenuating anti-tumor activity. Hence, our findings give further insights into a crucial, Sq-BLCA-specific role of the ERBB signaling pathway proposing improved effectiveness of anti-EGFR based regimens in combination with chemotherapeutics in squamous bladder cancers with wild-type EGFR-overexpression.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células de Transição/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/patologia , Linhagem Celular Tumoral , Estudos de Coortes , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Receptores ErbB/metabolismo , Cloridrato de Erlotinib/farmacologia , Cloridrato de Erlotinib/uso terapêutico , Feminino , Gefitinibe/farmacologia , Gefitinibe/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , Inibidores de Proteínas Quinases/uso terapêutico , RNA Interferente Pequeno/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/metabolismo , Receptor ErbB-3/antagonistas & inibidores , Receptor ErbB-3/metabolismo , Receptor ErbB-4/antagonistas & inibidores , Receptor ErbB-4/metabolismo , Transdução de Sinais/efeitos dos fármacos , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologiaRESUMO
Pyeloplasty is one of the most common urological reconstructive interventions. Since the presentation of the first open pyeloplasty by Anderson and Hynes in 1949, the management of ureteropelvic junction obstruction has dramatically developed. The most immense progress was made in the 1990s with the introduction of laparoscopy. A multitude of new minimal surgical techniques have been introduced since then. In the last few years, the innovations were based on refinement of already-existing techniques and technology. With this aim, single-port surgery, three-dimensional vision for laparoscopy, robotic technology, and alternative techniques for creating the anastomosis-like fibrin glue have been introduced. This unsystematic review is timely, and the scientific interest is to present and discuss some of the latest advances in surgical techniques and different approaches for the intra- and post-operative management in pyeloplasty. To the best of our knowledge, this is the only review looking at the recent advances in urological surgical techniques for pyeloplasty during the last few years with a focus on new technology and surgical techniques.
Assuntos
Procedimentos de Cirurgia Plástica/tendências , Obstrução Ureteral/cirurgia , Procedimentos Cirúrgicos Urológicos/tendências , Humanos , Pelve Renal/cirurgia , Laparoscopia , RobóticaRESUMO
PURPOSE: To analyze long-term quality-of-life (QoL) changes related to postoperative radiation therapy (RT) after radical prostatectomy. METHODS AND MATERIALS: Patients who received postoperative 3-dimensional conformal RT in the years 2003 to 2008 with 1.8 to 2.0 Gy fractions up to 66.0 to 66.6 Gy (n = 181) were surveyed using the Expanded Prostate Cancer Index Composite questionnaire before the beginning of RT (A); on the last day (B); and 2 months (C), 1 to 3 years (D), 6 to 9 years (E), and 10 to 13 years (F) after RT. RESULTS: Mean urinary bother, urinary incontinence bother, and bowel bother score changes (in relation to baseline at time A) of 13, 14, and 7 and 14, 15, and 7 were found at times E and F, respectively (P < .01 for all comparisons). Sexual function scores decreased 6 and 8 points on average (P < .01). Patient age at the time of RT had a considerable impact on urinary bother and urinary incontinence bother, with increasing differences over time when comparing patients aged <68 versus ≥68 years: 0 versus 7 and 0 versus 7 points at time D and 8 versus 23 and 6 versus 35 points at time F, respectively. Patients who did not respond to RT with a decreasing prostate-specific antigen level had greater urinary and urinary incontinence bother and bowel bother score changes >10 years after treatment (25 vs 12; P = .04, 36 vs 10; P = .03, and 20 vs 5; P = .07, respectively). A higher rectal dose was associated with greater acute and long-term bowel bother score decrease. No correlation was found between the dose to the bladder and QoL changes. CONCLUSIONS: In contrast to early evaluations in the first years, significantly decreasing QoL in the urinary, bowel, and sexual domains was found >5 years after RT. Aging is likely to be a major factor. Younger patients who responded to the treatment had the most favorable long-term QoL results. As 3-dimensional conformal RT was used in this study, intensity modulated concepts could result in improved outcomes.