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1.
Oncologist ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38908022

RESUMO

HER2, encoded by the ERBB2 gene, is an important druggable driver of human cancer gaining increasing importance as a therapeutic target in urothelial carcinoma (UC). The genomic underpinnings of HER2 overexpression in ERBB2 nonamplified UC are poorly defined. To address this knowledge gap, we investigated 172 UC tumors from patients treated at the University of California San Francisco, using immunohistochemistry and next-generation sequencing. We found that GATA3 and PPARG copy number gains individually predicted HER2 protein expression independently of ERBB2 amplification. To validate these findings, we interrogated the Memorial Sloan Kettering/The Cancer Genome Atlas (MSK/TCGA) dataset and found that GATA3 and PPARG copy number gains individually predicted ERBB2 mRNA expression independently of ERBB2 amplification. Our findings reveal a potential link between the luminal marker HER2 and the key transcription factors GATA3 and PPARG in UC and highlight the utility of examining GATA3 and PPARG copy number states to identify UC tumors that overexpress HER2 in the absence of ERBB2 amplification. In summary, we found that an increase in copy number of GATA3 and PPARG was independently associated with higher ERBB2 expression in patient samples of UC. This finding provides a potential explanation for HER2 overexpression in UC tumors without ERBB2 amplification and a way to identify these tumors for HER2-targeted therapies.

2.
Epidemiol Mikrobiol Imunol ; 73(1): 51-58, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38697840

RESUMO

The numbers of diagnosed and reported cases of infection with the SARS-CoV-2 virus causing the disease COVID-19, which grew into a global pandemic, have remained consistently low in all countries, including the Czech Republic, since May 2023, when the World Health Organization declared an end to the pandemic. However, it must be said that the measures implemented to control this infection did not meet all expectations. Although new mutations of the virus that can potentially cause disease, continue to emerge, it appears that most people have gradually learned to coexist with them. However, due to some unique properties of the SARS-CoV-2 virus and its variants, there will still be predisposed individuals who will develop illness and need hospitalization along with effective treatment to be supported and monitored by adequate laboratory tests. This article is a commentary on this issue and deals primarily with the diagnosis and care of early-phase COVID-19 patients. Author's translation of the article into English is available at: https://www.spadia.cz/media/2085/lessons fromthecovid-19pandemic.pdf.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , República Tcheca/epidemiologia , SARS-CoV-2 , Pandemias
3.
BMC Cancer ; 23(1): 1127, 2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-37980511

RESUMO

BACKGROUND: Bladder cancer poses a significant public health burden, with high recurrence and progression rates in patients with non-muscle-invasive bladder cancer (NMIBC). Current treatment options include bladder-sparing therapies (BST) and radical cystectomy, both with associated risks and benefits. However, evidence supporting optimal management decisions for patients with recurrent high-grade NMIBC remains limited, leading to uncertainty for patients and clinicians. The CISTO (Comparison of Intravesical Therapy and Surgery as Treatment Options) Study aims to address this critical knowledge gap by comparing outcomes between patients undergoing BST and radical cystectomy. METHODS: The CISTO Study is a pragmatic, prospective observational cohort trial across 36 academic and community urology practices in the US. The study will enroll 572 patients with a diagnosis of recurrent high-grade NMIBC who select management with either BST or radical cystectomy. The primary outcome is health-related quality of life (QOL) at 12 months as measured with the EORTC-QLQ-C30. Secondary outcomes include bladder cancer-specific QOL, progression-free survival, cancer-specific survival, and financial toxicity. The study will also assess patient preferences for treatment outcomes. Statistical analyses will employ targeted maximum likelihood estimation (TMLE) to address treatment selection bias and confounding by indication. DISCUSSION: The CISTO Study is powered to detect clinically important differences in QOL and cancer-specific survival between the two treatment approaches. By including a diverse patient population, the study also aims to assess outcomes across the following patient characteristics: age, gender, race, burden of comorbid health conditions, cancer severity, caregiver status, social determinants of health, and rurality. Treatment outcomes may also vary by patient preferences, health literacy, and baseline QOL. The CISTO Study will fill a crucial evidence gap in the management of recurrent high-grade NMIBC, providing evidence-based guidance for patients and clinicians in choosing between BST and radical cystectomy. The CISTO study will provide an evidence-based approach to identifying the right treatment for the right patient at the right time in the challenging clinical setting of recurrent high-grade NMIBC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03933826. Registered on May 1, 2019.


Assuntos
Neoplasias não Músculo Invasivas da Bexiga , Neoplasias da Bexiga Urinária , Humanos , Adjuvantes Imunológicos/uso terapêutico , Administração Intravesical , Vacina BCG/uso terapêutico , Cistectomia , Estudos Multicêntricos como Assunto , Invasividade Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Observacionais como Assunto , Estudos Prospectivos , Qualidade de Vida , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Ensaios Clínicos Pragmáticos como Assunto
4.
J Urol ; 207(3): 534-540, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34694916

RESUMO

PURPOSE: The utility of blue light cystoscopy (BLC) in patients receiving bacillus Calmette-Guérin (BCG) during post-treatment cystoscopy is not well understood. Our objective was to determine if BLC improves recurrence detection in patients with non-muscle invasive bladder cancer (NMIBC) undergoing BCG. MATERIALS AND METHODS: Using the prospective multi-institutional Cysview® Registry (2014-2019), patients with NMIBC who received BCG within 1 year prior to BLC were identified. Primary outcomes were recurrences and whether lesions were detected on white light cystoscopy (WLC), BLC or both. We calculated the percentage of cystoscopies with recurrences that were missed with WLC alone. The cystoscopy-level BLC false-positive rate was the proportion of cystoscopies with biopsies only due to BLC suspicious lesions without recurrence. RESULTS: Of 1,703 BLCs, 282 cystoscopies were in the analytic cohort. The overall recurrence rate was 45.0% (127). With only WLC, 13% (16/127) of recurrences would have been missed as 5.7% (16/282) of cystoscopies performed had recurrence only identified with BLC. Among 16 patients with recurrence missed with WLC, 88% (14) had carcinoma in situ. The cystoscopy-level BLC false-positive rate was 5% (15). CONCLUSIONS: BLC helped detect recurrences after recent BCG that would have been missed with WLC alone. Providers should consider BLC for high-risk patients undergoing BCG and should discuss the risk of false-positives with these patients. As clinical trials of novel therapies for BCG-unresponsive disease increase and there are no clear guidelines on BLC use for post-treatment cystoscopies, it is important to consider how variable BLC use could affect enrollment in and comparisons of these studies.


Assuntos
Vacina BCG/uso terapêutico , Cistoscopia/métodos , Recidiva Local de Neoplasia/diagnóstico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Biópsia , Carcinoma in Situ/tratamento farmacológico , Feminino , Humanos , Masculino , Estudos Prospectivos , Sistema de Registros , Estados Unidos
5.
BJU Int ; 130(1): 62-67, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34637596

RESUMO

OBJECTIVES: To evaluate the role of blue-light cystoscopy (BLC) in detecting invasive tumours that were not visible on white-light cystoscopy (WLC). PATIENTS AND METHODS: Using the multi-institutional Cysview registry database, patients who had at least one white-light negative (WL-)/blue-light positive (BL+) lesion with invasive pathology (≥T1) as highest stage tumour were identified. All WL-/BL+ lesions and all invasive tumours in the database were used as denominators. Relevant baseline and outcome data were collected. RESULTS: Of the 3514 lesions (1257 unique patients), 818 (23.2%) lesions were WL-/BL+, of those, 55 (7%) lesions were invasive (48 T1, seven T2; 47 unique patients) including 28/55 (51%) de novo invasive lesions (26 unique patients). In all, 21/47 (45%) patients had WL-/BL+ concommitant carcinoma in situ and/or another T1 lesions. Of 22 patients with a WL-/BL+ lesion who underwent radical cystectomy (RC), high-risk pathological features leading to RC was only visible on BLC in 18 (82%) patients. At time of RC, 11/22 (50%) patients had pathological upstaging including four (18%) with node-positive disease. CONCLUSIONS: A considerable proportion of invasive lesions are only detectable by BLC and the rate of pathological upstaging is significant. Our present findings suggest an additional benefit of BLC in the detection of invasive bladder tumours that has implications for treatment approach.


Assuntos
Cistoscopia , Neoplasias da Bexiga Urinária , Cistectomia , Humanos , Sistema de Registros , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
6.
J Wound Ostomy Continence Nurs ; 49(3): 247-250, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35523240

RESUMO

PURPOSE: The purpose of this study was to validate time frames for postoperative care following stoma surgery and to determine participants' current practice with convex pouching systems during the postoperative period. DESIGN: A Cross-sectional survey. SUBJECTS AND SETTING: The sample comprised 332 ostomy care specialists practicing in the United States. Most (n = 220; 66%) had more than 10 years' experience caring for patients with ostomies, 82% (n = 272) were certified WOC or ostomy care nurses (CWOCN and COCN), and 7% (n = 23) were board-certified colorectal surgeons. METHODS: A 23-item online questionnaire was created for purposes of the study. Items in the questionnaire queried professional background and experience caring for patients with an ostomy. A single item was used to identify postoperative care periods following ostomy surgery. Additional items queried current practice patterns related to use of convex pouching systems and the timing of their use. Data were collected from January 18 to February 8, 2021. RESULTS: Most respondents (n = 270; 90%) agreed with the following postoperative periods after ostomy surgery: immediate postoperative period (days 0-8); postoperative period (days 9-30); and transition phase (days 31-180). Most respondents (n = 274; 95%) indicated they would use a convex pouching system when clinically appropriate during the first 30 days following ostomy surgery and 79% (n = 228) indicated using a convex pouching system regardless of when the surgery was performed. Less than 1% (n = 2) indicated never using convexity within the first 30 days following stoma surgery, and only 3% (n = 8) indicated avoidance of convexity pouching systems in the immediate postoperative period. CONCLUSIONS: Findings indicate that use of convexity during the postoperative period is prevalent to provide a secure seal and predictable wear time.


Assuntos
Estomia , Estomas Cirúrgicos , Estudos Transversais , Humanos , Período Pós-Operatório , Inquéritos e Questionários
7.
Acta Chir Orthop Traumatol Cech ; 89(3): 204-207, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35815487

RESUMO

PURPOSE OF THE STUDY Population aging is connected with an increased incidence of chronic diseases. A common related problem is chronic skin ulcers, which, while not life-threatening, can significantly decrease the quality of the patient's life. The present study aims to evaluate new materials and methods to improve and accelerate the treatment of leg ulcers. MATERIAL AND METHODS Twenty-five patients with chronic ulcers treated using autologous growth factors applied on a nanofiber carrier were included in the cohort. The control group consisted of 15 patients treated using standard moist wound therapy. The surface area of the ulcer was measured on the 0th, 14th, 28th, 56th, 84th, 112th, 140th, 140th, and 168th day of treatment. Ulcer depth was measured on the 0th, 5th, 28th, 84th, and 168th day of treatment. Results were statistically processed and evaluated. RESULTS During the study, the defect area decreased in both the control and experimental group. Statistically significantly better results were observed in the experimental group relative to the progress of ulcer depth. The experimental group also had more healed ulcers. DISCUSSION Moistness is necessary for chronic wounds to heal; it is needed to ensure optimal cell growth, angiogenesis, and fibrinolysis. Wounds can be treated using non-active dressings with high absorption qualities; however, these do not guarantee optimal conditions for healing, or wounds can be treated with an interactive dressing that interacts with the wound surface. The third option for treatment is the use of bioactive materials that adhere to the wound and participate directly in the individual stages of healing. CONCLUSIONS The study found that autologous growth factors had statistically significant effects on the treatment of chronic ulcers. The authors believe that this method can accelerate the healing of primary post-injury or secondary postoperative wounds of lower leg soft tissues. Key words: trophic ulcer, autologous growth factors, microangiopathy, polyneuropathy, diabetes mellitus.


Assuntos
Úlcera da Perna , Nanofibras , Plasma Rico em Plaquetas , Humanos , Úlcera da Perna/terapia , Nanofibras/uso terapêutico , Projetos Piloto , Úlcera
8.
World J Urol ; 39(6): 1911-1916, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32737581

RESUMO

PURPOSE: To evaluate the clinical, pathological, and survival outcomes of bladder cancer in patients aged 18-40 years. METHODS: We identified 362,091 bladder cancer patients from the National Cancer Database between 2004-2013 and compared patients aged 18-40 years to those > 40 years of age with univariate analysis using Chi-square tests. A subset analysis was performed on patients who underwent cystectomy. Multivariable Cox regression was used for overall survival analysis. RESULTS: Our final analysis included 314,177 patients with 3314 (1.1%) patients aged 18-40 years. Patients aged 18-40 years had a lower male-to-female ratio (2.4 versus 3.0), a greater proportion of low-grade tumors (72.7% versus 48.3%, p < 0.001), non-muscle invasive tumors (90.3% versus 81.2%, p < 0.001), and variant histology (4.0% versus 3.3%, p < 0.001). Similar trends were observed at cystectomy including lower male-to-female ratio in the 18-40 years group (1.7 versus 3.1), a greater proportion of variant histology (25.0% versus 10.0%, p < 0.001); and 53.3% of those younger patients with variant histology were women. Patients aged 18-40 years who underwent cystectomy had a higher proportion of locally advanced disease (pT4 19.2% versus 14.6%, p = 0.004). Multivariable analyses in both cohorts demonstrated that variant histology was a predictor of worse overall survival. CONCLUSION: The majority of patients aged 18-40 years with bladder cancer present with low-grade, non-muscle-invasive disease associated with better survival. However, a subset of younger patients with a higher proportion of women presents with aggressive bladder cancer which may be partly explained by a higher prevalence of variant histology.


Assuntos
Cistectomia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/cirurgia , Adolescente , Adulto , Bases de Dados Factuais , Feminino , Humanos , Masculino , Estudos Retrospectivos , Taxa de Sobrevida , Estados Unidos/epidemiologia , Adulto Jovem
9.
J Urol ; 204(2): 239-246, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32074006

RESUMO

PURPOSE: Urothelial carcinoma of the luminal molecular subtype is associated with lower rates of pathological up staging from clinical stage T1-T2 to nonorgan confined (pT3 or greater and/or pN+) disease at radical cystectomy. However, approximately a third of luminal urothelial carcinoma cases were up staged to nonorgan confined disease, and these may be under treated if neoadjuvant chemotherapy is withheld. In this study we trained a genomic classifier to predict luminal nonorgan confined disease in patients diagnosed with clinically organ confined (cT1/T2) disease. MATERIALS AND METHODS: Specimens from transurethral resected high grade cT1-T2N0M0 urothelial carcinoma of the bladder that belonged to the luminal subtype (Seiler 2017) were randomly split into training (75) and testing (25) sets for the development of a single sample luminal up staging classifier using lasso/ridge-penalized logistic regression. All patients underwent radical cystectomy without neoadjuvant chemotherapy and the primary end point was up staging to nonorgan confined disease. A radical cystectomy cohort and a platinum treated neoadjuvant chemotherapy cohort were used to evaluate the luminal up staging classifier. RESULTS: Up staging to nonorgan confined disease occurred in 34% of luminal cases. The luminal up staging classifier predicted up staging in 32 of 34 cases, with 6 false-positives (AUC 0.96). The sensitivity for detection of luminal pN+ disease was 95% (20 of 21). Patients with predicted nonorgan confined luminal tumors had worse survival than those with organ confined luminal tumors (p=0.001). On multivariable analysis the luminal up staging classifier was a significant predictor of overall survival after adjusting for clinical variables available at transurethral resection. The luminal up staging classifier also predicted overall survival for aggressive luminal TCGA (The Cancer Genome Atlas) cases (n=83, p=0.043). In the neoadjuvant chemotherapy cohort the luminal up staging classifier predicted 9 up staging cases, all of which had excellent prognosis. CONCLUSIONS: A luminal up staging classifier was developed that distinguishes a subset of cT1-T2N0M0 luminal urothelial carcinoma cases at high risk for up staging to nonorgan confined disease at radical cystectomy and of death. Validation of this model in an independent, large patient cohort is necessary to determine how molecular stratification of luminal tumors could be used to guide treatment of these patients.


Assuntos
Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/patologia , Genômica , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Idoso , Carcinoma de Células de Transição/cirurgia , Cistectomia/métodos , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/classificação , Neoplasias da Bexiga Urinária/cirurgia
10.
BMC Urol ; 20(1): 103, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32680507

RESUMO

An amendment to this paper has been published and can be accessed via the original article.

11.
BMC Urol ; 20(1): 40, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32303266

RESUMO

BACKGROUND: Testicular sex cord stromal tumors (SCSTs) are managed similarly to germ cell tumors (GCTs); however, few studies have directly compared outcomes between these tumor types. Using the National Cancer Database (NCDB), we sought to compare overall and stage-specific all-cause mortality (ACM) between SCSTs versus GCTs. METHODS: NCDB was queried for patients diagnosed with SCSTs and GCTs between 2004 and 2013. Descriptive statistics were used to compare sociodemographic and clinical characteristics between groups. Univariable and multivariable Cox proportional hazards regression analyses were used to assess associations with ACM. RESULTS: We identified 42,192 patients diagnosed with testicular cancer between 2004 and 2013, with 280 having SCSTs and 41,912 patients having GCTs. Median age for SCSTs and GCTs was 45 (interquartile range [IQR] 34-59) and 34 (IQR 27-43), respectively (p < 0.001). Median follow-up was 39 and 52 months, respectively. Overall, patients with SCSTs had greater risk of ACM compared to those with GCTs (HR 1.69, 95% CI 1.14-2.50). Private insurance, greater education, and fewer comorbidities were associated with reduced risk of ACM (p < 0.05 for all). Among those with stage I disease, tumor type was not associated with ACM on multivariable analysis. Among those with stage II/III disease, patients with SCSTs had increased risk of ACM compared to patients with GCTs (HR 3.29, 95% CI 1.89-5.72). CONCLUSIONS: Patients with advanced SCSTs had worse survival outcomes compared to those with advanced GCTs. These data suggest a need for further investigation to ascertain effective management recommendations for SCSTs.


Assuntos
Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Embrionárias de Células Germinativas/patologia , Tumores do Estroma Gonadal e dos Cordões Sexuais/mortalidade , Tumores do Estroma Gonadal e dos Cordões Sexuais/patologia , Neoplasias Testiculares/mortalidade , Neoplasias Testiculares/patologia , Adulto , Bases de Dados Factuais , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Estados Unidos
12.
Curr Urol Rep ; 19(12): 102, 2018 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-30357502

RESUMO

PURPOSE OF REVIEW: Epigenetics refers to processes that alter gene expression without altering primary DNA. Over that past decade, there is a growing focus on epigenetic mechanisms in cancer research and its importance in cancer biology. This review summarizes epigenetic dysregulation in bladder cancer. RECENT FINDINGS: Epigenetic alterations are overall shared across various grades and stages of bladder cancer. High grade invasive tumors demonstrate a greater degree and intensity of methylation and may have a unique methylation pattern. Environmental exposures may influence epigenetic alterations directly independent of genomic change. Non-coding RNAs play an important role in cancer phenotype, especially in the context of integrative genomic analyses. DNA hypermethylation and non-coding RNAs have potential as robust bladder cancer biomarkers; however, they require further study and validation. Changes in chromatin and histone modification are attractive targets for therapy and are currently in clinical trials. Epigenetic dysregulation may be an important key in improving the understanding of bladder cancer pathogenesis, especially through integrative genomic analyses. Deeper understanding of these pathways can help identify clinically relevant biomarkers and therapeutic targets to validate for diagnosis, monitoring, prognosis, and treatment for bladder cancer.


Assuntos
Carcinoma de Células de Transição/genética , Metilação de DNA/genética , Epigênese Genética , Código das Histonas/genética , RNA não Traduzido/genética , Neoplasias da Bexiga Urinária/genética , Carcinoma de Células de Transição/patologia , Humanos , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Bexiga Urinária/patologia
13.
Cancer ; 123(23): 4574-4582, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28881475

RESUMO

BACKGROUND: Risk stratification of patients with urothelial carcinoma of the bladder (UCB) after cystectomy has important clinical and research implications. The authors assessed the relative effect of tumor stage and lymph node status on cancer-specific survival (CSS) after cystectomy and developed a simplified risk-assessment tool. METHODS: In total, 14,828 patients who underwent cystectomy with lymph node dissection for UCB were identified from the Surveillance, Epidemiology, and End Results database (1988-2011). The relative importance of tumor stage and lymph node status with regard to CSS was assessed using stratified Kaplan-Meier and Cox proportional-hazards analyses. The patients were split randomly into development and validation cohorts. Additional validation using overall survival was performed on 19,362 patients from the National Cancer Data Base. The Cancer of Bladder Risk Assessment (COBRA) tool was created using a Cox model incorporating age, tumor stage, and lymph node density. Performance was validated using observed versus expected survival plots and the Harrell concordance index. RESULTS: Patients with muscle invasive (T2), lymph node-positive disease had a survival curve similar to that in patients with extravesical (T3 and T4), lymph node-negative disease (2-year CSS, 67% and 70%, respectively). Each point increase in the COBRA score (range, 0-7) was associated with a 1.61-fold increase (95% confidence interval, 1.56-fold to 1.65-fold increase) in the risk of bladder cancer death in the development cohort. The model accurately stratified patients across risk levels in the development cohort and the 2 validation cohorts (C-index, 0.712, 0.705, and 0.68, respectively). CONCLUSIONS: The COBRA score offers a straightforward, validated risk-stratification tool that incorporates the relative contribution of tumor stage and lymph node involvement to patient prognosis after cystectomy for UCB. Cancer 2017;123:4574-4582. © 2017 American Cancer Society.


Assuntos
Cistectomia/mortalidade , Excisão de Linfonodo/mortalidade , Neoplasias da Bexiga Urinária/mortalidade , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Medição de Risco , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
15.
Indian J Urol ; 31(4): 297-303, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26604440

RESUMO

Non-muscle-invasive bladder cancer (NMIBC) is characterized by a tendency for recurrence and capacity for progression. Intravesical instillation therapy has been employed in various clinical settings, which are summarized within this review. Several chemotherapeutic agents have shown clinical efficacy in reducing recurrence rates in the post-transurethral resection of bladder tumor (TURBT) setting, including mitomycin C (MMC), doxorubicin, and epirubicin. Mounting evidence also supports the use of intravesical MMC following nephroureterectomy to reduce later urothelial bladder recurrence. In the adjuvant setting, bacillus Calmette-Guérin (BCG) immunotherapy is an established first-line agent in the management of carcinoma in situ (CIS) and high-grade non muscle invasive urothelial carcinoma (UC). Among high and intermediate-risk patients (based on tumor grade, size, and focality) improvements in disease-free intervals have been seen with adjunctive administration of MMC prior to scheduled BCG dosing. Following failure of first-line intravesical therapy, gemcitabine and valrubicin have demonstrated modest activity, though valrubicin remains the only agent currently Food and Drug Administration (FDA)-approved for the treatment of BCG-refractory CIS. Techniques to optimize intravesical chemotherapy delivery have also been explored including pharmacokinetic methods such as urinary alkalization and voluntary dehydration. Chemohyperthermia and electromotive instillation have been associated with improved freedom from recurrence intervals but may be associated with increased urinary toxicity. Improvements in therapeutic selection may be heralded by novel opportunities for genomic profiling and refinements in clinical risk stratification.

17.
Curr Opin Urol ; 24(5): 517-23, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24921905

RESUMO

PURPOSE OF REVIEW: The true clinical significance of variant histology is controversial and diagnosis is challenging, especially in the setting of nonmuscle invasive (NMI) disease. If the presence of variant architecture in NMI identifies a high-risk population with a worse prognosis and better suited for early aggressive intervention (i.e., radical cystectomy), then treatment recommendations should reflect this notion. This review outlines the current evidence and determines whether histologic variants should change management of patients with nonmuscle invasive bladder cancer. RECENT FINDINGS: Patients with high-risk NMI tumors and variant histology should be offered early cystectomy, especially if harboring pure squamous, adenocarcinoma, sarcomatoid, plasmacytoid, or micropapillary disease. In patients with small cell disease, systemic primary chemotherapy is the ideal option followed by local therapy for primary tumor control. For squamous/glandular differentiation, nested variant, and other rare variants, intravesical therapy is an option based on standard risk stratification in patients with NMI disease. Diligence is needed in the presence of variant histology to minimize the risk of understaging as well as close surveillance to not compromise the opportunity of cure. SUMMARY: The management of nonmuscle invasive bladder cancer with variant histology is challenging, largely in part to the high risk of understaging and the background of already existing controversy regarding the management of high-risk NMI disease for standard urothelial cell carcinoma (early cystectomy vs. intravesical therapy). Future studies should be focused identifying if variant architecture confers different tumor biology than that of pure urothelial carcinoma, and if this difference translates into innovations in bladder sparing therapies.


Assuntos
Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/terapia , Gerenciamento Clínico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Carcinoma de Células Pequenas/diagnóstico , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/terapia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Carcinoma de Células de Transição/diagnóstico , Terapia Combinada , Cistectomia , Tratamento Farmacológico , Humanos , Prognóstico , Resultado do Tratamento , Neoplasias da Bexiga Urinária/diagnóstico
18.
Urol Oncol ; 42(6): 176.e21-176.e28, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38553264

RESUMO

BACKGROUND: The gold standard for detecting bladder cancer is cystoscopy with biopsy or transurethral resection confirming histologic diagnosis. URO17® employs a chromogenically labeled monoclonal antibody to keratin 17 (k17), an intermediate filament cytoskeleton molecule associated with bladder, pancreatic, and cervical cancers. Preliminary studies evaluating k17 demonstrated a high sensitivity and specificity for the detection of bladder cancer, supporting the need for further study. OBJECTIVE: To evaluate the sensitivity and specificity of URO17. METHODS: This is a cross-sectional study of participants undergoing urologic procedures between July 6, 2018 and July 17, 2019 at a single institution. Patients undergoing cystectomy, endoscopic bladder and/or upper tract procedure for probable urothelial carcinoma comprised cases; patients undergoing urologic procedures for other reasons comprised the control group (i.e. prostatectomy, nephrectomy, etc.). Voided urine samples were at the time of procedure; a minority of participants underwent multiple resections in the study period, thus, as many as three urine samples were taken from any given participant. Samples were distributed for blinded testing with URO17. Sensitivity and specificity were calculated. RESULTS: In 152 participants and 167 samples, URO17 demonstrated an overall sensitivity of 90% and 92% and a specificity of 88% and 87%, respectively. In 76 participants and 91 samples from patients with suspected urothelial carcinoma, the sensitivity was 90% and 92%, and the specificity was 50% and 54%, respectively. No controls demonstrated a positive URO17 result, and URO17 superseded urine cytology detection of low-grade and high-grade Ta. False positive results were associated with inflamed tissue or urothelial atypia on histology; the large majority had a history of intravesical therapy. CONCLUSION: Limitations include cross-sectional design and convenience sampling. URO17 may improve sensitivity of urine cytology in the detection of urothelial cancer, though further study is required to refine the application of this biomarker in clinical practice.


Assuntos
Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/urina , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Masculino , Estudos Transversais , Feminino , Idoso , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Biomarcadores Tumorais/urina , Biomarcadores Tumorais/análise , Idoso de 80 Anos ou mais
19.
Cancer Med ; 13(7): e7116, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38553953

RESUMO

BACKGROUND: Financial toxicity of bladder cancer care may influence how patients utilize healthcare resources, from emergency department (ED) encounters to office visits. We aim to examine whether greater household net worth (HHNW) confers differential access to healthcare resources after radical cystectomy (RC). METHODS: This population-based cohort study examined the association between HHNW and healthcare utilization costs in the 90 days post-RC in commercially insured patients with bladder cancer. Costs accrued from the index hospitalization to 90 days after including health plan costs (HPC) and out-of-pocket costs (OPC). Multivariable logistic regression models were generated by encounter (acute inpatient, ED, outpatient, and office visit). RESULTS: A total of 141,903 patients were identified with HHNW categories near evenly distributed. Acute inpatient encounters incurred the greatest HPC and OPC. Office visits conferred the lowest HPC while ED visits had the lowest OPC. Black patients harbored increased odds of an acute inpatient encounter (OR 1.22, 95% CI 1.16-1.29) and ED encounter (OR 1.20, 95% CI 1.14-1.27) while Asian (OR 0.76, 95% CI 0.69-0.85) and Hispanic (OR 0.74, 95% CI 0.69-0.78, p < 0.001) patients had lower odds of an outpatient encounter, compared to White counterpart. Increasing HHNW was associated with decreasing odds of acute inpatient or ED encounters and greater odds of office visits. CONCLUSIONS: Lower HHNW conferred greater risk of costly inpatient encounters while greater HHNW had greater odds of less costly office visits, illustrating how financial flexibility fosters differences in healthcare utilization and lower costs. HHNW may serve as a proxy for financial flexibility and risk of financial hardship than income alone.


Assuntos
Cistectomia , Neoplasias da Bexiga Urinária , Humanos , Estados Unidos , Estudos de Coortes , Declarações Financeiras , Custos de Cuidados de Saúde , Neoplasias da Bexiga Urinária/cirurgia , Estudos Retrospectivos , Serviço Hospitalar de Emergência
20.
Cancers (Basel) ; 16(7)2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38610946

RESUMO

The use of blue light cystoscopy (BLC) has been shown to improve bladder tumor detection. However, data demonstrating the efficacy of BLC across different races are limited. Herein, we aim to evaluate heterogeneity in the characteristics of BLC for the detection of malignant lesions among various races. Clinicopathologic information was collected from patients enrolled in the multi-institutional Cysview® registry (2014-2021) who underwent transurethral resection or biopsy of bladder tumors. Outcome variables included sensitivity and negative and positive predictive values of BLC and white light cystoscopy (WLC) for the detection of malignant lesions among various races. Overall, 2379 separate lesions/tumors were identified from 1292 patients, of whom 1095 (85%) were Caucasian, 96 (7%) were African American, 51 (4%) were Asian, and 50 (4%) were Hispanic. The sensitivity of BLC was higher than that of WLC in the total cohort, as well as in the Caucasian and Asian subgroups. The addition of BLC to WLC increased the detection rate by 10% for any malignant lesion in the total cohort, with the greatest increase in Asian patients (18%). Additionally, the positive predictive value of BLC was highest in Asian patients (94%), while Hispanic patients had the highest negative predictive value (86%). Our study showed that regardless of race, BLC increases the detection of bladder cancer when combined with WLC.

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