RESUMEN
RATIONALE: Bladder urothelial carcinoma (UC) is a common urinary system tumor that is generally diagnosed by cystoscopy combined with pathological biopsy. However, complete exophytic UC of the bladder is very rare and difficult to diagnose. Early diagnosis and accurate identification of such tumors, followed by aggressive surgical treatment, is essential for the management of these patients. PATIENT CONCERNS: An 84-year-old man was admitted to the hospital with dysuria, a poor diet, and significant weight loss. DIAGNOSIS: Pelvic computed tomography and magnetic resonance imaging revealed an exteriophytic round mass on the right lateral wall of the bladder. Cystoscopy revealed a necrotic mass on the right lateral wall of the bladder cavity, and no tumor cells were found following the biopsy. The tumor was removed via partial cystectomy, and the pathological result indicated high-grade muscle-invasive UC. INTERVENTIONS: The patient refused radical cystectomy and underwent laparoscopic partial cystectomy plus pelvic lymph node dissection followed by cisplatin plus gemcitabine chemotherapy. OUTCOMES: The patient's mental state and appetite were significantly improved after the urinary tube was removed 1 week after surgery. His general state was significantly improved after 1 month of follow-up but died of acute cerebral infarction 3 months after surgery. LESSONS: UC of the bladder may grow completely out of the bladder without symptoms such as gross hematuria; thus, early diagnosis is difficult. For high-risk individuals, regular imaging tests may help to detect tumors early. Partial cystectomy is a reliable surgical modality for bladder preservation in such patients.
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Cistectomía , Neoplasias de la Vejiga Urinaria , Humanos , Masculino , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/cirugía , Anciano de 80 o más Años , Cistectomía/métodos , Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/cirugía , Carcinoma de Células Transicionales/patología , Resultado Fatal , Tomografía Computarizada por Rayos X , Imagen por Resonancia MagnéticaRESUMEN
Urine cytology is a non-invasive, cost-efficient, and sensitive test to detect high-grade urothelial carcinoma. The Paris System (TPS) for Reporting Urinary Cytology is an evidence-based system that uses the risk of malignancy to guide patient management. Since its inception, TPS has standardized urine cytology reports, facilitating communication among pathologists and between pathologists and clinicians. It is imperative to correlate the urine cytology findings with the concurrent tissue sample to avoid false-negative and false-positive results when possible. Several ancillary tests and artificial intelligence algorithms are being developed to increase the accuracy of urine cytology interpretation.
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Citodiagnóstico , Neoplasias Urológicas , Humanos , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/diagnóstico , Citodiagnóstico/métodos , Citodiagnóstico/tendencias , Sistema Urinario/patología , Orina/citología , Neoplasias Urológicas/patología , Neoplasias Urológicas/diagnóstico , Urotelio/patologíaAsunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Neoplasias Renales/genética , Neoplasias Renales/diagnóstico , Neoplasias Renales/patología , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/patología , Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/patología , Hallazgos Incidentales , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/patología , Detección Precoz del Cáncer , Neoplasias Urológicas/genética , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/patologíaRESUMEN
PURPOSE: To compare the diagnostic performance of photodynamic diagnosis (PDD) enhanced with oral 5-aminolaevulinic acid between the suspected upper tract urothelial carcinoma (UTUC) and bladder urothelial carcinoma (BUC) cases. METHODS: This retrospective study included 18 patients with suspected UTUC who underwent ureteroscopy (URS) with oral 5-ALA in the PDD-URS cohort between June 2018 and January 2019; and 110 patients with suspected BUC who underwent transurethral resection of bladder tumour (TURBT) in the PDD-TURBT cohort between January 2019 and March 2023. Sixty-three and 708 biopsy samples were collected during diagnostic URS and TURBT, respectively. The diagnostic accuracy of white light (WL) and PDD in the two cohorts was evaluated, and false PDD-positive samples were pathologically re-evaluated. RESULTS: The area under the receiver operating characteristic curve (AUC) of PDD was significantly superior to that of WL in both cohorts. The per biopsy sensitivity, specificity, and positive and negative predictive values of PDD in patients in the PDD-URS and PDD-TURBT cohorts were 91.2 vs. 71.4, 75.9 vs. 75.3, 81.6 vs. 66.3, and 88.0 vs. 79.4%, respectively. The PDD-URS cohort exhibited a higher AUC than did the PDD-TURBT cohort (0.84 vs. 0.73). Seven of four false PDD-positive samples (57.1%) in the PDD-URS cohort showed potential precancerous findings compared with eight of 101 (7.9%) in the PDD-TURBT cohort. CONCLUSION: The diagnostic performance of PDD in the PDD-URS cohort was at least equivalent to that in the PDD-TURBT cohort.
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Ácido Aminolevulínico , Carcinoma de Células Transicionales , Fármacos Fotosensibilizantes , Neoplasias de la Vejiga Urinaria , Humanos , Estudios Retrospectivos , Ácido Aminolevulínico/administración & dosificación , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/diagnóstico , Masculino , Femenino , Anciano , Persona de Mediana Edad , Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/patología , Fármacos Fotosensibilizantes/administración & dosificación , Administración Oral , Neoplasias Ureterales/patología , Neoplasias Ureterales/diagnóstico , Neoplasias Renales/diagnóstico , Neoplasias Renales/patología , Ureteroscopía , Anciano de 80 o más AñosRESUMEN
Objectives: To evaluate the clinical value of the Paris system for reporting urinary cytology (TPS) in the diagnosis of urothelial carcinoma (UC). Methods: A total of 1 744 cytological diagnostic records (from 751 cases) were collected retrospectively. All specimens were voided urines and histopathology as the gold standard. The sensitivity and specificity of urinary cytological diagnosis of UC and risk of high grade malignant (ROHM) in each diagnostic category were compared. Results: There were 360 cases with histopathology. The percentage of negative for high-grade urothelial carcinoma (NHGUC) was 30.1% (226/751), atypical urothelial cells (AUC) was 29.8% (224/751), suspicious for high-grade urothelial carcinoma (SHGUC) was 16.8% (126/751), high grade urothelial carcinoma (HGUC) was 21.2% (159/751), and non-urothelial malignancy (NUM) was 2.1% (16/751). The histpathologic ROHM corresponding to each cytological diagnosis category were 27.3% for NHGUC, 32.7% for AUC, 74.7% for SHGUC, 96.6% for HGUC and 100.0% for NUM, respectively. ROHM of SHGUC was significantly higher than that of AUC group, and the difference between the two groups was statistically significant (Pï¼0.001). ROHM of HGUC group was significantly higher than that of SHGUC group, and the difference was statistically significant (Pï¼0.001). With SHGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 76.7% (165/215) and 85.7% (18/21), and with HGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 53.0% (114/215) and 100.0% (21/21), respectively. Conclusions: Urine cytology has high sensitivity and specificity in the diagnosis of HGUC. The malignant risk of TPS varies with different diagnosis category. The high malignant risk population in cancer hospital leads to the relatively high malignant proportion and ROHM in each diagnosis category. Urinary cytology TPS reporting system is helpful to clinical management and has good clinical application value.
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Citodiagnóstico , Sensibilidad y Especificidad , Humanos , Estudios Retrospectivos , Citodiagnóstico/métodos , Orina/citología , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/orina , Neoplasias de la Vejiga Urinaria/diagnóstico , Urotelio/patología , Neoplasias Urológicas/patología , Neoplasias Urológicas/orina , Neoplasias Urológicas/diagnóstico , Carcinoma de Células Transicionales/orina , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/diagnóstico , Femenino , Clasificación del Tumor , CitologíaRESUMEN
BACKGROUND: SMARCA4 is a component gene of the SWI/SNF (SWItch/Sucrose NonFermentable) chromatin remodeling complex; undifferentiated tumors associated with its functional deletion have been described in several organs. However, no established treatment for these tumors currently exists. CASE: In this study, we report a case of a SMARCA4-deficient undifferentiated urothelial carcinoma with high PD-L1 expression that was effectively treated with nivolumab after early relapse following treatment for non-invasive bladder cancer. The histological morphology of the rhabdoid-like undifferentiated tumor of unknown primary led us to suspect a SWI/SNF-deficient tumor, and subsequent immunostaining led to the diagnosis of a SMARCA4-deficient undifferentiated tumor. This effort also led to the identification of the developmental origin of this SMARCA4-deficient undifferentiated tumor as a non-invasive bladder cancer. We also carried out a detailed immune phenotypic assay on peripheral T cells. In brief, a phenotypic change of CD8+T cells from naive to terminally differentiated effector memory cells was observed. CONCLUSION: Regardless of the organ of cancer origin or cancer type, SWI/SNF-deficient tumors should be suspected in undifferentiated and dedifferentiated tumors, and immune checkpoint inhibitors may be considered as a promising treatment option for this type of tumor. The pathogenesis of SMARCA4-deficient anaplastic tumors awaits further elucidation for therapeutic development.
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Antígeno B7-H1 , ADN Helicasas , Nivolumab , Proteínas Nucleares , Factores de Transcripción , Neoplasias de la Vejiga Urinaria , Humanos , ADN Helicasas/genética , ADN Helicasas/deficiencia , Factores de Transcripción/genética , Factores de Transcripción/deficiencia , Factores de Transcripción/metabolismo , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/diagnóstico , Antígeno B7-H1/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/deficiencia , Proteínas Nucleares/metabolismo , Nivolumab/uso terapéutico , Masculino , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/diagnóstico , Anciano , Resultado del TratamientoRESUMEN
OBJECTIVE: Recently, the nuclear area has attracted attention as a morphological parameter to differentiate high-grade urothelial carcinoma (HGUC) cells from benign reactive cells. The nuclear long diameter (NLD) strongly correlates with the nuclear area and is easy to subjectively estimate. Therefore, this study examined the usefulness of the NLD-to-neutrophil diameter ratio for detecting HGUC cells in urine cytology. METHODS: This study included 29, 26 and 18 patients with HGUC, glomerular disease and urolithiasis respectively. An image analysis system was used to measure the NLD of HGUC and benign reactive cells (reactive renal tubular cells and reactive urothelial cells) and the neutrophil diameter that appeared in the voided urine in these cases. The NLD index was calculated using the NLD-to-neutrophil diameter ratio. We subsequently compared HGUC and benign reactive cells with respect to NLD and NLD indices. In addition, the HGUC cell group and benign reactive cell group were compared by selecting the five cells with the largest NLD and NLD index on each slide. RESULTS: The NLD and NLD indices of HGUC cells were significantly higher than those of benign reactive cells in all cells and in the five cells with the largest NLD and NLD indices. The cut-off value of the NLD index for detecting HGUC cells was 1.25 in all cells and 1.80 in the five cells with the largest NLD index. CONCLUSIONS: The NLD index is a useful parameter that can be introduced into routine microscopic examinations to differentiate HGUC cells from benign reactive cells.
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Urotelio , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Urotelio/patología , Núcleo Celular/patología , Citodiagnóstico/métodos , Anciano de 80 o más Años , Neutrófilos/patología , Neoplasias Urológicas/patología , Neoplasias Urológicas/diagnóstico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/diagnóstico , Adulto , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/diagnóstico , Diagnóstico DiferencialRESUMEN
BACKGROUND: Diagnostic ureteroscopy (URS) with or without biopsy remains a subject of contention in the management of upper tract urothelial carcinoma (UTUC), with varying recommendations across different guidelines. The study aims to analyse the decision-making and prognostic role of diagnostic ureteroscopy (URS) in high-risk UTUC patients undergoing curative surgery. MATERIALS AND METHODS: In this retrospective multi-institutional analysis of high-risk UTUC patients from the ROBUUST dataset, a comparison between patients who received or not preoperative URS and biopsy before curative surgery was carried out. Logistic regression analysis evaluated differences between patients receiving URS and its impact on treatment strategy. Survival analysis included 5-year recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS). After adjusting for high-risk prognostic group features, Cox proportional hazard model estimated significant predictors of time-to-event outcomes. RESULTS: Overall, 1,912 patients were included, 1,035 with preoperative URS and biopsy and 877 without. Median follow-up: 24 months. Robot-assisted radical nephroureterectomy was the most common procedure (55.1%), in both subgroups. The 5-year OS (Pâ¯=â¯0.04) and CSS (P < 0.001) were significantly higher for patients undergoing URS. The 5-year RFS (Pâ¯=â¯0.6), and MFS (Pâ¯=â¯0.3) were comparable between the 2 groups. Preoperative URS and biopsy were neither a significant predictor of worse oncological outcomes nor of a specific treatment modality. CONCLUSIONS: The advantage in terms of OS and CSS in patients undergoing preoperative URS could derive from a better selection of candidates for curative treatment. The treatment strategy is likely more influenced by tumor features than by URS findings.
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Carcinoma de Células Transicionales , Neoplasias Ureterales , Ureteroscopía , Humanos , Ureteroscopía/métodos , Masculino , Femenino , Estudios Retrospectivos , Pronóstico , Anciano , Carcinoma de Células Transicionales/cirugía , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/diagnóstico , Neoplasias Ureterales/cirugía , Neoplasias Ureterales/patología , Neoplasias Ureterales/mortalidad , Neoplasias Ureterales/diagnóstico , Persona de Mediana Edad , Toma de Decisiones Clínicas , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Neoplasias Renales/mortalidad , Neoplasias Renales/diagnósticoRESUMEN
Localized lymphedema of the genital region is a rare medical condition. It is named primary lymphedema if caused by a congenital malformation of the lymphatic system. Secondary lymphedemas might be induced by exogenous damage to lymphatic vessels as a result of surgical interventions, obesity, filariasis, radiotherapy or malignancy. We report a case of localized lymphedema of the genial region for which a previously unknown urothelial carcinoma turned out to be the underlying cause.
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Linfedema , Humanos , Linfedema/patología , Linfedema/etiología , Masculino , Anciano , Neoplasias de la Vejiga Urinaria/complicaciones , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/patología , Carcinoma de Células Transicionales/complicaciones , Carcinoma de Células Transicionales/cirugía , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/diagnósticoRESUMEN
Urothelial carcinoma is characterized by the presence of a wide spectrum of histopathologic features and molecular alterations that contribute to its morphologic and genomic heterogeneity. It typically harbors high rates of somatic mutations with considerable genomic and transcriptional complexity and heterogeneity that is reflective of its varied histomorphologic and clinical features. This review provides an update on the recent advances in the molecular characterization and novel molecular taxonomy of urothelial carcinoma and variant histologies.
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Carcinoma de Células Transicionales , Humanos , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/diagnóstico , Mutación , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias Urológicas/patología , Neoplasias Urológicas/genética , Neoplasias Urológicas/diagnóstico , Urotelio/patologíaRESUMEN
PURPOSE: Despite many efforts, no reliable urinary marker system has so far shown the potential to substitute cystoscopy. Measuring volatile organic compounds (VOCs) from urine is a promising alternative. VOCs are metabolic products which can be measured from the headspace of urine samples. Previous studies confirmed that the urine of bladder tumor patients has a different VOC profile than healthy controls. In this pilot study, the feasibility of discriminating VOCs from urine of bladder cancer patients from that of healthy control subjects was investigated. Aim of this study was to investigate whether VOC-based diagnosis of bladder cancer from urine samples is feasible using multicapillary column ion mobility spectrometry (MCC/IMS) and to identify potential molecular correlates to the relevant analytes. METHODS: Headspace measurements of urine samples of 30 patients with confirmed transitional cell carcinoma (TCC) and 30 healthy controls were performed using MCC/IMS. In the results of the measurements, peaks showing significant differences between both groups were identified and implemented into a decision tree with respect to achieve group separation. Molecular correlates were predicted using a pre-defined dataset. RESULTS: Eight peaks with significantly differing intensity were identified, 5 of which were highly significant. Using a six-step decision tree, MCC/IMS showed a sensitivity of 90% and specificity of 100% in group separation. CONCLUSION: VOC-based detection of bladder cancer is feasible. MCC/IMS is a suitable method for urine-based diagnosis and should be further validated. The molecular characteristics and metabolic background of the analytes require further workup.
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Carcinoma de Células Transicionales , Espectrometría de Movilidad Iónica , Neoplasias de la Vejiga Urinaria , Compuestos Orgánicos Volátiles , Humanos , Neoplasias de la Vejiga Urinaria/orina , Neoplasias de la Vejiga Urinaria/diagnóstico , Compuestos Orgánicos Volátiles/orina , Proyectos Piloto , Espectrometría de Movilidad Iónica/métodos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Carcinoma de Células Transicionales/orina , Carcinoma de Células Transicionales/diagnóstico , Estudios de Factibilidad , Anciano de 80 o más Años , Biomarcadores de Tumor/orinaRESUMEN
Upper tract urothelial carcinoma (UTUC) presents diagnostic challenges due to small biopsy specimen size, poor orientation, and technical obstacles that can yield equivocal diagnoses. This uncertainty often mandates repeated biopsies to evaluate the necessity of nephroureterectomy. Prior studies have suggested cytokeratin 17 (CK17) immunostain as an adjunctive tool for diagnosing bladder urothelial neoplasia in both urine cytology and tissue biopsy specimens. We evaluated the utility of CK17 in differentiating UTUC from benign urothelium and its ability to stratify low-grade from high-grade neoplasia. Our study involved a cohort of previously diagnosed cytology (n = 29) and tissue specimens from biopsies and resections (n = 85). We evaluated CK17 staining percentage in cytology and tissue samples and localization patterns in biopsy/resection samples. Our findings showed a statistically significant distinction (p < 0.05) between UTUC and benign tissue specimens based on full thickness localization pattern (odds ratio 8.8 [95% CI 1.53-67.4]). The percentage of CK17 staining failed to significantly differentiate neoplastic from non-neoplastic cases in cytology or tissue samples. Additionally, based on prior research showing the efficacy of CK20/CD44/p53 triple panel in bladder urothelial neoplasia, we utilized tissue microarrays to evaluate if these markers could distinguish UTUC from benign urothelium. We found that CK20/CD44/p53, individually or in combination, could not distinguish urothelial neoplasia from non-neoplasia. Full thickness CK17 urothelial localization by immunohistochemistry was highly reproducible with excellent interobserver agreement and may play a supplementary role in distinguishing upper tract urothelial neoplasia from benign urothelium.
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Biomarcadores de Tumor , Receptores de Hialuranos , Inmunohistoquímica , Queratina-17 , Queratina-20 , Proteína p53 Supresora de Tumor , Urotelio , Humanos , Biomarcadores de Tumor/análisis , Biopsia , Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/metabolismo , Diagnóstico Diferencial , Receptores de Hialuranos/análisis , Receptores de Hialuranos/metabolismo , Queratina-17/análisis , Queratina-20/análisis , Queratina-20/metabolismo , Clasificación del Tumor , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Proteína p53 Supresora de Tumor/análisis , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/patología , Urotelio/patología , Urotelio/químicaRESUMEN
Bladder cancer is the 6th most common malignancy in the United States, with urothelial carcinomas comprising over 95% of cases of bladder cancer, and commands a significant disease burden in Rhode Island. Imaging studies can provide valuable diagnostic information for urothelial carcinomas at initial presentation and are routinely used for noninvasive staging, treatment response monitoring, and post-treatment surveillance. This review aims to discuss and highlight three imaging modalities: ultrasonography, computed tomography, and magnetic resonance imaging, with particular focus on the notable features and appearance of urothelial carcinoma on each modality and their relative utility throughout the disease course. A general overview of disease epidemiology and treatment practices is also provided.
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Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Ultrasonografía , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/epidemiología , Neoplasias de la Vejiga Urinaria/diagnóstico , Carcinoma de Células Transicionales/diagnóstico por imagen , Carcinoma de Células Transicionales/epidemiología , Carcinoma de Células Transicionales/diagnóstico , Rhode Island/epidemiologíaRESUMEN
Canine urothelial carcinoma (UC) and prostate carcinoma (PC) frequently exhibit the BRAFV595E mutation, akin to the BRAFV600E mutation common in various human cancers. Since the initial discovery of the BRAF mutation in canine cancers in 2015, PCR has been the standard method for its detection in both liquid and tissue biopsies. Considering the similarity between the canine BRAFV595E and human BRAFV600E mutations, we hypothesized that immunohistochemistry (IHC) using a BRAFV600E-specific antibody could effectively identify the canine mutant BRAFV595E protein. We tested 122 canine UC (bladder n = 108, urethra n = 14), 21 PC, and benign tissue using IHC and performed digital droplet PCR (ddPCR) on all 122 UC and on 14 IHC positive PC cases. The results from ddPCR and IHC were concordant in 99% (135/136) of the tumours. Using IHC, BRAFV595E was detected in 72/122 (59%) UC and 14/21 (65%) PC. Staining of all benign bladder and prostate tissues was negative. If present, mutant BRAF staining was homogenous, with rare intratumour heterogeneity in three (4%) cases of UC. Additionally, the BRAFV595E mutation was more prevalent in tumours with urothelial morphology, and less common in glandular PC or UC with divergent differentiation. This study establishes that BRAFV600-specific IHC is a reliable and accurate method for detecting the mutant BRAFV595E protein in canine UC and PC. Moreover, the use of IHC, especially with tissue microarrays, provides a cost-efficient test for large-scale screening of canine cancers for the presence of BRAF mutations. This advancement paves the way for further research to define the prognostic and predictive role of this tumour marker in dogs and use IHC to stratify dogs for the treatment with BRAF inhibitors.
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Enfermedades de los Perros , Inmunohistoquímica , Mutación , Neoplasias de la Próstata , Proteínas Proto-Oncogénicas B-raf , Neoplasias de la Vejiga Urinaria , Perros , Animales , Enfermedades de los Perros/genética , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/patología , Proteínas Proto-Oncogénicas B-raf/genética , Masculino , Neoplasias de la Próstata/veterinaria , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Inmunohistoquímica/veterinaria , Neoplasias de la Vejiga Urinaria/veterinaria , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/diagnóstico , Femenino , Carcinoma/veterinaria , Carcinoma/genética , Carcinoma/patología , Carcinoma/metabolismo , Carcinoma/diagnóstico , Carcinoma de Células Transicionales/veterinaria , Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/metabolismo , Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/patologíaRESUMEN
C-reactive protein (CRP) may reflect a pro-inflammatory tumor microenvironment and could represent a biomarker to select patients with urothelial carcinoma more likely to benefit from therapies directed at modulating tumor-promoting inflammation. We performed a systematic review to evaluate survival outcomes based on pre-treatment CRP values in urothelial carcinoma. The hazard ratios (HRs) of survival such as overall survival (OS) and progression-free survival (PFS) between groups with high versus low CRP values were pooled by the random-effect model meta-analyses. Overall, 28 studies comprising 6789 patients were identified for meta-analyses. High CRP levels were associated with shorter OS (HR=1.96 [95% CI: 1.64-2.33], p < 0.01), particularly in advanced disease treated with immune checkpoint blockade (ICB, HR=1.78 [1.47-2.15], p < 0.01). Similar findings were observed in ICB-treated patients with PFS. These findings suggest that CRP could be an attractive biomarker to select patients with urothelial carcinoma for strategies seeking to modulate tumor-promoting inflammation.
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Biomarcadores de Tumor , Proteína C-Reactiva , Humanos , Biomarcadores de Tumor/sangre , Proteína C-Reactiva/análisis , Carcinoma de Células Transicionales/sangre , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/tratamiento farmacológico , Pronóstico , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/sangre , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias Urológicas/mortalidad , Neoplasias Urológicas/patología , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/sangreRESUMEN
BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a noninvasive technique that provides valuable insights into molecular profiles and tumor disease management. This study aimed to evaluate the prognostic significance of circulating tumor DNA (ctDNA) in urothelial carcinoma (UC) through a systematic review and meta-analysis. METHODS: A comprehensive search was conducted in MEDLINE, EMBASE, and the Cochrane Library from the inception to December 2023. Studies investigating the prognostic value of ctDNA in UC were included. Hazard ratios (HRs) of disease-free survival (DFS) and overall survival (OS) were extracted. Overall meta-analysis and subgroup exploration stratified by metastatic status, ctDNA sampling time, treatment type, and detection method was performed using the R software (version 4.2.2). RESULTS: A total of 16 studies with 1725 patients were included. Fourteen studies assessed the association between baseline ctDNA status and patient outcomes. Patients with elevated ctDNA levels exhibited significantly worse DFS (HR=6.26; 95% CI: 3.71-10.58, P <0.001) and OS (HR=4.23; 95% CI: 2.72-6.57, P <0.001) regardless of metastatic status, ctDNA sampling time, treatment type, and detection methods. Six studies evaluated the prognostic value of ctDNA dynamics in UC. Patients who showed a decrease or clearance in ctDNA levels during treatment or observation demonstrated more favorable DFS (HR=0.26, 95% CI: 0.17-0.41, P <0.001) and OS (HR=0.21, 95% CI: 0.11-0.38, P <0.001) compared to those who did not. The association remained consistent across the subgroup analysis based on metastatic status and detection methods. In the immune checkpoint inhibitor-treated setting, both lower baseline ctDNA level and ctDNA decrease during the treatment were significantly associated with more favorable oncologic outcomes. Furthermore, specific gene mutations such as FGFR3 identified in ctDNA also demonstrated predictive value in UC patients. CONCLUSION: This meta-analysis demonstrates a strong association of ctDNA status and its dynamic change with survival outcomes in UC, suggesting substantial clinical utility of ctDNA testing in prognosis prediction and decision making in this setting.
Asunto(s)
ADN Tumoral Circulante , Humanos , ADN Tumoral Circulante/sangre , ADN Tumoral Circulante/genética , Pronóstico , Carcinoma de Células Transicionales/sangre , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/diagnóstico , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Neoplasias Urológicas/sangre , Neoplasias Urológicas/mortalidad , Neoplasias Urológicas/genética , Neoplasias Urológicas/patología , Neoplasias Urológicas/diagnóstico , Neoplasias de la Vejiga Urinaria/sangre , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/diagnóstico , Supervivencia sin EnfermedadRESUMEN
Urinary cytology using the Paris system is still the method of choice for screening high-grade urothelial carcinomas. However, the use of the objective criteria described in this terminology shows a lack of inter- and intra-observer reproducibility. Moreover, if its sensitivity is excellent on instrumented urine, it remains insufficient on voided urine samples. Urinary cytology appears to be an excellent model for the application of artificial intelligence to improve performance, since the objective criteria of the Paris system are defined at cellular level, and the resulting diagnostic approach is presented in a highly "algorithmic" way. Nevertheless, there is no commercially available morphological diagnostic aid, and very few predictive devices are still undergoing clinical validation. The analysis of different systems using artificial intelligence in urinary cytology rises clear prospects for mutual contributions.
Asunto(s)
Inteligencia Artificial , Citodiagnóstico , Urinálisis , Humanos , Carcinoma de Células Transicionales/orina , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/diagnóstico , Citodiagnóstico/métodos , Sensibilidad y Especificidad , Urinálisis/métodos , Neoplasias de la Vejiga Urinaria/orina , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/diagnóstico , Orina/citología , Neoplasias Urológicas/orina , Neoplasias Urológicas/patología , Neoplasias Urológicas/diagnósticoAsunto(s)
Urotelio , Humanos , Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/patología , Citodiagnóstico/métodos , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/diagnóstico , Orina/citología , Neoplasias Urológicas/patología , Neoplasias Urológicas/diagnóstico , Urotelio/patologíaRESUMEN
Currently, there are no reliable prognostic factors to determine which upper tract urothelial carcinoma (UTUC) patients will progress after radical nephroureterectomy (RNU). We aim to evaluate whether liquid-biopsy-based biomarkers (circulating tumor cells (CTCs), cell-free DNA (cfDNA), and circulating tumor DNA (ctDNA)) were able to predict clinical outcomes in localized UTUC patients undergoing RNU. Twenty patients were prospectively enrolled between 2021 and 2023. Two blood samples were collected before RNU and three months later. CTCs and cfDNA were isolated and evaluated using the IsoFlux system and Quant-iT PicoGreen dsDNA kit, respectively. Droplet digital PCR was performed to determine ctDNA status. Cox regression analysis was performed on CTCs, cfDNA, and ctDNA at two different follow-up time points to examine their influence on tumor progression and cancer-specific survival (CSS). During a median follow-up of 18 months, seven (35%) patients progressed and three (15%) died. Multivariate analysis demonstrated that cfDNA levels three months after RNU are a significant predictor of tumor progression (HR = 1.085; p = 0.006) and CSS (HR = 1.168; p = 0.029). No associations were found between CTC enumeration and ctDNA status with any of the clinical outcomes evaluated. The evaluation of cfDNA levels in clinical practice could improve the disease management of UTUC patients.