RESUMEN
OBJECTIVE: To evaluate the prognostic value of programmed death ligand-1 (PD-L1) and programmed death-1 (PD-1) expression in patients with upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: A retrospective multicentre study was conducted in 283 patients with UTUC treated with radical nephroureterectomy (RNU) between 2000 and 2015 at 10 French hospitals. Immunohistochemistry analyses were performed using 2 mm-core tissue microarrays with NAT105® and 28.8® antibodies at a 5% cut-off for positivity on tumour cells and tumour-infiltrating lymphocytes to evaluate PD-L1 and PD-1 expression, respectively. Multivariable Cox regression models were used to determine the independent predictors of recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). RESULTS: Overall, 63 (22.3%) and 220 (77.7%) patients with UTUC had PD-L1-positive and -negative disease, respectively, while 91 (32.2%) and 192 (67.8%) had PD-1-positive and -negative disease, respectively. Patients who expressed PD-L1 or PD-1 were more likely to have pathological tumour stage ≥pT2 (68.3% vs 49.5%, P = 0.009; and 69.2% vs 46.4%, P < 0.001, respectively) and high-grade (90.5% vs 70.0%, P = 0.001; and 91.2% vs 66.7%, P < 0.001, respectively) disease with lymphovascular invasion (52.4% vs 17.3%, P < 0.001; and 39.6% vs 18.2%, P < 0.001, respectively) as compared to those who did not. In multivariable Cox regression analysis adjusting for each other, PD-L1 and PD-1 expression were significantly associated with decreased RFS (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.09-3.08, P = 0.023; and HR 1.59, 95% CI 1.01-2.54, P = 0.049; respectively), CSS (HR 2.73, 95% CI 1.48-5.04, P = 0.001; and HR 1.96, 95% CI 1.12-3.45, P = 0.019; respectively) and OS (HR 2.08, 95% CI 1.23-3.53, P = 0.006; and HR 1.71, 95% CI 1.05-2.78, P = 0.031; respectively). In addition, multivariable Cox regression analyses evaluating the four-tier combination of PD-L1 and PD-1 expression showed that only PD-L1/PD-1-positive patients (n = 38 [13.4%]) had significantly decreased RFS (HR 3.07, 95% CI 1.70-5.52; P < 0.001), CSS (HR 5.23, 95% CI 2.62-10.43; P < 0.001) and OS (HR 3.82, 95% CI 2.13-6.85; P < 0.001) as compared to those with PD-L1/PD-1-negative disease (n = 167 [59.0%]). CONCLUSIONS: We observed that PD-L1 and PD-1 expression were both associated with adverse pathological features that translated into an independent and cumulative adverse prognostic value in UTUC patients treated with RNU.
RESUMEN
OBJECTIVE: To assess PD-L1 expression in tumor (TC) and tumor infiltrating immune cells (IC) as a predictive factor of BCG therapy failure in high-risk NMIBC. MATERIALS AND METHODS: Patients treated with complete resection followed by bladder BCG instillation for high-risk NMIBC were included. Early recurrence (ER) was defined as tumor recurrence after BCG induction course. The association between ER and immuno-histochemistry PD-L1 (E1L3N clone) expression by tumors cells (TC) and tumor infiltrating immune cells (IC) was investigated using an exact Fisher test variant. RESULTS: A total of 186 patients were included, of whom 38 (20.4%) were ER, 35 (18.8%) were positive for TC PD-L1 expression and 60 (32.3%) were positive for IC PD-L1. ER was not significantly (p = 0.97) more frequent in the TC PD-L1 ≥ 1% group (n = 7, 20.0%) than in the TC PD-L1-negative group (n = 31, 20.5%). Patients with IC PD-L1 negative had ER in 15 (19.2%) cases and patients with IC PD-L1 ≥ 1% had ER in 23 (21.3%) cases. PD-L1-positive expression for IC (threshold > 1%) was correlated with immune infiltrate density (95.2% dense immune infiltrate vs 47.2% low immune infiltrate, p < 0.05), with increased expression of PD-L1 by IC after BCG therapy (p = 0.006). CONCLUSION: No association was observed between immuno-histochemistry PD-L1 positivity and ER after BCG therapy. Nevertheless, the relationship between immune infiltrate and PD-L1 positivity confirmed the interest of assessing the immune infiltrate density to define tumor's profile.
Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Antígeno B7-H1/biosíntesis , Vacuna BCG/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/metabolismo , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/análisis , Estudios de Cohortes , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/química , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
OBJECTIVES: To compare the diagnostic performance of computed tomography, magnetic resonance imaging and contrast enhanced ultrasonography for the assessment of complex renal cysts. METHODS: We carried out a prospective single-center study from January 2012 to December 2013. We included patients with Bosniak category 2F or 3 renal cysts found on computed tomography and reviewed by two expert radiologists. Magnetic resonance imaging and contrast-enhanced ultrasonography were then carried out. Patients with a Bosniak ≥3 cyst on magnetic resonance imaging, as well as those upgraded as appearing malignant on contrast-enhanced ultrasonography, were surgically managed. Imaging results were compared with histological data. For patients without surgery, imaging examinations were compared with follow-up data. For each imaging examination, diagnostic performance and Cohen's kappa coefficient were assessed. RESULTS: A total of 47 patients were included. The median follow up was 36 months (range 17-48 months). At initial computed tomography, cysts were classified as Bosniak 2F and Bosniak ≥3 in 34 and 13 patients, respectively. Magnetic resonance imaging found 13 Bosniak ≥3 cysts, and contrast-enhanced ultrasonography upgraded six more patients with cysts that appeared malignant. A total of 19 patients had surgery. Histological analysis reported 14 malignant tumors. No tumor progression was found in followed-up patients. Computed tomography showed poor sensitivity (36%) and specificity (76%; κ = 0.11). Magnetic resonance imaging showed 71% sensitivity and 91% specificity (κ = 0.64). Contrast-enhanced ultrasonography showed high sensitivity (100%) and specificity (97%), and a negative predictive value at 100% (κ = 0.95). CONCLUSIONS: The present results suggested that contrast-enhanced ultrasonography could be useful in improving the assessment of complex renal cysts. Indeed, computed tomography accuracy might be limited in this indication requiring further investigations to determine the best treatment strategy.
Asunto(s)
Enfermedades Renales Quísticas/diagnóstico por imagen , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Ultrasonografía , Adulto , Anciano , Medios de Contraste , Femenino , Francia , Humanos , Enfermedades Renales Quísticas/patología , Enfermedades Renales Quísticas/cirugía , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
PURPOSE: Predictive factors of T1 nonmuscle invasive bladder cancer evolution that could guide treatment decision making are lacking. We assessed the prognostic value of muscularis mucosa invasion in nonmuscle invasive bladder cancer. MATERIALS AND METHODS: In a national multicenter study patients with primary T1 nonmuscle invasive bladder cancer were recruited from 6 French hospitals. All patients had undergone transurethral resection of bladder tumor. All T1 tumors were substaged according to muscularis mucosa invasion as T1a-no invasion beyond the muscularis mucosa or T1b-invasion beyond the muscularis mucosa with muscle preservation. Subsequent central pathology review was then done by a single referent uropathologist. Muscularis mucosa invasion was tested as a prognostic factor for survival on univariate and multivariate analysis. RESULTS: A total of 587 patients were enrolled in the study, including 388 (66%) with T1a and 199 (34%) with T1b tumors. Median followup after transurethral resection of bladder tumor was 35 months (IQR 14-54). There was no significant difference between groups T1a and T1b except high tumor grade in T1b cases (p <0.0001). After central review, initial pathological substaging was confirmed in 84% of cases. On multivariate analysis muscularis mucosa invasion (T1b substage) was significantly associated with recurrence-free (p = 0.03), progression-free (p = 0.0002) and cancer specific (p = 0.02) survival. The main study limitation was absent systematic subsequent transurethral resection of bladder tumor. CONCLUSIONS: Muscularis mucosa invasion appears to be highly predictive of T1 nonmuscle invasive bladder cancer behavior. Consequently, systematic T1a vs T1b discrimination should be highly advocated by urologists and pathologists. We believe that it could aid in crucial decision making when choosing between conservative management and radical cystectomy remains a moot point.
Asunto(s)
Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/patología , Músculo Liso/patología , Recurrencia Local de Neoplasia/patología , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología , Anciano , Análisis de Varianza , Biopsia con Aguja , Carcinoma de Células Transicionales/cirugía , Cistectomía/métodos , Cistoscopía/métodos , Bases de Datos Factuales , Supervivencia sin Enfermedad , Femenino , Francia , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Membrana Mucosa/patología , Análisis Multivariante , Invasividad Neoplásica/patología , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
Bronchogenic cysts are benign lesions, which are usually described at the chest level. We present here a case report of a retroperitoneal bronchogenic cyst. A 77-year-old man presented with a left retroperitoneal tumor discovered by scanner. There was no endocrine disruption. Excision of the lesion was performed and final diagnosis was a bronchogenic cyst. Current widespread use of modern radiology enables increased discovery of such "incidentalomes". In the future, pathologists will be routinely faced with this type of diagnosis, which up to now has been described as exceptional.
Asunto(s)
Quiste Broncogénico/diagnóstico , Hallazgos Incidentales , Tomografía Computarizada por Rayos X , Anciano , Quiste Broncogénico/diagnóstico por imagen , Quiste Broncogénico/patología , Quiste Broncogénico/cirugía , Diagnóstico Diferencial , Humanos , Imagen por Resonancia Magnética , Masculino , Neoplasias Retroperitoneales/diagnóstico , Espacio RetroperitonealRESUMEN
BACKGROUND: The current pathological tumour-node-metastasis (pTNM) classification for upper tract urothelial carcinoma (UTUC) does not include any risk stratification of pT3 renal pelvicalyceal tumours. OBJECTIVE: To assess the prognostic impact of pT3 subclassification in a multicentre cohort of patients with UTUC of the renal pelvicalyceal system undergoing radical nephroureterectomy (RNU). DESIGN, SETTING, AND PARTICIPANTS: Data from all consecutive patients treated with RNU for pT3 renal pelvicalyceal UTUC at 14 French centres from 1995 to 2013 were reviewed retrospectively. INTERVENTION: A central pathology review (CPR) was used to stratify pT3 patients into those with infiltration of the renal parenchyma on a microscopic level (pT3a) versus those with infiltration of the renal parenchyma visible on gross inspection of the resection specimen and/or invasion of peripelvic fat (pT3b). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Inverse probability weighting (IPW)-adjusted Cox regression analyses were used to compare recurrence-free survival (RFS) and cancer-specific survival (CSS) between pT3a and pT3b patients. RESULTS AND LIMITATIONS: Overall, 202 patients were included and further stratified into pT3a (n = 98; 48.5%) and pT3b (n = 104; 51.5%) subgroups. Median time to follow-up in the weighted population was 68 (interquartile range, 50-95) mo. In IPW-adjusted Cox regression analyses, pT3b versus pT3a substage was associated with a significant adverse effect on RFS (hazard ratio [HR] = 2.02; 95% confidence interval [CI] = [1.36-3.01]; p < 0.001) and CSS (HR = 1.84; 95% CI = [1.20-2.82]; p = 0.005). The study is limited by its retrospective design. CONCLUSIONS: Using IPW-adjusted analyses after the CPR, we observed that RNU patients with pT3b renal pelvicalyceal UTUC had adverse prognosis as compared with those with pT3a disease. As such, this subclassification could help refine the current pTNM system for UTUC. PATIENT SUMMARY: In this report, we looked at the prognostic interest of stratifying patients with pT3 renal pelvicalyceal upper tract urothelial carcinoma based on the extent of local invasion. We found that those with extensive infiltration (pT3b) had adverse prognosis as compared with those with limited infiltration (pT3a). This information could be provided on pathology reports to further guide clinical decision making.
Asunto(s)
Carcinoma de Células Transicionales , Neoplasias Renales , Neoplasias de la Vejiga Urinaria , Carcinoma de Células Transicionales/patología , Humanos , Neoplasias Renales/patología , Estadificación de Neoplasias , Nefroureterectomía , Pronóstico , Puntaje de Propensión , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
BACKGROUND: Magnetic resonance imaging (MRI) is today strongly recommended in prostate cancer (PCa) diagnosis. Therefore, MRI/ultrasound (MRI/US) fusion-guided biopsy is becoming the new standard patients management. METHODS: We report our experience during the last 4 years using this technique, with a protocol of 6 random cores (instead of the most used 12 cores protocol) associated to the target cores (2 to 3 per lesion). Our study involved 236 patients including real life routine practice: biopsy naïve patients (n=107), patients with previous negative standard prostate biopsies (n=67) and patients in PCa active surveillance (n=62). Finally, 76 patients have a robotic radical prostatectomy. RESULTS: Mean age of the population was 66 years. Median PSA was 8.5 ng/mL. Overall and significant cancer detection were respectively 66.6% and 38.5%, with a large difference considering biopsy history: 63.5% in biopsy naïve patient, 53.7% in patient with previous negative biopsies and 82.3% in patients under active surveillance. Targeted biopsies missed 28 cancers among 8 were significant and standard biopsies missed 33 cancers among 14 were significant. Moreover, concordance between biopsy samples and radical prostatectomy specimens was evaluated at 80%. CONCLUSIONS: Comparing to literature data, similar results were observed in our retrospective study, even with reduced random cores, suggesting a real change in patients management in particular in active surveillance group with a reclassification rate of 56.4% using the Epstein criteria.
RESUMEN
Aldosterone, produced by the adrenals and under the control of plasma angiotensin and potassium levels, regulates hydromineral homeostasis and blood pressure. Here we report that the neuropeptide substance P (SP) released by intraadrenal nerve fibres, stimulates aldosterone secretion via binding to neurokinin type 1 receptors (NK1R) expressed by aldosterone-producing adrenocortical cells. The action of SP is mediated by the extracellular signal-regulated kinase pathway and involves upregulation of steroidogenic enzymes. We also conducted a prospective proof-of-concept, double blind, placebo-controlled clinical trial aimed to investigate the impact of the NK1R antagonist aprepitant on aldosterone secretion in healthy male volunteers (EudraCT: 2008-003367-40, ClinicalTrial.gov: NCT00977223). Participants received during two 7-day treatment periods aprepitant (125 mg on the 1st day and 80 mg during the following days) or placebo in a random order at a 2-week interval. The primary endpoint was plasma aldosterone levels during posture test. Secondary endpoints included basal aldosterone alterations, plasma aldosterone variation during metoclopramide and hypoglycaemia tests, and basal and stimulated alterations of renin, cortisol and ACTH during the three different stimulatory tests. The safety of the treatment was assessed on the basis of serum transaminase measurements on days 4 and 7. All pre-specified endpoints were achieved. Aprepitant decreases aldosterone production by around 30% but does not influence the aldosterone response to upright posture. These results indicate that the autonomic nervous system exerts a direct stimulatory tone on mineralocorticoid synthesis through SP, and thus plays a role in the maintenance of hydromineral homeostasis. This regulatory mechanism may be involved in aldosterone excess syndromes.
Asunto(s)
Aldosterona/sangre , Aprepitant/farmacología , Antagonistas del Receptor de Neuroquinina-1/farmacología , Receptores de Neuroquinina-1/metabolismo , Sustancia P/metabolismo , Adolescente , Corteza Suprarrenal/metabolismo , Glándulas Suprarrenales/metabolismo , Adulto , Aldosterona/metabolismo , Células Cultivadas , Humanos , Hipoglucemia/sangre , Masculino , Metoclopramida , Mineralocorticoides/biosíntesis , Placebos/administración & dosificación , Prueba de Estudio Conceptual , Estudios Prospectivos , Transaminasas/sangre , Adulto JovenRESUMEN
OBJECTIVE: Recent studies performed in mice revealed that the neuropeptide 26RFa regulates glucose homeostasis by acting as an incretin and by increasing insulin sensitivity. However, in humans, an association between 26RFa and the regulation of glucose homeostasis is poorly documented. In this study, we have thus investigated in detail the distribution of 26RFa and its receptor, GPR103, in the gut and the pancreas, and determined the response of this peptidergic system to an oral glucose challenge in obese patients. DESIGN AND METHODS: Distribution of 26RFa and GPR103 was examined by immunohistochemistry using gut and pancreas tissue sections. Circulating 26RFa was determined using a specific radioimmunoassay in plasma samples collected during an oral glucose tolerance test. RESULTS: 26RFa and GPR103 are present all along the gut but are more abundant in the stomach and duodenum. In the stomach, the peptide and its receptor are highly expressed in the gastric glands, whereas in the duodenum, ileum and colon they are present in the enterocytes and the goblet cells. In the pancreatic islets, the 26RFa/GPR103 system is mostly present in the ß cells. During an oral glucose tolerance test, plasma 26RFa profile is different between obese patients and healthy volunteers, and we found strong positive correlations between 26RFa blood levels and the BMI, and with various parameters of insulin secretion and insulin resistance. CONCLUSION: The present data suggest an involvement of the 26RFa/GPR103 peptidergic system in the control of human glucose homeostasis.
RESUMEN
CONTEXT: In the human adrenal, serotonin (5-HT), released by mast cells stimulates corticosteroid secretion through activation of type 4 serotonin receptors (5-HT4R). In primary pigmented nodular adrenocortical disease cells, activation of the cAMP/protein kinase A (PKA) pathway by PRKAR1A mutations triggers upregulation of the 5-HT synthesizing enzyme tryptophan hydroxylase (TPH) and the 5-HT4, 5-HT6, and 5-HT7 receptors. Because ACTH stimulates cortisol secretion through activation of PKA, adrenocortical tissues exposed to sustained stimulation by ACTH may harbor increased expression of TPH and 5-HT4/6/7 receptors. OBJECTIVE: To investigate the effects of long-term ACTH stimulation on the serotonergic pathway in adrenals of patients with high plasma or intra-adrenal ACTH levels. METHODS: Adrenal tissues were obtained from patients with Cushing disease, ectopic secretion of ACTH [paraneoplastic Cushing syndrome; (paraCS)], 21-hydroxylase deficiency (21-OHD), primary bilateral macronodular adrenal hyperplasia with intra-adrenal ACTH presence, or cortisol-producing adenomas. TPH and 5-HT4/6/7 receptor expression was investigated using RT-PCR and immunochemistry in comparison with normal adrenals. Primary cultured adrenocortical cells originating from a patient with paraCS were incubated with 5-HT and 5-HTR agonists/antagonists. RESULTS: TPH and/or 5-HT4/6/7 receptors were overexpressed in the different types of tissues. In paraCS cultured cells, the cortisol response to 5-HT was exaggerated compared with normal adrenal cells and the stimulatory action of 5-HT was reduced by 5-HT4R antagonist. CONCLUSION: Our results indicate that prolonged activation of the cAMP/PKA pathway by ACTH induces an aberrant serotonergic stimulatory loop in the adrenal cortex that likely participates in the pathogenesis of corticosteroid hypersecretion.
Asunto(s)
Glándulas Suprarrenales/metabolismo , Hormona Adrenocorticotrópica/metabolismo , Serotonina/metabolismo , Transducción de Señal , Adenoma/metabolismo , Neoplasias de las Glándulas Suprarrenales/metabolismo , Hormona Adrenocorticotrópica/sangre , Adulto , Síndrome de Cushing/metabolismo , AMP Cíclico/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/metabolismo , Cultivo Primario de Células , Proteínas Quinasas/metabolismo , Receptores de Serotonina/metabolismo , Esteroide 21-Hidroxilasa , Triptófano Hidroxilasa/metabolismo , Regulación hacia ArribaRESUMEN
INTRODUCTION: The management of congenital urological malformations is sometimes complex and may require urinary diversion. Cystectomy is usually performed, but sometimes the bladder is left in place due to the presence of a pelvic cloaca and the morbidity related to this type of surgery. MATERIAL: The authors report three cases of patients treated by urinary diversion for a congenital malformation without primary resection of the bladder RESULTS: In the absence of any infectious complications, bladder carcinoma on an excluded native bladder was diagnosed at the age of 3 years, 4 years and 38 years, respectively. Histological examination showed transitional cell carcinoma in two cases and gastrointestinal-type adenocarcinoma of the bladder in 1 case. CONCLUSION: The risk of secondary development of carcinoma in an excluded bladder during management of (congenital urological malformations is not negligible. Primary cystectomy therefore appears to be preferable. In the presence of a pelvic cloaca making this surgical resection unreasonable, it appears important to exclude the formation of a pyocyst by annual abdominal ultrasound. The authors also recommend cystoscopy and urine cytology with lavage to detect degeneration of the bladder mucosa.
Asunto(s)
Adenocarcinoma/diagnóstico , Carcinoma de Células Transicionales/diagnóstico , Neoplasias de la Vejiga Urinaria/diagnóstico , Vejiga Urinaria/anomalías , Adenocarcinoma/cirugía , Adulto , Carcinoma de Células Transicionales/cirugía , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Vejiga Urinaria/cirugía , Derivación UrinariaRESUMEN
AIM: To assess the potential predictive value of natural resistance-associated macrophage protein 1 (NRAMP1) and human glutathione peroxidase 1 (hGPX1) polymorphism in non-muscle-invasive bladder cancer treated with bacillus Calmette-Guerin (BCG) instillation, we conducted an original ancillary multicenter study. PATIENTS AND METHODS: We evaluated patients included in the multicenter URO-BCG 4 trial, who received three weekly instillations of one-third dose BCG every 6 months (group I) or two weekly instillations every 3 months (group II) for 3 years. For clinical evaluation we also evaluated tumor recurrence and muscle progression. NRAMP1 and hGPX1 polymorphism analyses were performed on blood DNA. NRAMP1 exon 15 and hGPX1 exon 1c were amplified using Type-it Microsatellite PCR Kit® for multiplex polymerase chain reaction. RESULTS: From June 2004 to April 2010, 146 randomized patients were included in this retrospective study. Blood samples were obtained from 107 patients. With 36 months of follow-up, 13.6% of patients had a tumor recurrence and muscle-invasive progression was observed in 4.3% of patients. Concerning NRAMP1 D543N polymorphism, patients with allele A had no tumor recurrence or muscle-invasive progression. No significant difference was observed in gene polymorphism distribution between groups I and II. Moreover, we did not observe any significant association of gene polymorphisms, tumor recurrence or muscle-invasive progression, event time and disease-free survival. CONCLUSION: Our results suggest that no significant difference was found for NRAMP1 and hGPX1 gene polymorphisms associated with recurrence time, muscle invasion frequency and disease-free survival, nevertheless, we observed that the NRAMP1 D543N GG genotype group had a shorter time to tumor recurrence.
Asunto(s)
Proteínas de Transporte de Catión/genética , Glutatión Peroxidasa/genética , Músculos/patología , Mycobacterium bovis/metabolismo , Polimorfismo Genético/genética , Neoplasias de la Vejiga Urinaria/genética , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Músculos/microbiología , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/microbiología , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/microbiología , Neoplasias de la Vejiga Urinaria/patología , Glutatión Peroxidasa GPX1RESUMEN
Nested variant urothelial carcinoma is a recently identified variant of urothelial carcinoma which is difficult to diagnose due to its resemblance to other benign bladder lesions, such as hyperplasia of Von Brünn nests. The authors present three clinical cases of this variant of urothelial carcinoma and emphasize the importance of clinical, cytological, histological and immunohistochemical criteria for the diagnosis and the need for early and adapted therapeutic management, as this type of bladder tumour, wrongly considered to be benign up until the early 1990s, is just as invasive as high-grade urothelial carcinoma.
Asunto(s)
Carcinoma de Células Transicionales/patología , Neoplasias de la Vejiga Urinaria/patología , Anciano , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The authors report two clinical cases of cystic nephroma in adults observed in the department over the last 10 years. The nonspecific clinical findings and the poor contribution of imaging examinations make this rare disease difficult to diagnose. Only histological examination can confirm the diagnosis and eliminate multilocular cystic renal carcinoma or necrotic pseudocystic carcinoma. Based on a review of the literature, the authors emphasize recent pathophysiological and immunohistochemical data that could improve the management of this benign disease, in which malignant transformation is also possible.
Asunto(s)
Neoplasias Renales , Tumor de Wilms , Femenino , Humanos , Neoplasias Renales/diagnóstico , Neoplasias Renales/terapia , Persona de Mediana Edad , Tumor de Wilms/diagnóstico , Tumor de Wilms/terapiaRESUMEN
AIM: To assess, in a prospective clinical research study, a new non-invasive and reliable test to accurately detect tumor protein 53 (TP53) and fibroblast growth factor receptor-3 (FGFR3) mutations in cells in urine. MATERIALS AND METHODS: TP53 mutations were analyzed using the functional analysis of separated allele in yeast (FASAY) method, which allows functional analysis of the P53 protein, and FGFR3 mutations were assessed with the SNaPshot system, detecting the eight most frequent point-mutations of this gene. Chi-square test or Fisher's exact test were used to compare TP53 and FGFR3 mutations in the tumors according to tumor stage and grade. RESULTS: TP53 and FGFR3 mutations in bladder tumors increased and decreased respectively with increasing tumor stage and cellular grade (p<0.05 and p<0.001, respectively). A total of 103 tumor/urinary sediment couples were analyzed. TP53 or FGFR3 mutations were observed in 76 tumors. The sensitivity for the detection of this type of mutation in urine was 46%, the specificity was 81%, the positive predictive value was 94% and the negative predictive value was 37%. CONCLUSION: Our original data confirmed the feasibility of TP53 and FGFR3 mutation detection in urine sediment. These measurements, together with urine cytology, may increase tumor detection. The sensitivity of the TP53/FGFR3 phenotype test in the urine was less than 50% and was not able to replace standard cystoscopy in the diagnosis of bladder tumors.
Asunto(s)
Mutación/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/orina , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/orina , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/orina , Análisis Mutacional de ADN , Electroforesis en Gel de Agar , Humanos , Estadificación de Neoplasias , Fenotipo , Proyectos Piloto , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
CONTEXT: Adrenal mast cells can stimulate aldosterone secretion through the local release of serotonin (5-HT) and activation of the 5-HT4 receptor (5-HT4). In aldosterone-producing adenomas (APAs), 5-HT4 receptor is overexpressed and the administration of 5-HT4 receptor agonists to patients with APA increases plasma aldosterone levels. These data and the well-documented role of mast cells in tumorigenesis suggest that mast cells may be involved in the pathophysiology of APA. OBJECTIVE: The study aimed at investigating the occurrence of mast cells in a series of APA tissues and to examine the influence of mast cells on aldosterone secretion. DESIGN: The occurrence of mast cells in APAs was investigated by immunohistochemistry. Mast cell densities were compared with clinical data. The influence of mast cells on aldosterone production was studied by using cultures of human mast cell and adrenocortical cell lines. RESULTS: In APA tissues, the density of mast cells was found to be increased in comparison with normal adrenals. Mast cells were primarily observed in adrenal cortex adjacent to adenomas or in the adenomas themselves, distinguishing two groups of APAs. A subset of adenomas was found to contain a high density of intratumoral mast cells, which was correlated with aldosterone synthase expression and in vivo aldosterone secretory parameters. Administration of conditioned medium from cultures of human mast cell lines to human adrenocortical cells induced a significant increase in aldosterone synthase (CYP11B2) mRNA expression and aldosterone production. CONCLUSION: APA tissues commonly contain numerous mast cells that may influence aldosterone secretion through the local release of regulatory factors.
Asunto(s)
Adenoma/metabolismo , Adenoma/patología , Neoplasias de la Corteza Suprarrenal/metabolismo , Neoplasias de la Corteza Suprarrenal/patología , Aldosterona/metabolismo , Mastocitos/patología , Adenoma/genética , Neoplasias de la Corteza Suprarrenal/genética , Aldosterona/farmacología , Recuento de Células , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/genética , Hiperaldosteronismo/metabolismo , Hiperaldosteronismo/patología , Hiperplasia , Mastocitos/efectos de los fármacos , Mastocitos/fisiología , Análisis por Micromatrices , Estudios RetrospectivosRESUMEN
26RFa is a hypothalamic neuropeptide that promotes food intake. 26RFa is upregulated in obese animal models, and its orexigenic activity is accentuated in rodents fed a high-fat diet, suggesting that this neuropeptide might play a role in the development and maintenance of the obese status. As obesity is frequently associated with type 2 diabetes, we investigated whether 26RFa may be involved in the regulation of glucose homeostasis. In the current study, we show a moderate positive correlation between plasma 26RFa levels and plasma insulin in patients with diabetes. Plasma 26RFa concentration also increases in response to an oral glucose tolerance test. In addition, we found that 26RFa and its receptor GPR103 are present in human pancreatic ß-cells as well as in the gut. In mice, 26RFa attenuates the hyperglycemia induced by a glucose load, potentiates insulin sensitivity, and increases plasma insulin concentrations. Consistent with these data, 26RFa stimulates insulin production by MIN6 insulinoma cells. Finally, we show, using in vivo and in vitro approaches, that a glucose load induces a massive secretion of 26RFa by the small intestine. Altogether, the present data indicate that 26RFa acts as an incretin to regulate glucose homeostasis.
Asunto(s)
Glucosa/metabolismo , Homeostasis/fisiología , Hipotálamo/metabolismo , Incretinas/metabolismo , Neuropéptidos/metabolismo , Animales , Línea Celular Tumoral , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Ratones , Obesidad/metabolismoRESUMEN
The authors report their experience of four cases of bladder leiomyoma. Although MRI is currently the reference radiological examination, the diagnosis must be confirmed by histological examination. The various diagnostic steps and resulting therapeutic indications are described with a review of the literature.
Asunto(s)
Leiomioma , Neoplasias de la Vejiga Urinaria , Algoritmos , Femenino , Humanos , Leiomioma/diagnóstico , Leiomioma/cirugía , Masculino , Persona de Mediana Edad , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
INTRODUCTION: Malignant tumours of the renal parenchyma are accompanied by extension to the inferior vena cava in 4% to 10% of cases. The objective of this study was to compare DNA ploidy and proliferation index of renal cell carcinoma (RCC) with renal vein (RV) thrombus and RCC with inferior vena cava (IVC) thrombus and to investigate a correlation between these markers and Fuhrman grade and patient survival. MATERIAL AND METHODS: A retrospective study was conducted in 58 patients with RCC and venous thrombus (40 in the RV and 18 in the IVC). Flow cytometry (FCM) and MiBI antibody immunolabelling (Ki-67 index) were performed on the healthy parenchyma, the renal tumour and the venous thrombus. Eighteen tumours with inferior vena cava thrombus were compared to 40 tumours with renal vein thrombus. Fuhrman grade, the presence of capsular rupture, invasion of the perirenal fat, and the presence of sarcomatoid transformation were investigated for a possible correlation with survival. RESULTS: No difference of expression of Ki-67 antigen expression was observed between the two populations of renal tumours with thrombus (RV/IVC), but a significant difference was observed for the two types of thrombus (RV/IVC). A difference in ploidy index was observed was also observed between tumours with RV and IVC thrombus (p<0.005). The tumours had less intense MiB1 immunolabelling and a lower DNA ploidy than their corresponding renal vein and inferior vena cava thrombi (Ki-67: 1.07% vs 5.12%, p<0.01: DNA index: 1.61 vs 1.87, p<0.01). A correlation between Fuhrman grade and tumour DNA index was demonstrated (1.149 for low grade tumours and 1.857 for high grade tumours, p<0.05). Sarcomatoid transformation, capsular effraction and capsular rupture were significantly correlated with Fuhrman grade (p<0.01) and patient survival (p<0.05). CONCLUSION: The proliferation index is not a prognostic factor, but DNA ploidy appears to be more useful because of its correlation with Fuhrman grade and the level of extension of the thrombus (RV/IVC). The proliferation index and ploidy appear to be involved in the process of carcinogenesis and venous thrombus.