RESUMEN
OBJECTIVE: The data describing the urologic extracolonic cancers associated with Lynch syndrome (hereditary non-polyposis colorectal cancer [HNPCC]) are variable. The aim of our study was to establish the frequency of mutations in mismatch repair (MMR) genes in patients with upper urinary tract transitional cell carcinoma (UUT-TCC) and to evaluate the clinical benefits of a systematic screening. METHODS: Specimen blocks were obtained from 146 patients treated for UUT-TCC in our center. Clinicopathological characteristics and survival data of patients were collected (median follow-up = 42.5 months). Immunohistochemistry was performed by tissue microarray (TMA), in order to detect mutations in mismatch repair genes. Results obtained after TMA analysis were confirmed at a molecular level by microsatellite instability (MSI) analysis. RESULTS: Mutations in mismatch repair genes were detected in seven patients (4.8%) at immunohistochemistry screening, and confirmed by MSI analysis for five of them (3.4%). Clinicopathological characteristics and survival data did not differ significantly in patients with instability compared with patients without. After a median follow-up of 42.5 months, none of them experienced a new HNPCC manifestation. CONCLUSION: The frequency of mutations in mismatch repair genes in UUT-TCC was very low, with a good accuracy of immunohistochemistry. Systematic screening should not be proposed in daily practice.
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Biomarcadores de Tumor/genética , Carcinoma de Células Transicionales/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Reparación de la Incompatibilidad de ADN/genética , Neoplasias Renales/genética , Inestabilidad de Microsatélites , Proteínas de Neoplasias/genética , Neoplasias Ureterales/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Adenosina Trifosfatasas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Enzimas Reparadoras del ADN , Proteínas de Unión al ADN/genética , Femenino , Marcadores Genéticos , Humanos , Masculino , Repeticiones de Microsatélite , Persona de Mediana Edad , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto , Homólogo 1 de la Proteína MutL , Proteína 2 Homóloga a MutS/genética , Proteínas Nucleares/genética , Estudios Retrospectivos , Análisis de Matrices Tisulares , Adulto JovenRESUMEN
The aim of this study was to evaluate the expression levels of microRNAs (miRNAs) in bladder tumors in order to identify miRNAs involved in bladder carcinogenesis with potential prognostic implications. Expression levels of miRNAs were assessed by quantitative real-time RT-PCR in 11 human normal bladder and 166 bladder tumor samples (86 non-muscle-invasive bladder cancer (NMIBC) and 80 muscle-invasive bladder cancer (MIBC)). The expression level of 804 miRNAs was initially measured in a well-defined series of seven NMIBC, MIBC and normal bladder samples (screening set). The most strongly deregulated miRNAs in tumor samples compared to normal bladder tissue were then selected for RT-PCR validation in a well-characterized independent series of 152 bladder tumors (validation set), and in six bladder cancer cell lines. Expression levels of these miRNAs were tested for their association with clinical outcome. A robust group of 15 miRNAs was found to be significantly deregulated in bladder cancer. Except for two miRNAs, miR-146b and miR-9, which were specifically upregulated in MIBC, the majority of miRNAs (n = 13) were deregulated in the same way in the two types of bladder tumors, irrespective of pathological stage : three miRNAs were upregulated (miR-200b, miR-182 and miR-138) and the other 10 miRNAs were downregulated (miR-1, miR-133a, miR-133b, miR-145, miR-143, miR-204, miR-921, miR-1281, miR-199a and miR-199b). A 3-miRNA signature (miR-9, miR-182 and miR-200b) was found to be related to MIBC tumor aggressiveness and was associated with both recurrence-free and overall survival in univariate analysis with a trend to significance in the multivariate analysis (p = 0.05). Our results suggested a promising individual prognostic value of these new markers.
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Carcinoma de Células Transicionales/genética , MicroARNs/genética , Neoplasias de los Músculos/genética , Neoplasias de la Vejiga Urinaria/genética , Vejiga Urinaria/metabolismo , Biomarcadores de Tumor/genética , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/patología , Perfilación de la Expresión Génica , Humanos , Neoplasias de los Músculos/mortalidad , Neoplasias de los Músculos/patología , Clasificación del Tumor , Invasividad Neoplásica , Estadificación de Neoplasias , Análisis de Secuencia por Matrices de Oligonucleótidos , Pronóstico , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
BACKGROUND: Chromophobe renal cell carcinoma (chRCC) and renal oncocytoma are two distinct but closely related entities with strong morphologic and genetic similarities. While chRCC is a malignant tumor, oncocytoma is usually regarded as a benign entity. The overlapping characteristics are best explained by a common cellular origin, and the biologic differences between chRCC and oncocytoma are therefore of considerable interest in terms of carcinogenesis, diagnosis and clinical management. Previous studies have been relatively limited in terms of examining the differences between oncocytoma and chromophobe RCC. METHODS: Gene expression profiling using the Affymetrix HGU133Plus2 platform was applied on chRCC (n = 15) and oncocytoma specimens (n = 15). Supervised analysis was applied to identify a discriminatory gene signature, as well as differentially expressed genes. High throughput single-nucleotide polymorphism (SNP) genotyping was performed on independent samples (n = 14) using Affymetrix GeneChip Mapping 100 K arrays to assess correlation between expression and gene copy number. Immunohistochemical validation was performed in an independent set of tumors. RESULTS: A novel 14 probe-set signature was developed to classify the tumors internally with 93% accuracy, and this was successfully validated on an external data-set with 94% accuracy. Pathway analysis highlighted clinically relevant dysregulated pathways of c-erbB2 and mammalian target of rapamycin (mTOR) signaling in chRCC, but no significant differences in p-AKT or extracellular HER2 expression was identified on immunohistochemistry. Loss of chromosome 1p, reflected in both cytogenetic and expression analysis, is common to both entities, implying this may be an early event in histogenesis. Multiple regional areas of cytogenetic alterations and corresponding expression biases differentiating the two entities were identified. Parafibromin, aquaporin 6, and synaptogyrin 3 were novel immunohistochemical markers effectively discriminating the two pathologic entities. CONCLUSIONS: Gene expression profiles, high-throughput SNP genotyping, and pathway analysis effectively distinguish chRCC from oncocytoma. We have generated a novel transcript predictor that is able to discriminate between the two entities accurately, and which has been validated both in an internal and an independent data-set, implying generalizability. A cytogenetic alteration, loss of chromosome 1p, common to renal oncocytoma and chRCC has been identified, providing the opportunities for identifying novel tumor suppressor genes and we have identified a series of immunohistochemical markers that are clinically useful in discriminating chRCC and oncocytoma.
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Adenoma Oxifílico/genética , Biomarcadores de Tumor/genética , Carcinoma de Células Renales/genética , Cromosomas Humanos Par 1 , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Pruebas Genéticas/métodos , Neoplasias Renales/genética , Polimorfismo de Nucleótido Simple , Adenoma Oxifílico/química , Adenoma Oxifílico/diagnóstico , Acuaporina 6/análisis , Biomarcadores de Tumor/análisis , Carcinoma de Células Renales/química , Carcinoma de Células Renales/diagnóstico , Análisis Citogenético , Diagnóstico Diferencial , Dosificación de Gen , Redes Reguladoras de Genes , Humanos , Inmunohistoquímica , Neoplasias Renales/química , Neoplasias Renales/diagnóstico , Proteínas de la Membrana/análisis , Proteínas del Tejido Nervioso/análisis , Oportunidad Relativa , Análisis de Secuencia por Matrices de Oligonucleótidos , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Sinaptogirinas , Proteínas Supresoras de Tumor/análisisRESUMEN
BACKGROUND: Deep infiltrating endometriosis (DIE) is presented as a disease with high recurrence risk. Bladder DIE is the most frequent location in cases of urinary endometriosis. Surgical removal has been recommended for bladder DIE but long-term outcomes remains unevaluated. The objectives of this study are to evaluate the rate of recurrence after partial cystectomy for patients presenting with bladder DIE and to outline the surgical modalities for handling associated posterior DIE nodules. METHODS: Seventy-five consecutive patients with histologically proved bladder DIE were enrolled at a single tertiary academic center between June 1992 and December 2007. A partial cystectomy was performed for each patient. Complete surgical exeresis of all associated symptomatic DIE lesions was carried out during the same surgical procedure. Bladder DIE patients were classified into three groups: patients with isolated bladder DIE (Group A); patients with associated symptomatic posterior DIE (Group B); patients with associated asymptomatic posterior DIE (Group C). Bladder DIE recurrence was defined as a clinical reappearance of the disease or radiological evidence that mandated a new surgical procedure. We assessed pelvic pain symptoms pre- and post-operatively using a 10-cm visual analogue scale. RESULTS: In a series of 627 patients with DIE, we observed 75 patients (12%) with bladder DIE. With a 50.9 +/- 44.6 months mean follow-up after partial cystectomy no patient presented evidence of bladder DIE recurrence. Post-operatively, we observed a significant improvement with respect to pain symptoms, with only two patients (2.7%) developing major complications during follow-up. Among patients with non-operated associated asymptomatic posterior DIE lesions (n = 15), a second surgical procedure indicated for pain symptoms was necessary in only one patient (6.7%). CONCLUSIONS: For patients presenting with bladder DIE, no patients required further surgery for bladder recurrence after radical surgery consisting in partial cystectomy. Exeresis of associated posterior DIE nodules is indicated only when they are symptomatic.
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Endometriosis/cirugía , Enfermedades de la Vejiga Urinaria/cirugía , Adulto , Cistectomía/efectos adversos , Cistectomía/métodos , Endometriosis/patología , Endometriosis/fisiopatología , Femenino , Humanos , Persona de Mediana Edad , Dolor/fisiopatología , Recurrencia , Factores de Tiempo , Resultado del Tratamiento , Enfermedades de la Vejiga Urinaria/patología , Enfermedades de la Vejiga Urinaria/fisiopatología , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the rate of intrinsic ureteral endometriosis in patients presenting with severe ureteral endometriosis. DESIGN: Observational study between June 1992 and December 2007. SETTING: University tertiary referral center. PATIENT(S): Twenty-nine patients presenting deeply infiltrating endometriosis (DIE) with severe ureteral endometriosis. Severe ureteral endometriosis was defined as DIE lesions causing significant obstruction to the urinary flow with ureteral stenosis. INTERVENTION(S): Complete surgical exeresis of DIE lesions. MAIN OUTCOME MEASURE(S): Pre- and peroperative evaluation associated with histologic analysis. Intrinsic ureteral endometriosis was defined as presence of DIE lesions infiltrating the ureteral muscularis. RESULT(S): In a series of 627 patients with histologic proved DIE, we observed 29 (4.6%) patients with severe ureteral endometriosis. Ureteral lesions (n = 34) were right sided in 7 (24.1%) patients, left sided in 17 (58.6%) patients, and bilateral in 5 (17.3%) patients. Eleven (37.9%) patients presented intrinsic lesions. Out of the 34 ureteral lesions 13 (38.2%) were intrinsic. In cases of radical ureteral surgery (n = 21 patients; n = 24 ureteral lesions) intrinsic ureteral DIE was observed in 52.4% (11 cases) of the patients and in 54.2% (13 cases) of the ureteral lesions. CONCLUSION(S): The prevalence of intrinsic ureteral endometriosis is underestimated. This result must be taken into account when specifying the surgical modalities for patients presenting with severe ureteral endometriosis.
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Endometriosis/epidemiología , Endometriosis/cirugía , Enfermedades Ureterales/epidemiología , Enfermedades Ureterales/cirugía , Procedimientos Quirúrgicos Urológicos , Adulto , Endometriosis/complicaciones , Endometriosis/patología , Femenino , Estudios de Seguimiento , Procedimientos Quirúrgicos Ginecológicos/métodos , Humanos , Persona de Mediana Edad , Enfermedades del Ovario/complicaciones , Enfermedades del Ovario/epidemiología , Periodo Posparto , Embarazo , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/patología , Complicaciones del Embarazo/cirugía , Prevalencia , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Enfermedades Ureterales/complicaciones , Enfermedades Ureterales/patología , Procedimientos Quirúrgicos Urológicos/métodosRESUMEN
BACKGROUND: Actors of the angiogenesis pathways are targets for the new promising targeted therapies already used in several malignancies. In bladder cancer, antiangiogenic molecules could also add to already existing treatment options. OBJECTIVE: To evaluate the involvement of angiogenesis pathways in bladder carcinogenesis and identify new molecular markers having a clinical implication. DESIGN, SETTING, AND PARTICIPANTS: Expression levels of 40 genes involved in angiogenesis were assessed by quantitative real time RT-PCR in 157 urothelial tumour bladder samples obtained from patients who underwent transurethral bladder resection or radical cystectomy between 2001 and 2005. Pathologic tumour staging showed: 73 non-muscle-invasive bladder tumours (30 low-grade pTa, 14 high-grade pTa, and 29 high-grade pT1), and 84 muscle-invasive tumours (> or = pT2), all of high grade. RT-PCR results were associated with a survival analysis. RESULTS AND LIMITATIONS: VEGFA, MET, CXCR4, and IL8 were significantly overexpressed in tumour samples as compared to normal bladder tissue. VEGFA overexpressions were found in 89% of non-muscle-invasive and 66% of muscle-invasive tumour samples. In univariate analysis, for invasive tumours, VEGFA overexpression was associated with a poorer outcome in both overall and disease-free survival (p=0.011 and 0.026 respectively) at a 13-mo median follow-up. Multivariate analysis retained T stage, N status, and VEGFA overexpression as independent prognostic factors in both overall and disease-free survival (p=0.02 and p=0.04, respectively, for VEGFA). CONCLUSIONS: This study shows that, in bladder cancer, VEGFA status could be used as a prognostic factor at the individual level. VEGFA overexpression could guide a rationalized use of the costly antiangiogenic therapies which could therefore become part of the treatment options in bladder cancer.
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Carcinoma de Células Transicionales/genética , ARN Mensajero/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias de la Vejiga Urinaria/genética , Factor A de Crecimiento Endotelial Vascular/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/irrigación sanguínea , Carcinoma de Células Transicionales/química , Carcinoma de Células Transicionales/mortalidad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Neovascularización Patológica , Pronóstico , ARN Mensajero/genética , Estudios Retrospectivos , Análisis de Supervivencia , Neoplasias de la Vejiga Urinaria/irrigación sanguínea , Neoplasias de la Vejiga Urinaria/química , Neoplasias de la Vejiga Urinaria/mortalidad , Factor A de Crecimiento Endotelial Vascular/análisisRESUMEN
Juxtaglomerular cell tumor (JGCT), first described in 1967, is a rare tumor of the kidney that derived from specialized smooth muscle cells of the wall of the glomerular afferent arteriole. Less than 100 cases have been published, mainly as isolated case reports or small series. JGCTs are considered benign, but the clinical follow-up is short in most reported cases. Only 1 metastatic case has been reported to date, raising the question of tumors of uncertain malignant potential rather than clearly benign neoplasms. Genomic features have been studied in only 2 cases that showed gain of chromosome 10 as well as loss of chromosomes 9, 11q, and X. The present work studied the genomic characteristics of 2 additional cases of JGCT by comparative genomic hybridization. Similarly to the 2 previously reported cases, these 2 tumors showed loss of chromosomes 9 and 11, suggesting recurrent chromosomal imbalances. In addition, 1 case showed gain and loss of entire chromosomes, similar to a previous case studied by karyotyping. Such an aneuploid karyotype may reflect a potential for malignancy as previously reported. Thus, JGCT might be better considered as a tumor of uncertain malignant potential and then necessitates a prolonged follow-up. Future clinicopathologic and genomic studies of large retrospective and prospective series may help to better understand the biology of this fascinating entity.
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Cromosomas Humanos Par 11/genética , Cromosomas Humanos Par 9/genética , Aparato Yuxtaglomerular/patología , Neoplasias Renales/genética , Aberraciones Cromosómicas , Humanos , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Hibridación de Ácido NucleicoRESUMEN
OBJECTIVE: In the literature, most data regarding the outcome of patients with clinical stage T1a prostate cancer were established before the prostate-specific antigen (PSA) era. The aim of our study was to determine the predictive factors of progression in patients with T1a prostate cancer diagnosed in the PSA era. METHODS: Consecutive patients (n=144) with newly diagnosed T1a prostate cancer (tumor involving < or =5% of the resected prostatic tissue) were included. None of them was treated before evidence of tumor progression confirmed by prostate needle biopsies. The associations between tumor characteristics and time to cancer progression were assessed using Cox regression analysis. RESULTS: With a mean follow-up of 5.1 yr, 30 patients (21%) experienced cancer progression. Five adverse parameters were significantly associated with cancer progression: preoperative PSA> or =10 ng/ml, postoperative PSA> or =2 ng/ml, prostate weight > or =60 g, weight of resected tissue > or =40 g, and Gleason score> or =6. The 5-yr progression rate was 12% if fewer than two of these parameters were present, whereas it was 47% if two or more parameters were present (p<0.001). CONCLUSION: In the PSA era the risk of progression associated with T1a prostate cancer can be predicted using five criteria, and two groups of patients can be defined. The patients at low risk of progression may be good candidates for surveillance. In those with a high risk of progression, a more aggressive treatment should be discussed.
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Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/patología , Anciano , Anciano de 80 o más Años , Biopsia con Aguja , Progresión de la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Neoplasias de la Próstata/terapia , Curva ROC , Factores de RiesgoRESUMEN
OBJECTIVE: To introduce the use of a portfolio (PF) as a learning and evaluation tool for hospital medical students in a urology department. METHODS: In the course of 6 consecutive 3-month sessions, 36 medical students each constituted a PF. After having chosen a urological topic, each student identified his/her learning needs and constructed a PF by collecting various types of information (books, medical articles, internet, orals, ...) with the aid of a tutor. The PF had to be established in the form of a series of questions asked by the student followed by answers provided by the information collected. The PF was scored (out of 20) and contributed to validation of the session. Students completed a satisfaction questionnaire. RESULTS: All students were validated (mean score: 14.2/20). Results of the satisfaction questionnaire showed that, although no student had previously performed a PF, 27/30 expressed the desire to establish a PF for another training attachment. This questionnaire also showed that the PF helps to improve theoretical knowledge (30/36), the needs in relation to professional practice (17/36), the ability to select data (34/36), and is a good self-learning tool (36/36). The major difficulty encountered by students concerned sorting of data (26/36) and written formulation of questions and answers (35/36). CONCLUSION: The PF appears to be a good learning and evaluation tool that can be used in surgical training attachments. It guides students in their personal study and highlights the quality of their reasoning.
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Educación Médica , Estudiantes de Medicina/psicología , Urología/educación , Curriculum , Evaluación Educacional , Humanos , Encuestas y CuestionariosRESUMEN
OBJECTIVES: To evaluate the prognostic significance of subtyping papillary renal cell carcinoma (PRCC) into type 1 and type 2 tumors. METHODS: From 1995 to 2004, 1358 patients underwent surgery for renal cell carcinoma, of whom 130 had PRCC alone on the specimen. The tumor characteristics, including their subtype, were analyzed; small basophilic cells and large eosinophilic cells were defined type 1 and type 2 tumors, respectively. Survival analyses were performed retrospectively. RESULTS: Of the 130 patients (110 men and 20 women, mean age 60.6 +/- 15.3 years) with PRCC, 102 underwent radical nephrectomy (78.4%) and 28 underwent partial nephrectomy (21.6%). The median tumor size was 4.5 cm (range 0.5 to 21). The comparison of the 68 (52.3%) type 1 PRCCs and 62 (47.7%) type 2 PRCCs revealed that type 2 tumors were associated with a greater stage and grade and microvascular invasion significantly (P <0.001) more often. The median follow-up was 48 months (range 2 to 111). Of the 130 patients, 22 died of cancer-specific causes, 5 (7%) with type 1 and 17 (27%) with type 2 tumors (P = 0.002). The overall and disease-free survival rate was 89% and 92% in type 1 tumors and 55% and 44% in type 2 tumors, respectively. Univariate analysis identified tumor type, stage (P <0.001), grade (P <0.001), microvascular invasion (P <0.001), an absence of foam cells (P <0.001), the presence of sarcomatoid cells (P = 0.001), and tumor necrosis (P = 0.007) as prognostic factors. Multivariate analysis retained tumor type (P = 0.034) and TNM stage (P <0.001). CONCLUSIONS: The results of our study have shown that histologic subtyping of PRCC allows for the identification of an independent prognostic factor.
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Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Factores de Edad , Anciano , Biopsia con Aguja , Carcinoma de Células Renales/clasificación , Carcinoma de Células Renales/cirugía , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Neoplasias Renales/clasificación , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Nefrectomía/métodos , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores Sexuales , Análisis de SupervivenciaRESUMEN
OBJECTIVE: To determine preoperative risk factors of postoperative voiding dysfunction after tension-free vaginal tape (TVT) procedure. METHODS: In 2004, 100 patients with genuine stress urinary incontinence underwent surgery by the TVT procedure. Preoperative and postoperative urodynamic study was performed for each patient. Postoperatively, patients' perception of result and quality of life were assessed on two validated scales, namely, Mesure du Handicap Urinaire (MHU) and Ditrovie. Voiding dysfunction was defined by a postoperative peak flow rate of <15 ml/s at 3 mo. Clinical and urodynamic parameters were compared and analysed. RESULTS: At 3 mo, 20 patients (20%) showed evidence of voiding dysfunction despite the absence of clinical symptoms in 14 of them (70%). Multivariate analysis showed that age (p<0.038) and preoperative peak flow rate (p<0.001) were independent risk factors for voiding dysfunction. Parity, menopausal status, body mass index, and maximal urethral closure pressure were not statistically related to the risk of voiding dysfunction. CONCLUSIONS: This study confirms the existence of an important rate of postoperative voiding dysfunction, mostly asymptomatic, and identifies age and preoperative maximal peak flow rate as independent preoperative risk factors. Identification of voiding dysfunction in patients may lead to better follow-up and early detection of late potential complications of suburethral procedures.
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Cabestrillo Suburetral/efectos adversos , Incontinencia Urinaria de Esfuerzo/cirugía , Trastornos Urinarios/etiología , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Trastornos Urinarios/epidemiologíaRESUMEN
We report the case of a 42-year-old man with a synovial sarcoma of the prostate, metastatic at presentation, who after aggressive chemotherapy followed by extensive surgery developed a complex pelvic fistula involving the lower ureter, bladder, and enteral structures. The patient was a poor candidate for surgery because of his short life expectancy and poor health status. Conservative management with bilateral nephrostomy tubes did not allow sufficient fistulous output for symptomatic relief. Using the percutaneous access already in place, we performed bilateral ureteral embolization with coils. Complete ureteral occlusion was obtained with a minimally invasive procedure and allowed total symptomatic relief.
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Embolización Terapéutica/instrumentación , Fístula Intestinal/terapia , Neoplasias de la Próstata/complicaciones , Sarcoma/complicaciones , Fístula Urinaria/etiología , Fístula Urinaria/terapia , Adulto , Humanos , MasculinoRESUMEN
We chose to introduce a portfolio as a learning and assessment tool in a practical training session of urological surgery for undergraduate medical students. Our primary objectives were to develop the students' self reflexive ability in front of complex medical cases and to teach them how to identify their learning needs in a short period of time, on a specific topic. Students completed, during their training session, a portfolio on a urological topic under the constant supervision of a tutor. The students were evaluated on their portfolio's presentation with a 20-point grade grid known in advance. Even in a surgical training session, a portfolio can be a useful learning and assessment tool. It clearly encourages self-reflection and pre-professional practice.
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Documentación , Educación de Pregrado en Medicina , Evaluación Educacional/métodos , Aprendizaje , Procedimientos Quirúrgicos Urológicos/educación , Hospitales , HumanosRESUMEN
OBJECTIVE: To test different approaches of evaluation of the ErbB2 status in a large series of human transitional cell carcinoma (TCC) of the bladder with the prospect of finding targeted therapies. METHODS: ErbB2 status of 73 human TCC samples was analyzed by both immunohistochemistry (IHC) and by quantification of mRNA levels of expression using real-time reverse transcription-polymerase chain reaction (RT-PCR). Additionally, 18 bladder samples were studied for ERBB2 gene amplification by real-time quantitative PCR. RESULTS: Twenty-five tumors (34.2%) overexpressed ERBB2 mRNA compared to normal bladder samples; this alteration appeared in low-grade and low-stage tumors (pTaG1). Twenty-four (32.9%) tumors showed moderate (++) or strong (+++) immunostaining. A very strong agreement was found between the two methods (kappa = 0.97, 95% confidence interval, 0.90-1). ErbB2 status was not associated with tumor stage. Of the 18 bladder samples tested for ERBB2 gene amplification, only one showed ERBB2 DNA amplification. CONCLUSIONS: ErbB2 overexpression occurs in about one third of bladder TCCs. This overexpression can be detected by RT-PCR with a very good correlation with IHC. RT-PCR can therefore be used for cases considered doubtful on IHC rather than gene amplification studies because, in TCC, gene amplification is not the predominant mechanism of both mRNA and protein overexpression. Accurate quantification of ErbB2 status is mandatory for the use of anti-ErbB2-targeted therapies in bladder TCC.
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Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/genética , Regulación Neoplásica de la Expresión Génica , ARN Mensajero/análisis , Receptor ErbB-2/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Neoplasias de la Vejiga Urinaria/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , ARN Mensajero/biosíntesisRESUMEN
PURPOSE: The ErbB driven growth pathway has been implicated in most human epithelial malignancies. Therefore, its blockade is a promising therapeutic strategy and several candidate drugs are currently undergoing clinical trials. Paradoxically little is known of the expression pattern or clinical significance of the 4 ErbB receptors and their 11 ligands in TCC of the bladder. MATERIALS AND METHODS: To obtain further insight into the molecular pathogenesis of TCC we used quantitative real-time reverse transcriptase-polymerase chain reaction assay to quantify mRNA expression of the 4 ERBB and their 11 known ligand genes, including recently described EPGN/epigen, in 73 tumor samples. RESULTS: The level of mRNA of 4 ligand genes (EGF, NRG1, NRG2 and NRG3) was extremely low, that is detectable but not quantifiable. Six genes were over expressed (ERBB2, TGFA, HB-EGF, AREG, EREG and EPGN), 3 were under expressed (ERBB1, ERBB4 and NRG4) and 2 were over or under expressed (ERBB3 and BTC). ERBB2 and AREG expression differed between early stage tumors (pTa grade 1) and normal samples. The most marked differences in expression were ERBB3, EREG and NRG4 between superficial and muscle invasive tumors (p = 0.0069, 0.00007 and 0.0000001, respectively), and TGFA and NRG4 between low and high grade superficial tumors, and between pT1 or greater and pTa tumors. CONCLUSIONS: This study shows the involvement of the ERBB family and ligand genes in TCC. Most receptor and ligand genes are deregulated at different stages of carcinogenesis, implying that they should be studied simultaneously. Quantitative real-time reverse transcriptase-polymerase chain reaction could be used to determine ErbB signaling pathway status in individuals with a view to tailored therapy.
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Carcinoma de Células Transicionales/genética , Receptores ErbB/genética , Regulación Neoplásica de la Expresión Génica , Receptor ErbB-2/genética , Receptor ErbB-3/genética , Neoplasias de la Vejiga Urinaria/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Ligandos , Masculino , Persona de Mediana Edad , ARN Mensajero/análisis , ARN Mensajero/biosíntesis , Receptor ErbB-4RESUMEN
Clinical trials in urothelial cancer exclude a large population of patients. An observational study evaluated the behavior of frail patients not eligible for cisplatin- or carboplatin-based regimens. Urothelial cancer patients requiring chemotherapy with either chronic renal failure (creatinine clearance <60 ml/min), and/or performance status (PS) > or =2 and/or cardiac dysfunction were prospectively observed. The treatment associated gemcitabine 1200 mg/m and oxaliplatin 85 mg/m, bimonthly (GO). Over 2 years, 31 of 45 (69%) patients with urothelial cancer requiring chemotherapy were not eligible for cisplatin- or carboplatin-based chemotherapy. Sixteen (52%) had a PS > or =2, 23 (74%) had creatinine clearance <60 ml/min, and 20 (65%) had an underlying cardiopathy. A total of 178 cycles of GO were administered (median 6 per patient, range 2-12). No aggravation of renal or cardiac status was noted. Acute grade 3 and 4 neutropenia and thrombocytopenia were observed in 16 and 13% of patients, respectively, with one febrile neutropenia. The median progression-free and overall survival values were 4.2 and 9.5 months, respectively. The majority of urothelial cancer patients have severe renal or cardiac comorbidities, and we conclude that in this subset of patients the combination of gemcitabine and oxaliplatin is well tolerated, and its clinical activity warrants further evaluation.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Urológicas/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Creatinina/orina , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Femenino , Cardiopatías/complicaciones , Humanos , Fallo Renal Crónico/complicaciones , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Análisis de Supervivencia , Resultado del Tratamiento , Neoplasias Urológicas/complicaciones , Neoplasias Urológicas/patología , GemcitabinaRESUMEN
INTRODUCTION: To comply with current legislation, French medical schools organize theoretical speciality teaching for medical students in speciality poles or in global modules. The objective of this study was to assess the theoretical, practical and assessment modalities of Urology teaching based on a survey. METHODS: In January 2004, a four-part questionnaire was sent to all urology teachers in 45 French universities. These 4 parts concerned: modalities of theoretical teaching, modalities of practical teaching, assessment modalities, evaluation of teaching, each evaluated by several questions. RESULTS: The response rate was 64.4% (29/45). Twelve medical schools chose teaching by speciality poles and 15 chose modular teaching. CCAs (Senior Registrars) played a greater role in modular teaching than in speciality pole teaching (75% and 53.3% of medical schools). Among the 12 medical schools with a speciality pole organization, 7 provided integrated teaching. An average of 23% of students of any one year receive Urology teaching during their training. Most medical schools conduct evaluation of theoretical (82.7%) and practical teaching (65.5%). CONCLUSION: Speciality teaching can be performed according to a polar or modular organization. A modular organization would be theoretically more appropriate to achieve the objective of a global approach to medicine, but artificial grouping of diseases can sometimes complicate speciality teaching in a speciality as diverse as Urology.
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Educación de Pregrado en Medicina , Enseñanza/métodos , Urología/educación , Francia , Humanos , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To report our preliminary experience with trastuzumab (Herceptin) in the management of metastatic transitional cell carcinoma of the urinary tract. PATIENTS AND METHODS: From november 2001 to august 2002, six patients received trastuzumab for metastatic transitional cell carcinoma of the bladder (n=5) or renal pelvic cancer (n=1). Trastuzumab was administered as a first-line therapy in 2 patients, a second-line therapy in 3, and a third-line therapy in 1. Each patient received a weekly intravenous administration of trastuzumab (initial dose of 4 mg/kg, followed by 2mg/kg for other courses). A total of 6 courses was given. In 4 patients, trastuzumab was administered in association with paclitaxel (175 mg/m2) and carboplatin (area under the curve of 6). One patient received the same combination of trastuzumab and paclitaxel, but without carboplatin. The remaining patient received only trastuzumab. RESULTS: The trastuzumab-based regimen achieved partial regression of metastases in all patients. Initial regression of metastases varied between 30% and 80%. The therapy was well tolerated. Treatment-related toxicity was moderate in all patients, except for one who experienced transient grade 4 neutropenia. Five patients died from cancer. The interval between trastuzumab initiation and patient death ranged from 8 to 22 months. The remaining patient was still alive 28 months after trastuzumab initiation. CONCLUSIONS: Our preliminary data suggest that trastuzumab-based therapy may be safe and effective in metastatic transitional cell carcinoma of the urinary tract. Prospective trials are needed to further investigate this therapeutic option.
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Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Carcinoma de Células Transicionales , Neoplasias Urológicas , Anciano , Anticuerpos Monoclonales Humanizados , Carboplatino/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/metabolismo , Carcinoma de Células Transicionales/patología , Quimioterapia Combinada , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Paclitaxel/uso terapéutico , Proyectos Piloto , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Estudios Retrospectivos , Trastuzumab , Resultado del Tratamiento , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/metabolismo , Neoplasias Urológicas/patologíaRESUMEN
OBJECTIVE: Repeated biopsies in patients with a high risk of prostate cancer only allow a small proportion of new cancer diagnosis. The aim of this study was to evaluate the use of combined MRI and magnetic resonance spectroscopy imaging (MRSI) for these patients. METHODS: Between April 2003 and April 2004, 42 patients with negative multiple cores prostatic biopsies and serum PSA>4 ng/ml underwent a combined MRI/MRSI analysis. Suspicious zones on standard MRI included low intensity signals on T2 weighted images. A high choline+creatine-to-citrate ratio defined a MRSI suspicious zone. A 10 cores following peripheral biopsy scheme was done to which were added supplementary biopsies on the MRI/MRSI suspicious zones. RESULTS: The mean age was 62.3 years (51-74), the mean pre-biopsy serum PSA was 12 (3.87-35), the mean free/total PSA ratio was 11% (5-20). The mean number of previous prostate biopsy rounds was 2.04. 15 prostate cancers were diagnosed (35.7%). In 9 cases, abnormal MRI/MRSI findings and positive biopsy sites were located on the same prostatic zones. In 5 cases, MRSI alone located the positive biopsy zones. Sensitivity of combined MRI/MRSI in this study was 73.3%; specificity, positive predictive value, negative predictive value and accuracy were 96.3%, 91.6%, 86.6% and 88% respectively. CONCLUSIONS: This preliminary study shows that the combination of MRI and MRSI might be able to guide and therefore limit the number of iterative biopsies and cores for patients who are at high risk of having a prostate cancer. In some cases, MRSI alone allows identification of neoplasic prostatic zones. Other studies are needed to confirm these data.