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1.
Eur Ann Otorhinolaryngol Head Neck Dis ; 136(5): 361-366, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31196801

RESUMO

BACKGROUND: Preoperative assessment of mandibular bone invasion in squamous cell carcinoma of the oral cavity and oropharynx is crucial for optimizing bone resection. The principal aim of this study was to evaluate the diagnostic value of CT and MR imaging for the diagnosis of mandibular bone invasion compared to the histological reference. In addition, we assessed the survival impact of bone invasion. PATIENTS AND METHODS: A single-center retrospective study included all consecutive patients treated by mandibular bone interruption for squamous cell carcinoma of the oral cavity and/or oropharynx. RESULTS: Sixty-eight patients were included. Prevalence of bone invasion on histology was 43%. Sensitivity, specificity and positive and negative predictive value were respectively 70%, 71%, 66% and 76% for CT compared with histologic analysis, 83%, 50%, 59% and 78% for MRI, and 83%, 62% 62%, 83% for associated CT and MRI. The two tests showed good agreement, with kappa index 0.69 (95% CI, 0.49-0.89) (P<0.0001). There was no difference in overall survival (log-rank>0.70) between the groups with and without bone invasion. CONCLUSION: CT and MRI are complementary for preoperative assessment of mandibular bone invasion, be it cortical and/or medullary, and in some cases may allow mandibular bone-sparing.


Assuntos
Carcinoma de Células Escamosas/patologia , Mandíbula/diagnóstico por imagem , Mandíbula/patologia , Neoplasias Bucais/patologia , Invasividade Neoplásica , Neoplasias Orofaríngeas/patologia , Carcinoma de Células Escamosas/mortalidade , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Neoplasias Orofaríngeas/mortalidade , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X
2.
Prog Urol ; 29(2): 108-115, 2019 Feb.
Artigo em Francês | MEDLINE | ID: mdl-30638756

RESUMO

INTRODUCTION: No studies of French hospital registries for prostate cancer (PCa) have been published since the 2012 USPSTF recommendations. MATERIAL: This is a multicenter cohort study based on hospital data of prostate biopsies (PB) in 3 health centers between 2001 and 2016. The main objective is to describe the evolution of incident cases of PCa. The secondary objectives are to describe the number of cases per stage of PCa and the distribution of the first treatments. RESULTS: In total, 11,491 PB series diagnosed 5927 cases of PCa. The median age was 67 [61-73] years and the median PSA was 7.8 [5.5-13] ng/mL. The number of cases increased until 2006 before decreasing from 2006 to 2013 and then stabilizing from 2013 to 2016. The proportion of incident cases was: (1) for the stable metastatic stage around 8 [7-10]%, (2) for cases with PSA<10 ng/mL increasing from 46% to 75% in 2010 down to 64% in 2016, (3) for the grade 1 group decreasing from 59% to 33 % between 2011 and 2016. The proportion of active surveillance treatment for low-risk cancers increased from 5 to 60% and surgery decreased from 73 to 33%. CONCLUSION: The evolution of the incident cases showed a decrease from 2006 to 2013 and a stability until 2016. The number of cases with PSA<10 ng/mL decreased since 2010 and the proportion of the options of treatment by surveillance increased strongly to the detriment of the surgery for low risks. LEVEL OF EVIDENCE: 3.


Assuntos
Programas de Rastreamento/métodos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/epidemiologia , Idoso , Biópsia , Estudos de Coortes , França/epidemiologia , Hospitais , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia
3.
World J Urol ; 37(2): 261-268, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30116963

RESUMO

PURPOSE: To analyse the impact of the presence of extra-target non-clinically significant cancer (NCSC) after high-intensity focused ultrasound (HIFU) hemiablation on oncological results. To analyse radical treatment free survival (RTFS) rates at 2-3 years follow-up. METHODS: Retrospective single-centre study of 55 patients treated by primary HIFU hemiablation from 2010 to 2016. Inclusion criteria were unilateral MRI detected CSC, stage ≤ T2b, Gleason score (GS) ≤ 7, at least 6 mm distant from prostate apex. MRI with systematic and targeted biopsies was performed at diagnosis. Follow-up included clinical examination, PSA every 6 month, MRI and biopsies at 1 year and in case of PSA elevation. HIFU retreatment was possible. Whole-gland treatment was indicated in case of positive biopsies with GS ≥ 7 or maximum cancer core length > 5 mm, any GS. RESULTS: Mean follow-up was 33 months (SD: 17-49 months). Presence or not of an extra-target NCSC in the untreated part of the gland had no impact on RTFS at univariate analysis (p = 0.29). 10 (18%) patients had a salvage whole-gland treatment after a median follow-up of 26 months (IQR 17-28). RTFS at 2 and 3 years were 92% and 80%. CONCLUSION: Presence or not of an extra-target NCSC in the untreated part of the gland had no impact on RTFS. NCSC lesion can be left untreated and actively monitored. RTFS was 80% at 3 years which support the concept of focal/partial treatment as a treatment option of CSC prostate cancer.


Assuntos
Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Próstata/patologia , Próstata/cirurgia , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Terapia de Salvação , Análise de Sobrevida , Resultado do Tratamento , Ultrassom Focalizado Transretal de Alta Intensidade
4.
Ann Oncol ; 29(8): 1814-1821, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29945238

RESUMO

Background: Management of localized prostate cancer (PCa) is a major clinical challenge since most of these cancers would not evolve but a majority of patients will still undergo a life-changing radical surgery. Molecular studies have shown that PCa can be classified according to their genomic alterations but none of the published PCa molecular classifications could identify a subtype corresponding to non-evolutive tumours. Materials and methods: Multi-omics molecular profiling was carried out on post-radical prostatectomy material from a cohort of 130 patients with localized PCa. We used unsupervised classification techniques to build a comprehensive classification of prostate tumours based on three molecular levels: DNA copy number, DNA methylation, and mRNA expression. Merged data from our cohort and The Cancer Genome Atlas cohort were used to characterize the resulting tumour subtypes. We measured subtype-associated risks of biochemical relapse using Cox regression models and survival data from five cohorts including the two aforementioned. Results: We describe three PCa molecular subtypes associated with specific molecular characteristics and different clinical outcomes. Particularly, one subtype was strongly associated with the absence of biochemical recurrence. We validated this finding on 746 samples from 5 distinct cohorts (P = 3.41 × 10-8, N = 746 tumour samples), and showed that our subtyping approach outperformed the most popular prognostic molecular signatures to accurately identify a subset of patients with a non-evolutive disease. We provide a set of 36 transcriptomic biomarkers to robustly identify this subtype of non-evolutive cases whose prevalence was estimated to 22% of all localized PCa tumours. Conclusion: At least 20% of patients with localized PCa can be accurately predicted to have a non-evolutive disease on the basis of their molecular subtype. Those patients should not undergo immediate surgery and rather be placed under active surveillance.


Assuntos
Adenocarcinoma/terapia , Biomarcadores Tumorais/genética , Seleção de Pacientes , Neoplasias da Próstata/terapia , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Idoso , Metilação de DNA , Conjuntos de Dados como Assunto , Progressão da Doença , Intervalo Livre de Doença , Epigênese Genética , Estudos de Viabilidade , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Próstata/patologia , Próstata/cirurgia , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/genética , Neoplasias da Próstata/mortalidade , Estudos Retrospectivos , Medição de Risco/métodos , Conduta Expectante
5.
Prog Urol ; 28(8-9): 425-433, 2018 Jun.
Artigo em Francês | MEDLINE | ID: mdl-29789235

RESUMO

OBJECTIVES: To analyze, in patients with prostate cancer (PC) potentially eligible for active surveillance (AS), whether multiparametric-MRI (mp-MRI) predicts presence of clinically significant cancer on radical prostatectomy (RP) specimen. METHODS: We identified 77 men with PC eligible for AS (PSA≤15ng/mL, stage≤T2a, Gleason score≤6, up to 3 positive cores, maximal cancer core length≤5mm) who underwent RP between 01/2008 and 08/2015. All patients had prebiopsy mp-MRI followed by systematic±targeted biopsies. For each patient, the likelihood of the presence of cancer on mp-MRI was assigned using Likert scale (1 to 5). The predictive factors for the presence of significant cancer on RP specimen (Gleason score≥7 and/or tumoral maximal diameter>10mm) were evaluated using logistic regression. RESULTS: Median age was 61 and median PSA was 6.7ng/mL. Overall, 49 (64%) patients had a positive mp-MRI (score≥3). Clinically significant cancer on RP specimen was found in 45 (58%) patients (69% in MRI-positive patients vs 39% in MRI-negative patients). In multivariate analysis, a positive MRI was a predictive factor for the presence of significant cancer on the surgical specimen (OR=3.0; CI95% [1.01-8.88]; P=0.04), as was age (OR=1.17; CI95% [1.05-1.31]; P=0.004) and PSAD (OR=1.10; CI95% [1.01-1.20]; P=0.02). CONCLUSION: Mp-MRI is a useful exam for selecting patients eligible for AS even if the situation remains unclear after prostate biopsies including targeted biopsies. Upon confirmation by further studies, mp-MRI should be considered as an independent criterion before entering an AS program. LEVEL OF EVIDENCE: 4.


Assuntos
Tomada de Decisões , Imageamento por Ressonância Magnética , Próstata/patologia , Prostatectomia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/cirurgia , Conduta Expectante , Idoso , Tomada de Decisões/fisiologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Seleção de Pacientes , Valor Preditivo dos Testes , Prognóstico , Prostatectomia/métodos , Neoplasias da Próstata/patologia
6.
Eur Ann Otorhinolaryngol Head Neck Dis ; 134(3): 155-160, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27988199

RESUMO

OBJECTIVE: Desmoid tumours of the head and neck in children are rare, local invasive and potentially fatal tumours. The purpose of this review is to discuss the management of these tumours in the light of a case series and a review of the literature. MATERIAL AND METHODS: This retrospective study summarised the medical data of children treated for desmoid tumours of the head and neck between 1976 and 2014. RESULTS: Five of the 6 children were treated by radical surgical resection, with positive surgical margins (R1) in 2 cases, followed by recurrence requiring further resection. One child with a very advanced lesion was treated by weekly methotrexate and vinorelbine chemotherapy for 18months, allowing 93% reduction of tumour volume without recurrence. CONCLUSIONS: Desmoid tumours of the head and neck in children are more aggressive than their adult counterparts and are associated with high morbidity and mortality and a high recurrence rate. CT and MRI imaging assessment should preferably be performed before biopsy. External beam radiotherapy must be avoided in children as it is less effective than in adults, and is responsible for long-term cosmetic and functional sequelae and even a risk of second tumours. Treatment is surgical whenever radical resection is possible. In patients presenting an excessive risk of morbidity and mortality, chemotherapy devoid of long-term adverse effects (such as methotrexate in combination with a Vinca alkaloid) can be proposed. Long-term follow-up must be ensured due to the risk of recurrence.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fibromatose Agressiva/patologia , Fibromatose Agressiva/terapia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Fibromatose Agressiva/mortalidade , Fibromatose Agressiva/cirurgia , Seguimentos , França , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Lactente , Recém-Nascido , Masculino , Invasividade Neoplásica , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
7.
Clin Genet ; 92(1): 99-103, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28032338

RESUMO

Steroidogenic factor 1 (encoded by SF1/NR5A1) is a transcription factor with multiple target genes involved in the development and function of multiple steroidogenic and non-steroidogenic tissues. NR5A1 mutations lead to several phenotypes, including sex reversal, spermatogenesis failure, premature ovarian failure and adrenocortical insufficiency. The implication of NR5A1 mutations in spleen development anomalies was recently highlighted. We provide new evidence of this involvement, describing a novel heterozygous non-sense NR5A1 mutation in a 46,XY-DSD with polysplenia female proband and her father, who had hypospadias and asplenia.


Assuntos
Insuficiência Adrenal/genética , Hipospadia/genética , Insuficiência Ovariana Primária/genética , Fator Esteroidogênico 1/genética , Adolescente , Insuficiência Adrenal/patologia , Criança , Feminino , Heterozigoto , Humanos , Hipospadia/patologia , Masculino , Mutação , Insuficiência Ovariana Primária/patologia , Processos de Determinação Sexual/genética , Espermatogênese/genética , Baço/crescimento & desenvolvimento , Baço/patologia
8.
Basic Clin Androl ; 26: 14, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27833751

RESUMO

BACKGROUND: Secreting interstitial cell (Leydig cell) tumors are rare. In adults, the clinical picture and steroid levels are variable. CASE PRESENTATION: This paper presents a case of left testicular tumor, showing azoospermia with normal serum level of total testosterone, collapsed FSH and LH, and high delta4 androstenedione. Histopathological investigation revealed a Leydig cell tumor. TESE allowed spermatozoa extraction and freezing. Testicular histology found hypospermatogenesis and germ-cell aplasia with interstitial fibrosis. Surgical resection of the tumor resulted in normalization of gonadotropins and fall in serum delta4 androstenedione to subnormal levels in the postoperative period confirming that the tumor was secreting delta4 androstenedione. It was hypothesized that high delta4 androstenedione resulted in intra tumoral 17 ß-HSD overtaken by delta4 androstenedione or that 17 ß-HSD activity in the tumor was different from that of normal Leydig cells. Three months after surgery sperm analysis found a complete recovery of spermatogenesis. A spontaneous pregnancy occurred 3 months after surgery and a girl was born. CONCLUSIONS: In this case, the diagnosis of testicular Leydig cell tumor secreting delta4 androstenedione was made in a context of azoospermia.


INTRODUCTION: Les tumeurs testiculaires interstitielles (ou tumeurs testiculaires à cellules de Leydig) à expression endocrine sont rares. Chez l'adulte le tableau clinique et le bilan hormonal sont variables. PRÉSENTATION DU CAS: Cet article présente le cas d'une tumeur testiculaire gauche dans un contexte d'azoospermie. Le bilan hormonal montre des gonadotrophines effondrées, une testostéronémie normale et une delta4 androstenedione augmentée. L'examen anatomopathologique a mis en évidence une tumeur à cellule de Leydig. La TESE a permis l'extraction et la congélation de spermatozoïdes. L'histologie a retrouvé un aspect mixte d'hypospermatogenèse diminuée incomplète et d'aplasie. Dans les suites de l'orchidectomie partielle gauche les taux de gonadotrophines se sont normalisés ainsi que le taux de delta4 androstenedione. L'hypothèse physiopathologique est que l'augmentation de la delta4 androstenedione résulte de la sursaturation de la 17 ß-HSD intra-tumoral ou que l'activité de la 17 ß-HSD intra-tumoral est différente de celle dans les cellules de Leydig normales. Trois mois après la chirurgie, le spermogramme a montré une normalisation des paramètres spermatiques et une grossesse spontanée est survenue permettant la naissance d'une petite fille. CONCLUSION: Dans ce cas clinique, le diagnostic de tumeur testiculaire à cellule de Leydig sécrétant de la delta4 androstenedione a été fait dans un contexte d'azoospermie.

9.
Rev Stomatol Chir Maxillofac Chir Orale ; 117(6): 442-445, 2016 Dec.
Artigo em Francês | MEDLINE | ID: mdl-27519792

RESUMO

INTRODUCTION: Osteoid osteoma is a benign osseous tumor affecting mainly young men. Although it develops essentially in long bones, some cases occurring in face, mainly in mandible, were related. To our knowledge, only one single case was described in zygomatic bone. OBSERVATION: A 71-year-old man consulted for a right periorbital pain evolving since months with night recrudescence. The pain was not relieved by standard analgesics. Clinical examination was strictly normal. CT scan showed a low-density bone lesion surrounded by a peripheral osseocondensation line within the body of the right zygoma with intense uptake at bone scintigraphy. The patient benefited from surgical excision of the lesion. Pain stopped immediately. Histological examination assessed an osteoid osteoma. DISCUSSION: Zygomatic localization and late occurrence are rare concerning osteoid osteomas. Many ways of management have been reported but surgical excision remains the gold standard.


Assuntos
Neoplasias Ósseas/patologia , Osteoma Osteoide/patologia , Zigoma/patologia , Idoso , Neoplasias Ósseas/cirurgia , Dor Facial/etiologia , Dor Facial/patologia , Dor Facial/cirurgia , Humanos , Masculino , Osteoma Osteoide/cirurgia , Tomografia Computadorizada por Raios X , Zigoma/diagnóstico por imagem , Zigoma/cirurgia
10.
Histol Histopathol ; 30(12): 1447-54, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25986951

RESUMO

OBJECTIVE: To delineate the histopathological characteristics of nasal mucosa in refractory chronic rhinosinusitis with nasal polyps (CRSwNP) in order to demonstrate subtypes of nasal polyps and their potential relation with lower airway comorbidity. STUDY DESIGN: Clinical- and pathological-based cross-sectional study Methods: Nasal polyp specimens were prospectively collected from patients with refractory CRSwNP referred to our institution for endoscopic sinus surgery. Oral and topical steroids were stopped 1 month before surgery. The pathological analysis was conducted by 2 independent reviewers with light microscopy on Hematoxylin-Eosin-Saffron stained slides. Each observer fulfilled a standardized protocol with cell count and stromal characterization on the most representative field. Mean grading scores were established. Morphological aspects were compared with the cell distribution and the clinical conditions. RESULTS: Among 36 patients, three subtypes of nasal polyps were depicted: eosinophilic edematous (64%), fibrous (9%) and intermediate with mixed edematous and collagen stromal structure (27%). Basement membrane thickening and seromucous gland hyperplasia were observed in the fibrosis sub-type (p<0.03). Eosinophilic mucosal infiltrate was significantly increased (p=0.026) in patients with concomitant pulmonary disease (n=21). Nasal polyp distribution was not influenced by asthma, allergy, previous surgery and smoking. CONCLUSION: Our 3-subtype classification of refractory CRSwNP in Caucasian population shows a predominant edematous structure whatever the clinical conditions may have been. Eosinophilia as a major factor of adaptive immune response in nasal inflammation is a feature of concomitant pulmonary disease. Further studies concerning mucosal remodelling and outcome assessment after sinus surgery are required to evaluate the impact of our classification on a daily basis.


Assuntos
Pólipos Nasais/classificação , Rinite/classificação , Sinusite/classificação , Membrana Basal/patologia , Contagem de Células , Doença Crônica , Colágeno/metabolismo , Estudos Transversais , Edema/patologia , Eosinófilos/patologia , Feminino , Humanos , Pneumopatias/complicações , Pneumopatias/patologia , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/patologia , Pólipos Nasais/patologia , Estudos Prospectivos , Rinite/patologia , Sinusite/patologia , População Branca
11.
Prog Urol ; 25(3): 157-68, 2015 Mar.
Artigo em Francês | MEDLINE | ID: mdl-25614075

RESUMO

OBJECTIVE: To assess long term biochemical recurrence free survival after radical prostatectomy according to open, laparoscopic and robot-assisted surgical approach and clinicopathological stage. MATERIAL AND METHODS: A cohort study of 1313 consecutive patients treated by radical prostatectomy for localized or locally advanced prostate cancer between 2000 and 2013. Open surgery (63.7%), laparoscopy (10%) and robot-assisted laparoscopy (26.4%) were performed. Biochemical recurrence was defined by PSA>0,1ng/mL. The biochemical recurrence free survival was described by Kaplan Meier method and prognostic factors were analysed by multivariable Cox regression. RESULTS: Median follow-up was 57 months (IQR: 31-90). Ten years biochemical recurrence free survival was 88.5%, 71.6% and 53.5% respectively for low, intermediate and high-risk D'Amico groups. On multivariable analysis, the worse prognostic factor was Gleason score (P<0.001). Positive surgical margins rate was 53% in pT3 tumours and 24% in pT2 tumours (P<0.001). Biochemical recurrence free survival (P=0.06) and positive surgical margins rate (P=0.87) were not statistically different between the three surgical approaches. CONCLUSION: Biochemical recurrence free survival in our study does not differ according to surgical approach and is similar to published series. Ten years biochemical recurrence free survival for high-risk tumours without hormone therapy is 54% justifying the role of surgery in the therapeutic conversations in this group of tumours. LEVEL OF EVIDENCE: 3.


Assuntos
Laparoscopia , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos , Idoso , Estudos de Coortes , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Fatores de Tempo
12.
Prog Urol ; 24(15): 954-65, 2014 Nov.
Artigo em Francês | MEDLINE | ID: mdl-25199727

RESUMO

PURPOSE: Upper tract urothelial carcinomas (UTUC) are rare tumors. Pathologist have a crucial role in establishing the diagnosis and the evaluation of the prognosis of these tumors. MATERIAL AND METHODS: A systematic review of the scientific literature was performed in the Medline database (PubMed) using different associations of the following key words alone or concomittantly: ureter; renal pelvis; urothelial carcinoma; specimen; pathology; histology; classification; grade; stage; prognosis. A particular search was done on the characteristics of the specimen management provided by urologists to pathologists and main prognostic specificities expected in UTUCs. RESULTS: Urinary cytology and biopsies are useful to provide the grade of the tumor according to the WHO classification 2004. The urologist needs to depict the clinical context to the pathologist in order to eliminate differential diagnosis. The main prognostic informations provided by the pathologist from the specimen analysis are the following: stage (TNM 2009), grade (WHO 2004), carcinoma in situ, location within upper tract, multifocality, necrosis, tumor size, lymphovascular invasion, margins and potentially microsatellite status when a HNPCC case is suspected. CONCLUSION: The pathologic analysis of a UTUC specimen needs nowadays to fulfill standardised international criteria of quality. However, specific additional aspects reported in the literature (e.g., lymphovascular invasion) are not systematically depicted.


Assuntos
Carcinoma de Células de Transição/patologia , Neoplasias Urológicas/patologia , Urotélio/patologia , Adenocarcinoma/patologia , Biópsia , Carcinoma Neuroendócrino/patologia , Carcinoma Papilar/patologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células de Transição/genética , Humanos , Imuno-Histoquímica , Metástase Linfática , Instabilidade de Microssatélites , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Neoplasias Urológicas/genética
13.
Oncogene ; 33(17): 2204-14, 2014 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-23708657

RESUMO

Prostate cancer (PCa) is one of the major public health problems in Western countries. Recently, the TMPRSS2:ERG gene fusion, which results in the aberrant expression of the transcription factor ERG, has been shown to be the most common gene rearrangement in PCa. Previous studies have determined the contributions of this fusion in PCa disease initiation and/or progression in vitro and in vivo. In this study on TMPRSS2:ERG regulation in PCa, we used an androgen receptor and TMPRSS2:ERG fusion double-negative PCa cell model: PC3c. In three cell clones with different TMPRSS2:ERG expression levels, ectopic expression of the fusion resulted in significant induction of cell migration and invasion in a dose-dependent manner. In agreement with this phenotype, high-throughput microarray analysis revealed that a set of genes, functionally associated with cell motility and invasiveness, were deregulated in a dose-dependent manner in TMPRSS2:ERG-expressing cells. Importantly, we identified increased MMP9 (Metalloproteinase 9) and PLXNA2 (Plexin A2) expression in TMPRSS2:ERG-positive PCa samples, and their expression levels were significantly correlated with ERG expression in a PCa cohort. In line with these findings, there was evidence that TMPRSS2:ERG directly and positively regulates MMP9 and PLXNA2 expression in PC3c cells. Moreover, PLXNA2 upregulation contributed to TMPRSS2:ERG-mediated enhancements of PC3c cell migration and invasion. Furthermore, and importantly, PLXNA2 expression was upregulated in metastatic PCa tumors compared with localized primary PCa tumors. This study provides novel insights into the role of the TMPRSS2:ERG fusion in PCa metastasis.


Assuntos
Metaloproteinase 9 da Matriz/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas de Fusão Oncogênica/metabolismo , Neoplasias da Próstata/metabolismo , Receptores de Superfície Celular/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Proteínas de Fusão Oncogênica/genética , Fenótipo , Neoplasias da Próstata/patologia , Transcriptoma
16.
Photodiagnosis Photodyn Ther ; 10(3): 296-303, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23993856

RESUMO

OBJECTIVES: To evaluate photodynamic therapy (PDT) using 5-ALA-induced protoporphyrin IX (PPIX) in an in vivo hypoxic tumor model and its monitoring using MRI. MATERIAL AND METHODS: Dunning R3327-AT2 tumors were grafted in the neck of Copenhagen rats. PDT using 150 mg 5-ALA/kg i.v. was performed by focal interstitial illumination of the photosensitized tumor (λ=633 nm; fluence=100 J/cm(2)). MRI at baseline and 2 days after treatment (T1, T2 and dynamic gadolinium enhanced sequences) were performed. Necrosis volumes were determined on post-procedure MRI. Tumors were resected 2 days post-PDT and obtained necrosis was determined histopathologically. Intra-tumoral PPIX distribution was evaluated using confocal microscopy and tissue porphyrin quantification. RESULTS: Twenty rats were treated divided into three groups: continuous (n=7), fractionated illumination (n=7), and a control group receiving only light or only ALA or neither (n=6). Baseline MRI confirmed the hypoxic character of tumors. Necrosis volumes determined on posttreatment MRI were not reproducible and presented with important geometric and volumetric variability. Average necrosis volumes of 0.39 cc (0-0.874 cc) in the continuous group, 0.24 cc (0.107-0.436 cc) in the fractionated group and 0.012 cc (0-0.071 cc) in the control group were observed. Intra-tumoral PPIX distribution was heterogeneous and PPIX quantification revealed low intra-tumoral concentration. CONCLUSION: Necrosis volumes induced by 5-ALA-mediated PDT were highly variable and non reproducible, probably because of lack of intra-tissular oxygen. Photosensitizer was poorly represented inside the tumor and its distribution was heterogeneous. Our study suggests that 5-ALA-mediated PDT might not be the best management option for hypoxic prostatic adenocarcinoma.


Assuntos
Ácido Aminolevulínico/administração & dosagem , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Protoporfirinas/administração & dosagem , Animais , Hipóxia Celular , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada/métodos , Masculino , Ratos , Resultado do Tratamento
17.
World J Urol ; 31(1): 13-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22996759

RESUMO

PURPOSE: To evaluate utility of diffusion-weighted magnetic resonance imaging (DWI) to detect and predict the histological characteristics of upper urinary tract urothelial carcinomas (UTUCs). MATERIALS AND METHODS: We retrospectively evaluated 20 suspicious lesions from 19 patients. MRI study included conventional sequences and DWI with apparent diffusion coefficient (ADC) maps calculated between b = 0 and b = 1,000. ADC values were measured within two different regions of interest (ROI): a small identical ROI placed in the most restrictive part of the tumour and a larger ROI covering two-thirds of the mass surface. The mean ADC values of the tumours were compared with that of normal renal parenchyma using an unpaired Student's t test. Association between ADC values and histological features was tested using non-parametric tests. RESULTS: Overall, 18 tumours were confirmed histologically as UTUCs. DWI failed to detect two cases of UTUCs (one CIS and one small tumour of 5 mm). There was no statistically significant difference in ADC values measured with the small or large ROI (p = 0.134). The mean ADC value of UTUC was significantly lower than that of the normal renal parenchyma (p < 0.001). No statistical association was found between ADC values and pathological features (location, p = 0.35; grade, p = 0.98; muscle-invasive disease, p = 0.76 and locally advanced stage, p = 0.57). CONCLUSION: DWI may be interesting tool for detecting UTUCs regarding the difference of ADC values between the tumours and surrounding healthy tissues. In regard to low frequency of UTUCs, the association of ADC values and histological characteristics need further investigations in a large prospective multi-institutional study.


Assuntos
Carcinoma de Células de Transição/diagnóstico , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Renais/diagnóstico , Neoplasias Ureterais/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pelve Renal , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
18.
Prog Urol ; 22(12): 692-700, 2012 Oct.
Artigo em Francês | MEDLINE | ID: mdl-22999115

RESUMO

OBJECTIVES: To analyze the impact of preoperative clinical data that could influence the undertaking of small renal masses (size<4cm) and to direct patients towards surgery or observance or radiofrequency. PATIENTS AND METHODS: From January 2000 to December 2010, 253 small renal masses were included in a retrospective study. Renal masses less than 3cm were compared to the 3 to 4cm masses. Clinical data, pathological data and follow-up was noted prospectively on the database and we analyzed it according to the treatment done (surgery, radiofrequency or observation). RESULTS: Surgical treatment, radiofrequency and observation were performed for 214 (86.4%), 15 (5.9%), and 24 (9.5%) patients respectively. The treatments of the patients differed in the two groups (<3cm vs. 3-4cm) and the appeal to radiofrequency and observation was more frequent for elder patients (>65years old) and for those whom performance status (ECOG status) greater or equal to 1. Cancer specific survival was not statistically different for the two groups (average: 87.5% after 5years, mean 33months follow-up, P=0.7). Independent risk factors of recurrence were Fuhrman grade, synchronous tumors, noddles invasion and metastatic progression. Positive surgical margins were not a risk factor of recurrence (P=0.6). CONCLUSION: Age and performance status are the two main clinical data, which influence the treatment for patients with small renal masses. Radiofrequency and observation were undertaken more regularly for elder and altered ones. The use of scales as Charlson Index or Lee scale could help to choose more easily according to global morbidity and mortality.


Assuntos
Neoplasias Renais/terapia , Fatores Etários , Carcinoma/mortalidade , Carcinoma/patologia , Carcinoma/terapia , Ablação por Cateter , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Recidiva Local de Neoplasia , Nefrectomia , Estudos Retrospectivos , Conduta Expectante
19.
Rev Epidemiol Sante Publique ; 60(2): 131-9, 2012 Apr.
Artigo em Francês | MEDLINE | ID: mdl-22424751

RESUMO

BACKGROUND: In 2005, following the first cancer plan of the national health authorities, a general cancer registry was established in northern France, in a territory designated as a "zone in proximity to the city of Lille" (ZPL). The aim of the present work was to evaluate the completeness of the registry's first year of incident cancer registration (2005) and to compare the observed cancer incidence in the "ZPL" with the estimated incidence in France. METHODS: Completeness was assessed using the average number of sources per case, the percentage of histological verification and a method of independent case ascertainment (mortality/incidence ratio). A direct standardization on the world population was used to calculate the ZPL/France ratios of standardized incidence rates. Analyses were conducted for 21 cancer sites. RESULTS: In 2005, 3635 cases of invasive cancer were recorded by the registry. The average number of sources per case was 2.7 and histological proof was available for 91.4% of cases. Mortality/incidence ratios showed satisfactory completeness of the data for men for most cancer sites. For women however, for cancer sites for which the number of cases was low, data will have to be confirmed during the subsequent years of observation. A lack of completeness was found for cutaneous melanoma. In men, an overincidence was identified for cancers of lip-mouth-pharynx, larynx, esophagus, lung, liver, bladder, kidney and colon-rectum. In women, an overincidence has been identified for cancers of lip-mouth-pharynx, liver, bladder, colon-rectum, corpus uteri and ovaries. CONCLUSION: The first year of incidence validated at the "Registre général des cancers de Lille et de sa région" shows a completeness of records with regards to studied criteria. The comparison with national data shows an overincidence of cancers related to tobacco and alcohol consumption in the geographical area covered by the registry. The incidence of lip-mouth-pharynx cancer in men is the highest of all French registries.


Assuntos
Neoplasias/epidemiologia , Saúde Pública/estatística & dados numéricos , Sistema de Registros , Feminino , França , Humanos , Incidência , Masculino , Prontuários Médicos
20.
Prog Urol ; 22(2): 93-9, 2012 Feb.
Artigo em Francês | MEDLINE | ID: mdl-22284593

RESUMO

CONTEXT: Clinical and pathological characteristics of renal cell carcinoma (RCC) of patients younger than 40 years old are not well known. The objective of this study was to analyze these characteristics by comparison to a group of patients aged 58 to 62. METHODS: Retrospective study of a group of patients aged less than 40 years old (group 1, n=44) and a group of patients aged 58 to 62 years old (group 2; n=106) treated surgically for a renal mass from January 2000 to July 2009. A comparative analysis of clinical, pathological characteristics and of cancer-specific survival was performed. Specific survival was calculated with the Kaplan-Meier method and compared with the Log-Rank test. Univariate and multivariable analysis were performed to assess and quantify the effect of age on cancer-specific survival. Covariates were gender, age group, tumor size, pT stage, histological sub-type and Fuhrman grade. RESULTS: Clinical and pathological characteristics were similar in both groups (P>0.05) except for histological sub-type (56% of clear cell RCC for group 1 versus 82% for group 2). In the group of patients younger than 40 years, translocation RCC represented 23% of all RCCs. Cancer-specific survival at five years was similar in both groups (80% and 76% for group 1 and 2 respectively, P>0.58). Fuhrman grade was the only independent prognostic factor of cancer-specific survival (P=0.001). CONCLUSION: Patients younger than 40 years were more likely to have a translocation RCC than their older counterparts for who clear cell RCC represented the main histological sub-type. Cancer-specific survival was similar between both groups. Only a systematic specific immunostaining for TFE3 or TFEB will allow to assess the exact incidence and prognosis of this entity.


Assuntos
Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/diagnóstico , Adolescente , Adulto , Fatores Etários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
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