Le carcinome épidermoïde du pénis: évaluation clinique et thérapeutique de la tumeur primitive

Squamous cell carcinoma of the penis is a rare tumor. According to the TNM classification (UICC 2009), a precise physical examination, sometimes matched with imaging, is required for the staging of penile carcinoma. Physical examination of the primary tumor, which allows for an evaluation of the tumor’s morphology and physical characteristics, is essential in particular, in order to detect an infiltration of albuginea of the corpus cavernosa and/or an invasion of the urethra. When physical examination appears to be insufficient, ultrasound and especially MRI with intracavernosal injection of prostaglandin E1 are useful, particularly in order to improve the selection of patients eligible for conservative treatment. When tumors have evolved, amputation techniques have proven to be the best option. However, tumors localized only on the glans and prepuce imperatively require the use of conservative techniques, either surgery or radiotherapy.     

FGF2 mediates DNA repair in epidermoid carcinoma cells exposed to ionizing radiation

Abstract Purpose: Fibroblast growth factor 2 (FGF2) is a well-known survival factor. However, its role in DNA repair is poorly documented. The present study was designed to investigate in epidermoid carcinoma cells the potential role of FGF2 in DNA repair. Materials and methods: The side population (SP) with cancer stem cell-like properties and the main population (MP) were isolated from human A431 squamous carcinoma cells. Radiation-induced DNA damage and repair were assessed using the alkaline comet assay. FGF2 expression was quantified by enzyme linked immunosorbent assay (ELISA). Results: SP cells exhibited rapid repair of radiation induced DNA damage and a high constitutive level of nuclear FGF2. Blocking FGF2 signaling abrogated the rapid DNA repair. In contrast, in MP cells, a slower repair of damage was associated with low basal expression of FGF2. Moreover, the addition of exogenous FGF2 accelerated DNA repair in MP cells. When irradiated, SP cells secreted FGF2, whereas MP cells did not. Conclusions: FGF2 was found to mediate DNA repair in epidermoid carcinoma cells. We postulate that carcinoma stem cells would be intrinsically primed to rapidly repair DNA damage by a high constitutive level of nuclear FGF2. In contrast, the main population with a low FGF2 content exhibits a lower repair rate which can be increased by exogenous FGF2.     

Detection of Alzheimer's disease in general medicine: preliminary results of a Sentinelles general practitioner's network survey

CONTEXT: The availability of cholinesterase inhibitors has reinforced the need for early detection of Alzheimer's disease in which the general practitioner plays a key role. This study seeks to appraise the diagnostic procedures of Alzheimer's disease in general medicine. METHOD: A postal survey of 1176 general practitioners belonging to the French Sentinelles network. RESULTS: Response rate: 43%. The surveyed doctors have seen 1.5 new cases in 2002, and were in charge of the follow-up of four patients. Reasons leading to consultation were: memory impairment (84%), memory impairment together with decline in daily functioning and disorientation (42%). Seventy-six per cent of the Sentinelles used the MMSE, 91% referred the patient to a specialist. Fifty-four per cent announced the diagnosis to the patient; 94% to the family. Twenty-six per cent of the surveyed doctors systematically used the DSM-IV criteria and 77% considered early diagnosis valuable. CONCLUSION: The results of this survey show that Alzheimer's disease is still under-diagnosed in general medicine in spite of the general practitioner's favourable opinion as to early diagnosis of the disease. Compared to his European colleagues, French general practitioner's attitude is characterized by frequent referral to a specialist service, follow-up of diagnostic criteria and frequency of disclosure of diagnosis to the family.     

Molecular characterization of pancreatic serous microcystic adenomas: evidence for a tumor suppressor gene on chromosome 10q

Pancreatic serous microcystic adenomas (SCAs) are rare, benign tumors with a striking female preference. Virtually no information is available about chromosomal or genetic anomalies in this disease. We performed extensive molecular characterization of 21 cases of formalin-fixed, paraffin-embedded sporadic SCAs consisting in genome-wide allelic loss analysis with 79 microsatellite markers covering all 22 autosomes, assessment of microsatellite instability, and mutational analysis of the VHL, K-ras, and p53 genes in nine cases for which frozen tissue was available. Although no case showed microsatellite instability of the type seen in mismatch repair-deficient tumors, a relatively low fractional allelic loss of 0.08 was found. Losses on chromosome 10q were the most frequent event in SCAs (50% of cases), followed by allelic losses on chromosome 3p (40% of cases). Moderately frequent losses (>25% of cases) were found on chromosomes 1q, 2q, and 7q. The VHL gene, located on chromosome 3p, had somatic inactivating mutations in two of nine cases (22%), whereas no mutations were found in either K-ras or p53, in agreement with the finding that all 21 cases stained negative for p53 by immunohistochemistry. Our study indicates that the involvement of chromosomal arms 10q and 3p is characteristic of SCAs and that the VHL gene is involved in a subset of sporadic cases.     

Apolipoprotein E phenotypes in demented and cognitively impaired patients with and without cerebrovascular disease

Controversy exists regarding the apolipoprotein E (ApoE) epsilon4 allele association with vascular dementia (VaD), ranging from increased epsilon4 frequency, similar to that found for Alzheimer's disease (AD), to no association between the epsilon4 allele and VaD. To clarify further the relationship between ApoE alleles polymorphism and cerebrovascular disease (CVD) in demented and cognitively impaired patients, we examined the ApoE phenotypes in a sample of 280 patients: 155 with AD, 21 with VaD, 32 with mixed dementia (MD), 45 with mild cognitive impairment (MCI) but without CVD, and 27 in which vascular disease was the most probable cause of cognitive decline [vascular mild cognitive impairment (VMCI)]. Our results show that the frequency of the ApoE epsilon4 allele in patients over 70 years old with clinically diagnosed VaD and VMCI does not differ significantly from that of controls. In contrast, ApoE epsilon4 allele-bearing individuals had greater risk of having late-onset AD (OR = 8.8; 95% CI 3.7-21.0), or non-vascular cognitive impairment (OR = 7.0; 95% CI 2.5-19.0).     

Prognostic Value of the Lymphovascular Invasion in High-Grade Stage pT1 Bladder Cancer

PurposeHigh-grade (HG) stage pT1 bladder cancers have the highest recurrence and progression rates of all non–muscle-invasive bladder cancers. Some prognostic factors for recurrence and progression have been identified: multifocal HG pT1, concomitant carcinome in situ, tumor diameter >3 cm, infiltration of the deep lamina propria, and persistence of pT1 tumor on a second transurethral resection of the bladder. The objective of this study was to determine whether the presence of lymphovascular invasion (LVI) is also a prognostic factor that must be taken into account.Materials and MethodsThis retrospective study was performed with 108 patients with HG stage pT1 bladder cancer: 89 patients were treated conservatively (transurethral resection of the bladder plus bacille Calmette-Guérin therapy), and 19 patients underwent early cystectomy. The mean (SD) follow-up was 47.8 ± 41.2 months. Classic prognostic factors and LVI were analyzed in terms of overall survival, specific survival, recurrence-free survival, and progression-free survival.ResultsThirty-six percent of patients had LVI on the chips of the first transurethral resection of the bladder. Five-year overall survival and specific survival were 40% and 75%, respectively. Multivariate analysis of risk factors showed a significant reduction of overall survival in the presence of LVI (P = .007). The presence of LVI was also a factor of poor prognosis in the case of delayed cystectomy (P = .010) but not in the case of early cystectomy.ConclusionsIdentification of LVI on the first resection of a HG stage pT1 bladder cancer is a significant prognostic factor for overall survival.