Thérapie focale du cancer de la prostate: rationnel, résultats et perspectives [Focal therapy in prostate cancer: rationale, results and perspectives].

Focal therapy is a novel treatment strategy in prostate cancer aiming to treat only the area of the gland harbouring clinically significant disease. The overall objective is to maintain the oncological benefit of active treatment while minimising treatment-related morbidity. Leading centres are currently evaluating various minimally invasive technologies in a rigorous manner. Oncological and functional results in mid-term are encouraging with low rate of urinary incontinence and erectile dysfunction. However, the oncological outcome needs to be evaluated in the long-term in the light of the prolonged natural history of the disease.

Qualité de vie avant et 6 mois après angioplastie coronaire transluminale percutanée

Summary Background: Percutaneous transluminal coronary angioplasty (PTCA) is an effective and minimally invasive treatment for angina pectoris, but its impact on patient's quality of life has not been extensively studied with specific questionnaires. Methods: Over a 6 month period, ail patients suffering from angina, planned for elective PTCA, and available for a 6 months follow-up, were included in the study. The specific "Seattle Angina Questionnaire" (SAQ) was administered the day before and 6 months after PTCA. The decision to implant a coronary stent was left to the cardiologist in charge of the procedure. Results: 112 patients were initially included (39 PTCA and 62 PTCA with stent im-plantation). There was no difference in gender, age, angina severity and type of coronary lesion between the two groups. Follow-up at 6 months was available for 101 patients (90%). Quality of life was dramatically improved in 4 of 5 SAQ dimensions (physical limitation, angina stability, angina frequency, disease perception, p <0.001). Only treatment satisfaction was worse at follow-up then before the procedure (p = 0.03), in particular satisfaction with received explanations, belief that everything possible was donc to treat angina, and global satisfaction. A stent implantation had no impact on these results. Conclusions: PTCA for ischaemic cardiac disease improved not only physical abilities, but also quality of life dramatically. Dissatisfaction with treatment could be corrected with better information during follow-up. SAQ is easy to use and could be selected as a monitoring instrument. Résumé Contexte: Le traitement de l'angine de poitrine par angioplastie coronaire transluminale per-cutanée (PTCA) est efficace et peu invasif, mais son impact sur la qualité de vie des patients a été relativement peu étudié avec des questionnaires spécifiques. Méthode: Durant 6 mois, tous les patients souffrant d'une angine de poitrine pour qui une PTCA élective était envisagée, et qui étaient disponibles pour un suivi à 6 mois ont été inclus dans l'étude. Le questionnaire spécifique «Seattle Angina Questionnaire» (SAQ) a été utilisé le jour avant et 6 mois après la procédure. La décision d'implanter un stent était laissée au cardiologue au moment de la procédure. Résultats: 112 patients ont été initialement inclus. Trente-neuf d'entre eux ont été traités avec une PTCA, et 62 avec une PTCA et l'implantation de stent. Il n'y avait pas de différence de sexe, d'âge, de sévérité de l'angine de poitrine, et de type de lésion coronaire entre les deux groupes. Un suivi à 6 mois a été possible pour 101 patients (90% de la cohorte initiale). La qualité de vie a été améliorée de façon spectaculaire dans 4 des 5 dimensions du SAQ (limites physiques, stabilité de l'angor, fréquence de l'angor, perception de l'angor, p <0,001). Seule, la satisfaction avec le traitement était pire lors du suivi qu'avant l'intervention (p = 0,03), en particulier la satisfaction avec les explications reçues, la conviction que tous les moyens avaient été utilisés pour le traitement, et la satisfaction globale. L'implantation d'un stent n'a eu aucun impact sur ces résultats.

Oral flurbiprofen metabolic ratio assessment using a single-point dried blood spot.

We investigated whether a single blood measurement using the minimally invasive technique of a finger prick to draw a blood sample of 5 µl (to yield a dried blood spot (DBS)) is suitable for the assessment of flurbiprofen (FLB) metabolic ratio (MR). Ten healthy volunteers who had been genotyped for CYP2C9 were recruited as subjects. They received FLB alone in session 1 and FLB with fluconazole in session 2. In session 3, the subjects were pretreated for 4 days with rifampicin and received FLB with the last dose of rifampicin on day 5. Plasma and DBS samples were obtained between 0 and 8 h after FLB administration, and urine was collected during the 8 h after administration. The pharmacokinetic profiles of the drugs were comparable in DBS and plasma. FLB's apparent clearance values decreased by 35% in plasma and DBS during session 2 and increased by 75% in plasma and by 30% in DBS during session 3. Good correlations were observed between MRs calculated from urine, plasma, and DBS samples.

Laser treatment of 13 benign oral vascular lesions by three different surgical techniques

Objectives: Benign Oral Vascular Lesions (BOVLs) are a group of vascular diseases characterized by congenital, inflammatory or neoplastic vascular dilations clinically evidenced as more or less wide masses of commonly dark bluish color. If traumatized BOVLs are characterized by a great risk of hemorrhage and their treatment usually requires great caution to prevent massive bleeding. In the last decades lasers have dramatically changed the way of treatment of BOVLs permitting the application of even peculiar techniques that gave interesting advantages in their management reducing hemorrhage risks. The aim of this study was to evaluate the capabilities and disadvantages of three laser assisted techniques in the management of BOVLs. Study design: In this study 13 BOVLs were treated by three different laser techniques: the traditional excisional biopsy (EB), and two less invasive techniques, the transmucosal thermocoagulation (TMT) and the intralesional photocoagulation (ILP). Two different laser devices were adopted in the study: a KTP laser (DEKA, Florence, Italy, 532nm) and a GaAlAs laser (Laser Innovation, Castelgandolfo, Italy, 808nm) selected since their great effectiveness on hemoglobin. Results: In each case, lasers permitted safe treatments of BOVLs without hemorrhages, both during the intervention and in the post-operative period. The minimally invasive techniques (TMT and ILP) permitted even the safe resolution of big lesions without tissue loss. Conclusions: Laser devices confirm to be the gold standard in BOVLs treatment, permitting even the introduction of minimal invasive surgery principles and reducing the risks of hemorrhage typical of these neoplasms. As usual in laser surgery, it is necessary a clear knowledge of the devices and of the laser-tissue interaction to optimize the results reducing risks and disadvantages

Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque.

High levels of HIV-1 replication during the chronic phase of infection usually correlate with rapid progression to severe immunodeficiency. However, a minority of highly viremic individuals remains asymptomatic and maintains high CD4+ T cell counts. This tolerant profile is poorly understood and reminiscent of the widely studied nonprogressive disease model of SIV infection in natural hosts. Here, we identify transcriptome differences between rapid progressors (RPs) and viremic nonprogressors (VNPs) and highlight several genes relevant for the understanding of HIV-1-induced immunosuppression. RPs were characterized by a specific transcriptome profile of CD4+ and CD8+ T cells similar to that observed in pathogenic SIV-infected rhesus macaques. In contrast, VNPs exhibited lower expression of interferon-stimulated genes and shared a common gene regulation profile with nonpathogenic SIV-infected sooty mangabeys. A short list of genes associated with VNP, including CASP1, CD38, LAG3, TNFSF13B, SOCS1, and EEF1D, showed significant correlation with time to disease progression when evaluated in an independent set of CD4+ T cell expression data. This work characterizes 2 minimally studied clinical patterns of progression to AIDS, whose analysis may inform our understanding of HIV pathogenesis.

Suprachoroidal electrotransfer: a nonviral gene delivery method to transfect the choroid and the retina without detaching the retina.

Photoreceptors and retinal pigment epithelial cells (RPE) targeting remains challenging in ocular gene therapy. Viral gene transfer, the only method having reached clinical evaluation, still raises safety concerns when administered via subretinal injections. We have developed a novel transfection method in the adult rat, called suprachoroidal electrotransfer (ET), combining the administration of nonviral plasmid DNA into the suprachoroidal space with the application of an electrical field. Optimization of injection, electrical parameters and external electrodes geometry using a reporter plasmid, resulted in a large area of transfected tissues. Not only choroidal cells but also RPE, and potentially photoreceptors, were efficiently transduced for at least a month when using a cytomegalovirus (CMV) promoter. No ocular complications were recorded by angiographic, electroretinographic, and histological analyses, demonstrating that under selected conditions the procedure is devoid of side effects on the retina or the vasculature integrity. Moreover, a significant inhibition of laser induced-choroidal neovascularization (CNV) was achieved 15 days after transfection of a soluble vascular endothelial growth factor receptor-1 (sFlt-1)-encoding plasmid. This is the first nonviral gene transfer technique that is efficient for RPE targeting without inducing retinal detachment. This novel minimally invasive nonviral gene therapy method may open new prospects for human retinal therapies.

The histone-interacting domain of nuclear factor I activates simian virus 40 DNA replication in vivo.

Efficient initiation of SV40 DNA replication requires transcription factors that bind auxiliary sequences flanking the minimally required origin. To evaluate the possibility that transcription factors may activate SV40 replication by acting on the chromatin structure of the origin, we used an in vivo replication system in which we targeted GAL4 fusion proteins to the minimally required origin. We found that the proline-rich transcriptional activation domain of nuclear factor I (NF-I), which has been previously shown to interact with histone H3, specifically activates replication. Evaluation of a series of deletion and point mutants of NF-I indicates that the H3-binding domain and the replication activity coincide perfectly. Assays with other transcription factors, such as Sp1, confirmed the correlation between the interaction with H3 and the activation of replication. These findings imply that transcription factors such as NF-I can activate SV40 replication via direct interaction with chromatin components, thereby contributing to the relief of nucleosomal repression at the SV40 origin.

No major impact of skin aging on the response of skin blood flow to a submaximal local thermal stimulus.

OBJECTIVE: This study was undertaken to investigate how aging affects dermal microvascular reactivity in skin areas differentially exposed to sunlight, and therefore to different degrees of photoaging. METHODS: We assessed, in young (18-30 years, n = 13) and aged males (≥60 years, n = 13), the thigh, forearm, and forehead's skin vasodilatory response to local heating (LTH) with a LDI. In each subject and at each location, local Tskin was brought from 34°C (baseline) to 39 or 41°C for 30 minutes, to effect submaximal vasodilation, with maximal vasodilation then elicited by further heating to 44°C. RESULTS: The CVCs evaluated at baseline and after maximal vasodilation (CVCmax ) were higher in the forehead than in the two other anatomical locations. On all locations, CVCmax decreased with age but less markedly in the forehead compared to the two other locations. When expressed in % of CVCmax , the plateau increase of CVCs in response to submaximal temperatures (39 and 41°C) did not vary with age, and minimally so with location. CONCLUSION: Skin aging, whether intrinsic or combined with photoaging, reduces the maximal vasodilatory capacity of the dermal microcirculation, but not its reactivity to local heating.

Prevention and management of potential adverse events during transapical aortic valve replacement.

BACKGROUND AND AIM OF THE STUDY: Transapical transcatheter aortic valve replacement (TAVR) is a new minimally invasive technique with a known risk of unexpected intra-procedural complications. Nevertheless, the clinical results are good and the limited amount of procedural adverse events confirms the usefulness of a synergistic surgical/anesthesiological management in case of unexpected emergencies. METHODS: A review was made of the authors' four-year database and other available literature to identify major and minor intra-procedural complications occurring during transapical TAVR procedures. All implants were performed under general anesthesia with a balloon-expandable Edwards Sapien stent-valve, and followed international guidelines on indications and techniques. RESULTS: Procedural success rates ranged between 94% and 100%. Life-threatening apical bleeding occurred very rarely (0-5%), and its incidence decreased after the first series of implants. Stent-valve embolization was also rare, with a global incidence ranging from 0-2%, with evidence of improvement after the learning curve. Rates of valve malpositioning ranged from 0% to < 3%, whereas the risk of coronary obstruction ranged from 0% to 3.5%. Aortic root rupture and dissection were dramatic events reported in 0-2% of transapical cases. Stent-valve malfunction was rarely reported (1-2%), whereas the valve-in-valve bailout procedure for malpositioning, malfunctioning or severe paravalvular leak was reported in about 1.0-3.5% of cases. Sudden hemodynamic management and bailout procedures such as valve-in-valve rescue or cannulation for cardiopulmonary bypass were more effective when planned during the preoperative phase. CONCLUSION: Despite attempts to avoid pitfalls, complications during transapical aortic valve procedures still occur. Preoperative strategic planning, including hemodynamic status management, alternative cannulation sites and bailout procedures, are highly recommended, particularly during the learning curve of this technique.

The role of laparoscopic biopsies in lumbar spondylodiscitis.

Infection of an intervertebral disk is a serious condition. Diagnosis often is elusive and difficult. It is imperative to obtain appropriate microbiological specimens before initiation of treatment. The authors describe a 51-year-old woman with lumbar spondylodiscitis that was because of infection after the placement of an epidural catheter for postoperative analgesia. A spinal magnetic resonance imaging confirmed the diagnosis, but computed tomography-guided fine needle biopsy did not provide adequate material for a microbiologic diagnosis. Laparoscopic biopsies of the involved disk provided good specimens and a diagnosis of Propionibacterium acnes infection. The authors believe that this minimally invasive procedure should be performed when computed tomography-guided fine needle biopsy does not provide a microbiologic diagnosis in spondylodiscitis.

A new clinical test in diagnosing quadriceps tendon rupture.

INTRODUCTION: Extensor mechanism ruptures might be easily overlooked and misdiagnosed, and delayed diagnosis of quadriceps tendon rupture is frequent. However, the literature recommends early surgical repair within 72 h. PATIENTS AND METHODS: This paper describes a new simple clinical diagnostic test that directly evaluates the integrity of the distal 5 cm of the quadriceps tendon itself. It consists of inserting a needle in the tendon, proximal to the suspected rupture and mobilising the knee joint. RESULTS: The suspected ruptured quadriceps tendons with a positive 'needle' diagnostic test were confirmed intra-operatively. CONCLUSIONS: This minimally invasive and easily available technique should be considered in the diagnostic work-up and treatment planning of patients with suspected tears of the quadriceps tendon.

A methodology to estimate the potential to move inpatient to one day surgery.

BACKGROUND: The proportion of surgery performed as a day case varies greatly between countries. Low rates suggest a large growth potential in many countries. Measuring the potential development of one day surgery should be grounded on a comprehensive list of eligible procedures, based on a priori criteria, independent of local practices. We propose an algorithmic method, using only routinely available hospital data to identify surgical hospitalizations that could have been performed as one day treatment. METHODS: Moving inpatient surgery to one day surgery was considered feasible if at least one surgical intervention was eligible for one day surgery and if none of the following criteria were present: intervention or affection requiring an inpatient stay, patient transferred or died, and length of stay greater than four days. The eligibility of a procedure to be treated as a day case was mainly established on three a priori criteria: surgical access (endoscopic or not), the invasiveness of the procedure and the size of the operated organ. Few overrides of these criteria occurred when procedures were associated with risk of immediate complications, slow physiological recovery or pain treatment requiring hospital infrastructure. The algorithm was applied to a random sample of one million inpatient US stays and more than 600 thousand Swiss inpatient stays, in the year 2002. RESULTS: The validity of our method was demonstrated by the few discrepancies between the a priori criteria based list of eligible procedures, and a state list used for reimbursement purposes, the low proportion of hospitalizations eligible for one day care found in the US sample (4.9 versus 19.4% in the Swiss sample), and the distribution of the elective procedures found eligible in Swiss hospitals, well supported by the literature. There were large variations of the proportion of candidates for one day surgery among elective surgical hospitalizations between Swiss hospitals (3 to 45.3%). CONCLUSION: The proposed approach allows the monitoring of the proportion of inpatient stay candidates for one day surgery. It could be used for infrastructure planning, resources negotiation and the surveillance of appropriate resource utilization.

Buccal swabs allow efficient and reliable microsatellite genotyping in amphibians

Buccal swabs have recently been used as a minimally invasive sampling method in genetic studies of wild populations, including amphibian species. Yet it is not known to date what is the level of reliability for microsatellite genotypes obtained using such samples. Allelic dropout and false alleles may affect the genotyping derived from buccal samples. Here we quantified the success of microsatellite amplification and the rates of genotyping errors using buccal swabs in two amphibian species, the Alpine newt Triturus alpestris and the Green tree frog Hyla arborea, and we estimated two important parameters for downstream analyses, namely the number of repetitions required to achieve typing reliability and the probability of identity among genotypes. Amplification success was high, and only one locus tested required two to three repetitions to achieve reliable genotypes, showing that buccal swabbing is a very efficient approach allowing good quality DNA retrieval. This sampling method which allows avoiding the controversial toe-clipping will likely prove very useful in the context of amphibian conservation.

Neurotrophic activity of human adipose stem cells isolated from deep and superficial layers of abdominal fat.

New approaches to the clinical treatment of traumatic nerve injuries may one day utilize stem cells to enhance nerve regeneration. Adipose-derived stem cells (ASC) are found in abundant quantities and can be harvested by minimally invasive procedures that should facilitate their use in such regenerative applications. We have analyzed the properties of human ASC isolated from the deep and superficial layers of abdominal fat tissue obtained during abdominoplasty procedures. Cells from the superficial layer proliferate significantly faster than those from the deep layer. In both the deep and superficial layers, ASC express the pluripotent stem cell markers oct4 and nanog and also the stro-1 cell surface antigen. Superficial layer ASC induce the significantly enhanced outgrowth of neurite-like processes from neuronal cell lines when compared with that of deep layer cells. However, analysis by reverse transcription with the polymerase chain reaction and by enzyme-linked immunosorbent assay has revealed that ASC isolated from both layers express similar levels of the following neurotrophic factors: nerve growth factor, brain-derived neurotrophic factor and glial-derived neurotrophic factor. Thus, human ASC show promising potential for the treatment of traumatic nerve injuries. In particular, superficial layer ASC warrant further analysis of their neurotrophic molecules.