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Biomedical subjects

René Yiou

Publications and source records attributed to René Yiou.

At least 19 recordsLinked to original sources

Saturation biopsy protocol enhances prediction of pT3 and surgical margin status on prostatectomy specimen.

A 21-samples saturation biopsy procedure (SBP) was developed in order to improve prostate cancer detection rate. Out of 650 patients who underwent this protocol, 150 had a clinically localized prostate cancer and underwent a radical prostatectomy. The number of cores positive for tumor was assessed in the SBP, and also in the sextant component of the SBP (SC) and in the non-sextant component of the SBP (NSC). Numbers of cores positive for tumor on SBP, SC, and NSC were significantly higher in pT3 group versus pT2 (P < 0.001 each) and in positive surgical margins (PSM) group versus no PSM (P < 0.001 each). When comparing area under the curve obtained from SBP with those obtained from NSC and SC, the SBP showed higher accuracy than the NSC and the SC for the prediction of pT3 and PSM. On multivariate analyses, SC and NSC were independent predictors of pT3 and PSM on radical prostatectomy.

Aged↗

Applying problem-based learning to the teaching of anatomy: the example of Harvard Medical School.

The introduction of problem-based learning techniques into the teaching of anatomy has been subject to great controversies. This paper debates the rationale behind this concept using the example of the curriculum of Harvard Medical School in which problem-based learning techniques have been used during the past 20 years. The anatomy curriculum is covered during the eight first weeks of the medical studies, and is an original combination of discussions of clinical cases in small groups, and work in gross anatomy, histology and radiology laboratories. The lectures are reduced to the minimum and emphasize general concepts. In this setting, the learning of anatomy is mostly led by students who have prepared for the different laboratory sessions and tutorials. The implementation of problem-based learning to the teaching of anatomy requires a close follow-up of each student with regular feedbacks on his work. Tutorials must be considered as a cornerstone between lectures and work in laboratories. Traditional aspects of the teaching of anatomy, such as work in dissection laboratories, are given an important role as they are aimed to clear-up misunderstood points. Further studies are required to compare at the long term the level of medical students who learned anatomy in a problem based versus traditional learning setting.

Anatomy↗

Simulation training in video-assisted urologic surgery.

The current system of surgical education is facing many challenges in terms of time efficiency, costs, and patient safety. Training using simulation is an emerging area, mostly based on the experience of other high-risk professions like aviation. The goal of simulation-based training in surgery is to develop not only technical but team skills. This learning environment is stress-free and safe, allows standardization and tailoring of training, and also objectively evaluate performances. The development of simulation training is straightforward in endourology, since these procedures are video-assisted and the low degree of freedom of the instruments is easily replicated. On the other hand, these interventions necessitate a long learning curve, training in the operative room is especially costly and risky. Many models are already in use or under development in all fields of video-assisted urologic surgery: ureteroscopy, percutaneous surgery, transurethral resection of the prostate, and laparoscopy. Although bench models are essential, simulation increasingly benefits from the achievements and development of computer technology. Still in its infancy, virtual reality simulation will certainly belong to tomorrow's teaching tools.

Clinical Competence↗

The striated urethral sphincter of the pig shows morphological and functional characteristics essential for the evaluation of treatments for sphincter insufficiency.

PURPOSE: New treatments are currently under investigation for intrinsic sphincter insufficiency. However, animal models in which to study the resting urethral tone generated by the striated urethral sphincter are still lacking. We describe the striated urethral sphincter in the pig. We investigated its participation in resting urethral tone with the aim of developing new tools for evaluating therapies for sphincter insufficiency. MATERIALS AND METHODS: A total of 15 female pigs were used in this study. Anatomy of the striated urethral sphincter was described via transpubic and endoscopic approaches. Participation of the striated urethral sphincter in resting urethral tone was assessed by analysis of urethral pressure profilometry (maximum urethral closure pressure, functional urethral length and area under the curve) before and after curare injection or by destruction of the striated urethral sphincter by endoscopic electrocautery. Serial urethral cross sections were immunostained for slow/fast myosin and digitalized for 3-dimensional reconstructions to determine striated urethral sphincter volume. RESULTS: The striated urethral sphincter was Omega-shaped and it encircled the distal third of the urethra. A mean peak intraurethral pressure +/- SEM of 58.9 +/- 13.4 cm H(2)O was noted in front of the striated urethral sphincter. Curare injection and endoscopic injury decreased maximum urethral closure pressure by 48.4% and 51.1%, functional urethral length by 10.3% and 15.3%, and area under the curve by 47% and 64%, respectively. The striated urethral sphincter consisted of 52% slow and 48% fast myofibers. Its mean volume was 0.87 cm. CONCLUSIONS: The striated urethral sphincter of the female pig shows the morphological and functional features of a tonic muscle. Methods of measuring resting urethral tone generated by the striated urethral sphincter represent original tools for evaluating therapies for intrinsic sphincter insufficiency.

Actins↗

Failure of differentiation into mature myotubes by muscle precursor cells with the side-population phenotype after injection into irreversibly damaged striated urethral sphincter.

We previously showed that the injection of a heterogeneous population of muscle precursor cells (MPCs) into striated urethral sphincter irreversibly damaged by electrocoagulation results in the formation of functional myotubes. To gain further insights into the role played by the different types of MPCs, we elected to sort the MPCs by Hoechst 33342 staining/fluorescence-activated cell-sorter analysis before injection. We found that the side population (SP) cells (muscle stem cells) injected in isolation survived, whereas the main population (MP) cells did not. However, the SP cells failed to differentiate into mature myotubes, as observed previously with unfractionated MPCs containing both SP and MP cells. This result suggests that interactions between SP and MP cells are required for the formation of myotubes in a nonregenerating muscle. In the setting of sphincter insufficiency, injection of MPCs at different stages of maturation may be a better option than purified muscle stem cells.

Animals↗

Comparison of early oncologic results of laparoscopic radical prostatectomy by extraperitoneal versus transperitoneal approach.

PURPOSE: Compare the early oncological results of laparoscopic radical prostatectomy performed by either an extraperitoneal or a transperitoneal approach. METHODS: 330 consecutive men underwent laparoscopic radical prostatectomy for localized prostate cancer, the first 165 by transperitoneal approach, and the last 165 by extraperitoneal approach. Clinical stage, serum PSA, Gleason score of biopsy were recorded, as well as operating time, surgical and medical complications, blood loss, length of hospital stay and catheterization time. The weight of the specimen, pathological stage (1997 TNM classification) and status of the surgical margins were noted. The Fisher test as well as the chi2-test were used for statistical analysis. Differences were considered significant when p < 0.05. RESULTS: There were no significant differences between the two groups in terms of preoperative characteristics except for Gleason score of the biopsies which was higher in the extraperitoneal group (p < 0.0001). The operating time was longer with the transperitoneal approach (248.5 min vs. 220.0 min, p < 0.0001). There was no difference in transfusion rate (1.2% vs. 5.4%, transperitoneal vs. extraperitoneal, respectively, p = 0.6). There was no difference in hospital stay, medical and surgical complications. Respectively, in the transperitoneal and extraperitoneal groups, there were 108 and 88 pT2 tumors. There were no differences in terms of positive surgical margins between the two groups, 23% and 29.7% (p = 0.21) overall, 13.0% and 17.0% (p = 0.42) in pT2 tumors and 43.6% and 44.7% (p = 0.99) in pT3 tumors. CONCLUSIONS: Extraperitoneal approach offers the same early oncological results as transperitoneal approach with a shorter operative time.

Humans↗

Docetaxel and zoledronic acid in patients with metastatic hormone-refractory prostate cancer.

OBJECTIVE: To evaluate the safety and efficacy of combined docetaxel-zoledronic acid treatment in patients with metastatic hormone-refractory prostate cancer (HRPC), as bisphosphonates are reported have a synergistic antitumoral effect when combined with taxanes. PATIENTS AND METHODS: Between January 2001 and June 2003, 14 patients with HRPC were treated; their mean (range) age was 71 (57-86) years and mean prostate-specific antigen (PSA) level 202 (6-489) ng/mL. Five patients had had previous chemotherapy (cyclophosphamide in two, mitoxantrone-prednisolone in three). The response criteria were the Karnofsky performance status, a positive response in mean daily analgesic consumption (defined as a decrease by more than half), decreased serum PSA (by more than half) at 8 weeks, blood transfusion, bone scan at 6 months, skeletal-related events and survival. RESULTS: Patients received a mean (range) of 7.3 (6-10) cycles of therapy; there was no reported drug-related toxicity and all patients stayed at home for their treatment. Only three patients required a blood transfusion and no bone fractures were reported. At 2 months, six patients requiring analgesic drugs decreased their consumption by more than half (anti-inflammatory, paracetamol, narcotics) and eight had a reduction in PSA by more than half; of these eight with a PSA response at 2 months, six had biochemical progression with a mean delay of 6.2 (3-11) months. At 6 months, five patients had disease progression on bone scan. Nine patients had chemo-naïve hormone-refractory prostate cancer; three had biochemical progression at 2 months and two of these had progression on their bone scan. Two patients died at 7 and 15 months of follow-up; the mean follow-up was 10.2 (6-15) months. Using Kaplan-Meier plots, biochemical progression-free survivals were five of 14 at 6 months and two of 14 at 12 months; overall survival was 12 of 14 at 6 and 12 months. CONCLUSION: Docetaxel-zoledronic acid therapy is safe and decreased the serum PSA by more than half at 2 months in more than half the patients. Prospective randomized trials are needed to assess this new approach.

Aged↗

[Cell therapy for urethral sphincter incompetence by muscle precursor cell autograft].

This article reviews cell therapy for muscle diseases and describes the development of a treatment for urethral sphincter insufficiency by muscle precursor cell (MPC) autograft. These studies were conducted in several successive steps, comprising: 1) comparative study of the cellular mechanisms of regeneration of skeletal striated muscle and urethral striated sphincter and development of a method of extraction of MPC; 2) creation of an animal model of sphincter injury reproducing chronic denervation lesions and fibrosis responsible for sphincter insufficiency in human; 3) study of the biology of intrasphincteric transplantation of MPC extracted from peripheral muscle, taking into account the interactions between these cells and the peripheral nervous system.

Animals↗

Restoration of functional motor units in a rat model of sphincter injury by muscle precursor cell autografts.

BACKGROUND: Urinary incontinence is a debilitating condition that affects primarily elderly individuals. One major mechanism results from chronic denervation of the striated urethral sphincter with associated fibrosis. The authors investigated the fate of muscle precursor cells (MPC) injected into a model of striated urethral sphincter injury that reproduces the histopathologic changes of sphincter insufficiency. METHODS: The striated urethral sphincter of older male rats was damaged by electrocoagulation. MPC were isolated from limb myofiber explants, infected with an adenovirus carrying the transgene encoding beta-galactosidase, and injected into the sphincter of the same animal 37 days after injury. Animals were killed 5 and 30 days after injection for assessment of sphincter function and the formation of motor units. RESULTS: Electrocoagulation resulted in an irreversible destruction of both sphincteric myofibers and nerve endings, with a functional incapacity of the damaged sphincter to sustain an increase in bladder pressure; atrophy and fibrosis developed after 1 month. Injection of MPC resulted in the formation of beta-galactosidase-expressing myotubes in the sphincter that persisted beyond 30 days. The regenerated myotubes carried acetylcholine receptors associated with a nerve ending and were thus considered to form anatomic motor units. Urodynamic studies confirmed the restoration of 41% of sphincter function 1 month after MPC injection. CONCLUSIONS: The authors showed that MPC isolated from limb muscles of an older animal can recapitulate a myogenic program when injected into an irreversibly injured sphincter. The maturation of MPC activates nerve regeneration and restores functional motor units.

Animals↗

The regeneration process of the striated urethral sphincter involves activation of intrinsic satellite cells.

The regeneration of adult skeletal muscle is mediated by satellite cells. Classically, these are considered to be somitically derived cells that colonize the limbs during early embryogenesis. The striated urethral sphincter presents specific developmental characteristics that distinguish it from skeletal muscles, such as the non-somitic origin of its precursor cells and the late formation of its myofibers. This prompted us to determine whether the striated urethral sphincter can regenerate after injury by the same mechanism as skeletal muscles. By means of the single myofiber explant culture technique we investigated the presence of satellite cells in the striated urethral sphincter of male mice and evaluated their ability to recapitulate a myogenic program. In addition, a myotoxic substance (notexin) was injected into the sphincter in order to provoke rapid destruction of the myofibers; the regeneration process was studied by means of electrophysiological and histological techniques. Satellite cells expressing pax7 were found attached to the sphincteric myofibers. They proliferated and expressed MyoD, Myf5 and desmin after 2 days in culture. After 10 days, they formed multinucleated myotubes expressing alpha-actinin-2. In vivo, complete recovery of the striated urethral sphincter, as assessed by normalization of muscle strength and of myofiber number and diameter, was observed after 3 weeks, and resulted from the fusion of myogenic cells. These results demonstrate that the striated urethral sphincter can regenerate by means of a myogenic program involving intrinsic satellite cells. The therapeutic implications of this knowledge and the possible origin of the sphincteric satellite cells are discussed.

Animals↗

Laparoscopic and robotic surgical training in urology.

The most important change in urology during the past decade was the development of minimally invasive surgery, particularly laparoscopy. However, the main drawback of laparoscopy is a steep learning curve, which results from the significant changes in the surgical environment. Although laparoscopy can provide important advantages for the patient, including decreased length of hospitalization, decreased analgesic requirement, and a shortened postoperative convalescence, one concern has been whether laparoscopic techniques should be learned solely in the operating room. For example, sports, music, and aviation are practiced before an actual performance is ever undertaken. In this review, the advantages and limitations of all available training modalities in minimally invasive surgery are described. Testing basic laparoscopic skills on inanimate models, becoming familiar with the principles of dissection and hemostasis on living animals, and studying surgical anatomy on cadavers should be considered as indispensable and complementary elements for laparoscopic training in the future. In addition, telementoring with the help of modern image processing and virtual reality eventually may become the basis of tomorrow's surgical instruction.

Clinical Competence↗