Thrombin-sensitive photodynamic agents: a novel strategy for selective synovectomy in rheumatoid arthritis.

Protease-sensitive macromolecular prodrugs have attracted interest for bio-responsive drug delivery to sites with up-regulated proteolytic activities such as inflammatory or cancerous lesions. Here we report the development of a novel polymeric photosensitizer prodrug (T-PS) to target thrombin, a protease up-regulated in synovial tissues of rheumatoid arthritis (RA) patients, for minimally invasive photodynamic synovectomy. In T-PS, multiple photosensitizer units are tethered to a polymeric backbone via short, thrombin-cleavable peptide linkers. Photoactivity of the prodrug is efficiently impaired due to energy transfer between neighbouring photosensitizer units. T-PS activation by exogenous and endogenous thrombin induced an increase in fluorescence emission by a factor of 16 after in vitro digestion and a selective fluorescence enhancement in arthritic lesions in vivo, in a collagen-induced arthritis mouse model. In vitro studies on primary human synoviocytes showed a phototoxic effect only after enzymatic digestion of the prodrug and light irradiation, thus demonstrating the functionality of T-PS induced PDT. The developed photosensitizer prodrugs combine the passive targeting capacity of macromolecular drug delivery systems with site-selective photosensitizer release and activation. They illuminate lesions with pathologically enhanced proteolytic activity and induce cell death, subsequent to irradiation.

Applications de la chirurgie robotique transorale dans les tumeurs de la sphère ORL [The role of transoral robotic surgery in head and neck cancer].

Since 2000 and the commercialisation of the Da Vinci robotic system, indications for robotic surgery are rapidly increasing. Recent publications proved superior functional outcomes with equal oncologic safety in comparison to conventional open surgery. Its field of application may extend to the nasopharynx and skull base surgery. The preliminary results are encouraging. This article reviews the current literature on the role of transoral robotic surgery in head and neck cancer.

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.

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.

A prospective development study investigating focal irreversible electroporation in men with localised prostate cancer: Nanoknife Electroporation Ablation Trial (NEAT).

INTRODUCTION: Focal therapy may reduce the toxicity of current radical treatments while maintaining the oncological benefit. Irreversible electroporation (IRE) has been proposed to be tissue selective and so might have favourable characteristics compared to the currently used prostate ablative technologies. The aim of this trial is to determine the adverse events, genito-urinary side effects and early histological outcomes of focal IRE in men with localised prostate cancer. METHODS: This is a single centre prospective development (stage 2a) study following the IDEAL recommendations for evaluating new surgical procedures. Twenty men who have MRI-visible disease localised in the anterior part of the prostate will be recruited. The sample size permits a precision estimate around key functional outcomes. Inclusion criteria include PSA ≤ 15 ng/ml, Gleason score ≤ 4 + 3, stage T2N0M0 and absence of clinically significant disease outside the treatment area. Treatment delivery will be changed in an adaptive iterative manner so as to allow optimisation of the IRE protocol. After focal IRE, men will be followed during 12 months using validated patient reported outcome measures (IPSS, IIEF-15, UCLA-EPIC, EQ-5D, FACT-P, MAX-PC). Early disease control will be evaluated by mpMRI and targeted transperineal biopsy of the treated area at 6 months. DISCUSSION: The NEAT trial will assess the early functional and disease control outcome of focal IRE using an adaptive design. Our protocol can provide guidance for designing an adaptive trial to assess new surgical technologies in the challenging landscape of health technology assessment in prostate cancer treatment.

Stab wounds in a Swiss emergency department: a series of 80 consecutive cases.

Background: Interpersonal violence is a worldwide social reality which seems to increasingly affect even the safest of countries, such as Switzerland. In this country, road traffic accidents, as well as professional and recreational activities, are the main providers of trauma-related injuries. The incidence of penetrative trauma related to stab wounds seems to be regularly increasing in our ED. The question arises of whether our strategies in trauma management are adapted to deal efficiently with these injuries.Methods: To answer this question, the study analysed patients admitted for intentional penetrative injuries in a tertiary urban emergency department (ED) during a 23 month period. Demographics, conditions of the assault, injury type and treatments applied were analysed.Results: Eighty patients admitted due to an intentional penetrating trauma accounted for 0.2% of the surgical practice of our ED. The assault occurred equally in a public or a private context, mainly affecting young males during the night and the weekend. Sixty six patients (83%) were treated as out-patients. Only 10 patients needed surgery. None of them required damage control surgery. No patient died and the mean hospital stay was 5.5 days.Conclusions: The prevalence of stab wounds in Switzerland is low. These injuries rarely need complex, surgical procedures. Observational strategies should be considered according to the patient status.

Complément de table de transcodage des opérations VESKA (version 1986) - ICD-9-CM

Les tables de transcodage donnent les correspondances entre codes opératoires VESKA version 1986 et codes opératoires ICD-9-CM.

Laparoscopy in the era of enhanced recovery.

Laparoscopy is one of the cornerstones in the surgical revolution and transformed outcome and recovery for various surgical procedures. Even if these changes were widely accepted for basic interventions, like appendectomies and cholecystectomies, laparoscopy still remains challenged for more advanced operations in many aspects. Despite these discussion, there is an overwhelming acceptance in the surgical community that laparoscopy did transform the recovery for several abdominal procedures. The importance of improved peri-operative patient management and its influence on outcome started to become a focus of attention 20 years ago and is now increasingly spreading, as shown by the incoming volume of data on this topic. The enhanced recovery after surgery (ERAS) concept incorporates simple measures of general management, and requires multidisciplinary collaboration from hospital staff as well as the patient and the relatives. Several studies have demonstrated a significant decrease in postoperative complication rate, length of hospital stay and reduced overall cost. The key elements of success are fluid restriction, a functioning epidural and preoperative carbohydrate intake. With the expansion of laparoscopic techniques, ERAS increasingly incorporates laparoscopic patients, especially in colorectal surgery. However, the precise impact of laparoscopy on ERAS is still not clearly defined. Increasing evidence suggests that laparoscopy itself is an additional ERAS item that should be considered as routine where feasible in order to obtain the best surgical outcomes.

Fistulizing Crohn's disease.

Fistulas are common in Crohn's disease. A population-based study has shown a cumulative risk of 33% after 10 years and 50% after 20 years. Perianal fistulas were the most common (54%). Medical therapy is the main option for perianal fistula once abscesses, if present, have been drained, and should include antibiotics (both ciprofloxacin and metronidazole) and immunomodulators. Infliximab should be reserved for refractory patients. Surgery is often necessary for internal fistulas.

Computer-aided volume measurement of posttraumatic orbits reconstructed with AO titanium mesh plates: accuracy and reliability

PURPOSE: To prospectively evaluate the accuracy and reliability of "freehand" posttraumatic orbital wall reconstruction with AO (Arbeitsgemeinschaft Osteosynthese) titanium mesh plates by using computer-aided volumetric measurement of the bony orbits. METHODS: Bony orbital volume was measured in 12 patients from coronal CT scan slices using OsiriX Medical Image software. After defining the volumetric limits of the orbit, the segmentation of the bony orbital region of interest of each single slice was performed. At the end of the segmentation process, all regions of interest were grouped and the volume was computed. The same procedure was performed on both orbits, and thereafter the volume of the contralateral uninjured orbit was used as a control for comparison. RESULTS: In all patients, the volume data of the reconstructed orbit fitted that of the contralateral uninjured orbit with accuracy to within 1.85 cm3 (7%). CONCLUSIONS: This preliminary study has demonstrated that posttraumatic orbital wall reconstruction using "freehand" bending and placement of AO titanium mesh plates results in a high success rate in re-establishing preoperative bony volume, which closely approximates that of the contralateral uninjured orbit.