[Innovative therapeutic strategies for intravesical drug administration]. / Stratégies thérapeutiques innovantes pour l'administration médicamenteuse intravésicale.

INTRODUCTION: Perspectives for innovative pharmaceutical molecules and intravesical administration of pharmacological agents are presented in the present review carried out from a recent literature. MATERIALS AND METHODS: This review of the literature was built by using the PubMed and ScienceDirect databases running 20keywords revealing 34publications between 1983 and 2012. The number of referenced articles on ScienceDirect has increased in recent years, highlighting the interest of scientists for intravesical drug administration and the relevance of innovating drug delivery systems. RESULTS: Different modalities of intravesical administration using physical (e.g., iontophoresis, electroporation) or chemical techniques (e.g., enzyme, solvent, nanoparticles, liposomes, hydrogels) based on novel formulation methods are reported. Finally, the development of biopharmaceuticals (e.g., bacillus Calmette-Guérin, interferon α) and gene therapies is also presented and analyzed in this review. CONCLUSION: The present review exhibits new development in the pipeline for emerging intravesical drug administration strategies. Knowledge of all these therapies allows practitioners to propose a specific and tailored treatment to each patient with limiting systemic side effects.

Assessment of the selection process for myocutaneous flap repair and surgical complications in pelvic exenteration surgery.

BACKGROUND: This study aimed to explore and quantify the selection process to guide the decision on closure type (myocutaneous flap repair (MFR) or primary closure) for people undergoing pelvic exenteration. METHODS: This was a retrospective analysis of a prospectively maintained database with review of hospital records for verification and capture of missing data. Associations between four risk factors (previous radiotherapy, previous abdominoperineal resection, need for total exenteration, need for sacrectomy) were assessed individually and collectively as predictors of closure type and wound complications. RESULTS: A total of 203 pelvic exenteration procedures were reviewed (75 primary and 122 recurrent cancers). Thirty-nine patients (19·2 per cent) had MFR and 164 (80·8 per cent) primary closure. Patients who had MFR were significantly more likely to exhibit each risk factor, confirming the selective decision process. MFR had higher rates of complications across all four risk factors, individually and combined. In the primary closure group, there was a significant correlation between the number of risk factors and the proportion of patients with a complication (r = 0·25, P = 0·008). In contrast, no such relationship was found for the MFR group (r = 0·01, P = 0·973). Among patients who had any complication, the primary closure group had significantly lower rates of any wound dehiscence (15 of 64 versus 17 of 28; P < 0·001) and total infection (16 of 64 versus 14 of 28; P = 0·019) compared with the MFR group. CONCLUSION: Rates of wound and septic complications after pelvic exenteration were low in patients with fewer than two risk factors who had a primary closure. MFR had significantly higher complication rates, and should be reserved for patients with two or more risk factors or extensive skin involvement.

Evidence-based recommendations for the use of negative pressure wound therapy in chronic wounds: steps towards an international consensus.

AIM: Negative Pressure Wound Therapy (NPWT) has become widely adopted over the last 15 years and over 1000 peer-reviewed publications are available describing its use. Despite this, there remains uncertainty regarding several aspects of usage. In order to respond to this gap a global expert panel was convened to develop evidence-based recommendations describing the use of NPWT. In this communication the results of the study of evidence in chronic wounds including pressure ulcers, diabetic foot ulcers (DFU), venous leg ulcers (VLU), and ischaemic lower limb wounds are reported. METHODS: Evidence-based recommendations were obtained by a systematic review of the literature, grading of evidence, drafting of the recommendations by a global expert panel followed by a formal consultative consensus development program in which 422 independent healthcare professionals were able to agree or disagree with the recommendations. The criteria for agreement were set at 80% agreement. Evidence and recommendations were graded according to the SIGN (Scottish Intercollegiate Guidelines Network) classification system. RESULTS: The primary treatment goal of NPWT in most chronic wounds is to achieve wound closure (either by secondary intention or preparing the wound for surgical closure). Secondary goals commonly include: to reduce wound dimensions, and to improve the quality of the wound bed. Thirteen evidence based recommendations were developed in total to address these treatment goals; 4 for pressure ulcers, 4 for DFU, 3 for ischaemic lower limb wounds and 2 for VLU. CONCLUSION: The present evidence base is strongest for the use of NPWT in non-ischaemic DFU and weakest in VLU. The development of evidence-based recommendations for NPWT with direct validation from a large group of practicing clinicians offers a broader basis for consensus than work by an expert panel alone.

Evidence-based recommendations for negative pressure wound therapy: treatment variables (pressure levels, wound filler and contact layer)--steps towards an international consensus.

Negative pressure wound therapy (NPWT) is becoming a commonplace treatment in many clinical settings. New devices and dressings are being introduced. Despite widespread adoption, there remains uncertainty regarding several aspects of NPWT use. To respond to these gaps, a global expert panel was convened to develop evidence-based recommendations describing the use of NPWT. In a previous communication, we have reviewed the evidence base for the use of NPWT within trauma and reconstructive surgery. In this communication, we present results of the assessment of evidence relating to the different NPWT treatment variables: different wound fillers (principally foam and gauze); when to use a wound contact layer; different pressure settings; and the impact of NPWT on bacterial bioburden. Evidence-based recommendations were obtained by a systematic review of the literature, grading of evidence and drafting of the recommendations by a global expert panel. Evidence and recommendations were graded according to the Scottish Intercollegiate Guidelines Network (SIGN) classification system. In general, there is relatively weak evidence on which to base recommendations for any one NPWT treatment variable over another. Overall, 14 recommendations were developed: five for the choice of wound filler and wound contact layer, four for choice of pressure setting and five for use of NPWT in infected wounds. With respect to bioburden, evidence suggests that reduction of bacteria in wounds is not a major mode of action of NPWT.

Evidence-based recommendations for the use of Negative Pressure Wound Therapy in traumatic wounds and reconstructive surgery: steps towards an international consensus.

Negative pressure wound therapy (NPWT) has become widely adopted over the last 15 years and over 1000 peer reviewed publications are available describing its use. Despite this, there remains uncertainty regarding several aspects of usage. In order to respond to this gap a global expert panel was convened to develop evidence-based recommendations describing the use of NPWT. In this paper the results of the study of evidence in traumatic wounds (including soft tissue defects, open fractures and burns) and reconstructive procedures (including flaps and grafts) are reported. Evidence-based recommendations were obtained by a systematic review of the literature, grading of evidence, drafting of the recommendations by a global expert panel, followed by a formal consultative consensus development program in which 422 independent healthcare professionals were able to agree or disagree with the recommendations. The criteria for agreement were set at 80% approval. Evidence and recommendations were graded according to the SIGN (Scottish Intercollegiate Guidelines Network) classification system. Twelve recommendations were developed in total; 4 for soft tissue trauma and open fracture injuries, 1 for burn injuries, 3 for flaps and 4 for skin grafts. The present evidence base is strongest for the use of NPWT on skin grafts and weakest as a primary treatment for burns. In the consultative process, 11/12 of the proposed recommendations reached the 80% agreement threshold. The development of evidence-based recommendations for NPWT with direct validation from a large group of practicing clinicians offers a broader basis for consensus than work by an expert panel alone.

Pulmonary metastatic melanoma -- the survival benefit associated with positron emission tomography scanning.

OBJECTIVE: Positron emission tomography (PET) scanning is more sensitive at detecting metastatic disease than conventional radiological techniques. For patients with pulmonary metastatic melanoma, we investigate if PET scanning to detect occult extra pulmonary disease prior to thoracotomy and metastectomy is associated with improved survival compared to patients staged by conventional radiology. METHODS: Between November 1984 and December 1999, 121 patients (90 males, 31 females) have undergone a thoracotomy and pulmonary metastectomy for metastatic melanoma. The age range was 19-84 years (mean 57, median 59). In every case all palpable nodules were removed and the diagnosis confirmed histologically. A total of 68 (56%) patients had a PET scan preoperatively, 53 (44%) underwent conventional or nuclear imaging. Patients with only radiologically isolated pulmonary disease are included. RESULTS: Survival is 100% complete and totals 238 pt/years (mean 2.2 years, median 1.4 years). Survival (+/-SE) at 1, 3, 5 and 7 years for all patients is 68% (+/-4.5) (n=67), 36.6% (+/-5.2) (n=27), 22.1% (+/-4.8) (n=15) and 13.5% (+/-4.2) (n=7), respectively. Survival (+/-SE) was significantly better at 3 and 5 years in patients who underwent a PET scan preoperatively (Log rank P=0.002). There was no significant difference in survival by 7 years. CONCLUSIONS: There is a significant survival benefit associated with excluding extra pulmonary disease using a PET scan prior to thoracotomy and metastectomy. We recommend that PET scanning be used in the investigation of patients with pulmonary metastatic melanoma prior to metastectomy.

Potent inhibition of oxidative phosphorylation by marine natural products.

Many lipid-soluble extracts from various marine organisms have a nonspecific depressant effect on smooth muscle contractions. Novel compounds isolated from such lipid-soluble extracts were tested for their effects on the respiration of rat liver mitochondria and produced potent stimulation or inhibition of oxygen uptake by the mitochondria.