Locally enhanced chemotherapy by electroporation: clinical experiences and perspective of use of electrochemotherapy

ABSTRACT:  Electroporation is used to enhance drug diffusion and gene delivery into the cytosol. The combination of electroporation and cytotoxic drugs, electrochemotherapy (ECT), is used to treat metastatic tumor nodules located at the skin and subcutaneous tissue. The objective response rate following a single session of treatment exceeds 80%, with minimal toxicity for the patients. The efficacy of ECT in the bone and visceral metastasis is currently investigated, and Phase II studies have been completed. ECT has been used to treat skin primary tumors, except melanoma, and is under investigation for locally advanced pancreatic cancer. Early evidence suggests that treatment of tumor nodules with ECT recruits components of the immune system and eliciting a systemic immune response against cancer is a challenging clinical perspective. Considering the proven safety in several different clinical applications electroporation should be viewed as a clinical platform technology with wide perspectives for use in ECT, gene therapy and DNA vaccination

How Do Metal Ion Levels Change over Time in Hip Resurfacing Patients? A Cohort Study

Metal-on-metal hip resurfacing (MOM-HR) is offered as an alternative to traditional hip arthroplasty for young, active adults with advanced osteoarthritis. Nevertheless, concerns remain regarding wear and corrosion of the bearing surfaces and the resulting increase in metal ion levels. We evaluated three cohorts of patients with Birmingham hip resurfacing (BHR) at an average follow-up of 2, 5, and 9 years. We asked whether there would be differences in ion levels between the cohorts and inside the gender. Nineteen patients were prospectively analyzed. The correlation with clinical-radiographic data was also performed. Chromium, cobalt, nickel, and molybdenum concentrations were measured by atomic absorption spectrophotometry. Chromium and cobalt levels demonstrated a tendency to decrease over time. Such tendency was present only in females. An inverse correlation between chromium, implant size, and Harris hip score was present at short term; it disappeared over time together with the decreased ion levels. The prospective analysis showed that, although metal ion levels remained fairly constant within each patient, there was a relatively large variation between subjects, so mean data in this scenario must be interpreted with caution. The chronic high exposure should be carefully considered during implant selection, particularly in young subjects, and a stricter monitoring is mandatory

Effect of electric current stimulation in combination with external fixator on bone healing in a sheep fracture model

Biophysical stimulations with electric and electromagnetic fields have been demonstrated to accelerate the bone-healing rate. This study has been designed to investigate the effects of electricity directly connected with the central pins of an external fixator in an experimental osteotomy model in sheep. Thirty mg/kg of tetracycline chloride were administered on the 30th and on the 45th day after surgery for histomorphometric studies. Plain radiographs were obtained in standard projections every 15 days after surgery and were analyzed with a software program (Corel Photo-Paint Pro X2, Corel Corporation, Ottawa, Canada). The specimens obtained after 60 days were examined with histological analysis. The results show that biophysical treatment with alternating electricity in combination with external fixator enhances new-bone formation. The translational value of this study, due to the similarities between ovine and human species, suggests that this treatment could be useful in speeding the bone-healing rate both in animals and humans

Can Clinical and Surgical Parameters Be Combined to Predict How Long It Will Take a Tibia Fracture to Heal? A Prospective Multicentre Observational Study: The FRACTING Study

Background. Healing of tibia fractures occurs over a wide time range of months, with a number of risk factors contributing to prolonged healing. In this prospective, multicentre, observational study, we investigated the capability of FRACTING (tibia FRACTure prediction healING days) score, calculated soon after tibia fracture treatment, to predict healing time. Methods. The study included 363 patients. Information on patient health, fracture morphology, and surgical treatment adopted were combined to calculate the FRACTING score. Fractures were considered healed when the patient was able to fully weight-bear without pain. Results. 319 fractures (88%) healed within 12 months from treatment. Forty-four fractures healed after 12 months or underwent a second surgery. FRACTING score positively correlated with days to healing: r = 0.63 (p < 0.0001). Average score value was 7.3 \ub1 2.5; ROC analysis showed strong reliability of the score in separating patients healing before versus after 6 months: AUC = 0.823. Conclusions. This study shows that the FRACTING score can be employed both to predict months needed for fracture healing and to identify immediately after treatment patients at risk of prolonged healing. In patients with high score values, new pharmacological and nonpharmacological treatments to enhance osteogenesis could be tested selectively, which may finally result in reduced disability time and health cost savings

Evaluation of articular cartilage repair with pulsed electromagnetic fields in association with different surgical techniques in an experimental model in rabbits

Diverse tecniche di ingegneria tessutale sono state sviluppate per promuovere la riparazione delle lesioni della cartilagine articolare. Nonostante i buoni risultati clinici a breve termine, il tessuto rigenerato fallisce nel tempo poiché non possiede le caratteristiche meccaniche e funzionali della cartilagine articolare nativa. La stimolazione con campi elettromagnetici pulsati (CEMP) rappresenta un approccio terapeutico innovativo. I CEMP aumentano l’attività anabolica dei condrociti con conseguente incremento della sintesi della matrice, e limitano l’effetto catabolico delle citochine pro-infiammatorie riducendo la degradazione della cartilagine nel microambiente articolare. I CEMP agiscono mediante l’up-regolazione dei recettori adenosinici A2A potenziando il loro affetto anti-infiammatorio. Lo scopo di questo studio è stato quello di valutare l’effetto della stimolazione con CEMP sulla guarigione di difetti osteocondrali in un modello sperimentale nel coniglio. Un difetto osteocondrale del diametro di 4mm è stato eseguito nel condilo femorale mediale di entrambe le ginocchia di 20 conigli. A destra la lesione è stata lasciata a guarigione spontanea mentre a sinistra e stata trattata mediante inserimento di scaffold collagenico o trapianto di cellule mesenchimali midollari sul medesimo scaffold precedentemente prelevate dalla cresta iliaca. In base al trattamento eseguito 10 animali sono stati stimolati con CEMP 4 ore/die per 40 giorni mentre altri 10 hanno ricevuto stimolatori placebo. Dopo il sacrificio a 40 giorni, sono state eseguite analisi istologiche mediante un punteggio di O’Driscoll modificato. Confrontando le lesioni lasciate a guarigione spontanea, la stimolazione con CEMP ha migliorato significativamente il punteggio (p=0.021). Lo stesso risultato si è osservato nel confronto tra lesioni trattate mediante trapianto di cellule mesenchimali midollari (p=0.032). Nessuna differenza è stata osservata tra animali stimolati e placebo quando la lesione è stata trattata con il solo scaffold (p=0.413). La stimolazione con CEMP è risultata efficace nel promuovere la guarigione di difetti osteocartilaginei in associazione a tecniche chirurgiche di ingegneria tessutale.Several tissue engineering approaches have been developed to address hyaline cartilage lesions, but to date there is not a definitive procedure able to promote a repair tissue with the same mechanical and functional characteristics of native cartilage. Pulsed electromagnetic fields stimulation (PEMFs) represents an innovative therapeutic approach. PEMFs increases the anabolic activity of chondrocytes with consequent increase of matrix synthesis, and limits the catabolic effects of inflammatory cytokines, thus reducing cartilage degradation inside the surgical microenvironment. PEMFs mediate an upregulation of A2A adenosine receptors and a potentiation of their anti-inflammatory effects. This study aimed to determine the efficacy of PEMFs in experimental osteochondral defect healing in a rabbit model. Both knees joints of 20 rabbits were exposed and a 4mm diameter osteochondral defect was created in the medial femoral condile. The defect in the right knee was left untreated while in the left knee was filled either with collagen scaffold or with the same scaffold loaded with bone marrow-derived cells previously harvested from the iliac crest. According to the treatment performed 10 rabbits were given PEMF of four hours duration per day for 40 days while other 10 were given sham stimulators. At 40 days the animals were sacrificed and histological evaluation was performed. The quality of the repair tissue was graded with the O’Driscoll modified score and a statistical analysis was done. By comparing the defects left untreated PEMFs significantly improved the histological score (p=0.021). The same result was observed when comparing lesions treated with scaffold loaded with bone marrow-derived cells (p=0.032). No significant difference was found between stimulated or sham treated animals when the defect was filled with the scaffold alone (p=0.413). PEMFs was an effective method to improve healing of osteochondral defects in association with current surgical tissue engineering techniques

Biofisica e tissue engineering

Campi elettromagnetici pulsati in ortopedia e traumatologi

Hallux Valgus Surgery: the minimally invasive bunion correction

Minimally invasive surgery with the SERI technique for hallux valgus managemen

Bone mineral density of the proximal femur recovers after metal-on-metal hip resurfacing

Bone resorption of the proximal femur is a frequent complication of total hip replacement. As hip resurfacing (HR) may load the bone more physiologically, we measured proximal femur bone mineral density (BMD) in 21 patients with HR. DEXA analysis was performed in the 7 Gruen zones and in the femoral neck pre-operatively and at 3, 9, and 24-months post-operatively. In Gruen zone-2 the BMD ratio decreased to 90±18.8% (p=0.0009) at 3-months and completely restored at 24-months to 100±17.7% (p=0.01). In Gruen zone-7 the BMD ratio decreased to 93±15.3% (p=0.05) by 3 months and surpassed the baseline to 105±14.8% (p=0.01) at 24-months. A positive correlation was observed between valgus positioning of the femoral component and BMD in Gruen zone-2 and 7 respectively. HR preserves the bone-stock of the proximal femur. When the femoral component is implanted in a valgus position BMD is further enhanced, thus potentially reducing the risk of femoral neck fractures

Effects of Pulsed Electromagnetic Fields after Debridement and Microfracture of Osteochondral Talar Defects: Letter to the Editor

No abstract availabl