Characterization of a Novel Implant Intended to Expand and Reshape the Prostatic Urethra for the Treatment of Benign Prostatic Hyperplasia: A Pre-Clinical Feasibility Study in the Canine Model.

OBJECTIVE: To evaluate the safety, feasibility, and tissue response of a novel device for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia, using the first-generation Urocross Expander System (Mercury Expander System). METHODS: The implant was deployed and retrieved using flexible cystoscope in 8 adult male canines, separated into three study arms by retrieval date (1-, 6-, and 12- months post-deployment). Cystoscopy and urethrograms verified implant position/diameter; bladder neck and external sphincter function/changes; prostatic tissue response; and implant condition. One-month post-retrieval, the prostate and surrounding tissue was sectioned and evaluated by a veterinary pathologist. RESULTS: All implants were successfully deployed in the prostatic urethra. Urethral width was increased (6.9 ± 1.8 mm to 10.2 ± 0.6 mm, P = .012) and preserved through the dwell period. Urethral length and sphincter diameters didn't significantly change. All subjects (n = 8) remained continent without obstruction or retention. Adverse events included incisional site bleeding (n = 2) and transient hematuria (n = 3). One implant migrated into the bladder and spontaneously repositioned into the prostatic urethra. Post-retrieval, explant surfaces demonstrated no tissue growth, encrustation or stone formation. Imaging revealed contact site erythema and indentation, but no stones, strictures, perforations, erosions, nor ulcerations. Histopathology revealed glandular acinar changes, inflammation, and fibrosis. CONCLUSION: The first generation of the Urocross Expander System demonstrated a favorable safety profile in the canine model. Changes in the prostatic urethra shape were noted with an increase in urethral width during the dwell period with minimal tissue changes. Further, the implant didn't demonstrate any encrustation, tissue growth or stone formation.

Surface micropattern reduces colonization and medical device-associated infections.

PURPOSE: Surface microtopography offers a promising approach for infection control. The goal of this study was to provide evidence that micropatterned surfaces significantly reduce the potential risk of medical device-associated infections. METHODOLOGY: Micropatterned and smooth surfaces were challenged in vitro against the colonization and transference of two representative bacterial pathogens - Staphylococcus aureus and Pseudomonas aeruginosa. A percutaneous rat model was used to assess the effectiveness of the micropattern against device-associated S. aureus infections. After the percutaneous insertion of silicone rods into (healthy or immunocompromised) rats, their backs were inoculated with S. aureus. The bacterial burdens were determined in tissues under the rods and in the spleens. RESULTS: The micropatterns reduced adherence by S. aureus (92.3 and 90.5 % reduction for flat and cylindrical surfaces, respectively), while P. aeruginosa colonization was limited by 99.9 % (flat) and 95.5 % (cylindrical). The micropatterned surfaces restricted transference by 95.1 % for S. aureus and 94.9 % for P. aeruginosa, compared to smooth surfaces. Rats with micropatterned devices had substantially fewer S. aureus in subcutaneous tissues (91 %) and spleens (88 %) compared to those with smooth ones. In a follow-up study, immunocompromised rats with micropatterned devices had significantly lower bacterial burdens on devices (99.5 and 99.9 % reduction on external and internal segments, respectively), as well as in subcutaneous tissues (97.8 %) and spleens (90.7 %) compared to those with smooth devices. CONCLUSION: Micropatterned surfaces exhibited significantly reduced colonization and transference in vitro, as well as lower bacterial burdens in animal models. These results indicate that introducing this micropattern onto surfaces has high potential to reduce medical device-associated infections.

Increased Duration of Heating Boosts Local Drug Deposition during Radiofrequency Ablation in Combination with Thermally Sensitive Liposomes (ThermoDox) in a Porcine Model.

INTRODUCTION: Radiofrequency ablation (RFA) is used for the local treatment of liver cancer. RFA is effective for small (<3 cm) tumors, but for tumors > 3 cm, there is a tendency to leave viable tumor cells in the margins or clefts of overlapping ablation zones. This increases the possibility of incomplete ablation or local recurrence. Lyso-Thermosensitive Liposomal Doxorubicin (LTLD), is a thermally sensitive liposomal doxorubicin formulation for intravenous administration, that rapidly releases its drug content when exposed to temperatures >40°C. When used with RFA, LTLD releases its doxorubicin in the vasculature around the zone of ablation-induced tumor cell necrosis, killing micrometastases in the ablation margin. This may reduce recurrence and be more effective than thermal ablation alone. PURPOSE: The purpose of this study was to optimize the RFA procedure used in combination with LTLD to maximize the local deposition of doxorubicin in a swine liver model. Pigs were anaesthetized and the liver was surgically exposed. Each pig received a single, 50 mg/m2 dose of the clinical LTLD formulation (ThermoDox®). Subsequently, ablations were performed with either 1, 3 or 6 sequential, overlapping needle insertions in the left medial lobe with total ablation time of 15, 45 or 90 minutes respectively. Two different RFA generators and probes were evaluated. After the final ablation, the ablation zone (plus 3 cm margin) was dissected out and examined for doxorubicin concentration by LC/MS and fluorescence. CONCLUSION: The mean Cmax of plasma total doxorubicin was 26.5 µg/ml at the end of the infusion. Overall, increased heat time from 15 to 45 to 90 minutes shows an increase in both the amount of doxorubicin deposited (up to ~100 µg/g) and the width of the ablation target margin to which doxorubicin is delivered as determined by tissue homogenization and LC/MS detection of doxorubicin and by fluorescent imaging of tissues.

Superiority of using bipolar radiofrequency energy for internal mammary artery harvesting.

PURPOSE: The purpose of this study was to observe the acute effects of harvesting the porcine internal mammary artery using a novel bipolar (BP) radiofrequency energy device. DESCRIPTION: The internal mammary artery from 16 porcine subjects was harvested using monopolar electrosurgery, BP electrosurgery, ultrasonic coagulation, and mechanical dissection with clips. Segments were evaluated with respect to endothelial function and integrity and the strength of side-branch sealing. EVALUATION: Adenosine triphosphate-induced relaxation was greatest with internal mammary artery segments harvested by bipolar electrosurgery in comparison with monopolar electrosurgery (p = 0.0271), ultrasonic coagulation in comparison with monopolar electrosurgery (p = 0.0047), and mechanical clipping in comparison with monopolar electrosurgery (p = 0.0381). The standard error of the mean failed to demonstrate any significant difference in epithelial disruption among the four treatment groups. Clips and bipolar electrosurgery exhibited the most secure ligations with burst pressures exceeding 350 mm Hg. CONCLUSIONS: Internal mammary artery segments harvested using a novel BP electrosurgery retained a greater degree of endothelial function when compared with monopolar electrosurgery and ultrasonic coagulation. Side-branch sealing with BP electrosurgery was as secure as mechanical clips.

Effects of monopolar radiofrequency heating on intradiscal pressure in sheep.

BACKGROUND CONTEXT: No previous study has assessed the effect of monopolar radiofrequency (RF) heating on intradiscal pressure. PURPOSE: To determine the decrease in lumbar intradiscal pressure after monopolar RF heating. STUDY DESIGN/SETTING: Intradiscal pressure was measured in sheep lumbar discs treated with monopolar RF heating. METHODS: Two monopolar RF heat treatments at 90 degrees C were applied for 2 minutes each to lumbar intervertebral discs of sheep. Intradiscal pressure was measured in live sheep at 0, 7, 14, 21, and 28 days posttreatment. Pressure measurements were taken with a microtip pressure transducer. Electrodes were inserted but not activated in separate discs as a sham control. In vitro sheep spine of different age groups, loading conditions, and electrode orientations were similarly heat treated and intradiscal pressures were measured. RESULTS: Intradiscal pressure was significantly reduced 1 week after monopolar RF heating and remained stable through the 4-week observation period. The RF electrode orientation, the age, and the type of disc loading have significant effects on the amount of initial intradiscal pressure reduction. CONCLUSIONS: Monopolar RF heating can reduce intradiscal pressure in the lumbar spine of sheep.