Transrectal hybrid natural orifice transluminal endoscopic surgery (NOTES) nephrectomy in a porcine model.

OBJECTIVE: To examine feasibility of transrectal hybrid natural orifice translumenal endoscopic surgery (NOTES) nephrectomy in the porcine model. NOTES uses ports of entry to the peritoneal cavity instead of abdominal wall incisions, thereby eliminating visible scar and also potentially reducing postoperative pain. METHODS: After obtaining Institutional Animal Care and Use Committee approval, 3 female pigs (45 kg) underwent transrectal hybrid NOTES nephrectomy (2 right, 1 left). Pneumoperitoneum was created by a periumbilically-inserted 12-mm trocar, through which a laparoscope was advanced to obtain intraabdominal visualization. A horizontal incision was made 2 cm above the dentate line and a submucosal tunnel was created in the posterior rectal wall/presacral space. A dual-channel gastroscope was advanced through the submucosal tunnel and retroperitoneum to the level of the kidney using air insufflation. A window in the peritoneum was created and renal mobilization was completed. A transumbilically applied laparoscopic 45-mm stapler was used to transect the ureter and renal hilum. A specimen extraction bag was deployed transrectally and the specimen was delivered intact, followed by transrectal incision closure. RESULTS: Transrectal hybrid NOTES nephrectomy was successfully performed in all cases. Mean operative time was 180 minutes (30 minutes for rectal access). Estimated blood loss was 50 mL. On necropsy, no intraabdominal injuries were noted. CONCLUSIONS: In this initial report on feasibility of transrectal hybrid NOTES nephrectomy, we were able to perform the procedures with minimal blood loss and extract intact specimen. Survival studies are prerequisite to assess sterility and short- and long-term complications. This approach may be useful as an alternative to transvaginal access.

Myocardial functional recovery after fibroblast growth factor 2 gene therapy as assessed by echocardiography and magnetic resonance imaging.

BACKGROUND: Although it has been shown that gene therapy is capable of inducing neovascularization in ischemic myocardium, the functional significance of such therapeutic angiogenesis remains less certain. The purpose of this study was to investigate whether an experimental link could be made between the ability of a novel fibroblast growth factor 2 (FGF2) gene formulation to promote neovascularization, and its ability to restore myocardial function. METHODS: Fibroblast growth factor 2 gene was delivered by means of an adenovirus vector formulated in a collagen-based matrix to provide localized and sustained gene activity. Using a model of chronic myocardial ischemia, animals were randomized to either treatment of the ischemic area by injections of adenovirus vector-FGF2 or no treatment. Left ventricular function was assessed by rest and dobutamine stress echocardiography as well as contrast-enhanced and cine magnetic resonance imaging scans. Studies were repeated 6 weeks after treatment. Arteriogenesis was assessed by quantifying the total arteriolar wall area present in treated areas, using anti-alpha-actin immunohistochemistry and subsequent morphometric analyses. RESULTS: Echocardiographic results demonstrated a significant restoration of myocardial function in FGF2 gene-treated areas as measured by myocardial wall thickening (0.38 +/- 0.08 cm pretreatment versus 0.76 +/- 0.09 cm posttreatment; p < 0.05). This was demonstrated by comparing the ischemic zones of FGF2 gene-treated versus control-treated animals, as well as by comparing ischemic with nonischemic zones in individual animals This functional improvement was confirmed by cine magnetic resonance imaging, in which 68% (147 of 216) of the treated segments showed improvement in wall motion and there was no change in the untreated segments. Fibroblast growth factor 2 gene treatment also enhanced arteriogenesis within the ischemic zone, as FGF2 gene-treated animals showed a 340% increase in the total arteriolar wall area present versus control-treated animals. CONCLUSIONS: The function of ischemic myocardium can be restored by a novel FGF2 gene delivery method using a gene-activated matrix. The increased arteriogenesis as a result of FGF2 gene therapy leads to restoration of this myocardial function.

A physiologic flow chamber model to define intravascular ultrasound enhancement of fibrin using echogenic liposomes.

RATIONALE AND OBJECTIVES: Echogenic immunoliposomes (ELIP) for enhancement of vasoactive and pathologic components of endothelium and atherosclerosis have been developed. A physiologic flow chamber model has been developed to define intravascular ultrasound enhancement of a fibrin interface. METHODS: A IgG ELIP was used, which nonspecifically associated with fibrin, to demonstrate the suitability of this model. With varying doses of IgG ELIP, the fibrin wells were imaged at 1, 2, 4, 6, and 9 minutes. RESULTS: IgG ELIP enhanced fibrin versus saline (P < 0.005) was visible at 1 minute, lasted at least 9 minutes, and at 6 minutes the interface enhanced 27% +/- 6.1%. Enhancement was caused by increases in interface thickness and brightness. Enhancement increased with dose up to 8 mg lipid (n = 4 per time point). CONCLUSION: This model can quantitate the components of IVUS enhancement of an interface produced by ELIP. This model may allow for further development and understanding of ELIP and other targeted ultrasound contrast agents.