Laser-welded endoscopic endoluminal repair of iatrogenic esophageal perforation: an animal model.

OBJECTIVE: To test the feasibility of laser tissue welding (LTW) in creating an endoscopic transluminal repair of esophageal perforation. STUDY DESIGN: Animal model. SUBJECTS AND METHODS: A diode laser was used to create an endoluminal rabbit esophageal perforation repair. Burst pressures were compared with open incision, external suture, and external laser-augmented suture closure. Comparisons were performed five times and analyzed with Kruskal-Wallis analysis of variance and a post hoc Dunn method. RESULTS: The burst threshold of the endoluminal weld (54.78 +/- 5.84 mm Hg) was significantly higher than that of the open incision (6.5 +/- 1.94 mm Hg) and not significantly different than that of the external suture (37.18 +/- 1.97 mm Hg) or the laser-augmented suture group (71.60 +/- 7.58 mm Hg). CONCLUSION: Laser welding is a feasible method of creating endoluminal repairs with burst strengths comparable with external suture repair, which may allow a subset of patients to avoid traditional open approaches. This is the first reported animal model of LTW for endoscopic closure of iatrogenic esophageal perforation.

In vivo laser tissue welding in the rabbit maxillary sinus.

BACKGROUND: One of the challenges in the current expansion of endoscopic sinonasal surgery is the ability to adequately reconstruct the skull base. Laser tissue welding (LTW) uses laser energy coupled to a biological solder to produce tissue bonds with burst thresholds exceeding human intracranial pressure. This technology could be used to reduce the rate of postoperative cerebrospinal fluid (CSF) leak. We performed this study to determine whether LTW can create durable tissue bonds in sinonasal mucosa that support normal wound healing and produce minimal collateral thermal injury. METHODS: Bilateral maxillary sinus mucosal incisions were made in 20 New Zealand white rabbits and one side was repaired using LTW. Burst pressure thresholds were measured on postoperative days 0, 5, and 15 and were compared with control using a two- way ANOVA and a post hoc Tukey test. Welds were examined histologically for thermal injury, inflammation, and fibroplasia and graded on a 4-point scale by three blinded observers. RESULTS: The burst pressures of the LTW group were significantly higher than control on postoperative day 0 (120.85 mm Hg, N = 4, SD = 47.84 versus 7.85 mm Hg, N = 4, SD = 0.78), and day 5 (132.56 mm Hg, N = 8, SD = 24.02 versus 41.7 mm Hg, N = 8, SD = 7.2; p < 0.05). By postoperative day 15 there was no significant difference between LTW (169.64 mm Hg, N = 8, SD = 18.49) and control (160.84 mm Hg, N = 8, SD = 14.16) burst thresholds. There was no evidence of thermal injury to the surrounding tissue in any group as well as no difference between experimental group and control with respect to inflammation or fibroplasia. CONCLUSION: This is the first in vivo study showing that LTW is capable of producing tissue bonds exceeding human intracranial pressure with negligible thermal injury in sinonasal tissue. Welding can be performed endoscopically using a fiberoptic cable and may be useful in CSF leak and skull base repair.

Functional consequences of polyamine synthesis inhibition by L-alpha-difluoromethylornithine (DFMO): cellular mechanisms for DFMO-mediated ototoxicity.

L-Alpha-difluoromethylornithine (DFMO) is a chemopreventive agent for colon cancer in clinical trials. Yet, the drug produces an across-frequency elevation of the hearing threshold, suggesting that DFMO may affect a common trait along the cochlear spiral. The mechanism for the ototoxic effects of DFMO remains uncertain. The cochlear duct is exclusively endowed with endocochlear potential (EP). EP is a requisite for normal sound transduction, as it provides the electromotive force that determines the magnitude of the receptor potential of hair cells. EP is generated by the high throughput of K(+) across cells of the stria vascularis, conferred partly by the activity of Kir4.1 channels. Here, we show that the ototoxicity of DFMO may be mediated by alteration of the inward rectification of Kir4.1 channels, resulting in a marked reduction in EP. These findings are surprising given that the present model for EP generation asserts that Kir4.1 confers the outflow of K(+) in the stria vascularis. We have proposed an alternative model. These findings should also enable the rational design of new pharmaceuticals devoid of the untoward effect of DFMO.