The Sutureless Excimer Laser Anastomosis Clip Pilot Study: a feasibility and safety study.

BACKGROUND: The excimer laser-assisted non-occlusive anastomosis (ELANA) bypass technique may have the advantage of its non-occlusive design in the treatment of last-resort cases where endovascular treatment or direct clipping is considered to be unsafe. However, the technique remains technically challenging. Therefore, a sutureless ELANA Clip device (SEcl) was developed to simplify the technique avoiding tedious anastomosis stitching in depth. The present study investigates the clinical feasibility and safety of the SEcl technique. METHODS: Three patients with complex and large aneurysms in the anterior circulation were selected after multidisciplinary consensus that the aneurysms were too complex for endovascular or direct clipping treatment options. Bypass surgery was considered as a last-resort treatment option, and after preoperative evaluation and informed consent, SEcl bypass surgery was performed. Applicability, technical aspects and patient outcomes are assessed. RESULTS: All aneurysms were excluded from the circulation. The creation of the intracranial anastomosis was easier and faster. No device-related serious adverse events were encountered, and all outcomes were favorable (one patient stable Modified Rankin Scale, two patients improved). CONCLUSION: The SEcl anastomosis technique is feasible and, considering the severity of the disease, relatively safe. It can be considered a treatment option in very difficult-to treat last-resort aneurysm cases. From this study, further developments in minimizing clip size and application in cardiac surgery are initiated.

Histological and magnetic resonance imaging assessment of Liqoseal in a spinal in vivo pig model.

BACKGROUND: Liqoseal (Polyganics, B.V.) is a dural sealant patch for preventing postoperative cerebrospinal fluid (CSF) leakage. It has been extensively tested preclinically and CE (Conformité Européenne) approved for human use after a first cranial in-human study. However, the safety of Liqoseal for spinal application is still unknown. The aim of this study was to assess the safety of spinal Liqoseal application compared with cranial application using histology and magnetic resonance imaging characteristics. METHODS: Eight female Dutch Landrace pigs underwent laminectomy, durotomy with standard suturing and Liqoseal application. Three control animals underwent the same procedure without sealant application. The histological characteristics and imaging characteristics of animals with similar survival times were compared to data from a previous cranial porcine model. RESULTS: Similar foreign body reactions were observed in spinal and cranial dura. The foreign body reaction consisted of neutrophils and reactive fibroblasts in the first 3 days, changing to a chronic granulomatous inflammatory reaction with an increasing number of macrophages and lymphocytes and the formation of a fibroblast layer on the dura by day 7. Mean Liqoseal plus dura thickness reached a maximum of 1.2 mm (range 0.7-2.0 mm) at day 7. CONCLUSION: The spinal dural histological reaction to Liqoseal during the first 7 days was similar to the cranial dural reaction. Liqoseal did not swell significantly in both application areas over time. Given the current lack of a safe and effective dural sealant for spinal application, we propose that an in-human safety study of Liqoseal is the logical next step.

Spinal fixation after laminectomy in pigs prevents postoperative spinal cord injury.

BACKGROUND: A safe, effective, and ethically sound animal model is essential for preclinical research to investigate spinal medical devices. We report the initial failure of a porcine spinal survival model and a potential solution by fixating the spine. METHODS: Eleven female Dutch Landrace pigs underwent a spinal lumbar interlaminar decompression with durotomy and were randomized for implantation of a medical device or control group. Magnetic resonance imaging (MRI) was performed before termination. RESULTS: Neurological deficits were observed in 6 out of the first 8 animals. Three of these animals were terminated prematurely because they reached the predefined humane endpoint. Spinal cord compression and myelopathy was observed on postoperative MRI imaging. We hypothesized postoperative spinal instability with epidural hematoma, inherent to the biology of the model, and subsequent spinal cord injury as a potential cause. In the subsequent 3 animals, we fixated the spine with Lubra plates. All these animals recovered without neurological deficits. The extent of spinal cord compression on MRI was variable across animals and did not seem to correspond well with neurological outcome. CONCLUSION: This study shows that in a porcine in vivo model of interlaminar decompression and durotomy, fixation of the spine after lumbar interlaminar decompression is feasible and may improve neurological outcomes. Additional research is necessary to evaluate this hypothesis.

Minimizing complications in a porcine survival craniotomy model.

A large craniotomy survival porcine model is useful for scientific research. The surgical approaches and complications of craniotomies in pigs have not been published before. This study describes how large craniotomies were performed in 46 pigs and how the risk of complications was minimized. The major complications were direct postoperative epidural hematomas (n = 3) and sagittal sinus rupture (n = 4). The measures taken to prevent postoperative epidural hematomas consisted of optimizing anesthesia, using bone wax to stop trabecular bleeding, increasing blood pressure before bone flap replacement, tranexamic acid administration, and postoperative recovery of the pigs in the prone position in a dedicated hammock. After these measures, no pig died from a postoperative epidural hematoma. Iatrogenic sagittal sinus rupture occurred in cases where the dura shifted into the craniotome during craniotomy. The dura was detached from the skull through drill holes with custom elevators before craniotomy to minimize the risk of a sagittal sinus rupture. In conclusion, pigs can undergo craniotomy and survive if the right measures are put in place.

Safety and biodegradability of a synthetic dural sealant patch (Liqoseal) in a porcine cranial model.

Background: Liqoseal consists of a watertight layer of poly(ester)ether urethane and an adhesive layer containing polyethylene glycol-N-hydroxysuccinimide (PEG-NHS). It is designed to prevent cerebrospinal fluid (CSF) leakage after intradural surgery. This study assessed the safety and biodegradability of Liqoseal in a porcine craniotomy model. Methods: In 32 pigs a craniotomy plus durotomy was performed. In 15 pigs Liqoseal was implanted, in 11 control pigs no sealant was implanted and in 6 control pigs a control dural sealant (Duraseal or Tachosil) was implanted. The safety of Liqoseal was evaluated by clinical, MRI and histological assessment. The degradation of Liqoseal was histologically estimated. Results: Liqoseal, 2 mm thick before application, did not swell and significantly was at maximum mean thickness of 2.14 (±0.37) mm at one month. The foreign body reaction induced by Liqoseal, Duraseal and Tachosil were comparable. Liqoseal showed no adherence to the arachnoid layer and was completely resorbed between 6 and 12 months postoperatively. In one animal with Liqoseal, an epidural fluid collection containing CSF could not be excluded. Conclusion: Liqoseal seems to be safe for intracranial use and is biodegradable. The safety and performance in humans needs to be further assessed in clinical trials.

Usefulness of Sealants for Dural Closure: Evaluation in an In Vitro Model.

BACKGROUND: Cerebrospinal fluid (CSF) leakage occurs in 4% to 32% of cranial surgeries and is associated with significant patient burden and expense. The use of sealant as an adjunct to primary dural closure is assumed to help prevent CSF leakage. OBJECTIVE: To examine the utility of different sealants for dural closure using an in Vitro model. METHODS: We evaluated 9 commonly used dural sealants, including Tachosil (Takeda Inc, Osaka, Japan), Adherus (Hyperbranch Inc, Durham, North Carolina), Duraform (Codman, Raynham, Massachusetts), Tissudura (Baxter, Deerfield, Illinois), Hemopatch (Baxter), TissuePatchDural (Tissuemed, Leeds, United Kingdom), Tisseel (Baxter), Duragen Secure (Integra, Plainsboro, New Jersey), and Duraseal, (Integra). Sealants were tested in 2 novel in Vitro setups using fresh porcine dura: the first tested the acute burst pressure of a sealed 3-mm gap, while the second examined resistance to a pressure wave mimicking intracranial pressure for 72 h. RESULTS: Adherus showed the highest mean burst pressure (87 ± 47 mmHg) followed by Tachosil (71 ± 16 mmHg) and Duraseal (51 ± 42 mmHg); these were the only 3 sealants showing burst pressures above normal physiological intracranial pressure. In the 72-h setup, only Adherus and Duraseal maintained appropriate sealing for the duration of the experiment. Tachosil released from the dura after 1.4 h (95% confidence interval, -1.8-4.7). CONCLUSION: Given the high cost of sealants and the results of this study, we advocate a critical attitude toward sealant application as an adjunct to classic dural closure.

Patency, flow, and endothelialization of the sutureless Excimer Laser Assisted Non-occlusive Anastomosis (ELANA) technique in a pig model.

OBJECT: The purpose of this study was to assess flow, patency, and endothelialization of bypasses created with the sutureless Excimer Laser Assisted Non-occlusive Anastomosis (SELANA) technique in a pig model. METHODS: In 38 pigs, a bypass was made on the left common carotid artery (CCA), using the right CCA as a graft, with 2 SELANAs. Bypass flow was measured using single-vessel flowmetry. The pigs were randomly assigned to 1 of 12 survival groups (1, 2, 3, 4, 5, 6, 7, and 10 days; 2 and 3 weeks; and 3 and 6 months). One extra animal underwent the procedure and then was killed after 1 hour of bypass patency to serve as a control. Angiography was performed just before the animals were killed, to assess bypass patency. Scanning electron microscopy and histological studies were used to evaluate the anastomoses after planned death. RESULTS: The mean SELANA bypass flow was not significantly different from the mean flow in the earlier ELANA (Excimer Laser Assisted Non-occlusive Anastomosis) pig study at opening and follow-up. Overall SELANA bypass patency (87%) was not significantly different from the ELANA patency of 86% in the earlier study. Complete SELANA endothelialization was observed after 2-3 weeks, compared with 2 weeks in the earlier ELANA study. CONCLUSIONS: The SELANA technique is not inferior to the current ELANA technique regarding flow, patency, and endothelialization. A pilot study in patients is a logical next step.