Sunday, April 11, 2010

Concerns Raised About Synthetic Glue for Hernia Repair

Boston—A study showing adverse effects from a synthetic cyanoacrylate tissue sealant used in an animal hernia model won the award for best paper in general surgery at the 2006 annual meeting of the Society of Laparoendoscopic Surgeons. Although the brand of synthetic surgical glue tested in the study is approved for use only in Europe, at least one other manufacturer of cyanoacrylate sealant is seeking approval from the FDA for its use in vascular surgery.
The study, in 16 rats, found that in all cases, the glue prevented tissue from adhering to or integrating with the mesh, impaired tissue flexibility and resulted in a severe inflammatory response marked by large seroma formations.
The cyanoacrylate examined in the study was Glubran 2, made by the Italian firm GEM S.r.l. (Viareggio, Italy) and approved for use in Europe in both traditional and laparoscopic surgery.
“It seems not very appropriate for hernia repair in an experimental model, to say the least,” said the lead author of the study, Alexander H. Petter-Puchner, MD, a surgical resident at the Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in Vienna, Austria.
Surgeons who heard the report said it comes amid a welcomed stream of studies into novel means for fixing mesh during hernia repair.
“There are a bunch of these cyanoacrylates that have been used clinically or investigationally as tissue adhesives,” said Raymond J. Lanzafame, MD, the immediate past president of the Society of Laparoendoscopic Surgeons. “The good news is that some of the the cyanoacrylate compounds are hydrophilic. But they, like the currently available cyanoacrylates, do generate a pretty intense inflammatory response. If it’s a version that isn’t broken down by the body in some way, it can turn out as bad as, if not worse than, a suture granuloma in terms of producing pain and irritation.”
Phillip Shadduck, MD, of Regional Surgical Associates in Durham, N.C., said in an interview after Dr. Petter-Puchner’s presentation that while a strong inflammatory response was seen in the study, newer cyanoacrylates might not evoke the same reaction. “We’ve learned in the abdomen, and now in the abdominal wall, that the chemistry of the cyanoacrylates makes a big difference in the inflammatory response it activates,” he said. “There are newer cyanoacrylates coming out in an effort to elicit less of an inflammatory response.”
One such cyanoacrylate, designed to be biodegradable, was approved for use in Europe in February 2005 as an adjunct to sutures during peripheral vascular reconstructions. The product, Omnex, is made by Closure Medical Corporation in Raleigh, N.C., which was recently acquired by Johnson & Johnson. (Dr. Shadduck reported that he has done consulting on the Omnex product.)
In March at the annual meeting of the Society for Clinical Vascular Surgery, results from a trial of 150 patients at 15 centers in the United States and Europe showed significant benefits for Omnex as an adjunctive sealant for vascular anastomoses compared with Surgicel Nu-Knit Absorbable Hemostat (Johnson & Johnson). The study found a statistically significant difference in time to hemostasis between the sealant, with a mean of 119.3 seconds, compared with Surgicel, with a mean of 403.8 seconds (P<0.001). Among patients in the Omnex group, 54.5% had immediate hemostasis, compared with only 10% in the Surgicel group (P<0.001). No significant difference in incidence of adverse events occurred between the two groups (P=0.60).
Using a compound similar to the one approved for external use in the United States under the trade name Dermabond, Omnex is under consideration by the FDA for internal use during vascular surgery.
Whether Omnex would have the kind of detrimental effects in hernia repair that were seen in Dr. Petter-Puchner’s study of Glubran 2 is unclear, but the chief of minimally invasive surgery at the department of surgery, Keck School of Medicine of USC, Los Angeles, said he would be “wary” of such a use.
“The artificial glues, or glues that have any artificial nature, stay around in the body and create a foreign body reaction,” said Namir Katkhouda, MD, who published the first study using a fibrin sealant, Tisseel, for mesh fixation in hernia repair (Ann Surg2001;233:18-25). “Some people have spun around the concept of using sealants in mesh fixation to these other adhesives [with artificial components]. I am absolutely wary of them. The important difference between the fibrin sealants and any artificial sealant is that the fibrin is naturally removed by the body at 10 days. That’s what you want.”
Tisseel, made by Baxter (Irvine, Calif.), is widely used in Europe for mesh fixation, but is currently approved in the United States only for cardiopulmonary bypass surgery, splenic repair and colostomy closure. A spokesman for Baxter said the company has a “strong desire” to broaden the indications for Tisseel in the United States.
In his award-winning paper, Dr. Petter-Puchner presented data on 20 Sprague Dawley rats, in which two defects per animal were created in the abdominal wall left and right of the linea alba (1.5 cm in diameter), with the peritoneum was spared. The lesions were left untreated for 10 days to achieve a chronic condition and then were covered with 2 cm×2 cm of mesh sealed with Glubran 2. Four of the animals were sacrificed after 17 days, eight after four weeks and another eight after 12 weeks. The meshes were then biomechanically tested and histology was performed.
At the 12-week mark, the hook-pull test revealed a loss of mesh adhesion wherever the sealant had been used. “There was no tissue integration through the mesh and histology revealed strong inflammation,” Dr. Petter-Puchner said during his presentation. “We also saw a huge seroma formation.”
Using a suction cone to test the elasticity of the tissue, his group found 4.2 mm of deformation in untreated areas, but just one-tenth that much in areas where Glubran had been applied, demonstrating a loss of flexibility.

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