Ann Thorac Surg 1997;63:352-355
© 1997 The Society of Thoracic Surgeons
Original Article: General Thoracic
Gelatin-Resorcinol-Formaldehyde-Glutaraldehyde Glue-Spread Stapler Prevents Air Leakage From the Lung
Hiroaki Nomori, MD,
Hirotoshi Horio, MD
Department of Surgery, Saiseikai Central Hospital, Tokyo, Japan
Accepted for publication September 12, 1996.
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Abstract
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Background. To reinforce the staple line of the emphysematous lung and thereby prevent air leakage during thoracoscopic operations, we have developed a procedure of lung excision that uses a gelatin-resorcinol-formaldehyde-glutaraldehyde (GRFG) glue-spread stapler.
Methods. Formaldehyde-glutaraldehyde (FG) jelly is prepared by mixing FG fluid with 2.5% sodium carboxymethyl cellulose. The FG jelly is placed in the stapler groove and staple holes, and a gelatin-resorcinol (GR) mixture is applied. The GRFG glue-spread stapler was applied to emphysematous lung cutting during thoracoscopic operations in 10 cases.
Results. An adhesion-strength test showed no difference in glue adhesion between FG fluid and FG jelly. An experiment using swine lung showed that with this newly developed stapler, no resistance in firing occurred, and GRFG glue covered every staple hole. Clinical application in 10 cases with emphysematous lung demonstrated no air leakage from the staple line, even long after the operation.
Conclusions. Emphysematous lung excision using the GRFG glue-spread stapler during thoracoscopic operations is useful in preventing air leakage from the staple line and is a simple, safe, and low-cost procedure.
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Introduction
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The most common complication after emphysematous lung excision is intraoperative or prolonged air leakage from the staple line [1, 2]. The use of gelatin-resorcinol-formaldehyde-glutaraldehyde (GRFG) glue as a tissue adhesive and hemostatic agent was first reported in 1966 [3, 4]. Since 1979, GRFG glue has been used successfully in operations for aortic dissection as a tissue adhesive and hemostatic agent [57]. Using these characteristics of GRFG glue, we have developed a procedure for lung excision using a GRFG glue-spread stapler to prevent air leakage from the staple line. In this report, we present the procedure, results of experiments, and preliminary clinical applications.
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Material and Methods
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The GRFG glue is manufactured by Cardial SA (Saint-Etienne, France). We use a 45-mm endoscopic stapler (ELC 45; Ethicon, Inc, Cincinnati, OH) for lung excision during thoracoscopic operations. To give viscosity to the formaldehyde-glutaraldehyde (FG) fluid, 2.5% sodium carboxymethyl cellulose (Koso Chemical Co, Ltd, Tokyo, Japan) is mixed with FG fluid to produce a jelly-like substance. After 0.2 mL of this FG jelly is placed on the reloading unit, the jelly is extended to the central groove and all staple holes using a spatula (Fig 1A
). Then 0.4 mL of the gelatin-resorcinol (GR) mixture is added (Fig 1B
). The FG jelly and the GR mixture are applied to the anvil jaw in the same manner.

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Fig 1. . (A) Formaldehyde-glutaraldehyde (FG) jelly, 0.2 mL, is placed on the reloading unit and then extended into the central groove and all staple holes using a spatula. (B) Gelatin-resorcinol (GR) mixture, 0.4 mL, is then spread on the reloading unit.
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The stapler must be applied to the cutting site within 3 minutes after GRFG glue is spread on the stapler, within which time the GR mixture is polymerized by the FG jelly (Fig 2A
). The cutting line must not be changed after the stapler jaws are closed, because doing so detaches the GRFG glue from the stapler. Firing the instrument expels the FG jelly from the groove and staple holes, thoroughly mixing the GR and FG. After the instrument is fired, the jaws must be kept closed for about 2 minutes before removal from the lung to enable the GR mixture to link sufficiently with the FG jelly and to optimize adherence of the GRFG glue to the staple line (Fig 2B
). If the stapler is to be used in further excision, the anvil jaw is cleaned by brushing.

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Fig 2. . (A) The gelatin-resorcinol-formaldehyde-glutaraldehyde (GRFG) glue-spread endoscopic stapler is applied at the cutting site. (B) Glue covers the staple line.
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To examine the difference in adhesion between the FG fluid and FG jelly, we performed an adhesion-strength test using bovine pericardial strips (Bio-Vascular Inc, Saint Paul, MN). Two bovine pericardial strips, 4 cm long and 1 cm wide, were used (Fig 3
). The concentrations of carboxymethyl cellulose in the FG jelly were prepared at 1%, 2%, 2.5%, and 3%. We spread 0.1 mL of the FG fluid or jelly and 0.2 mL of the GR mixture on both edges of the strips 1 x 1 cm in size. Each edge of the two strips was attached firmly each other with the compression 1.0 kg in weight. Ten minutes later, both edges of the strips were pulled horizontally by a spring scale machine (IM-20DX; Intesco Co, Matsudo, Japan), and the weight at the point when the strips pulled apart was measured. This experiment was repeated four times.

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Fig 3. . Adhesion-strength test. Two bovine pericardial strips, overlapped at the edges after spreading of the gelatin-resorcinolformaldehyde-glutaraldehyde glue, were pulled away from each other using a spring scale.
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Before clinical application, we experimented with stapler use six times on one swine lung. We used this procedure in 10 cases of emphysematous lung from May to August 1996. Of these, 5 cases involved giant emphysematous bullae resection, 4 lung carcinomas within the conspicuously emphysematous lung were resected by wedge resection, and 1 case of chronic obstructive pulmonary disease involved volume reduction operation. Histologic types of lung carcinomas were adenocarcinoma in 3 and squamous cell carcinoma in 1. Informed consent for using the GRFG glue-spread stapler was obtained from all patients before operation.
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Results
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The adhesion-strength test showed that the adhesive ability of the glue using the GR mixture and FG fluid was 1.4 ± 0.2 kg (Fig 4
). Combinations using FG jelly scored 1.5 ± 0.3 kg at a concentration of 1%, 1.5 ± 0.4 kg at 2%, 1.4 ± 0.2 kg at 2.5%, and 1.2 ± 0.3 kg at 3% of carboxymethyl cellulose. No difference in adhesive effect was observed between use of the original FG fluid and FG jelly.

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Fig 4. . Results of the adhesion-strength test show no difference in adhesion between the original formaldehyde-glutaraldehyde (FG) fluid (sodium carboxymethyl cellulose [CMC] 0%) and the FG jellies (sodium carboxylmethyl cellulose 1% to 3%). Bars = mean ± standard deviation.
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In the swine lung experiment, the margin cut by the stapler demonstrated that sufficient GRFG glue covered the staple line (Fig 5
). Glue did not adversely affect the advance of the knife within the stapler, even on overlapping stapler application.

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Fig 5. . Whitish gelatin-resorcinol-formaldehyde-glutaraldehyde glue (arrows) covers the staple line in the experiment using swine lung.
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In clinical applications in the 9 cases with emphysematous giant bullae or lung carcinoma, we observed no evidence of intraoperative or postoperative air leakage from the staple line and no other complications, such as infection or anaphylactic reaction. Except for 1 case, all chest tubes were removed within 4 days (mean, 2.8 days) after operation. In the remaining patient, who received volume reduction for chronic obstructive pulmonary disease, no intraoperative air leakage occurred from the staple line, but persistent air leakage occurred from the injured lung because of separation of the adhesive pleura, which resulted in removal of the chest tube 8 days after operation. Histologic studies showed glue coverage over the pleural surface of the emphysematous lung (Fig 6
).

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Fig 6. . Histologic studies from emphysematous lung excision in chronic obstructive pulmonary disease show glue coverage (arrows) of the pleural surface. (Hematoxylin and eosin; x50.)
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Comment
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Conventional emphysematous lung excision using a stapler causes problems of air leakage from the staple line because of the weakness of the tissue itself [1, 2]. Especially in video-assisted thoracoscopic surgery, air leakage from the staple line is often difficult to localize and suture, which may result in open thoracotomy or prolonged air leakage after operation.
The GRFG glue has been used successfully for hemostasis and as an adhesive agent in reconstructive vascular operations [57]. An experiment using rabbit lung also reported the usefulness of GRFG glue in pneumostasis of the injured lung [8]. In video-assisted thoracoscopic surgery, however, GRFG glue is difficult to apply accurately to the correct site, and the optimum ratio of the GR and FG components is difficult to determine. Compared with the procedure of dripping GRFG glue at the staple line under a thoracoscope, our procedure has the following advantages: (1) GRFG glue is spread accurately at the staple line and with the optimum ratio of GR and FG components; (2) GRFG glue covers each staple hole, which creates more effective pneumostasis; (3) GR and FG are mixed and linked sufficiently by closing the stapler jaws; and (4) excess FG fluid, which is highly histotoxic, is prevented from spilling out around the staple line.
Several procedures have been used to prevent or stop air leakage from the staple line during thoracoscopic operations. Fibrin glue used for such leakage has the disadvantage of low tissue adhesion, which often results in the recurrence of air leakage, and involves the risks of anaphylactic reaction and viral infection [8, 9]. To minimize air leakage from the staple line, Cooper and associates [1, 10] developed the use of bovine pericardial strips to buttress the staples. Compared with this procedure, our technique has the following advantages: (1) The cost of GRFG glue is approximately $100 per reloading unit, much cheaper than that of the bovine pericardial strips, which cost approximately $970 per reloading unit; and (2) even in overlapping applications of the stapler, the knife within the stapler can be smoothly advanced without resistance. The GRFG glue-spread stapler also appears to prevent hemorrhage from the staple line because GRFG itself is also hemostatic [47].
Before using FG jelly for spreading GRFG glue on the stapler, we had used the original FG fluid for 7 cases with emphysematous lung. The procedure using the FG fluid required that bone wax be packed at the central site of the groove to prevent FG fluid from spilling from the groove. This procedure had the following disadvantages: (1) bone wax packed at the central site of the groove generated some resistance to knife advancement within the stapler, and (2) bone wax packing caused trouble with multiple use of reloading units. We therefore developed the FG jelly to give viscosity to the FG fluid. The FG jelly, because of its viscosity, does not spill from the groove or staple holes, regardless of the angle. The adhesion-strength test showed no decrease of adhesive ability caused by using FG jelly as opposed to the original FG fluid. In addition, all kinds of staplers can be used for this procedure when the FG jelly is used.
The following points must be noted when using the GRFG glue-spread stapler: (1) After GRFG glue is added to the stapler, it must be used within 3 minutes, because the GR and FG components completely polymerize 5 to 10 minutes after contact; (2) the cutting line must not be changed after closing the stapler jaws, because this action detaches the GRFG glue from the jaws; and (3) after the stapler is fired, the jaws must be kept closed for at least 2 minutes to facilitate mixing of GR and FG and to ensure sufficient tissue adhesion.
The precise effect of the GRFG glue-spread stapler in preventing air leakage should be assessed by an air-leakage test using an animal model. Swine lung excised by a stapler without GRFG glue evinced no air leakage from the staple line, even at 60 cm H2O of pressure loading, however. From the results of our preliminary clinical experiments, including volume reduction operation for chronic obstructive pulmonary disease, we believe that the GRFG glue-spread stapler is useful in preventing air leakage from the staple line in the emphysematous lung. This is also a simple, safe, and low-cost procedure.
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Footnotes
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Address reprint requests to Dr Nomori, Department of Surgery, Saiseikai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo 108, Japan.
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References
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- Cooper JD, Trulock EP, Triantafillou AN, et al. Bilateral pneumectomy (volume reduction) for chronic obstructive pulmonary disease. J Thorac Cardiovasc Surg 1995;109:10619.[Abstract/Free Full Text]
- McKenna RJ Jr, Brenner M, Gelb AF, et al. A randomized, prospective trial of stapled lung reduction versus laser bullectomy for diffuse emphysema. J Thorac Cardiovasc Surg 1996;111:31722.[Abstract/Free Full Text]
- Tatooles CJ, Braunwald NS. The use of crosslinked gelatin as a tissue adhesive to control hemorrhage from liver and kidney. Surgery 1966;60:85761.[Medline]
- Braunwald NS, Gay W, Tatooles CJ. Evaluation of crosslinked gelatin as a tissue adhesive and hemostatic agent: an experimental study. Surgery 1966;59:102430.[Medline]
- Guilmet D, Bachet J, Goudot B, et al. Use of biological glue in acute aortic dissection. J Thorac Cardiovasc Surg 1979;77:51621.[Abstract]
- Bachet J, Goudot B, Teodori G, et al. Surgery of type A acute aortic dissection with gelatin-resorcine-formol biological glue: a twelve-year experience. J Cardiovasc Surg 1990;31:26373.[Medline]
- Bachet J, Gigou F, Laurian C, Bical O, Goudot B, Guilmet D. Four-year clinical experience with gelatin-resorcine-formol biological glue in acute aortic dissection. J Thorac Cardiovasc Surg 1982;83:2127.[Medline]
- Bellotto F, Johnson RG, Weintraub RM, Foley J, Thurer RL. Pneumostasis of injured lung in rabbits with gelatin-resorcinol formaldehyde-glutaraldehyde tissue adhesive. Surg Gynecol Obstet 1992;174:2214.[Medline]
- Mitsuhata H, Horiguchi Y, Saitoh J, et al. An anaphylactic reaction of topical fibrin glue. Anesthesiology 1994;81:10747.[Medline]
- Cooper JD. Technique to reduce air leaks after resection of emphysematous lung. Ann Thorac Surg 1994;57:10389.[Abstract]
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