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THE USE OF PLASTIC ADHESIVE IN PULMONARY SURGERY
THE USE OF PLASTIC ADHESIVE I N P U L M O N A R Y
SURGERY
Robert ]. Wilder, M.D. (by invitation),
invitation),
Michael Bryant (by invitation),
D
Herman Playforth
(by
and Mark M. Ravitch, M.D., Baltimore,
Md.
the past several years, the adhesion of living tissue with a glue or paste substance has intrigued many investigators. This report concerns experiments with a plastic adhesive called "Eastman 910 monomer" (methyl2-cyanoacrylate). It differs from previous adhesives in the fact that polymer ization occurs without the use of excessive pressure, heat, or the addition of a catalyzer. The adhesive forms a strong bond within seconds to minutes and adherence is not influenced by the presence of water or by temperature elevation. Polymerization is catalyzed either by modest pressures or by minute amounts of water. The plastic adhesive is resistant to alcohol, benzene, and acetone, but is slightly affected by weak acids or bases. It forms a strong bond between large numbers of materials, with polyethylene as one exception. Since 1960, reports have appeared concerning the use of Eastman 910 ad hesive for arteries,1"6 veins,7 skin,8 intestine, 9 bone,10 dural substitutes, 11 ex tremity transection, 12 nephrotomy closure,13 and for the control of hemor rhage. 14 In December of 1961, Dr. John E. Healey, Jr., 15 stated that his group was testing plastic adhesive in the repair of body tissues, such as the bile ducts, ureters, intestines and, in 1962, he reported on its use for bronchial closure.16 Our experiments were designed to determine the value of a rapidly poly merizing adhesive in pulmonary surgery. Eastman 910 monomer was, there fore, used for closing bronchi, for sealing raw parenchymal surfaces, and for anastomosing bronchi. In addition, three methods of bronchial stump closure— silk sutures, tantalum staples, and adhesive—were compared in the face of heavy bacterial contamination. URING
METHOD
Four groups of experiments were set up. Group 1.—Left or right pneumonectomy in mongrel dogs, weighing 12 to 16 kilograms, was performed under general anesthesia. The bronchial closure From the Departments of Surgery, Baltimore City Hospitals and the Johns Hopkins University School of Medicine, Baltimore, Md. Supported by a Grant-in-Ald from Ethicon, Inc., and by National Institutes of Health Grant H-5245. Read at the Porty-third Annual Meeting of The American Association for Thoracic Surgery at Houston, Texas. April 8-10, 1963.
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was carried out using Eastman 910 monomer only. In order to close the bronchus, a noncrushing Satinsky-type clamp was used to occlude the bronchus temporarily and the open bronchial stump was dried with a gauze sponge. Two or three drops of liquid adhesive from the cold-sterilized container were applied to the inside of the bronchial stump. The bronchial walls were then approximated with moderate pressure by using the fingers or a right-angle clamp. All instruments used were siliconized to prevent adherence of the tissue to the instruments as a result of spillage. Firm pressure was applied for 30 to 60 seconds after which the clamp was removed. The bronchial closure was tested under water and, if necessary, the closure was repeated with ad ditional adhesive applied both to the inside of the stump and also over the edges of the closed bronchus. The stump, deliberately a long one, was left un covered and the chest closed. No chest tubes were used and the animal was returned to his cage after spontaneous respiration was reestablished. Animals were sacrificed immediately and at intervals in order to examine the closure. Group 2.—In an attempt to determine the efficacy of adhesive closure in the face of bacterial contamination, the entire circumference of the open bronchus was painted with a swab from a 16 hour broth culture of Staphylococcus aureus. After 2 minutes, the orifice was dried with a second swab and bronchial closure was performed. In an initial control group of 18 animals, the bronchi so prepared were closed with interrupted silk sutures. The bronchial stump was left long and free in the pleural cavity in order to provide a severe test. The contaminated bronchus was then closed in 10 animals with interrupted silk sutures, in 10 animals with the Russian stapling device UKB 40 using tantalum staples, and in 10 animals with Eastman 910 monomer. In all cases, the bronchial stump was purposely left long and there was no closure of the mediastinal pleura or any other tissue over the stump. Hemostasis was secured and the pleural cavity was closed. After spontaneous respiration was re-established, the dog was returned to his cage. Group 3A.—This group consisted of 9 dogs in which an attempt was made to determine the value of sealing a raw pulmonary parenchymal sur face with Eastman 910 monomer. Segments of the upper lobe, approximately 5 by 2 cm., were amputated just distal to a noncrushing rubber-shod intes tinal clamp used to keep the raw surface free from blood and air leaks during application of the adherent. As soon as the surface was dry, 10 to 20 drops of adhesive were applied to the raw surface. Polymerization of the ad hesive was accelerated by applying several drops of water. This procedure was repeated two to three times until the entire surface appeared sealed. The clamp was removed, the lung expanded, and the chest was closed with out a chest tube. Group 3B.—In 23 dogs, a 5 by 2 cm. tip of upper lobe was amputated distal to a noncrushing clamp left on for 3 to 4 minutes ordinarily needed for application of Eastman 910 adhesive. In 9 control animals, the lungs were then inflated, the chest was closed without tube drainage, and the dogs were returned to their cages. In ten additional animals, a pericardial patch was
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applied to the raw surface using 3 to 5 drops of Eastman 910 monomer. Finger pressure was applied to the patch in order to polymerize the adhesive. After 2 to 3 minutes, the clamp was released, the lung was expanded, and the chest closed. After the dog breathed spontaneously, he was returned to his cage. Group 4.—In this series, attempts were made to re-anastomose a tran sected left main-stem bronchus with the use of Eastman 910 monomer. After the bronchus was cleaned and transected, the proximal and distal ends of the bronchus were brought together and several drops of adhesive were applied to the severed ends. Several methods were used to bring the ends together and apply pressure to induce polymerization. At first, with the use of stay sutures, the divided ends of the bronchus were brought together with the distal stump adherent to the inside of the proximal stump. Attempts at eversion of the anastomotie junction were not successful. After confirming the fact that Eastman 910 monomer did not adhere to polyethylene, a polyethylene tube was used as a stent and two temporary approximation sutures made it possible to bring together the divided bronchus without inserting one end into another. A pericardial patch with additional adherent was wrapped around the anastomosis. The chest was closed without tube drainage and, after spontaneous respirations had resumed, a bronchoscope was passed and the stent was removed with a bronchoscopic forceps. The animal was then returned to his cage. RESULTS
Group 1.—In Group 1, pneumonectomy was performed and the bronchial stump was closed with Eastman 910 monomer. Eighteen attempts were made in this series. Four animals were sacrificed immediately and the bronchial closure was tested by blocking the expiratory valve of the automatic respirator and by raising the pressure in the bronchial tree until the bronchial closure leaked. It required a pressure between 70 and 80 mm. Hg before an air leak appeared and a pressure between 82 and 100 mm. Hg before the bronchial closure ruptured completely. Similar tests performed on 2 animals with suture closure of the bronchus and 2 with tantalum staple closure demonstrated air leaks between 30 and 50 mm. Hg but no complete rupture, even at pressures of 300 mm. Hg. Four additional animals were sacrificed from 3 to 7 days after bronchial closure for inspection. The bronchi were all sealed and the pleural cavity clean. The security of the closure was again tested in 2 and it was possible to reach a pressure of 120 mm. Hg before a leak was noted. Eight of the 10 remaining animals were well up to the time of sacrifice 2*4 months later. Bronchograms revealed well-healed bronchial stumps. Post mortem examination demonstrated air-tight closures that resisted pressures up to 300 mm. Hg. Histologic sections taken 2y 2 months after the bronchial closure demonstrated minimal submucosal fibrosis and minimal inflammation. The cilia in the area about the closure were lost. In several areas, various-shaped spaces were present in the mucosa representing residual adhesive. In addition, there was minimal squamous metaplasia at the closure. Sections at 5 months revealed only minimal
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fibrosis and no squamous metaplasia. Of the 2 animals that died, one succumbed 5 hours after the operation. The bronchial stump was securely closed and there was some congestion and atelectasis of the opposite lung. This was thought to be a death due to anesthesia. A second animal died 28 days after operation. Post mortem bronchogram and inflation demonstrated no leak. The remaining lung was grossly infected with abscess formation in the lower lobe. Group 2.—In Group 2, to establish more strenuous tests for bronchial closure, 18 control animals underwent pneumonectomy and silk suture closure of the staphylococeus-contaminated bronchus. Of these 18 animals, 12 died within the first 7 days. Bronchopleural fistulas could be demonstrated by x-ray and postmortem examination in 8 of the 12 animals that died within the first week. In 2 of the 4 animals that died with no bronchopleural fistulas demon strated, empyema and pulmonary infection were present. In the 2 other animals, except for minimal atelectasis, there was no obvious cause of death. The remaining 6 animals were followed and 3 additional late deaths occurred with demonstrable bronchopleural fistula formation in each instance. When the 3 animals that survived were finally sacrificed after 3 months, the bronchi were found securely healed and capable of withstanding pressures of 300 mm. Hg. After this preliminary control series, the staphylococcus-inoculated bron chial stumps of 30 animals who underwent pneumonectomy were closed in 10 dogs each, with tantalum staples, silk sutures, and Eastman 910 monomer. In the 10 experiments in which the bronchi were closed with silk sutures, 7 animals died within the first week. Bronchopleural fistulas could be demon strated in 6 of them. The remaining animals survived until the twenty-sixth day when an additional animal died without obvious reason. In those 10 animals in which the bronchus was closed with tantalum staples with the Eussian stapling device, 7 animals died during the first week and an additional animal died on the eleventh postoperative day. Bronchopleural fistulas were confirmed in all cases. Of the 10 animals in which the bronchus was closed with Eastman 910 monomer, 7 animals died postoperatively and a broncho pleural fistula could be demonstrated in 6. The obvious cause of death in these animals was air leak and empyema. It is clear that the results are essentially similar in all three groups as far as the mortality rate and formation rate of bronchopleural fistulas are concerned. The usual day of death was on the fourth or fifth day for all groups. In the surviving animals, however, closure of the contaminated bronchi with sutures or tantalum staples resulted in healing with ultimate rejection of the silk suture or tantalum staple from the suture line. In those animals that survived after closure with adhesive, there was no gross foreign body to reject (Fig. 1). The adhesive was not grossly visible but various-shaped spaces, presumably representing bits of adhesive, could be made out microscopically in the mucosa and submucosa at 21/2 months and at 5 months (Fig. 2). Even though these animals survived and the bronchi were sealed, there was marked subacute and chronic reaction around the closure on histologic examination with all three methods of closure.
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Group 3A.—A method for sealing a raw edge of pulmonary parenchyma might prove quite valuable. An attempt was made, therefore, to seal a raw surface of the lung with adhesive. In 9 animals, a noncrushing rubber-shod clamp was applied to the parenchyma and a small portion of the upper lobe, approximately 2 by 5 cm., was amputated. It was then possible to dry the raw
Fig. 1.—Autopsy appearance of bronchial stumps 2% months after closure of staphylococcus-contaminated bronchi. A, Silk closure—the bronchus is securely closed but the silk is working its way into the lumen. B, Tantalum staple closure—in contrast to the invariable experience with clean bronchial closures in clinical practice, the staples here are working loose, although the bronchus is firmly healed. C, Adhesive closure—the bronchus is securely sealed without gross foreign body rejection.
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surface and apply a large quantity of adhesive. As soon as the adhesive was applied, several drops of water were added to polymerize the glue. Three of 9 animals were alive and well after 5 months. Six animals died from the fifth to the twenty-first day. The most frequent cause of death was air leak and atelectasis and infection from the raw area. In those animals that died, the adhesive appeared to curl away from the edges and flake, allowing airleaks and infection to occur (Fig. 3). These leaks were peripheral and could
Fig. 2.—Adhesive closure of contaminated bronchus. Minimal submucosal reaction, and squamous metaplasia present 5 months after adhesive closure of a staphylococcus-contaminated bronchus. (Hematoxylin and eosin; X50 ; reduced %.)
not be demonstrated by postmortem bronchograms. In all animals that survived and were sacrificed 5 months later, the area of the pulmonary resection was markedly adherent to the chest wall. Histologic examination revealed variousshaped spaces where adhesive was still present and a marked reaction in the lung below, with ghost cells and a zone of acute inflammation and purulent bronchitis and abscess formation (Fig. 4, A ) . Group 3B.—Amputation of the tip of an upper lobe was performed in 14 animals with removal of a 2 by 5 cm. area of lung. The raw area was covered with a pericardial patch secured with adhesive. Twelve animals sur vived for approximately 3 months before being sacrificed. Two animals died 28 and 44 days after the procedure and postmortem examination demonstrated total empyema. In these two instances, the patches were still present but ap peared to be loose and not adherent to the parenchyma. In the 12 animals who survived and were sacrificed after 3 months, the pericardium was found
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to be an integral part of the pleural surface, shrunken in area but still recognizable. There were only filmy adhesions. Histologic examination (Pig. 4,5) confirmed the survival of the patch which was slightly edematous but healed to the lung parenchyma as demonstrated by fibroblastic invasion of the pericardium at certain points. Microscopic examination of the lung under neath the patch revealed normal healthy lung tissues in some instances and, more commonly, small areas of atelectasis and chronic inflammation. Since much of the experiment was based on the survival of animals, it was decided to test the effect of amputating a small area of lung. In 9 control animals a similar 2 by 5 cm. tip of upper lobe was amputated as before and the chest was closed. The animal was put back in his cage without further treat ment except for expansion of the lung. Six animals survived, the amputated tip of the lung was markedly adherent to the chest wall and there was fibrotic reaction and old, localized hemothorax present. In the 12 of 14 ani mals that survived in which a pericardial patch had been used, the lung was totally expanded, the pleural cavity was clean, and only a few filmy adhesions were present between the patch and the chest wall. Group 4.—In Group 4, transection and re-anastomosis of the left main-stem bronchus was performed in 18 animals. Application of Eastman 910 monomer to the divided ends was not simple and the adherent frequently ran onto the other tissue. It was possible, however, to glue the two ends together and the animal survived. In the first four experiments, with the transected bronchus brought together using two temporary stay sutures for approximation, all animals sur vived without leakage. With this method the distal stump usually became in serted into the proximal stump. At sacrifice 3 months to 5 months later, there was almost complete stenosis at the anastomosis in one animal and moderate to minimal stenosis in the 3 others, although there was full expansion of the lungs. In these 3 animals the lining of the bronchus was grossly healed, although microscopically there was marked submucosal fibrosis and chronic inflammatory reaction. The use of a stent allowed the operator to slide the bronchial ends together and compress them against a firm surface in order to polymerize the adhesive. Because Eastman 910 monomer does not adhere to polyethylene, tubes of this substance were used as stents in 14 animals. In the first 4 of this group, the animals were tested immediately after the anastomosis and all animals developed small air leaks at 20 to 35 mg. Hg and large leaks at higher airway pressures. In the next 10 animals, therefore, a pericardial patch was wrapped around the anastomosis for additional support. Technical mishaps resulted in the immediate death of 2 animals, and 2 died on the second and third postoperative days of bronchopleural fistulas. Postmortem bronchograms demonstrated a small leak at the anastomosis in each animal but the lumen itself was not compromised. Six animals are alive and well, but for periods too short to allow for determination of the ultimate character of the anastomosis.
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Pig. 3.—Appearance of Eastman 910 monomer 11 days after application to a segmental surface. The adhesive is brittle and has retracted from the edges of the wound. Sealing is not complete.
T-.
Pig. 4.—A, 11 days after application of adhesive only to raw lung surface. Various-shaped spaces on the surface of the specimen represent the adhesive applied directly to a pulmonary segmental area. Marked reaction below the adhesive is present with ghost cells and a zone of acute inflammation. (Hematoxylin and eosin; X50 ; reduced %.) B, Appearance of pericardia! patch 3 months after application with Eastman 910 monomer. Note minimal reaction in pulmonary parenchyma and growth of nbroblasts from the pul monary parenchyma Into the pericardial patch. (Hematoxylin and eosin; X50 ; reduced Vi.)
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DISCUSSION
The adhesive action ,6f alkyl 2-cyanoaerylates was discovered during an investigation of polymers from 1, 1-disubstituted ethylenes. 17 A drop of highly purified ethyl-2-cyanoacrylate was placed between the prisms of an Abbe refractometer in order to obtain its refractive index. When an attempt was made to open the refractometer, the prisms could not be pulled apart. 17 As a result, methyl-2-cyanoacrylate (Eastman 910 monomer) was developed. Previous inves tigations by other workers seem to indicate that plastic adhesives of this nature will find a place in surgery.1"16 Its role either as an adjunctive or as a definitive agent is not yet completely elucidated. The dog bronchus may be completely closed with the use of Eastman 910 monomer. In the present series of experiments, comparison of silk suture, tantalum staple, and adhesive closures indicates that methyl-2-cyanoacrylate was as successful as the other two standardized techniques. Experiments in which uncontaminated bronchi were closed demonstrated a solid union. There was, however, minimal squamous metaplasia and submucosal inflammatory reac tion present, even after 3 months. Except for this reaction, the application of adhesive did not interfere with proper healing. In two instances it was necessary to apply the adhesive two or three times before complete sealing was accom plished. The use of adhesive alone on a raw surface of lung did not appear satisfac tory. Fig. 3 illustrates the flaky and crusty appearance of the paste approxi mately 11 days after application. The adhesive appeared to control hemorrhage but was not adequate for sealing of the bronchi. In the animals in which a piece of pericardium was applied, the patch adhered and survived satisfactorily as was indicated by survival of 12 out of 14 animals. The adhesive did not appear to interfere with healing of the pericardial patch and the pericardium became an integral part of the lung surface. The 2 dogs that died did so 28 and 44 days after the procedure and, in these instances, the patch appeared to be loose at several points and not an integral part of the parenchyma. It is interesting to note that dogs with pericardial patches and dogs without any treatment did better after amputation of the tip of lung, 2 by 5 cm., than those dogs which had adhesive only applied to the raw area. The use of adhesive for bronchial anastomosis certainly appears possible, but the technique requires further evaluation. The problem of maintaining an adequate lumen has been overcome by using a polyethylene stent which is removed bronchoscopically at the completion of the procedure. "With the increasing use of preoperative irradiation for pulmonary cancer, and the resulting friable tissue frequently encountered, the use of adhesive for bronchial closure or as an adjunct to suture or metallic closure may be an addi tion to the surgeon's armamentarium. Its use alone as a surface sealing agent is contraindicated from these experiments. With pericardial patches, however, Eastman 910 monomer seals raw segmental areas allowing the patch to become an integral part of the pleural surface. It is certainly possible to anastomose the
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transected bronchus with adhesive but the advantage of this method and the technical problems involved need further investigation. SUMMARY
1. Fourteen bronchial closures after pneumonectomy have been successfully performed with Eastman 910 monomer in the dog. 2. A comparison of staphylococcus-contaminated bronchial stumps closed with silk sutures, tantalum staples, and adhesive demonstrated no difference be tween the three methods, with high failure rates in all. 3. Pericardial patches applied with adhesive to the raw surface of pul monary parenchyma prevented blood loss and air leaks and became an integral part of the lung surface. Use of adhesive alone resulted in the death of two thirds of the animals. 4. Bronchial anastomosis with adhesive alone is possible with the aid of a polyethylene stent. REFERENCES 1. Carton, C. A., Kessler, L. A., Seidenberg, B., and Hurwitt, E. S.: A Plastic Adhesive Method of Small Blood Vessel Surgery, World Neurol. 1: 4, 1960. 2. Kessler, L. A., and Carton, C. A.: Experimental Studies in Surgery of Small Blood Vessels With the Use of Plastic Adhesive. I I I . Prevention of Aneurysmal Dilata tion, S. Forum 1 1 : 403, 1960. 3. Carton, C. A., Kessler, L. A., Seidenberg, B., and Hurwitt, E. S.: Experimental Studies in the Surgery of Small Blood Vessels. IV. Non-Suture Anastomosis of Arteries and Veins, Using Flanged Ring Prostheses and Plastic Adhesive, S. Forum 1 1 : 238, 1960. 4. Carton, C. A., Kessler, L. A., Seidenberg, B., and H u r w i t t , E. S.: Experimental Studies in Surgery of Small Blood Vessels. I I . Patching of Arteriotomy Using a Plastic Adhesive, J . Neurosurg. 18: 2, 1961. 5. Healy, J . E., Jr., Moore, E. B., Brooks, B. J., and Sheena, K. S.: A Vascular Clamp for Circumferential Repair of Blood Vessels, Surgery 5 1 : 4, 1962. 6. Healey, J . E., Jr., Clark, R. L., Gallager, H. S., O'Neill, P., and Sheena, K. S.: Nonsuture Repair of Blood Vessels, Ann. Surg. 155: 6, 1962. 7. Healey, J . E., Jr., Brooks, B. J., Gallager, S., Moore, E, B., and Sheena, K. S.: A Technique for Nonsuture Repair of Veins, J . Surg. Res. 1: 4, 1961. 8. Ashley, F . L., Polak, T., and Berman, O. D.: Nonsutured Closure of Skin Lacerations and Nonsutured Grafting of Skin With a Rapidly Polymerizing Adhesive, Quart. Bull. Northwestern Univ. Med. School 36: No. 3, 1962. 9. Inou, T.: Studies on the Surgical Use of Plastic Adhesive, Am. J . Proctol. 13: 4, 1962. 10. Lighterman, I., and Farrell, J . J . : Treatment of Experimentally Induced Mandibular Fractures With Plastic Polymers, S. Forum 13: 466, 1962. 11. Albin, M. S., D'Agostino, A. N., White, R. J., and Grindlay, J . H . : Nonsuture Sealing of a Dural Substitute Utilizing a Plastic Adhesive, Methyl-2-cyanoacrylate, J . Neurosurg. 19: 545, 1962. 12. MacDonald, G. L., Jr., Tose, L., and Deterling, R. A., J r . : A Technique for Reimplantation of t h e Dog Limb Involving the Use of a Mechanical Stapling Device and a Rapidly Polymerizing Adhesive, S. Forum 13: 88, 1962. 13. Mathes, G. L., and Terry, J . W., J r . : Non-suture Closure of Nephrotomy, . J . Urol. 89: 122, 1963. 14. Braunwald, N. S., and Awe, W. C.: Control of Hemorrhage From the Heart and Aorta Utilizing a Plastic Adhesive, Surgery 5 1 : 786, 1962. 15. Healey, J . E., Jr., Clark, R. L., Gallager, H. S., O'Neill, P., and Sheena, K. S.: Non suture Repair of Blood Vessels, Ann. Surg. 155: 817, 1962. 16. Healey, J . E., Jr., Sheena, K. S., Gallager, H. S., Clark, R. L., and O'Neill, P . : The Use of a Plastic Adhesive in the Technique of Bronchial Closure, S. Forum 13: 153, 1962. 17. Coover, H. W., Jr., Joyner, F . B., Shearer, N. H., Jr., and Wicker, T. H., J r . : Chemistry and Performance of Cyanoacrylate Adhesives, S P E Journal, Vol. 15, 1959.
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DISCUSSION
DR. LYMAN A. EREWER, I I I , Los Angeles, Calif.—The authors have presented a most interesting study on the use of a plastic adhesive to seal the bronchial closures, bronchial anastomoses, and raw surface of the lung. In 1952 we presented to this Asso ciation a technique of applying a pedicled pericardia! fat graft for a similar purpose. I should like to present to you this morning our subsequent results with this technique. Like the authors, we found in experimental animals that the pericardial fat graft successfully sealed over open bronchi. I n the human the pericardial f a t pad being larger with a better blood supply is, therefore, a more satisfactory protective graft than in the experi mental animal. [Slide] This slide shows that the graft in a human has an excellent blood supply from the internal mammary artery, making this really a thoracic omentum. [Slide] Here you can see that the graft when developed is viable due to a satisfactory blood supply. I t is tightly sewn to the bronchial stump in four quadrants, protecting it much like a bathing cap. Our experience now covers over 500 cases, 472 lobectomies or pneumonectomies and 34 bronchoplastic or grafting procedures. This technique of sealing the bronchial stump with the graft has resulted in a decrease of bronchopleural fistula from 8 to less than 2 per cent. This technique is especially valuable in the diseased bronchus when the bronchus is friable and leaks after the closure. With the pedicled pericardial fat graft one need not be concerned now about little leaks, as the graft effectively seals the bronchial stump. On one occasion, in performing postoperative bronchial aspiration after a pneumonectomy, our resident much to his horror, poked the aspirating catheter through the stump of the right main bronchus. A large amount of bloody fluid was aspirated from the right pleural cavity. This patient was treated expectantly and we were relieved that the graft effectively sealed the opened bronchial stump. [Slide] Our method of bronchial closure has added to the successful healing of the bronchial stump. I t is most important to remember that the posterior membranous wall can be mobilized and brought up as a flap to the rigid cartilaginous ring without tension. The cartilage is a spring, whose function is to keep the bronchus open. Because it cannot be flattened out or squeezed together—the bronchial stump leaks. However, the membranous flap may be mobilized and sutured to the cartilaginous wall without tension to effect a stable closure. Like the authors, we found that suture material, which we once thought was important, is not important; what is important is the way the sutures are put in and that tensions on the closure is avoided. The thirty-four plastic operations on the trachea and bronchi are of considerable interest, but time permits the presentation of only one case. [Slide] This is a diagram of a carcinoma of the trachea which was resected from just at the level of the carina up into the cervical region. A fascia lata graft reinforced with wire mesh was used. The fat graft was placed around the distal stump. The sutures through the right stem bronchus did not hold and there was a distressing air leak. How ever, the thoracic omentum graft was sutured solidly around the anastomosis with no subsequent air leak. [Slide] The patient had a good airway and was well 3 months after operation until a fatal coronary thrombosis occurred. This is a postmortem specimen which shows the fat graft well fixed to both the right and left stem bronchi and the artificial trachea. The lumen of the trachea was adequate. The stent was covered with mucosa, and here you see where the fat graft had sealed the trachea. Thus, we have found that the pedicled pericardial fat graft, or thoracic omentum, will effectively seal the bronchial stump after pulmonary resection. I t is particularly effective when there is a diseased bronchus in which the sutures do not hold. We believe this will result in a lowered incidence of bronchopleural fistula, and will give the surgeon considerable security with regard to this unfortunate complication.
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The authors' results with Eastman 910 monomer plastic adhesive to seal raw sur faces of the lung and the bronchial stump, when challenged with infection, are impressive. Reports on clinical use will be of great interest. They are to be congratulated on an excellent study. DR. A L F R E D GOLDMAN, Beverly Hills, Calif.—It is extremely difficult to follow such a beautiful discussion as Dr. Brewer's, and the excellent paper by Dr. Wilder and Dr. Ravitch and their group. I wish to confine my remarks to that portion of the paper re lating to the tantalum staples and to that portion of tantalum stapling useful for re section of peripheral portions of the parenchyma. As you noticed in the presentation, they did not do quite so well with the peripheral resections. [Slide] This slide shows a Soviet instrument known as UKL-60. The main differ ence from the U K B used by Dr. Ravitch is the weight, nearly 500 grams, and the number and manner in which the staples are placed in the tissue. Like the U K B , it has only one purpose, that is to perform suture closure of open, gaping tissue, whether it is peripheral parenchyma, bronchi, or blood vessels. I n this respect it differs absolutely from the vascular suturing structures, the purpose of which is to perform suture patency. This is the magazine mounted on a movable jaw activated by the screw " S . " This jaw contains the staple pushers inside of " J - 2 , " and they are activated by this handle which is squeezed by the hand. The tantalum staples are 4 by 4.8 by 0.3 mm., and are ready for injection when the tissue to be sutured is compressed to 3 mm. thickness between the jaws " J - l " and " J - 2 . " The magazine holds twenty-one staples in two staggered rows, and, when ejected, they make forty-two stitches as shown here. [Slide] This slide is an x-ray film of the chest in a human bilateral pulmonary re section. Note the " B " shape of the sutures. [Slide] Dogs were used for study of lung wound healing. The lower suture line was for a cuff of lung, oversewn with running 5-0 silk. The upper was amputated flush with the suture line. This x-ray film was made 3 months after the thoraeotomy and shows less expansion in the oversewn silk suture line when compared with the flush amputation with out the silk being oversewn. [Slide] This slide shows the gross appearance of these two suture lines, the upper one here, and the oversewn one here. The obvious cleaner-looking healing is shown here as compared with the oversewn silk suture line. Microscopically there were less reaction of inflammatory cells in this suture line than in this one, where after 3 months, there was still some granulomatous formation. [Slide] By injecting the pulmonary artery with oily Dionosil the vasculature of the suture line can be studied in expansion and deflation. Note the absence of vascular dis tortion in both suture lines, as well as the ability of the suture line to expand with 20 mm. Hg. pressure at the trachea. Bronchial architecture is also maintained, as you can judge from the fact that the soft tissue vasculature is maintained, but this was also shown in the other studies. This slide shows that the expansibility of the suture line is maintained. [Slide] This slide shows a photomicrograph of higher power, magnified approximately ten times at the suture line. Note that the size of the openings in the stitches and the numerous patent blood vessels can be visualized. These are small blood vessels, some of which appear to go through the openings in these staples. This slide also shows that such' tantalum sutures are compressive but not necrotizing. We feel that this study repre sents, probably, some superior healing over ordinary silk suturing. We have used this instrument in 60 clinical cases and have been quite satisfied with it. DR. STANLEY F E L L , Bronx, N. Y.—At Montefiore Hospital we have been employing the Eastman 910 adhesive in studies similar to Dr. Wilder's. Our main concern has been the control of air leak from raw lung surfaces rather than from the bronchus, which is susceptible
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to suture closure. In dogs we created superficial raw areas of lung and glued them to adjacent intact lobes rather than applying grafts of any type. These broad, raw areas could be consistently glued with success. However, in wedge resections of 30 per cent to 50 per cent of a lobe we had a 50 per cent incidence of bronchopleural fistula, no matter how the glue was applied. Similarly, we evaluated the utilization of the adhesive in the management of spon taneous pneumothorax. Pneumothorax was induced in dogs via an intercostal catheter. The adhesive was instilled intrapleurally at another site. The lung was promptly re-expanded while the animal was positioned for maximum distribution of the adhesive. At re-exploration of these dogs' chests several weeks later, we did not produce a significant pleurodesis, but there was a high incidence of trapped lungs and empyema. I don't believe we can state at this time what clinical applications this adhesive will have in pulmonary surgery. I wish to thank the Association for the privilege of the floor.
SURGERY
Robert ]. Wilder, M.D. (by invitation),
invitation),
Michael Bryant (by invitation),
D
Herman Playforth
(by
and Mark M. Ravitch, M.D., Baltimore,
Md.
the past several years, the adhesion of living tissue with a glue or paste substance has intrigued many investigators. This report concerns experiments with a plastic adhesive called "Eastman 910 monomer" (methyl2-cyanoacrylate). It differs from previous adhesives in the fact that polymer ization occurs without the use of excessive pressure, heat, or the addition of a catalyzer. The adhesive forms a strong bond within seconds to minutes and adherence is not influenced by the presence of water or by temperature elevation. Polymerization is catalyzed either by modest pressures or by minute amounts of water. The plastic adhesive is resistant to alcohol, benzene, and acetone, but is slightly affected by weak acids or bases. It forms a strong bond between large numbers of materials, with polyethylene as one exception. Since 1960, reports have appeared concerning the use of Eastman 910 ad hesive for arteries,1"6 veins,7 skin,8 intestine, 9 bone,10 dural substitutes, 11 ex tremity transection, 12 nephrotomy closure,13 and for the control of hemor rhage. 14 In December of 1961, Dr. John E. Healey, Jr., 15 stated that his group was testing plastic adhesive in the repair of body tissues, such as the bile ducts, ureters, intestines and, in 1962, he reported on its use for bronchial closure.16 Our experiments were designed to determine the value of a rapidly poly merizing adhesive in pulmonary surgery. Eastman 910 monomer was, there fore, used for closing bronchi, for sealing raw parenchymal surfaces, and for anastomosing bronchi. In addition, three methods of bronchial stump closure— silk sutures, tantalum staples, and adhesive—were compared in the face of heavy bacterial contamination. URING
METHOD
Four groups of experiments were set up. Group 1.—Left or right pneumonectomy in mongrel dogs, weighing 12 to 16 kilograms, was performed under general anesthesia. The bronchial closure From the Departments of Surgery, Baltimore City Hospitals and the Johns Hopkins University School of Medicine, Baltimore, Md. Supported by a Grant-in-Ald from Ethicon, Inc., and by National Institutes of Health Grant H-5245. Read at the Porty-third Annual Meeting of The American Association for Thoracic Surgery at Houston, Texas. April 8-10, 1963.
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was carried out using Eastman 910 monomer only. In order to close the bronchus, a noncrushing Satinsky-type clamp was used to occlude the bronchus temporarily and the open bronchial stump was dried with a gauze sponge. Two or three drops of liquid adhesive from the cold-sterilized container were applied to the inside of the bronchial stump. The bronchial walls were then approximated with moderate pressure by using the fingers or a right-angle clamp. All instruments used were siliconized to prevent adherence of the tissue to the instruments as a result of spillage. Firm pressure was applied for 30 to 60 seconds after which the clamp was removed. The bronchial closure was tested under water and, if necessary, the closure was repeated with ad ditional adhesive applied both to the inside of the stump and also over the edges of the closed bronchus. The stump, deliberately a long one, was left un covered and the chest closed. No chest tubes were used and the animal was returned to his cage after spontaneous respiration was reestablished. Animals were sacrificed immediately and at intervals in order to examine the closure. Group 2.—In an attempt to determine the efficacy of adhesive closure in the face of bacterial contamination, the entire circumference of the open bronchus was painted with a swab from a 16 hour broth culture of Staphylococcus aureus. After 2 minutes, the orifice was dried with a second swab and bronchial closure was performed. In an initial control group of 18 animals, the bronchi so prepared were closed with interrupted silk sutures. The bronchial stump was left long and free in the pleural cavity in order to provide a severe test. The contaminated bronchus was then closed in 10 animals with interrupted silk sutures, in 10 animals with the Russian stapling device UKB 40 using tantalum staples, and in 10 animals with Eastman 910 monomer. In all cases, the bronchial stump was purposely left long and there was no closure of the mediastinal pleura or any other tissue over the stump. Hemostasis was secured and the pleural cavity was closed. After spontaneous respiration was re-established, the dog was returned to his cage. Group 3A.—This group consisted of 9 dogs in which an attempt was made to determine the value of sealing a raw pulmonary parenchymal sur face with Eastman 910 monomer. Segments of the upper lobe, approximately 5 by 2 cm., were amputated just distal to a noncrushing rubber-shod intes tinal clamp used to keep the raw surface free from blood and air leaks during application of the adherent. As soon as the surface was dry, 10 to 20 drops of adhesive were applied to the raw surface. Polymerization of the ad hesive was accelerated by applying several drops of water. This procedure was repeated two to three times until the entire surface appeared sealed. The clamp was removed, the lung expanded, and the chest was closed with out a chest tube. Group 3B.—In 23 dogs, a 5 by 2 cm. tip of upper lobe was amputated distal to a noncrushing clamp left on for 3 to 4 minutes ordinarily needed for application of Eastman 910 adhesive. In 9 control animals, the lungs were then inflated, the chest was closed without tube drainage, and the dogs were returned to their cages. In ten additional animals, a pericardial patch was
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applied to the raw surface using 3 to 5 drops of Eastman 910 monomer. Finger pressure was applied to the patch in order to polymerize the adhesive. After 2 to 3 minutes, the clamp was released, the lung was expanded, and the chest closed. After the dog breathed spontaneously, he was returned to his cage. Group 4.—In this series, attempts were made to re-anastomose a tran sected left main-stem bronchus with the use of Eastman 910 monomer. After the bronchus was cleaned and transected, the proximal and distal ends of the bronchus were brought together and several drops of adhesive were applied to the severed ends. Several methods were used to bring the ends together and apply pressure to induce polymerization. At first, with the use of stay sutures, the divided ends of the bronchus were brought together with the distal stump adherent to the inside of the proximal stump. Attempts at eversion of the anastomotie junction were not successful. After confirming the fact that Eastman 910 monomer did not adhere to polyethylene, a polyethylene tube was used as a stent and two temporary approximation sutures made it possible to bring together the divided bronchus without inserting one end into another. A pericardial patch with additional adherent was wrapped around the anastomosis. The chest was closed without tube drainage and, after spontaneous respirations had resumed, a bronchoscope was passed and the stent was removed with a bronchoscopic forceps. The animal was then returned to his cage. RESULTS
Group 1.—In Group 1, pneumonectomy was performed and the bronchial stump was closed with Eastman 910 monomer. Eighteen attempts were made in this series. Four animals were sacrificed immediately and the bronchial closure was tested by blocking the expiratory valve of the automatic respirator and by raising the pressure in the bronchial tree until the bronchial closure leaked. It required a pressure between 70 and 80 mm. Hg before an air leak appeared and a pressure between 82 and 100 mm. Hg before the bronchial closure ruptured completely. Similar tests performed on 2 animals with suture closure of the bronchus and 2 with tantalum staple closure demonstrated air leaks between 30 and 50 mm. Hg but no complete rupture, even at pressures of 300 mm. Hg. Four additional animals were sacrificed from 3 to 7 days after bronchial closure for inspection. The bronchi were all sealed and the pleural cavity clean. The security of the closure was again tested in 2 and it was possible to reach a pressure of 120 mm. Hg before a leak was noted. Eight of the 10 remaining animals were well up to the time of sacrifice 2*4 months later. Bronchograms revealed well-healed bronchial stumps. Post mortem examination demonstrated air-tight closures that resisted pressures up to 300 mm. Hg. Histologic sections taken 2y 2 months after the bronchial closure demonstrated minimal submucosal fibrosis and minimal inflammation. The cilia in the area about the closure were lost. In several areas, various-shaped spaces were present in the mucosa representing residual adhesive. In addition, there was minimal squamous metaplasia at the closure. Sections at 5 months revealed only minimal
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fibrosis and no squamous metaplasia. Of the 2 animals that died, one succumbed 5 hours after the operation. The bronchial stump was securely closed and there was some congestion and atelectasis of the opposite lung. This was thought to be a death due to anesthesia. A second animal died 28 days after operation. Post mortem bronchogram and inflation demonstrated no leak. The remaining lung was grossly infected with abscess formation in the lower lobe. Group 2.—In Group 2, to establish more strenuous tests for bronchial closure, 18 control animals underwent pneumonectomy and silk suture closure of the staphylococeus-contaminated bronchus. Of these 18 animals, 12 died within the first 7 days. Bronchopleural fistulas could be demonstrated by x-ray and postmortem examination in 8 of the 12 animals that died within the first week. In 2 of the 4 animals that died with no bronchopleural fistulas demon strated, empyema and pulmonary infection were present. In the 2 other animals, except for minimal atelectasis, there was no obvious cause of death. The remaining 6 animals were followed and 3 additional late deaths occurred with demonstrable bronchopleural fistula formation in each instance. When the 3 animals that survived were finally sacrificed after 3 months, the bronchi were found securely healed and capable of withstanding pressures of 300 mm. Hg. After this preliminary control series, the staphylococcus-inoculated bron chial stumps of 30 animals who underwent pneumonectomy were closed in 10 dogs each, with tantalum staples, silk sutures, and Eastman 910 monomer. In the 10 experiments in which the bronchi were closed with silk sutures, 7 animals died within the first week. Bronchopleural fistulas could be demon strated in 6 of them. The remaining animals survived until the twenty-sixth day when an additional animal died without obvious reason. In those 10 animals in which the bronchus was closed with tantalum staples with the Eussian stapling device, 7 animals died during the first week and an additional animal died on the eleventh postoperative day. Bronchopleural fistulas were confirmed in all cases. Of the 10 animals in which the bronchus was closed with Eastman 910 monomer, 7 animals died postoperatively and a broncho pleural fistula could be demonstrated in 6. The obvious cause of death in these animals was air leak and empyema. It is clear that the results are essentially similar in all three groups as far as the mortality rate and formation rate of bronchopleural fistulas are concerned. The usual day of death was on the fourth or fifth day for all groups. In the surviving animals, however, closure of the contaminated bronchi with sutures or tantalum staples resulted in healing with ultimate rejection of the silk suture or tantalum staple from the suture line. In those animals that survived after closure with adhesive, there was no gross foreign body to reject (Fig. 1). The adhesive was not grossly visible but various-shaped spaces, presumably representing bits of adhesive, could be made out microscopically in the mucosa and submucosa at 21/2 months and at 5 months (Fig. 2). Even though these animals survived and the bronchi were sealed, there was marked subacute and chronic reaction around the closure on histologic examination with all three methods of closure.
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Group 3A.—A method for sealing a raw edge of pulmonary parenchyma might prove quite valuable. An attempt was made, therefore, to seal a raw surface of the lung with adhesive. In 9 animals, a noncrushing rubber-shod clamp was applied to the parenchyma and a small portion of the upper lobe, approximately 2 by 5 cm., was amputated. It was then possible to dry the raw
Fig. 1.—Autopsy appearance of bronchial stumps 2% months after closure of staphylococcus-contaminated bronchi. A, Silk closure—the bronchus is securely closed but the silk is working its way into the lumen. B, Tantalum staple closure—in contrast to the invariable experience with clean bronchial closures in clinical practice, the staples here are working loose, although the bronchus is firmly healed. C, Adhesive closure—the bronchus is securely sealed without gross foreign body rejection.
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surface and apply a large quantity of adhesive. As soon as the adhesive was applied, several drops of water were added to polymerize the glue. Three of 9 animals were alive and well after 5 months. Six animals died from the fifth to the twenty-first day. The most frequent cause of death was air leak and atelectasis and infection from the raw area. In those animals that died, the adhesive appeared to curl away from the edges and flake, allowing airleaks and infection to occur (Fig. 3). These leaks were peripheral and could
Fig. 2.—Adhesive closure of contaminated bronchus. Minimal submucosal reaction, and squamous metaplasia present 5 months after adhesive closure of a staphylococcus-contaminated bronchus. (Hematoxylin and eosin; X50 ; reduced %.)
not be demonstrated by postmortem bronchograms. In all animals that survived and were sacrificed 5 months later, the area of the pulmonary resection was markedly adherent to the chest wall. Histologic examination revealed variousshaped spaces where adhesive was still present and a marked reaction in the lung below, with ghost cells and a zone of acute inflammation and purulent bronchitis and abscess formation (Fig. 4, A ) . Group 3B.—Amputation of the tip of an upper lobe was performed in 14 animals with removal of a 2 by 5 cm. area of lung. The raw area was covered with a pericardial patch secured with adhesive. Twelve animals sur vived for approximately 3 months before being sacrificed. Two animals died 28 and 44 days after the procedure and postmortem examination demonstrated total empyema. In these two instances, the patches were still present but ap peared to be loose and not adherent to the parenchyma. In the 12 animals who survived and were sacrificed after 3 months, the pericardium was found
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to be an integral part of the pleural surface, shrunken in area but still recognizable. There were only filmy adhesions. Histologic examination (Pig. 4,5) confirmed the survival of the patch which was slightly edematous but healed to the lung parenchyma as demonstrated by fibroblastic invasion of the pericardium at certain points. Microscopic examination of the lung under neath the patch revealed normal healthy lung tissues in some instances and, more commonly, small areas of atelectasis and chronic inflammation. Since much of the experiment was based on the survival of animals, it was decided to test the effect of amputating a small area of lung. In 9 control animals a similar 2 by 5 cm. tip of upper lobe was amputated as before and the chest was closed. The animal was put back in his cage without further treat ment except for expansion of the lung. Six animals survived, the amputated tip of the lung was markedly adherent to the chest wall and there was fibrotic reaction and old, localized hemothorax present. In the 12 of 14 ani mals that survived in which a pericardial patch had been used, the lung was totally expanded, the pleural cavity was clean, and only a few filmy adhesions were present between the patch and the chest wall. Group 4.—In Group 4, transection and re-anastomosis of the left main-stem bronchus was performed in 18 animals. Application of Eastman 910 monomer to the divided ends was not simple and the adherent frequently ran onto the other tissue. It was possible, however, to glue the two ends together and the animal survived. In the first four experiments, with the transected bronchus brought together using two temporary stay sutures for approximation, all animals sur vived without leakage. With this method the distal stump usually became in serted into the proximal stump. At sacrifice 3 months to 5 months later, there was almost complete stenosis at the anastomosis in one animal and moderate to minimal stenosis in the 3 others, although there was full expansion of the lungs. In these 3 animals the lining of the bronchus was grossly healed, although microscopically there was marked submucosal fibrosis and chronic inflammatory reaction. The use of a stent allowed the operator to slide the bronchial ends together and compress them against a firm surface in order to polymerize the adhesive. Because Eastman 910 monomer does not adhere to polyethylene, tubes of this substance were used as stents in 14 animals. In the first 4 of this group, the animals were tested immediately after the anastomosis and all animals developed small air leaks at 20 to 35 mg. Hg and large leaks at higher airway pressures. In the next 10 animals, therefore, a pericardial patch was wrapped around the anastomosis for additional support. Technical mishaps resulted in the immediate death of 2 animals, and 2 died on the second and third postoperative days of bronchopleural fistulas. Postmortem bronchograms demonstrated a small leak at the anastomosis in each animal but the lumen itself was not compromised. Six animals are alive and well, but for periods too short to allow for determination of the ultimate character of the anastomosis.
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Pig. 3.—Appearance of Eastman 910 monomer 11 days after application to a segmental surface. The adhesive is brittle and has retracted from the edges of the wound. Sealing is not complete.
T-.
Pig. 4.—A, 11 days after application of adhesive only to raw lung surface. Various-shaped spaces on the surface of the specimen represent the adhesive applied directly to a pulmonary segmental area. Marked reaction below the adhesive is present with ghost cells and a zone of acute inflammation. (Hematoxylin and eosin; X50 ; reduced %.) B, Appearance of pericardia! patch 3 months after application with Eastman 910 monomer. Note minimal reaction in pulmonary parenchyma and growth of nbroblasts from the pul monary parenchyma Into the pericardial patch. (Hematoxylin and eosin; X50 ; reduced Vi.)
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DISCUSSION
The adhesive action ,6f alkyl 2-cyanoaerylates was discovered during an investigation of polymers from 1, 1-disubstituted ethylenes. 17 A drop of highly purified ethyl-2-cyanoacrylate was placed between the prisms of an Abbe refractometer in order to obtain its refractive index. When an attempt was made to open the refractometer, the prisms could not be pulled apart. 17 As a result, methyl-2-cyanoacrylate (Eastman 910 monomer) was developed. Previous inves tigations by other workers seem to indicate that plastic adhesives of this nature will find a place in surgery.1"16 Its role either as an adjunctive or as a definitive agent is not yet completely elucidated. The dog bronchus may be completely closed with the use of Eastman 910 monomer. In the present series of experiments, comparison of silk suture, tantalum staple, and adhesive closures indicates that methyl-2-cyanoacrylate was as successful as the other two standardized techniques. Experiments in which uncontaminated bronchi were closed demonstrated a solid union. There was, however, minimal squamous metaplasia and submucosal inflammatory reac tion present, even after 3 months. Except for this reaction, the application of adhesive did not interfere with proper healing. In two instances it was necessary to apply the adhesive two or three times before complete sealing was accom plished. The use of adhesive alone on a raw surface of lung did not appear satisfac tory. Fig. 3 illustrates the flaky and crusty appearance of the paste approxi mately 11 days after application. The adhesive appeared to control hemorrhage but was not adequate for sealing of the bronchi. In the animals in which a piece of pericardium was applied, the patch adhered and survived satisfactorily as was indicated by survival of 12 out of 14 animals. The adhesive did not appear to interfere with healing of the pericardial patch and the pericardium became an integral part of the lung surface. The 2 dogs that died did so 28 and 44 days after the procedure and, in these instances, the patch appeared to be loose at several points and not an integral part of the parenchyma. It is interesting to note that dogs with pericardial patches and dogs without any treatment did better after amputation of the tip of lung, 2 by 5 cm., than those dogs which had adhesive only applied to the raw area. The use of adhesive for bronchial anastomosis certainly appears possible, but the technique requires further evaluation. The problem of maintaining an adequate lumen has been overcome by using a polyethylene stent which is removed bronchoscopically at the completion of the procedure. "With the increasing use of preoperative irradiation for pulmonary cancer, and the resulting friable tissue frequently encountered, the use of adhesive for bronchial closure or as an adjunct to suture or metallic closure may be an addi tion to the surgeon's armamentarium. Its use alone as a surface sealing agent is contraindicated from these experiments. With pericardial patches, however, Eastman 910 monomer seals raw segmental areas allowing the patch to become an integral part of the pleural surface. It is certainly possible to anastomose the
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transected bronchus with adhesive but the advantage of this method and the technical problems involved need further investigation. SUMMARY
1. Fourteen bronchial closures after pneumonectomy have been successfully performed with Eastman 910 monomer in the dog. 2. A comparison of staphylococcus-contaminated bronchial stumps closed with silk sutures, tantalum staples, and adhesive demonstrated no difference be tween the three methods, with high failure rates in all. 3. Pericardial patches applied with adhesive to the raw surface of pul monary parenchyma prevented blood loss and air leaks and became an integral part of the lung surface. Use of adhesive alone resulted in the death of two thirds of the animals. 4. Bronchial anastomosis with adhesive alone is possible with the aid of a polyethylene stent. REFERENCES 1. Carton, C. A., Kessler, L. A., Seidenberg, B., and Hurwitt, E. S.: A Plastic Adhesive Method of Small Blood Vessel Surgery, World Neurol. 1: 4, 1960. 2. Kessler, L. A., and Carton, C. A.: Experimental Studies in Surgery of Small Blood Vessels With the Use of Plastic Adhesive. I I I . Prevention of Aneurysmal Dilata tion, S. Forum 1 1 : 403, 1960. 3. Carton, C. A., Kessler, L. A., Seidenberg, B., and Hurwitt, E. S.: Experimental Studies in the Surgery of Small Blood Vessels. IV. Non-Suture Anastomosis of Arteries and Veins, Using Flanged Ring Prostheses and Plastic Adhesive, S. Forum 1 1 : 238, 1960. 4. Carton, C. A., Kessler, L. A., Seidenberg, B., and H u r w i t t , E. S.: Experimental Studies in Surgery of Small Blood Vessels. I I . Patching of Arteriotomy Using a Plastic Adhesive, J . Neurosurg. 18: 2, 1961. 5. Healy, J . E., Jr., Moore, E. B., Brooks, B. J., and Sheena, K. S.: A Vascular Clamp for Circumferential Repair of Blood Vessels, Surgery 5 1 : 4, 1962. 6. Healey, J . E., Jr., Clark, R. L., Gallager, H. S., O'Neill, P., and Sheena, K. S.: Nonsuture Repair of Blood Vessels, Ann. Surg. 155: 6, 1962. 7. Healey, J . E., Jr., Brooks, B. J., Gallager, S., Moore, E, B., and Sheena, K. S.: A Technique for Nonsuture Repair of Veins, J . Surg. Res. 1: 4, 1961. 8. Ashley, F . L., Polak, T., and Berman, O. D.: Nonsutured Closure of Skin Lacerations and Nonsutured Grafting of Skin With a Rapidly Polymerizing Adhesive, Quart. Bull. Northwestern Univ. Med. School 36: No. 3, 1962. 9. Inou, T.: Studies on the Surgical Use of Plastic Adhesive, Am. J . Proctol. 13: 4, 1962. 10. Lighterman, I., and Farrell, J . J . : Treatment of Experimentally Induced Mandibular Fractures With Plastic Polymers, S. Forum 13: 466, 1962. 11. Albin, M. S., D'Agostino, A. N., White, R. J., and Grindlay, J . H . : Nonsuture Sealing of a Dural Substitute Utilizing a Plastic Adhesive, Methyl-2-cyanoacrylate, J . Neurosurg. 19: 545, 1962. 12. MacDonald, G. L., Jr., Tose, L., and Deterling, R. A., J r . : A Technique for Reimplantation of t h e Dog Limb Involving the Use of a Mechanical Stapling Device and a Rapidly Polymerizing Adhesive, S. Forum 13: 88, 1962. 13. Mathes, G. L., and Terry, J . W., J r . : Non-suture Closure of Nephrotomy, . J . Urol. 89: 122, 1963. 14. Braunwald, N. S., and Awe, W. C.: Control of Hemorrhage From the Heart and Aorta Utilizing a Plastic Adhesive, Surgery 5 1 : 786, 1962. 15. Healey, J . E., Jr., Clark, R. L., Gallager, H. S., O'Neill, P., and Sheena, K. S.: Non suture Repair of Blood Vessels, Ann. Surg. 155: 817, 1962. 16. Healey, J . E., Jr., Sheena, K. S., Gallager, H. S., Clark, R. L., and O'Neill, P . : The Use of a Plastic Adhesive in the Technique of Bronchial Closure, S. Forum 13: 153, 1962. 17. Coover, H. W., Jr., Joyner, F . B., Shearer, N. H., Jr., and Wicker, T. H., J r . : Chemistry and Performance of Cyanoacrylate Adhesives, S P E Journal, Vol. 15, 1959.
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DISCUSSION
DR. LYMAN A. EREWER, I I I , Los Angeles, Calif.—The authors have presented a most interesting study on the use of a plastic adhesive to seal the bronchial closures, bronchial anastomoses, and raw surface of the lung. In 1952 we presented to this Asso ciation a technique of applying a pedicled pericardia! fat graft for a similar purpose. I should like to present to you this morning our subsequent results with this technique. Like the authors, we found in experimental animals that the pericardial fat graft successfully sealed over open bronchi. I n the human the pericardial f a t pad being larger with a better blood supply is, therefore, a more satisfactory protective graft than in the experi mental animal. [Slide] This slide shows that the graft in a human has an excellent blood supply from the internal mammary artery, making this really a thoracic omentum. [Slide] Here you can see that the graft when developed is viable due to a satisfactory blood supply. I t is tightly sewn to the bronchial stump in four quadrants, protecting it much like a bathing cap. Our experience now covers over 500 cases, 472 lobectomies or pneumonectomies and 34 bronchoplastic or grafting procedures. This technique of sealing the bronchial stump with the graft has resulted in a decrease of bronchopleural fistula from 8 to less than 2 per cent. This technique is especially valuable in the diseased bronchus when the bronchus is friable and leaks after the closure. With the pedicled pericardial fat graft one need not be concerned now about little leaks, as the graft effectively seals the bronchial stump. On one occasion, in performing postoperative bronchial aspiration after a pneumonectomy, our resident much to his horror, poked the aspirating catheter through the stump of the right main bronchus. A large amount of bloody fluid was aspirated from the right pleural cavity. This patient was treated expectantly and we were relieved that the graft effectively sealed the opened bronchial stump. [Slide] Our method of bronchial closure has added to the successful healing of the bronchial stump. I t is most important to remember that the posterior membranous wall can be mobilized and brought up as a flap to the rigid cartilaginous ring without tension. The cartilage is a spring, whose function is to keep the bronchus open. Because it cannot be flattened out or squeezed together—the bronchial stump leaks. However, the membranous flap may be mobilized and sutured to the cartilaginous wall without tension to effect a stable closure. Like the authors, we found that suture material, which we once thought was important, is not important; what is important is the way the sutures are put in and that tensions on the closure is avoided. The thirty-four plastic operations on the trachea and bronchi are of considerable interest, but time permits the presentation of only one case. [Slide] This is a diagram of a carcinoma of the trachea which was resected from just at the level of the carina up into the cervical region. A fascia lata graft reinforced with wire mesh was used. The fat graft was placed around the distal stump. The sutures through the right stem bronchus did not hold and there was a distressing air leak. How ever, the thoracic omentum graft was sutured solidly around the anastomosis with no subsequent air leak. [Slide] The patient had a good airway and was well 3 months after operation until a fatal coronary thrombosis occurred. This is a postmortem specimen which shows the fat graft well fixed to both the right and left stem bronchi and the artificial trachea. The lumen of the trachea was adequate. The stent was covered with mucosa, and here you see where the fat graft had sealed the trachea. Thus, we have found that the pedicled pericardial fat graft, or thoracic omentum, will effectively seal the bronchial stump after pulmonary resection. I t is particularly effective when there is a diseased bronchus in which the sutures do not hold. We believe this will result in a lowered incidence of bronchopleural fistula, and will give the surgeon considerable security with regard to this unfortunate complication.
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PLASTIC A D H E S I V E I N PULMONARY SURGERY
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The authors' results with Eastman 910 monomer plastic adhesive to seal raw sur faces of the lung and the bronchial stump, when challenged with infection, are impressive. Reports on clinical use will be of great interest. They are to be congratulated on an excellent study. DR. A L F R E D GOLDMAN, Beverly Hills, Calif.—It is extremely difficult to follow such a beautiful discussion as Dr. Brewer's, and the excellent paper by Dr. Wilder and Dr. Ravitch and their group. I wish to confine my remarks to that portion of the paper re lating to the tantalum staples and to that portion of tantalum stapling useful for re section of peripheral portions of the parenchyma. As you noticed in the presentation, they did not do quite so well with the peripheral resections. [Slide] This slide shows a Soviet instrument known as UKL-60. The main differ ence from the U K B used by Dr. Ravitch is the weight, nearly 500 grams, and the number and manner in which the staples are placed in the tissue. Like the U K B , it has only one purpose, that is to perform suture closure of open, gaping tissue, whether it is peripheral parenchyma, bronchi, or blood vessels. I n this respect it differs absolutely from the vascular suturing structures, the purpose of which is to perform suture patency. This is the magazine mounted on a movable jaw activated by the screw " S . " This jaw contains the staple pushers inside of " J - 2 , " and they are activated by this handle which is squeezed by the hand. The tantalum staples are 4 by 4.8 by 0.3 mm., and are ready for injection when the tissue to be sutured is compressed to 3 mm. thickness between the jaws " J - l " and " J - 2 . " The magazine holds twenty-one staples in two staggered rows, and, when ejected, they make forty-two stitches as shown here. [Slide] This slide is an x-ray film of the chest in a human bilateral pulmonary re section. Note the " B " shape of the sutures. [Slide] Dogs were used for study of lung wound healing. The lower suture line was for a cuff of lung, oversewn with running 5-0 silk. The upper was amputated flush with the suture line. This x-ray film was made 3 months after the thoraeotomy and shows less expansion in the oversewn silk suture line when compared with the flush amputation with out the silk being oversewn. [Slide] This slide shows the gross appearance of these two suture lines, the upper one here, and the oversewn one here. The obvious cleaner-looking healing is shown here as compared with the oversewn silk suture line. Microscopically there were less reaction of inflammatory cells in this suture line than in this one, where after 3 months, there was still some granulomatous formation. [Slide] By injecting the pulmonary artery with oily Dionosil the vasculature of the suture line can be studied in expansion and deflation. Note the absence of vascular dis tortion in both suture lines, as well as the ability of the suture line to expand with 20 mm. Hg. pressure at the trachea. Bronchial architecture is also maintained, as you can judge from the fact that the soft tissue vasculature is maintained, but this was also shown in the other studies. This slide shows that the expansibility of the suture line is maintained. [Slide] This slide shows a photomicrograph of higher power, magnified approximately ten times at the suture line. Note that the size of the openings in the stitches and the numerous patent blood vessels can be visualized. These are small blood vessels, some of which appear to go through the openings in these staples. This slide also shows that such' tantalum sutures are compressive but not necrotizing. We feel that this study repre sents, probably, some superior healing over ordinary silk suturing. We have used this instrument in 60 clinical cases and have been quite satisfied with it. DR. STANLEY F E L L , Bronx, N. Y.—At Montefiore Hospital we have been employing the Eastman 910 adhesive in studies similar to Dr. Wilder's. Our main concern has been the control of air leak from raw lung surfaces rather than from the bronchus, which is susceptible
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W I L D E R ET AL.
J. Thoracic and Cardiovas. Surg.
to suture closure. In dogs we created superficial raw areas of lung and glued them to adjacent intact lobes rather than applying grafts of any type. These broad, raw areas could be consistently glued with success. However, in wedge resections of 30 per cent to 50 per cent of a lobe we had a 50 per cent incidence of bronchopleural fistula, no matter how the glue was applied. Similarly, we evaluated the utilization of the adhesive in the management of spon taneous pneumothorax. Pneumothorax was induced in dogs via an intercostal catheter. The adhesive was instilled intrapleurally at another site. The lung was promptly re-expanded while the animal was positioned for maximum distribution of the adhesive. At re-exploration of these dogs' chests several weeks later, we did not produce a significant pleurodesis, but there was a high incidence of trapped lungs and empyema. I don't believe we can state at this time what clinical applications this adhesive will have in pulmonary surgery. I wish to thank the Association for the privilege of the floor.