Tissue glue for the endoscopist: Healing by sealing

Abstract

Seewald S, Brand B, Groth S, Omar S, Mendoza G, Seitz U, Yasuda I, Xikun H, Nam VC, Xu H, Thonke F, Soehendra N (Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany). Endoscopic sealing of pancreatic fistula by using N-butyl-2-cyanoacrylate. Gastrointest Endosc 2004;59:463–470.Seewald and his colleagues described a novel endoscopic approach to treat pancreatic fistula, which is a major management challenge for the surgeons and physicians taking care of patients with complicated pancreatic pathology. In this report, the authors describe sealing pancreatic fistulas by using N-butyl-2-cyanoacrylate. Twelve patients with pancreatic fistulas underwent endoscopic injection of N-butyl-2-cyanoacrylate into the fistulous tract, in addition to endoscopic drainage. Fistulas were closed successfully in 8 of 12 patients. A single treatment session was successful in 7 patients; a second session was required in 1 patient. In 2 patients, closure was temporary, and, in 1 patient, the treatment failed. One patient died 24 hours after treatment. He developed a pulmonary thromboembolism from a left popliteal vein thrombosis and died from complications of surgical thromboembolectomy. At autopsy, a pulmonary embolus was found, but there was no evidence of N-butyl-2-cyanoacrylate in the lungs. No procedure-related complication occurred over a median follow-up of 20.7 months (range, 9–51 months). In this preliminary study, the authors conclude that occlusion of pancreatic fistulas by using N-butyl-2-cyanoacrylate glue was safe and effective and obviated the need for surgery in a substantial proportion of patients.CommentIsn’t it surprising that glue technology has not been on our radar screens until recently, while our surgical colleagues have embraced it for quite a while! Because this topic is quite foreign to most endoscopists in the U.S., commentary on the elegant work of Seewald et al deserves a brief review of the basic concepts about tissue glue and its role in surgery and endoscopy.Tissue adhesives can be broadly defined as any substance that can hold tissues together or serve as a barrier to leakage, and these include fibrin sealants, glutaraldehyde glues, cyanoacrylates hydrogels, and collagen-based adhesives (Biomaterials 1998;19:1461–1466, Am J Surg 2001;182:40S–44S). Fibrin sealants have been shown to be effective in cardiovascular surgery for hemostasis (Ann Thor Surg 1987;84:548–553), sealing air leaks from lung procedures (Chest 1996;109:1653–1655), and treatment of bronchopleural fistulas (Chest 1990;97:1390–1392); in neurosurgery, to repair dural leaks and prevent CSF leaks (Neurosurgery 1999;44:332–337); in plastic surgery, to control bleeding after debridement of burn wounds (J Burn Care Rehabil 1988;9:619–622); in orthopedic surgery, to decrease bleeding in knee replacements (J Bone Joint Surg Am 1999;81:1580–1588); in head and neck surgery, to treat lymphatic leaks after radical neck dissections (Otolaryngol Head Neck Surg 2000;122;434–439); and in trauma surgery, to treat spleen and liver lacerations (J Trauma 1990;30:884–887). Glutaraldehyde glues are approved for repair of aortic dissection, to fill the dissection and provide a stronger arterial wall for the repair. Cyanoacrylate use is restricted to external or temporary application only, for example, in cosmetic surgery to avoid skin sutures (Plast Reconstr Surg 1998;102:2209–2219), in the emergency room to close smaller cuts or reapproximate lacerations that have deeper support sutures (Academic Emerg Med 2001;8:438–439), or repair of simple lacerations in children (Am Fam Physician 2000;61:1383–1388). Hydrogels have been shown to be useful in decreasing air leaks after thoracic surgery (Ann Thorac Surg 2001;71:1623–1629). Collagen-based adhesives have been shown to be useful in vascular surgery hemostasis (Ann Thorac Surg 2000;69:1376–1382) and in the prevention and treatment of CSF leaks (Spine 2001;26:1645–1650).Only two cyanoacrylates, N-butyl-2-cyanoacrylate (Histoacryl; B. Braun, Melsungen, Germany) and 2-octyl-cyanoarcylate (Dermabond; Ethicon Inc, Somerville, NJ), have been used for endoscopic therapy. Although N-butyl-2-cyanoacrylate has been used extensively outside the United States for endoscopic hemostasis of bleeding gastric varices (Endoscopy 1995;27:349–354, Am J Gastroenterol 2003;98:1982–1988), enteric varices (Endoscopy 2001;33:998), Dieulafoy’s lesion (Endoscopy 2004;36:183–185), and tumors (Endoscopy 2000;32:S69), and closure of gastrointestinal fistulas (Endoscopy 2001;33:184–186), biliary fistulas (Gastrointest Endosc 2002;56:916–919), and pancreatic fistulas (Gastrointest Endosc 2004;59:463–470), it has not yet been approved for use in the U.S. by the Food and Drug Administration (FDA). Although 2-octyl-cyanoarcylate is approved by the FDA for skin wound closure, there is no information on its role in the management of endoscopic closure of wounds and fistulas. Preliminary studies with this agent have been encouraging in the management of gastric fundal varices (Gastrointest Endosc 2002;55:572–575, 2004;59:553–558).Endoscopic use of glue deserves attention to certain procedural details. Endoscopists and endoscopic assistants: Protect your eyes and protect your patient’s eyes—glued eyelids can cost a career! Lubricate the endoscope tip with a silicone-based oil or Lipiodol (Ultra-Fluid; Guerbert GmbH, Sulzbach, Germany) to prevent glue sticking to the endoscope—avoid costly endoscope repairs! Dilute N-butyl-2-cyanoacrylate with Lipiodol in a ratio of 0.5 to 0.3 mL to see where it is being delivered during injection under fluoroscopy. Use injection catheters that are resistant to glue-induced dissolution of the hub and premature polymerization of Histoacryl (B. Braun Dexon GmbH, Spangenberg, Germany). Determine the dead volume of the injection catheter by injecting sterile distilled water, and follow the injection of glue mixture with an injection of sterile distilled water volume equal to the dead space volume of catheter; it is critical to flush it SLOWLY. Strict compliance with the above steps in glue injection is critical to come out clean without any sticky issues!Complications associated with the injection of N-butyl-2-cyanoacrylate, which turns into a glob and stays in the body forever, are quite unique. Four different types of complications have been reported with the injection of glue: those related to systemic inflammatory reaction to a foreign body (pain and fever); local tissue necrosis and foreign body reaction (mediastinitis, esophageal pleural fistula, duodenal ulcer perforation, pancreaticodudoneal necrosis, inflammatory pseudotumor of pancreatic tail) (Gastroenterol Clin Biol 1986;10:580–583, Gastrointest Endosc 2000;52:267–270, Endoscopy 2000;32:S23, Surgery 1989;106:901–903, J Gastroenterol 2004;39:475–478); thrombo-embolic complications (splenic, portal, pulmonary, coronary, cerebral, and inferior vena cava) (Endoscopy 2000;32:422–424, Gastrointest Endosc 2002;55:276–278, Endoscopy 1998;30:S89–S90, Clin Biol 1986;10:604–607, Gastrointest Endosc 2001;53:228–230); and septic complications (Gastrointest Endosc 2004;59:911–916).Now, let us look at the work of Seewald and his colleagues, internationally renowned for their expertise in the use of glue. Their goal was to report the safety and efficacy of N-butyl-2-cyanoacrylate injection into pancreatic fistulas.Seewald et al injected cyanoacrylate into 12 patients (pancreatic duct leakage with [n = 7] or without a pseudocyst [n = 4] and pancreatico-cutaneous fistula [n = 1]); prompt occlusion of the fistula occurred in 7 of 12 patients after a single injection. In 1 patient, 2 injections were required, and in 4 patients, it was not successful (closure of fistula was temporary in 1, treatment failed in 1, and 1 patient died 24 hours after treatment). Of note, a pancreaticogram obtained after injection of glue demonstrated a patent main pancreatic duct in all the patients and none of the patients developed clinical pancreatitis after fistula injection or any other local inflammatory complications or distant thrombo-embolic complications associated with the injection of glue. This can only be achieved by precise injection of the glue into the fistula (0.5 mL for small fistulas and larger volume for larger/longer fistula; range, 0.5–4 mL), without much extravasation into the pseudocyst or abdominal cavity or backflow into the main pancreatic duct—a testament to the extensive experience of the Hamburg group with the glue over the last decade. Seewald et al have shown that there were no serious adverse events with this procedure. Is it absolutely safe? Only time will tell us.Regarding the second question, efficacy of glue injection in sealing the pancreatic duct leaks in the treatment of pseudocysts or free leaks, let us review the current endoscopic management of pseudocysts and free leaks. Poke and drain the pseudocyst (pioneered by Richard Kozarek, 1985) works well for pseudocysts with no communication to the pancreatic duct (Gastrointest Endosc 1985;31:322–328). For pseudocysts communicating with the pancreatic duct, transpapillary stenting (siphoning the pancreatic juice into the duodenum) curtails further leakage, drains the pseudocyst, dries it up, and eventually heals the leak. Although transpapillary stenting has been shown to be effective in the management of pseudocysts and pancreatic fistulas in over 75% of patients (Gastrointest Endosc 1995;42:202–207, 1995;42:208–213, 1995;42:214–218, 1995;42:219–224, Endoscopy 2001;33:317–322), drawbacks include the risk of recurrence of leak (10%–20%) (Gastrointest Endosc 1995;42:219–224, 2002;56:7–17) and the need for repeated stent exchanges over a prolonged period with its attendant complications (stent migration, clogging, infection, and stent induced pancreatic damage) (Clin Gastroenterol Hepatol 2004;2:322–329). Sealing the leak with glue, for instantaneous closure of leak, could potentially avoid some of these problems. How efficacious is this new technique in sealing the pancreatic leak?Sealing the leak once and for all, as proposed by Seewald et al, would be a welcome addition to the endoscopic management of these complex patients. The authors have shown that glue is successful in the primary closure of the pancreatic duct leak not associated with a pseudocyst and in the closure of the pancreatic leak associated with a pseudocyst after the drainage of pseudocyst with transpapillary stenting. By quickly fixing the leak, one would obviate the need for prolonged stenting in the management of pancreatic leaks without associated pseudocysts (Endoscopy 2001;33:317–322).This report raises the following questions: Is sealing the leak with glue as an adjunct to stent therapy after resolution of pseudocyst any better compared with prolonged transpapillary stenting alone in terms of primary closure and prevention of recurrence of leaks? Does the glue allow us to cut short the duration of transpapillary stenting or totally eliminate the need for it in the management of pseudocysts? Should there be a paradigm shift in the management of pancreatic pseudocysts communicating with pancreatic ducts with the availability of sealants? Will it be better to drain the pseudocyst either by percutaneous or transgastric or transenteric route, thereby totally eliminating the need for prolonged stenting to siphon the pseudocyst, and seal the leak by injection of glue through pancreatic duct? Glue has been shown to be successful in the setting of chronic pancreatitis, whereas failures occurred in all three patients with a history of acute pancreatitis. Is ongoing active inflammation a detriment to the success of glue injections?In summary, this report is an important conceptual and technical advance in the management of patients with pancreatic leaks. The authors should be congratulated for introducing this novel concept in endoscopy, healing by sealing. Glue is certainly a welcome addition to the armamentarium, for now, at the disposal of those (outside the U.S.) involved in the management of pancreatic leaks. This reminds me of the quote by Confucius, “I hear and I forget. I see and I remember. I do and I understand.” Soehendra, (pioneer in endoscopic use of glue) do, and understand very well the value of glue in the management of complex pancreatic problems. The privileged few who have seen the master at work will remember it. Many of us in the U.S. have to wrestle with the idea of not rusting with time, but start exploring novel means of healing by sealing. Seewald S, Brand B, Groth S, Omar S, Mendoza G, Seitz U, Yasuda I, Xikun H, Nam VC, Xu H, Thonke F, Soehendra N (Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany). Endoscopic sealing of pancreatic fistula by using N-butyl-2-cyanoacrylate. Gastrointest Endosc 2004;59:463–470. Seewald and his colleagues described a novel endoscopic approach to treat pancreatic fistula, which is a major management challenge for the surgeons and physicians taking care of patients with complicated pancreatic pathology. In this report, the authors describe sealing pancreatic fistulas by using N-butyl-2-cyanoacrylate. Twelve patients with pancreatic fistulas underwent endoscopic injection of N-butyl-2-cyanoacrylate into the fistulous tract, in addition to endoscopic drainage. Fistulas were closed successfully in 8 of 12 patients. A single treatment session was successful in 7 patients; a second session was required in 1 patient. In 2 patients, closure was temporary, and, in 1 patient, the treatment failed. One patient died 24 hours after treatment. He developed a pulmonary thromboembolism from a left popliteal vein thrombosis and died from complications of surgical thromboembolectomy. At autopsy, a pulmonary embolus was found, but there was no evidence of N-butyl-2-cyanoacrylate in the lungs. No procedure-related complication occurred over a median follow-up of 20.7 months (range, 9–51 months). In this preliminary study, the authors conclude that occlusion of pancreatic fistulas by using N-butyl-2-cyanoacrylate glue was safe and effective and obviated the need for surgery in a substantial proportion of patients. CommentIsn’t it surprising that glue technology has not been on our radar screens until recently, while our surgical colleagues have embraced it for quite a while! Because this topic is quite foreign to most endoscopists in the U.S., commentary on the elegant work of Seewald et al deserves a brief review of the basic concepts about tissue glue and its role in surgery and endoscopy.Tissue adhesives can be broadly defined as any substance that can hold tissues together or serve as a barrier to leakage, and these include fibrin sealants, glutaraldehyde glues, cyanoacrylates hydrogels, and collagen-based adhesives (Biomaterials 1998;19:1461–1466, Am J Surg 2001;182:40S–44S). Fibrin sealants have been shown to be effective in cardiovascular surgery for hemostasis (Ann Thor Surg 1987;84:548–553), sealing air leaks from lung procedures (Chest 1996;109:1653–1655), and treatment of bronchopleural fistulas (Chest 1990;97:1390–1392); in neurosurgery, to repair dural leaks and prevent CSF leaks (Neurosurgery 1999;44:332–337); in plastic surgery, to control bleeding after debridement of burn wounds (J Burn Care Rehabil 1988;9:619–622); in orthopedic surgery, to decrease bleeding in knee replacements (J Bone Joint Surg Am 1999;81:1580–1588); in head and neck surgery, to treat lymphatic leaks after radical neck dissections (Otolaryngol Head Neck Surg 2000;122;434–439); and in trauma surgery, to treat spleen and liver lacerations (J Trauma 1990;30:884–887). Glutaraldehyde glues are approved for repair of aortic dissection, to fill the dissection and provide a stronger arterial wall for the repair. Cyanoacrylate use is restricted to external or temporary application only, for example, in cosmetic surgery to avoid skin sutures (Plast Reconstr Surg 1998;102:2209–2219), in the emergency room to close smaller cuts or reapproximate lacerations that have deeper support sutures (Academic Emerg Med 2001;8:438–439), or repair of simple lacerations in children (Am Fam Physician 2000;61:1383–1388). Hydrogels have been shown to be useful in decreasing air leaks after thoracic surgery (Ann Thorac Surg 2001;71:1623–1629). Collagen-based adhesives have been shown to be useful in vascular surgery hemostasis (Ann Thorac Surg 2000;69:1376–1382) and in the prevention and treatment of CSF leaks (Spine 2001;26:1645–1650).Only two cyanoacrylates, N-butyl-2-cyanoacrylate (Histoacryl; B. Braun, Melsungen, Germany) and 2-octyl-cyanoarcylate (Dermabond; Ethicon Inc, Somerville, NJ), have been used for endoscopic therapy. Although N-butyl-2-cyanoacrylate has been used extensively outside the United States for endoscopic hemostasis of bleeding gastric varices (Endoscopy 1995;27:349–354, Am J Gastroenterol 2003;98:1982–1988), enteric varices (Endoscopy 2001;33:998), Dieulafoy’s lesion (Endoscopy 2004;36:183–185), and tumors (Endoscopy 2000;32:S69), and closure of gastrointestinal fistulas (Endoscopy 2001;33:184–186), biliary fistulas (Gastrointest Endosc 2002;56:916–919), and pancreatic fistulas (Gastrointest Endosc 2004;59:463–470), it has not yet been approved for use in the U.S. by the Food and Drug Administration (FDA). Although 2-octyl-cyanoarcylate is approved by the FDA for skin wound closure, there is no information on its role in the management of endoscopic closure of wounds and fistulas. Preliminary studies with this agent have been encouraging in the management of gastric fundal varices (Gastrointest Endosc 2002;55:572–575, 2004;59:553–558).Endoscopic use of glue deserves attention to certain procedural details. Endoscopists and endoscopic assistants: Protect your eyes and protect your patient’s eyes—glued eyelids can cost a career! Lubricate the endoscope tip with a silicone-based oil or Lipiodol (Ultra-Fluid; Guerbert GmbH, Sulzbach, Germany) to prevent glue sticking to the endoscope—avoid costly endoscope repairs! Dilute N-butyl-2-cyanoacrylate with Lipiodol in a ratio of 0.5 to 0.3 mL to see where it is being delivered during injection under fluoroscopy. Use injection catheters that are resistant to glue-induced dissolution of the hub and premature polymerization of Histoacryl (B. Braun Dexon GmbH, Spangenberg, Germany). Determine the dead volume of the injection catheter by injecting sterile distilled water, and follow the injection of glue mixture with an injection of sterile distilled water volume equal to the dead space volume of catheter; it is critical to flush it SLOWLY. Strict compliance with the above steps in glue injection is critical to come out clean without any sticky issues!Complications associated with the injection of N-butyl-2-cyanoacrylate, which turns into a glob and stays in the body forever, are quite unique. Four different types of complications have been reported with the injection of glue: those related to systemic inflammatory reaction to a foreign body (pain and fever); local tissue necrosis and foreign body reaction (mediastinitis, esophageal pleural fistula, duodenal ulcer perforation, pancreaticodudoneal necrosis, inflammatory pseudotumor of pancreatic tail) (Gastroenterol Clin Biol 1986;10:580–583, Gastrointest Endosc 2000;52:267–270, Endoscopy 2000;32:S23, Surgery 1989;106:901–903, J Gastroenterol 2004;39:475–478); thrombo-embolic complications (splenic, portal, pulmonary, coronary, cerebral, and inferior vena cava) (Endoscopy 2000;32:422–424, Gastrointest Endosc 2002;55:276–278, Endoscopy 1998;30:S89–S90, Clin Biol 1986;10:604–607, Gastrointest Endosc 2001;53:228–230); and septic complications (Gastrointest Endosc 2004;59:911–916).Now, let us look at the work of Seewald and his colleagues, internationally renowned for their expertise in the use of glue. Their goal was to report the safety and efficacy of N-butyl-2-cyanoacrylate injection into pancreatic fistulas.Seewald et al injected cyanoacrylate into 12 patients (pancreatic duct leakage with [n = 7] or without a pseudocyst [n = 4] and pancreatico-cutaneous fistula [n = 1]); prompt occlusion of the fistula occurred in 7 of 12 patients after a single injection. In 1 patient, 2 injections were required, and in 4 patients, it was not successful (closure of fistula was temporary in 1, treatment failed in 1, and 1 patient died 24 hours after treatment). Of note, a pancreaticogram obtained after injection of glue demonstrated a patent main pancreatic duct in all the patients and none of the patients developed clinical pancreatitis after fistula injection or any other local inflammatory complications or distant thrombo-embolic complications associated with the injection of glue. This can only be achieved by precise injection of the glue into the fistula (0.5 mL for small fistulas and larger volume for larger/longer fistula; range, 0.5–4 mL), without much extravasation into the pseudocyst or abdominal cavity or backflow into the main pancreatic duct—a testament to the extensive experience of the Hamburg group with the glue over the last decade. Seewald et al have shown that there were no serious adverse events with this procedure. Is it absolutely safe? Only time will tell us.Regarding the second question, efficacy of glue injection in sealing the pancreatic duct leaks in the treatment of pseudocysts or free leaks, let us review the current endoscopic management of pseudocysts and free leaks. Poke and drain the pseudocyst (pioneered by Richard Kozarek, 1985) works well for pseudocysts with no communication to the pancreatic duct (Gastrointest Endosc 1985;31:322–328). For pseudocysts communicating with the pancreatic duct, transpapillary stenting (siphoning the pancreatic juice into the duodenum) curtails further leakage, drains the pseudocyst, dries it up, and eventually heals the leak. Although transpapillary stenting has been shown to be effective in the management of pseudocysts and pancreatic fistulas in over 75% of patients (Gastrointest Endosc 1995;42:202–207, 1995;42:208–213, 1995;42:214–218, 1995;42:219–224, Endoscopy 2001;33:317–322), drawbacks include the risk of recurrence of leak (10%–20%) (Gastrointest Endosc 1995;42:219–224, 2002;56:7–17) and the need for repeated stent exchanges over a prolonged period with its attendant complications (stent migration, clogging, infection, and stent induced pancreatic damage) (Clin Gastroenterol Hepatol 2004;2:322–329). Sealing the leak with glue, for instantaneous closure of leak, could potentially avoid some of these problems. How efficacious is this new technique in sealing the pancreatic leak?Sealing the leak once and for all, as proposed by Seewald et al, would be a welcome addition to the endoscopic management of these complex patients. The authors have shown that glue is successful in the primary closure of the pancreatic duct leak not associated with a pseudocyst and in the closure of the pancreatic leak associated with a pseudocyst after the drainage of pseudocyst with transpapillary stenting. By quickly fixing the leak, one would obviate the need for prolonged stenting in the management of pancreatic leaks without associated pseudocysts (Endoscopy 2001;33:317–322).This report raises the following questions: Is sealing the leak with glue as an adjunct to stent therapy after resolution of pseudocyst any better compared with prolonged transpapillary stenting alone in terms of primary closure and prevention of recurrence of leaks? Does the glue allow us to cut short the duration of transpapillary stenting or totally eliminate the need for it in the management of pseudocysts? Should there be a paradigm shift in the management of pancreatic pseudocysts communicating with pancreatic ducts with the availability of sealants? Will it be better to drain the pseudocyst either by percutaneous or transgastric or transenteric route, thereby totally eliminating the need for prolonged stenting to siphon the pseudocyst, and seal the leak by injection of glue through pancreatic duct? Glue has been shown to be successful in the setting of chronic pancreatitis, whereas failures occurred in all three patients with a history of acute pancreatitis. Is ongoing active inflammation a detriment to the success of glue injections?In summary, this report is an important conceptual and technical advance in the management of patients with pancreatic leaks. The authors should be congratulated for introducing this novel concept in endoscopy, healing by sealing. Glue is certainly a welcome addition to the armamentarium, for now, at the disposal of those (outside the U.S.) involved in the management of pancreatic leaks. This reminds me of the quote by Confucius, “I hear and I forget. I see and I remember. I do and I understand.” Soehendra, (pioneer in endoscopic use of glue) do, and understand very well the value of glue in the management of complex pancreatic problems. The privileged few who have seen the master at work will remember it. Many of us in the U.S. have to wrestle with the idea of not rusting with time, but start exploring novel means of healing by sealing. Isn’t it surprising that glue technology has not been on our radar screens until recently, while our surgical colleagues have embraced it for quite a while! Because this topic is quite foreign to most endoscopists in the U.S., commentary on the elegant work of Seewald et al deserves a brief review of the basic concepts about tissue glue and its role in surgery and endoscopy. Tissue adhesives can be broadly defined as any substance that can hold tissues together or serve as a barrier to leakage, and these include fibrin sealants, glutaraldehyde glues, cyanoacrylates hydrogels, and collagen-based adhesives (Biomaterials 1998;19:1461–1466, Am J Surg 2001;182:40S–44S). Fibrin sealants have been shown to be effective in cardiovascular surgery for hemostasis (Ann Thor Surg 1987;84:548–553), sealing air leaks from lung procedures (Chest 1996;109:1653–1655), and treatment of bronchopleural fistulas (Chest 1990;97:1390–1392); in neurosurgery, to repair dural leaks and prevent CSF leaks (Neurosurgery 1999;44:332–337); in plastic surgery, to control bleeding after debridement of burn wounds (J Burn Care Rehabil 1988;9:619–622); in orthopedic surgery, to decrease bleeding in knee replacements (J Bone Joint Surg Am 1999;81:1580–1588); in head and neck surgery, to treat lymphatic leaks after radical neck dissections (Otolaryngol Head Neck Surg 2000;122;434–439); and in trauma surgery, to treat spleen and liver lacerations (J Trauma 1990;30:884–887). Glutaraldehyde glues are approved for repair of aortic dissection, to fill the dissection and provide a stronger arterial wall for the repair. Cyanoacrylate use is restricted to external or temporary application only, for example, in cosmetic surgery to avoid skin sutures (Plast Reconstr Surg 1998;102:2209–2219), in the emergency room to close smaller cuts or reapproximate lacerations that have deeper support sutures (Academic Emerg Med 2001;8:438–439), or repair of simple lacerations in children (Am Fam Physician 2000;61:1383–1388). Hydrogels have been shown to be useful in decreasing air leaks after thoracic surgery (Ann Thorac Surg 2001;71:1623–1629). Collagen-based adhesives have been shown to be useful in vascular surgery hemostasis (Ann Thorac Surg 2000;69:1376–1382) and in the prevention and treatment of CSF leaks (Spine 2001;26:1645–1650). Only two cyanoacrylates, N-butyl-2-cyanoacrylate (Histoacryl; B. Braun, Melsungen, Germany) and 2-octyl-cyanoarcylate (Dermabond; Ethicon Inc, Somerville, NJ), have been used for endoscopic therapy. Although N-butyl-2-cyanoacrylate has been used extensively outside the United States for endoscopic hemostasis of bleeding gastric varices (Endoscopy 1995;27:349–354, Am J Gastroenterol 2003;98:1982–1988), enteric varices (Endoscopy 2001;33:998), Dieulafoy’s lesion (Endoscopy 2004;36:183–185), and tumors (Endoscopy 2000;32:S69), and closure of gastrointestinal fistulas (Endoscopy 2001;33:184–186), biliary fistulas (Gastrointest Endosc 2002;56:916–919), and pancreatic fistulas (Gastrointest Endosc 2004;59:463–470), it has not yet been approved for use in the U.S. by the Food and Drug Administration (FDA). Although 2-octyl-cyanoarcylate is approved by the FDA for skin wound closure, there is no information on its role in the management of endoscopic closure of wounds and fistulas. Preliminary studies with this agent have been encouraging in the management of gastric fundal varices (Gastrointest Endosc 2002;55:572–575, 2004;59:553–558). Endoscopic use of glue deserves attention to certain procedural details. Endoscopists and endoscopic assistants: Protect your eyes and protect your patient’s eyes—glued eyelids can cost a career! Lubricate the endoscope tip with a silicone-based oil or Lipiodol (Ultra-Fluid; Guerbert GmbH, Sulzbach, Germany) to prevent glue sticking to the endoscope—avoid costly endoscope repairs! Dilute N-butyl-2-cyanoacrylate with Lipiodol in a ratio of 0.5 to 0.3 mL to see where it is being delivered during injection under fluoroscopy. Use injection catheters that are resistant to glue-induced dissolution of the hub and premature polymerization of Histoacryl (B. Braun Dexon GmbH, Spangenberg, Germany). Determine the dead volume of the injection catheter by injecting sterile distilled water, and follow the injection of glue mixture with an injection of sterile distilled water volume equal to the dead space volume of catheter; it is critical to flush it SLOWLY. Strict compliance with the above steps in glue injection is critical to come out clean without any sticky issues! Complications associated with the injection of N-butyl-2-cyanoacrylate, which turns into a glob and stays in the body forever, are quite unique. Four different types of complications have been reported with the injection of glue: those related to systemic inflammatory reaction to a foreign body (pain and fever); local tissue necrosis and foreign body reaction (mediastinitis, esophageal pleural fistula, duodenal ulcer perforation, pancreaticodudoneal necrosis, inflammatory pseudotumor of pancreatic tail) (Gastroenterol Clin Biol 1986;10:580–583, Gastrointest Endosc 2000;52:267–270, Endoscopy 2000;32:S23, Surgery 1989;106:901–903, J Gastroenterol 2004;39:475–478); thrombo-embolic complications (splenic, portal, pulmonary, coronary, cerebral, and inferior vena cava) (Endoscopy 2000;32:422–424, Gastrointest Endosc 2002;55:276–278, Endoscopy 1998;30:S89–S90, Clin Biol 1986;10:604–607, Gastrointest Endosc 2001;53:228–230); and septic complications (Gastrointest Endosc 2004;59:911–916). Now, let us look at the work of Seewald and his colleagues, internationally renowned for their expertise in the use of glue. Their goal was to report the safety and efficacy of N-butyl-2-cyanoacrylate injection into pancreatic fistulas. Seewald et al injected cyanoacrylate into 12 patients (pancreatic duct leakage with [n = 7] or without a pseudocyst [n = 4] and pancreatico-cutaneous fistula [n = 1]); prompt occlusion of the fistula occurred in 7 of 12 patients after a single injection. In 1 patient, 2 injections were required, and in 4 patients, it was not successful (closure of fistula was temporary in 1, treatment failed in 1, and 1 patient died 24 hours after treatment). Of note, a pancreaticogram obtained after injection of glue demonstrated a patent main pancreatic duct in all the patients and none of the patients developed clinical pancreatitis after fistula injection or any other local inflammatory complications or distant thrombo-embolic complications associated with the injection of glue. This can only be achieved by precise injection of the glue into the fistula (0.5 mL for small fistulas and larger volume for larger/longer fistula; range, 0.5–4 mL), without much extravasation into the pseudocyst or abdominal cavity or backflow into the main pancreatic duct—a testament to the extensive experience of the Hamburg group with the glue over the last decade. Seewald et al have shown that there were no serious adverse events with this procedure. Is it absolutely safe? Only time will tell us. Regarding the second question, efficacy of glue injection in sealing the pancreatic duct leaks in the treatment of pseudocysts or free leaks, let us review the current endoscopic management of pseudocysts and free leaks. Poke and drain the pseudocyst (pioneered by Richard Kozarek, 1985) works well for pseudocysts with no communication to the pancreatic duct (Gastrointest Endosc 1985;31:322–328). For pseudocysts communicating with the pancreatic duct, transpapillary stenting (siphoning the pancreatic juice into the duodenum) curtails further leakage, drains the pseudocyst, dries it up, and eventually heals the leak. Although transpapillary stenting has been shown to be effective in the management of pseudocysts and pancreatic fistulas in over 75% of patients (Gastrointest Endosc 1995;42:202–207, 1995;42:208–213, 1995;42:214–218, 1995;42:219–224, Endoscopy 2001;33:317–322), drawbacks include the risk of recurrence of leak (10%–20%) (Gastrointest Endosc 1995;42:219–224, 2002;56:7–17) and the need for repeated stent exchanges over a prolonged period with its attendant complications (stent migration, clogging, infection, and stent induced pancreatic damage) (Clin Gastroenterol Hepatol 2004;2:322–329). Sealing the leak with glue, for instantaneous closure of leak, could potentially avoid some of these problems. How efficacious is this new technique in sealing the pancreatic leak? Sealing the leak once and for all, as proposed by Seewald et al, would be a welcome addition to the endoscopic management of these complex patients. The authors have shown that glue is successful in the primary closure of the pancreatic duct leak not associated with a pseudocyst and in the closure of the pancreatic leak associated with a pseudocyst after the drainage of pseudocyst with transpapillary stenting. By quickly fixing the leak, one would obviate the need for prolonged stenting in the management of pancreatic leaks without associated pseudocysts (Endoscopy 2001;33:317–322). This report raises the following questions: Is sealing the leak with glue as an adjunct to stent therapy after resolution of pseudocyst any better compared with prolonged transpapillary stenting alone in terms of primary closure and prevention of recurrence of leaks? Does the glue allow us to cut short the duration of transpapillary stenting or totally eliminate the need for it in the management of pseudocysts? Should there be a paradigm shift in the management of pancreatic pseudocysts communicating with pancreatic ducts with the availability of sealants? Will it be better to drain the pseudocyst either by percutaneous or transgastric or transenteric route, thereby totally eliminating the need for prolonged stenting to siphon the pseudocyst, and seal the leak by injection of glue through pancreatic duct? Glue has been shown to be successful in the setting of chronic pancreatitis, whereas failures occurred in all three patients with a history of acute pancreatitis. Is ongoing active inflammation a detriment to the success of glue injections? In summary, this report is an important conceptual and technical advance in the management of patients with pancreatic leaks. The authors should be congratulated for introducing this novel concept in endoscopy, healing by sealing. Glue is certainly a welcome addition to the armamentarium, for now, at the disposal of those (outside the U.S.) involved in the management of pancreatic leaks. This reminds me of the quote by Confucius, “I hear and I forget. I see and I remember. I do and I understand.” Soehendra, (pioneer in endoscopic use of glue) do, and understand very well the value of glue in the management of complex pancreatic problems. The privileged few who have seen the master at work will remember it. Many of us in the U.S. have to wrestle with the idea of not rusting with time, but start exploring novel means of healing by sealing.