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Fibrin glue–reinforced closure of postlaryngectomy pharyngocutaneous fistula
Fibrin Glue–Reinforced Closure of Postlaryngectomy Pharyngocutaneous Fistula Sam Wiseman, MD, Wesley Hicks, Jr, DDS, MD, Thom Loree, MD, Mazin Al-kasspooles, MD, and Nestor Rigual, MD* Pharyngocutaneous fistulization is a dreaded and devastating complication of laryngectomy. Although the specific risk factors are controversial, a history of prior radiation therapy has generally been accepted to be a major risk factor for developing this complication. We present a case of a postlaryngectomy pharyngocutaneous fistula developing in a previously irradiated patient that was successfully managed by incorporating fibrin glue into the surgical closure. We also discuss the underlying theoretical basis for this approach by reviewing the relevant literature. (Am J Otolaryngol 2002;23:368-373. Copyright 2002, Elsevier Science (USA). All rights reserved.) (Editorial Comment: Success in managing a fistula with fibrin glue in a single case does not prove it will be uniformly successful. Others have had less success. Nevertheless, this is an important report that bears critical review.)
previously irradiated patient that was successfully managed by incorporating fibrin glue into the fistula’s surgical closure. CASE REPORT
Pharyngocutaneous fistula (PCF) development is a significant complication of laryngectomy. Consequences of this complication may include prolonged hospitalization,1-3 delayed oral feeding,4 multiple surgeries,5 and death.6,7 Many investigators have reported a history of prior radiotherapy predisposing patients to fistula development.1-3,7-11 In our current era, when laryngectomy is increasingly reserved as salvage therapy for radiotherapy and chemotherapy treatment failures, PCF probably will continue to be a significant future source of patient morbidity. Fibrin glue has been successfully used for the management of multiple clinical problems in head and neck surgery.12-17 Fibrin glue has also been described to be a simple and safe method for facilitating closure of tracheoesophageal fistulae,18 tracheocutaneous fistulae,15 bronchopleural fistulae,19 and perianal fistulae.20 We present a case report of a postlaryngectomy pharyngocutaneous fistula occuring in a
From the Roswell Park Cancer Institute, Buffalo, NY. Address correspondence to Nestor Rigual, MD, Division of Head and Neck Surgery, Roswell Park Cancer Institute, Elm & Carlton streets, Buffalo, NY 14263. Copyright 2002, Elsevier Science (USA). All rights reserved. 0196-0709/02/2306-0009$35.00/0 doi:10.1053/ajot.2002.126318 368
Our patient is a 68-year-old African American man who presented to a local community hospital with a history of progressive voice hoarseness. He was investigated and diagnosed with a T2 N0 M0 squamous cell carcinoma of the glottic larynx. This primary tumor was treated at the peripheral center with external beam radiation therapy delivered to a total dose of 6,840 cGy. The following year he presented to Roswell Park Cancer Institute with progressive odynophagia, dysphagia, and weight loss. Examination and biopsy confirmed the presence of locally recurrent disease in the larynx. He subsequently underwent a salvage laryngectomy, bilateral comprehensive neck dissection, gastrostomy tube insertion, and a pectoralis major myocutaneous flap reconstruction of the surgical defect. His postoperative course was uneventful, and he was sent home 11 days postoperatively. Two days after hospital discharge he presented to our service with breakdown at the apex of his incision. On examination a pharyngocutaneous fistula was diagnosed; no other abnormality was present on clinical examination. He was admitted to our service and given intravenous antibiotics, maintained nil by mouth, enterally nourished via his gastrostomy tube, and clinically observed. Over
American Journal of Otolaryngology, Vol 23, No 6 (November-December), 2002: pp 368-373
FIBRIN GLUE CLOSURE OF PCF
Fig 1.
369
“Rosette” of pharyngeal mucosa herniating through pharyngocutaneous fistula.
the month that the fistula was conservatively managed it progressively decreased in size. The patient was sent home on gastrostomy feeds, given an enteral antibiotic, and instructed to avoid oral intake. Unfortunately the fistula persisted, and 3 weeks after discharge from the hospital, our patient required readmission for surgical closure of his persistent pharyngocutaneous fistula. Fistula closure was carried out with our patient under a general anesthetic. The fistula was initially circumferentially incised at the mucocutaneous junction. The wound edges were then minimally undermined in a manner that separated the mucosal layer from the skin–submucosal layer. Separation of these layers was challenging in this indurated, previously irradiated tissue. Initially, the “rosette” of mucosa herniating through the fistula tract (Fig 1) was resected. The mucosal closure was then carried out with simple interrupted absorbable sutures (Fig 2). To this layer was topically applied 4 mL of fibrin glue (Hemacure Corporation, Sarasota, FL). A coating of the entire closure was thus achieved (Fig 3).
After waiting a few minutes for the fibrin coating to solidify, we closed the skin–submucosal layer with simple interrupted nonabsorbable sutures (Fig 4). Blood loss from this procedure was negligible. The patient’s postoperative course was uneventful, and he was sent home from the hospital 1 week later. At our patient’s most recent clinical follow-up 6 months postoperatively, there was no evidence of recurrent disease. The fistula site has remained closed, and he is tolerating a liquid diet. DISCUSSION In all disciplines of surgery, fistulae, or abnormal communications between epithelialized surfaces, present the surgeon with formidable management challenges. In head and neck surgery it is the postlaryngectomy pharyngocutaneous fistula (PCF) that has remained a major source of patient morbidity.1-11,21,22 The reported incidence of postlaryngectomy PCF is between 7.4% and 65%.1-11,21,22 This variation in reported fistula
370
WISEMAN ET AL
Fig 2.
Mucosal closure using simple absorbable sutures (first layer of fistula closure).
incidence has been attributed to differences in the initial treatment of the patient (surgery or radiation therapy) and variability in patient selection for surgery of recurrent disease.1 As well, there is no universally accepted algorithm for managing these patients. In general, most PCF patients initially are managed conservatively with intravenous antibiotics, avoidance of oral intake, and local wound care.4,6 Some investigators have suggested a month of conservative management before attempting surgical repair.6,7 However, despite conservative measures approximately 30% of patients have persistent fistulae and require surgery for fistula closure.6 Some workers have attempted to address postlaryngectomy PCF by using techniques to prevent their development.23-25 In a retrospective study of 34 patients, Johansen et al demonstrated that prophylactic metronidazole and penicillin reduced the incidence of postlaryngectomy PCF when compared with the use of prophylactic penicillin alone.1 In 24 nonirradiated patients Koltai and Leipzig demonstrated that reinforcement of the pharyngeal suture line with
dermal grafts did not alter the incidence of fistulization postlaryngectomy.24 Other investigators have employed gastrointestinal reflux prophylaxis and delayed oral feeding to avoid fistula development.25 Despite the appeal of this strategy, measures taken to prevent fistulization postlaryngectomy have been of limited clinical utility. Thus, much of the current literature has focused on surgical techniques for fistula closure. Methods for repairing PCF have included direct suture,26 local or distant pedicle flaps,5,7,26 and free flaps.27,28 In a small proportion of patients undergoing PCF repair, the fistula will recur and become an ongoing source of patient morbidity.5 PCF can contribute to the development of other complications, including wound infection, wound abscess, carotid blowout, and death.6 Reported causes of death for PCF patients include carotid blowout, bronchopneumonia, mediastinitis, myocardial infarction, and sepsis.6 Although controversy exists regarding the specific factors that predispose patients to fistula development, the described risk factors for postlaryngectomy PCF include preopera-
FIBRIN GLUE CLOSURE OF PCF
Fig 3.
371
Coating of mucosal closure with fibrin glue (second layer of fistula closure).
tive radiotherapy,1-3,7-11 type of surgery,7,23 suture material used for pharyngeal reconstruction,9,21 type of pharyngeal closure,9 patient medical comorbidities,6,7 advanced tumor stage,10,21,22 surgeon experience,10 and postoperative anemia.8,11 Radiation therapy is toxic to patient tissues.29 Healing in radiated tissues is impaired because of the degeneration of fibroblasts and other cells in the treated field, as well as stromal collagen injury that blocks inflammatory and mesenchymal cell migration.30 Multiple investigators have reported an increased rate of wound complications in previously irradiated patients.1-3,7-11 It is in the previously irradiated, fistula-prone patient that surgical repair is an especially challenging problem. Currently, organ preservation chemotherapy and radiation therapy has become the first-line treatment of larynx cancer.31 In current management algorithms surgery is reserved for treatment failures, disease recurrences, and second primary tumors. Therefore, techniques that allow successful fistula closure with minimal associated patient mor-
bidity will continue to be clinically important. Early experiments using fibrin powder to control hemorrhage were first reported by Bergel in 1909.32 Cronkite et al and Tedrick and Warner in 1944 first described combining fibrinogen and thrombin for its adhesive effect to encourage skin graft adherence.33,34 Acceptance of this technique was limited at that time. In 1972, Matras et al used fibrin glue as a tissue adhesive in digital neural anastomoses.35 Only more recently has fibrin glue become accepted in North American medicine for its adhesive and hemostatic properties. The creation of a biostable union between 2 surfaces permit tissue adhesives to function as biologic “sealants.” Fibrin tissue adhesive, or fibrin glue, is dependent on the binding capacity of the fibrin clot for its adhesive properties.14 Fibrin glue systems are composed of 2 principal components—the sealer protein component and the thrombin component. The sealer protein is composed of fibrinogen and plasma proteins that include albumin, cold insoluble immunoglobulin (CIG), and factor
372
Fig 4.
WISEMAN ET AL
Skin–subcutaneous tissue closure using simple nonabsorbable sutures (third layer of fistula closure).
XIII. There are also a thrombin component, a calcium chloride component, and a fibrinolysis inhibitor component. When the components are combined, the thrombin converts the fibrinogen to fibrin, and clotting is initiated. When this occurs factor XIII in the presence of ionized calcium is activated to factor XIIIa. Factor XIIIa catalyzes the cross-linkage of fibrin and CIG that increases clot strength. The net result of these reactions is creation of an elastic coagulum, or fibrin clot, with both adhesive and hemostatic properties.12-14 As wound healing occurs, the clot is gradually phagocytosed, lysed, and absorbed. In wellvascularized tissues an active cellular response is present that leads to rapid clot degradation.14 The presence of an antifibrinolytic agent (aprotinin) in this adhesive slows clot degradation and allows the “seal” to endure.12-14 Thus, fibrin glue functions by mimicking the same processes that occur during the final phase of the coagulation cascade. In head and neck surgery fibrin glue has been used for reconstruction of the ossicular chain, fixation of the ossicles, synthetic ossicular
grafts, closing recurrent perforations of the tympanic membrane, neural anastomoses, hemostasis, graft fixation, sealing of bone, and sealing of dura.12-14 For the PCF patient, fibrin glue may represent a solution to the management challenge presented by a fistula. Fibrin glue has been used to reinforce tracheal anastomoses,36 esophageal anastomoses,37 small bowel anastomoses,38 and colonic anastomoses.39 Saclarides et al have reported experimental work in a rat model demonstrating that fibrin glue improves wound healing in intraoperatively irradiated small bowel anastomoses.38 Fibrin glue has been successfully used to close tracheoesophageal fistulae,18 tracheocutaneous fistulae,15 bronchopleural fistulae,19 and perianal fistulae.20 By exploiting its sealant properties, we have demonstrated the utility of fibrin glue in PCF repair. In addition, our technique for incorporating fibrin glue into a PCF repair may be achieved with relative technical ease and minimal patient morbidity. Although our experience is preliminary, we believe the role of
FIBRIN GLUE CLOSURE OF PCF
fibrin glue in the management of PCF shows promise and warrants further clinical study. REFERENCES 1. Johansen LV, Overgaard J, Elbrond O: Pharyngocutaneous fistulae after laryngectomy. Influence of previous radiotherapy and prophylactic metronidazole. Cancer 61:673-678, 1988 2. Weingrad DN, Spiro RH: Complications after laryngectomy. Am J Surg 146:517-520, 1983 3. Virtaniemi JA, Kumpulainen EJ, Hirvikoski PP, et al: The incidence and etiology of postlaryngectomy pharyngocutaneous fistulae. Head Neck 23:29-33, 2001 4. Weissler MC: Management of complications resulting from laryngeal cancer treatment. Otolaryngol Clin North Am 30:269-278, 1997 5. Rees R, Cary A, Shack RB, et al: Pharyngocutaneous fistulas in advanced cancer: Closure with musculocutaneous or muscle flaps. Am J Surg 154:381-383, 1987 6. Redaelli de Zinis LO, Ferrari L, Tomenzoli D, et al: Postlaryngectomy pharyngocutaneous fistula: Incidence, predisposing factors, and therapy. Head Neck 21:131-138, 1999 7. Papazoglou G, Doundoulakis G, Terzakis G, et al: Pharyngocutaneous fistula after total laryngectomy: Incidence, cause, and treatment. Ann Otol Rhinol Laryngol 103:801-805, 1994 8. Wei WI, Lam KH, Wong J, et al: Pharyngocutaneous fistula complicating total laryngectomy. Aust N Z J Surg 50:366-369, 1980 9. Sarkar S, Mehta SA, Tiwari J, et al: Complications following surgery for cancer of the larynx and pyriform fossa. J Surg Oncol 43:245-249, 1990 10. Mendelsohn MS, Bridger GP: Pharyngocutaneous fistulae following laryngectomy. Aust N Z J Surg 55:177179, 1985 11. Natvig K, Boysen M, Tausjo J: Fistulae following laryngectomy in patients treated with irradiation. J Laryngol Otol 107:1136-1139, 1993 12. Matras H: The use of fibrin sealant in oral and maxillofacial surgery. J Oral Maxillofac Surg 40:617-622, 1982 13. Matras H: Fibrin sealant in maxillofacial surgery. Development and indications. A review of the past 12 years. Facial Plast Surg 2:297-313, 1985 14. Toriumi DM, O’Grady K: Surgical tissue adhesives in otolaryngology-head and neck surgery. Otolaryngol Clin North Am 27:203-209, 1994 15. Romeo G: Applications of tissucol in larynx, trachea and neck surgery. Rev Laryngol Otol Rhinol (Bord) 10:121-122, 1989 16. Petersen JK: Clinical experience in oral surgery with human fibrin sealant. Int Dent J 35:277-279, 1985 17. Matras H: Fibrin seal: The state of the art. J Oral Maxillofac Surg 43:605-611, 1985 18. Wiseman NE: Endoscopic closure of recurrent tracheoesophageal fistula using Tisseel. J Pediatr Surg 30: 1236-1237, 1995 19. Scappaticci E, Ardissone F, Ruffini E, et al: As originally published in 1994: Postoperative bronchopleural fistula: Endoscopic closure in 12 patients. Updated in 2000. Ann Thorac Surg 69:1629-1630, 2000
373
20. Sentovich SM: Fibrin glue for all anal fistulas. J Gastrointest Surg 5:158-161, 2001 21. Soylu L, Kiroglu M, Aydogan B, et al: Pharyngocutaneous fistula following laryngectomy. Head Neck 20:2225, 1998 22. Fradis M, Podoshin L, Ben David J: Post-laryngectomy pharyngocutaneous fistula—a still unresolved problem. J Laryngol Otol 109:221-224, 1995 23. Herranz J, Sarandeses A, Fernandez MF, et al: Complications after total laryngectomy in nonradiated laryngeal and hypopharyngeal carcinomas. Otolaryngol Head Neck Surg 122:892-898, 2000 24. Koltai PJ, Leipzig B: Dermal graft for protection of the pharyngeal suture line in cancer surgery of the head and neck. Otolaryngol Head Neck Surg 89:260-263, 1981 25. Seikaly H, Park P: Gastroesophageal reflux prophylaxis decreases the incidence of pharyngocutaneous fistula after total laryngectomy. Laryngoscope 105:12201222, 1995 26. Kimura Y, Tojima H, Nakamura T, et al: Deltopectral flap for one-stage reconstruction of pharyngocutaneous fistulae following total laryngectomy. Acta Otolaryngol Suppl 511:175-178, 1994 27. de Vries EJ, Myers EN, Johnson JT, et al: Jejunal interposition for repair of stricture or fistula after laryngectomy. Ann Otol Rhinol Laryngol 99:496-498, 1990 28. Teknos TN, Myers LL, Bradford CR, et al: Free tissue reconstruction of the hypopharynx after organ preservation therapy: Analysis of wound complications. Laryngoscope 111:1192-1196, 2001 29. Moore MJ: The effect of radiation on connective tissue. Otolaryngol Clin North Am 17:389-399, 1984 30. Withers RH: Biologic basis of radiation therapy, in Perez C, Brady L (eds): Principles and Practice of Radiation Oncology. Philadelphia, PA, Lippincott, 1992, pp 64-69 31. Pignon JP, Bourhis J, Domenge C, et al: Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: Three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet 355:949-955, 2000 32. Bergel S: Uber Wirkungen des Fibrins. Dtsch Med Wochenschr 35:633, 1909 33. Cronkite EP, Lozner EL, Deaver JM: Use of thrombin and fibrinogen in skin grafting. JAMA 124:976, 1944 34. Tedrick RT, Warner ED. Fibrin fixation of skin transplants. Surgery 15:90, 1944 35. Matras H, Dinges HP, Lassmann H, et al: Zur nahaloshen interfaszikularen Nerevetransplantation im Tierexperiment. Wien Med Wochenschr 122:517-523, 1972 36. Kacker A, Huo J: Reinforcement of an end-to-end tracheal resection anastomosis with fibrin glue: A case report. Ear Nose Throat J 80:234-238, 2001 37. McCarthy PM, Trastek VF, Schaff HV, et al: Esophagogastric anastomoses: The value of fibrin glue in preventing leakage. J Thorac Cardiovasc Surg 93:234-239, 1987 38. Saclarides TJ, Woodard DO, Bapna M, et al: Fibrin glue improves the healing of irradiated bowel anastomoses. Dis Colon Rectum 35:249-252, 1992 39. Ussia G, Cuccomarino S, Ravo B, et al: Combined laparoendoscopic colon resection and anastomosis using the “no touch technique” and fibrin glue. An experimental study. Surg Endosc 12:1046-1050, 1998
previously irradiated patient that was successfully managed by incorporating fibrin glue into the fistula’s surgical closure. CASE REPORT
Pharyngocutaneous fistula (PCF) development is a significant complication of laryngectomy. Consequences of this complication may include prolonged hospitalization,1-3 delayed oral feeding,4 multiple surgeries,5 and death.6,7 Many investigators have reported a history of prior radiotherapy predisposing patients to fistula development.1-3,7-11 In our current era, when laryngectomy is increasingly reserved as salvage therapy for radiotherapy and chemotherapy treatment failures, PCF probably will continue to be a significant future source of patient morbidity. Fibrin glue has been successfully used for the management of multiple clinical problems in head and neck surgery.12-17 Fibrin glue has also been described to be a simple and safe method for facilitating closure of tracheoesophageal fistulae,18 tracheocutaneous fistulae,15 bronchopleural fistulae,19 and perianal fistulae.20 We present a case report of a postlaryngectomy pharyngocutaneous fistula occuring in a
From the Roswell Park Cancer Institute, Buffalo, NY. Address correspondence to Nestor Rigual, MD, Division of Head and Neck Surgery, Roswell Park Cancer Institute, Elm & Carlton streets, Buffalo, NY 14263. Copyright 2002, Elsevier Science (USA). All rights reserved. 0196-0709/02/2306-0009$35.00/0 doi:10.1053/ajot.2002.126318 368
Our patient is a 68-year-old African American man who presented to a local community hospital with a history of progressive voice hoarseness. He was investigated and diagnosed with a T2 N0 M0 squamous cell carcinoma of the glottic larynx. This primary tumor was treated at the peripheral center with external beam radiation therapy delivered to a total dose of 6,840 cGy. The following year he presented to Roswell Park Cancer Institute with progressive odynophagia, dysphagia, and weight loss. Examination and biopsy confirmed the presence of locally recurrent disease in the larynx. He subsequently underwent a salvage laryngectomy, bilateral comprehensive neck dissection, gastrostomy tube insertion, and a pectoralis major myocutaneous flap reconstruction of the surgical defect. His postoperative course was uneventful, and he was sent home 11 days postoperatively. Two days after hospital discharge he presented to our service with breakdown at the apex of his incision. On examination a pharyngocutaneous fistula was diagnosed; no other abnormality was present on clinical examination. He was admitted to our service and given intravenous antibiotics, maintained nil by mouth, enterally nourished via his gastrostomy tube, and clinically observed. Over
American Journal of Otolaryngology, Vol 23, No 6 (November-December), 2002: pp 368-373
FIBRIN GLUE CLOSURE OF PCF
Fig 1.
369
“Rosette” of pharyngeal mucosa herniating through pharyngocutaneous fistula.
the month that the fistula was conservatively managed it progressively decreased in size. The patient was sent home on gastrostomy feeds, given an enteral antibiotic, and instructed to avoid oral intake. Unfortunately the fistula persisted, and 3 weeks after discharge from the hospital, our patient required readmission for surgical closure of his persistent pharyngocutaneous fistula. Fistula closure was carried out with our patient under a general anesthetic. The fistula was initially circumferentially incised at the mucocutaneous junction. The wound edges were then minimally undermined in a manner that separated the mucosal layer from the skin–submucosal layer. Separation of these layers was challenging in this indurated, previously irradiated tissue. Initially, the “rosette” of mucosa herniating through the fistula tract (Fig 1) was resected. The mucosal closure was then carried out with simple interrupted absorbable sutures (Fig 2). To this layer was topically applied 4 mL of fibrin glue (Hemacure Corporation, Sarasota, FL). A coating of the entire closure was thus achieved (Fig 3).
After waiting a few minutes for the fibrin coating to solidify, we closed the skin–submucosal layer with simple interrupted nonabsorbable sutures (Fig 4). Blood loss from this procedure was negligible. The patient’s postoperative course was uneventful, and he was sent home from the hospital 1 week later. At our patient’s most recent clinical follow-up 6 months postoperatively, there was no evidence of recurrent disease. The fistula site has remained closed, and he is tolerating a liquid diet. DISCUSSION In all disciplines of surgery, fistulae, or abnormal communications between epithelialized surfaces, present the surgeon with formidable management challenges. In head and neck surgery it is the postlaryngectomy pharyngocutaneous fistula (PCF) that has remained a major source of patient morbidity.1-11,21,22 The reported incidence of postlaryngectomy PCF is between 7.4% and 65%.1-11,21,22 This variation in reported fistula
370
WISEMAN ET AL
Fig 2.
Mucosal closure using simple absorbable sutures (first layer of fistula closure).
incidence has been attributed to differences in the initial treatment of the patient (surgery or radiation therapy) and variability in patient selection for surgery of recurrent disease.1 As well, there is no universally accepted algorithm for managing these patients. In general, most PCF patients initially are managed conservatively with intravenous antibiotics, avoidance of oral intake, and local wound care.4,6 Some investigators have suggested a month of conservative management before attempting surgical repair.6,7 However, despite conservative measures approximately 30% of patients have persistent fistulae and require surgery for fistula closure.6 Some workers have attempted to address postlaryngectomy PCF by using techniques to prevent their development.23-25 In a retrospective study of 34 patients, Johansen et al demonstrated that prophylactic metronidazole and penicillin reduced the incidence of postlaryngectomy PCF when compared with the use of prophylactic penicillin alone.1 In 24 nonirradiated patients Koltai and Leipzig demonstrated that reinforcement of the pharyngeal suture line with
dermal grafts did not alter the incidence of fistulization postlaryngectomy.24 Other investigators have employed gastrointestinal reflux prophylaxis and delayed oral feeding to avoid fistula development.25 Despite the appeal of this strategy, measures taken to prevent fistulization postlaryngectomy have been of limited clinical utility. Thus, much of the current literature has focused on surgical techniques for fistula closure. Methods for repairing PCF have included direct suture,26 local or distant pedicle flaps,5,7,26 and free flaps.27,28 In a small proportion of patients undergoing PCF repair, the fistula will recur and become an ongoing source of patient morbidity.5 PCF can contribute to the development of other complications, including wound infection, wound abscess, carotid blowout, and death.6 Reported causes of death for PCF patients include carotid blowout, bronchopneumonia, mediastinitis, myocardial infarction, and sepsis.6 Although controversy exists regarding the specific factors that predispose patients to fistula development, the described risk factors for postlaryngectomy PCF include preopera-
FIBRIN GLUE CLOSURE OF PCF
Fig 3.
371
Coating of mucosal closure with fibrin glue (second layer of fistula closure).
tive radiotherapy,1-3,7-11 type of surgery,7,23 suture material used for pharyngeal reconstruction,9,21 type of pharyngeal closure,9 patient medical comorbidities,6,7 advanced tumor stage,10,21,22 surgeon experience,10 and postoperative anemia.8,11 Radiation therapy is toxic to patient tissues.29 Healing in radiated tissues is impaired because of the degeneration of fibroblasts and other cells in the treated field, as well as stromal collagen injury that blocks inflammatory and mesenchymal cell migration.30 Multiple investigators have reported an increased rate of wound complications in previously irradiated patients.1-3,7-11 It is in the previously irradiated, fistula-prone patient that surgical repair is an especially challenging problem. Currently, organ preservation chemotherapy and radiation therapy has become the first-line treatment of larynx cancer.31 In current management algorithms surgery is reserved for treatment failures, disease recurrences, and second primary tumors. Therefore, techniques that allow successful fistula closure with minimal associated patient mor-
bidity will continue to be clinically important. Early experiments using fibrin powder to control hemorrhage were first reported by Bergel in 1909.32 Cronkite et al and Tedrick and Warner in 1944 first described combining fibrinogen and thrombin for its adhesive effect to encourage skin graft adherence.33,34 Acceptance of this technique was limited at that time. In 1972, Matras et al used fibrin glue as a tissue adhesive in digital neural anastomoses.35 Only more recently has fibrin glue become accepted in North American medicine for its adhesive and hemostatic properties. The creation of a biostable union between 2 surfaces permit tissue adhesives to function as biologic “sealants.” Fibrin tissue adhesive, or fibrin glue, is dependent on the binding capacity of the fibrin clot for its adhesive properties.14 Fibrin glue systems are composed of 2 principal components—the sealer protein component and the thrombin component. The sealer protein is composed of fibrinogen and plasma proteins that include albumin, cold insoluble immunoglobulin (CIG), and factor
372
Fig 4.
WISEMAN ET AL
Skin–subcutaneous tissue closure using simple nonabsorbable sutures (third layer of fistula closure).
XIII. There are also a thrombin component, a calcium chloride component, and a fibrinolysis inhibitor component. When the components are combined, the thrombin converts the fibrinogen to fibrin, and clotting is initiated. When this occurs factor XIII in the presence of ionized calcium is activated to factor XIIIa. Factor XIIIa catalyzes the cross-linkage of fibrin and CIG that increases clot strength. The net result of these reactions is creation of an elastic coagulum, or fibrin clot, with both adhesive and hemostatic properties.12-14 As wound healing occurs, the clot is gradually phagocytosed, lysed, and absorbed. In wellvascularized tissues an active cellular response is present that leads to rapid clot degradation.14 The presence of an antifibrinolytic agent (aprotinin) in this adhesive slows clot degradation and allows the “seal” to endure.12-14 Thus, fibrin glue functions by mimicking the same processes that occur during the final phase of the coagulation cascade. In head and neck surgery fibrin glue has been used for reconstruction of the ossicular chain, fixation of the ossicles, synthetic ossicular
grafts, closing recurrent perforations of the tympanic membrane, neural anastomoses, hemostasis, graft fixation, sealing of bone, and sealing of dura.12-14 For the PCF patient, fibrin glue may represent a solution to the management challenge presented by a fistula. Fibrin glue has been used to reinforce tracheal anastomoses,36 esophageal anastomoses,37 small bowel anastomoses,38 and colonic anastomoses.39 Saclarides et al have reported experimental work in a rat model demonstrating that fibrin glue improves wound healing in intraoperatively irradiated small bowel anastomoses.38 Fibrin glue has been successfully used to close tracheoesophageal fistulae,18 tracheocutaneous fistulae,15 bronchopleural fistulae,19 and perianal fistulae.20 By exploiting its sealant properties, we have demonstrated the utility of fibrin glue in PCF repair. In addition, our technique for incorporating fibrin glue into a PCF repair may be achieved with relative technical ease and minimal patient morbidity. Although our experience is preliminary, we believe the role of
FIBRIN GLUE CLOSURE OF PCF
fibrin glue in the management of PCF shows promise and warrants further clinical study. REFERENCES 1. Johansen LV, Overgaard J, Elbrond O: Pharyngocutaneous fistulae after laryngectomy. Influence of previous radiotherapy and prophylactic metronidazole. Cancer 61:673-678, 1988 2. Weingrad DN, Spiro RH: Complications after laryngectomy. Am J Surg 146:517-520, 1983 3. Virtaniemi JA, Kumpulainen EJ, Hirvikoski PP, et al: The incidence and etiology of postlaryngectomy pharyngocutaneous fistulae. Head Neck 23:29-33, 2001 4. Weissler MC: Management of complications resulting from laryngeal cancer treatment. Otolaryngol Clin North Am 30:269-278, 1997 5. Rees R, Cary A, Shack RB, et al: Pharyngocutaneous fistulas in advanced cancer: Closure with musculocutaneous or muscle flaps. Am J Surg 154:381-383, 1987 6. Redaelli de Zinis LO, Ferrari L, Tomenzoli D, et al: Postlaryngectomy pharyngocutaneous fistula: Incidence, predisposing factors, and therapy. Head Neck 21:131-138, 1999 7. Papazoglou G, Doundoulakis G, Terzakis G, et al: Pharyngocutaneous fistula after total laryngectomy: Incidence, cause, and treatment. Ann Otol Rhinol Laryngol 103:801-805, 1994 8. Wei WI, Lam KH, Wong J, et al: Pharyngocutaneous fistula complicating total laryngectomy. Aust N Z J Surg 50:366-369, 1980 9. Sarkar S, Mehta SA, Tiwari J, et al: Complications following surgery for cancer of the larynx and pyriform fossa. J Surg Oncol 43:245-249, 1990 10. Mendelsohn MS, Bridger GP: Pharyngocutaneous fistulae following laryngectomy. Aust N Z J Surg 55:177179, 1985 11. Natvig K, Boysen M, Tausjo J: Fistulae following laryngectomy in patients treated with irradiation. J Laryngol Otol 107:1136-1139, 1993 12. Matras H: The use of fibrin sealant in oral and maxillofacial surgery. J Oral Maxillofac Surg 40:617-622, 1982 13. Matras H: Fibrin sealant in maxillofacial surgery. Development and indications. A review of the past 12 years. Facial Plast Surg 2:297-313, 1985 14. Toriumi DM, O’Grady K: Surgical tissue adhesives in otolaryngology-head and neck surgery. Otolaryngol Clin North Am 27:203-209, 1994 15. Romeo G: Applications of tissucol in larynx, trachea and neck surgery. Rev Laryngol Otol Rhinol (Bord) 10:121-122, 1989 16. Petersen JK: Clinical experience in oral surgery with human fibrin sealant. Int Dent J 35:277-279, 1985 17. Matras H: Fibrin seal: The state of the art. J Oral Maxillofac Surg 43:605-611, 1985 18. Wiseman NE: Endoscopic closure of recurrent tracheoesophageal fistula using Tisseel. J Pediatr Surg 30: 1236-1237, 1995 19. Scappaticci E, Ardissone F, Ruffini E, et al: As originally published in 1994: Postoperative bronchopleural fistula: Endoscopic closure in 12 patients. Updated in 2000. Ann Thorac Surg 69:1629-1630, 2000
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20. Sentovich SM: Fibrin glue for all anal fistulas. J Gastrointest Surg 5:158-161, 2001 21. Soylu L, Kiroglu M, Aydogan B, et al: Pharyngocutaneous fistula following laryngectomy. Head Neck 20:2225, 1998 22. Fradis M, Podoshin L, Ben David J: Post-laryngectomy pharyngocutaneous fistula—a still unresolved problem. J Laryngol Otol 109:221-224, 1995 23. Herranz J, Sarandeses A, Fernandez MF, et al: Complications after total laryngectomy in nonradiated laryngeal and hypopharyngeal carcinomas. Otolaryngol Head Neck Surg 122:892-898, 2000 24. Koltai PJ, Leipzig B: Dermal graft for protection of the pharyngeal suture line in cancer surgery of the head and neck. Otolaryngol Head Neck Surg 89:260-263, 1981 25. Seikaly H, Park P: Gastroesophageal reflux prophylaxis decreases the incidence of pharyngocutaneous fistula after total laryngectomy. Laryngoscope 105:12201222, 1995 26. Kimura Y, Tojima H, Nakamura T, et al: Deltopectral flap for one-stage reconstruction of pharyngocutaneous fistulae following total laryngectomy. Acta Otolaryngol Suppl 511:175-178, 1994 27. de Vries EJ, Myers EN, Johnson JT, et al: Jejunal interposition for repair of stricture or fistula after laryngectomy. Ann Otol Rhinol Laryngol 99:496-498, 1990 28. Teknos TN, Myers LL, Bradford CR, et al: Free tissue reconstruction of the hypopharynx after organ preservation therapy: Analysis of wound complications. Laryngoscope 111:1192-1196, 2001 29. Moore MJ: The effect of radiation on connective tissue. Otolaryngol Clin North Am 17:389-399, 1984 30. Withers RH: Biologic basis of radiation therapy, in Perez C, Brady L (eds): Principles and Practice of Radiation Oncology. Philadelphia, PA, Lippincott, 1992, pp 64-69 31. Pignon JP, Bourhis J, Domenge C, et al: Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: Three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet 355:949-955, 2000 32. Bergel S: Uber Wirkungen des Fibrins. Dtsch Med Wochenschr 35:633, 1909 33. Cronkite EP, Lozner EL, Deaver JM: Use of thrombin and fibrinogen in skin grafting. JAMA 124:976, 1944 34. Tedrick RT, Warner ED. Fibrin fixation of skin transplants. Surgery 15:90, 1944 35. Matras H, Dinges HP, Lassmann H, et al: Zur nahaloshen interfaszikularen Nerevetransplantation im Tierexperiment. Wien Med Wochenschr 122:517-523, 1972 36. Kacker A, Huo J: Reinforcement of an end-to-end tracheal resection anastomosis with fibrin glue: A case report. Ear Nose Throat J 80:234-238, 2001 37. McCarthy PM, Trastek VF, Schaff HV, et al: Esophagogastric anastomoses: The value of fibrin glue in preventing leakage. J Thorac Cardiovasc Surg 93:234-239, 1987 38. Saclarides TJ, Woodard DO, Bapna M, et al: Fibrin glue improves the healing of irradiated bowel anastomoses. Dis Colon Rectum 35:249-252, 1992 39. Ussia G, Cuccomarino S, Ravo B, et al: Combined laparoendoscopic colon resection and anastomosis using the “no touch technique” and fibrin glue. An experimental study. Surg Endosc 12:1046-1050, 1998