0016-5107/91/3702-0180$03.00/0 GASTROINTESTINAL ENDOSCOPY Copyright © 1991 by the American Society for Gastrointestinal Endoscopy
New Methods-New Materials Intralesional steroid injections for peptic esophageal strictures Michael Kirsch, Mark Blue, Robert K. Desai, Michael V. Sivak, Jr.,
MD MD MD MD
The majority of benign esophageal strictures are of peptic origin. t , 2 The clinical history typically includes chronic gastroesophageal reflux with progressive dysphagia. Medical management consists of reflux control measures and periodic mechanical esophageal dilations. Although some investigators have reported that the latter therapy is effective in treating benign esophageal strictures,2,3 others have demonstrated high recurrence rates with decreasing recurrence intervals after bougienage. 4 Clearly, some patients with benign strictures do not achieve acceptable symptom relief despite an intensive dilation schedule and gastroesophageal reflux therapy. These patients are often elderly with comorbid conditions that greatly increase the risk of surgical therapy. In addition, in our experience, some patients find bougienage uncomfortable and will delay needed dilation therapy despite the presence of symptoms. Successful treatment of benign esophageal strictures using intralesional steroid injections has been reported in uncontrolled studies. 5- s We report the results of a pilot study where two patients have demonstrated dramatic objective and subjective benefit after intralesional steroid injections of their strictures. METHODS
Two patients with benign peptic strictures of the esophagus were studied. Before entering the study, patient 1 underwent 10 esophageal dilation sessions in the preceding 14 months and patient 2 underwent 13 dilation sessions in the preceding 6 months. Both patients had very temporary symptomatic benefit after these dilations. Initially, both patients were assigned a dysphagia score from 0 to 21, similar to the method described by Penagini et al.,9 based on their ability to swallow certain foods easily. The following six foods, each with a different score value were given: water (1), applesauce (2), banana (3), unpeeled apple wedge (4), prunes (5), and white bread with the crust (6). Symptoms that developed after a test food was adminReceived May 30, 1990. For revision September 17, 1990. Accepted October 30, 1990. From The Cleveland Clinic Foundation, Cleveland, Ohio. Reprint requests: Michael V. Sivak, Jr., MD, The Cleveland Clinic Foundation, One Clinic Center, 9500 Euclid Avenue, Cleveland, Ohio 441955001.
180
istered were allowed to completely subside before continuing with subsequent test foods. A score of 0 indicates total dysphagia and a score of 21 indicates that all six foods were easily swallowed. Both patients had severe dysphagia upon entrance into the study. After a dysphagia score determination, each patient underwent a standard esophageal dilation using Savary-Gilliard dilators over a guidewire. This initial phase of the study was performed so that patients could serve as their own controls. When severe, persistent symptoms recurred, the dysphagia score determination was repeated. This was followed by a dilation to the same diameter as performed previously. During this dilation, patients received four injections of triamcinolone acetonide (Kenalog," 10 mg/ml; Squibb) in 0.5-ml aliquots into four quadrants of the most narrow region ofthe stricture using a standard sclerotherapy needle. For each patient, the study was concluded when the treatment phase was equal to the control phase. For example, in both patients studied, the control and treatment phases were each 3 weeks in duration as described below in Results. At the conclusion of the study, each patient returned for a final dysphagia score determination. Stricture size was assessed by barium esophagrams performed by an experienced gastrointestinal radiologist who was aware of the treatment schedule and study protocol. Esophagrams were performed before the initial endoscopy and repeated before the steroid injections and at the conclusion of the study. Stricture diameter was calculated by averaging two measurements taken from different views of the most narrow region of the stricture. During all follow-up visits, patients were questioned regarding their swallowing ability (improved, worse, or unchanged) and whether they believed they needed an esophageal dilation. Both patients were given standard treatment for gastroesophageal reflux with compliance stressed during telephone interviews and follow-up visits. At the conclusion of the study, data were analyzed for changes in the dysphagia score, subjective improvement, and stricture diameter. The study was approved by the Institutional Review Board of The Cleveland Clinic Foundation and informed consent was obtained.
RESULTS
Patient 1 initially experienced dysphagia characterized by sub-xyphoid pressure and eructation with all test foods except water and was assigned a dysphagia score of 1. At endoscopy, the 9.S-mm diameter endoscope could not be passed through the stricture and dilation to 15 mm was performed using a guidewire. After 3 weeks, he reported the complete return of symptoms and was assigned a dysphagia score of 3. After dilation to 15 mm, the steroid injections were performed as described. Three weeks later at the conclusion of the study, he was completely asymptomatic GASTROINTESTINAL ENDOSCOPY
eating all varieties of food including meat. At this time, he was assigned a dysphagia score of 21. Patient 2 initially experienced chest pressure after apple sauce and a banana, and vomited after the remaining foods were administered. He was assigned a dysphagia score of 1. The 9.8-mm diameter endoscope could not be passed through the stricture and dilation to 14 mm was performed. Symptoms returned after 10 days and in an additional 10 days he had an identical response to the test foods and was again assigned a dysphagia score of 1. After dilation to 14 mm, the steroid injections were performed. Three weeks later at the conclusion of the study, he was completely asymptomatic having no dietary restrictions. He swallowed all test foods without any difficulty and was assigned a dysphagia score of 21. In addition, both patients had dramatic subjective improvement after the steroid injections. Both patients felt that this was the longest asymptomatic period that they had ever experienced since they originally commenced dilation therapy. There were no adverse reactions to the treatment. After the study was completed, patient 1 ultimately required a standard esophageal dilation 3 months after the steroid injections. Remarkably, patient 2, who previously required dilation every 10 days, remained entirely asymptomatic until 2 months after the steroid injections at which time mild dysphagia returned. Both patients expressed interest in receiving additional steroid treatments. Stricture diameter in patient 1 was 3.0 mm initially and 3.5 mm before the steroid injections. At the conclusion of the study the diameter remained 3.5 mm despite the symptomatic improvement that occurred. Stricture diameter in patient 2 was 8.0 mm both initially and before the steroid injections. However, at the conclusion of the study when this patient was asymptomatic, the diameter was 20.0 mm (Fig. 1).
A
DISCUSSION
Intralesional steroid injections are effective in treating keloids, hypertrophic scars, and burn scars. lO, 11 The rationale for applying this therapy to peptic strictures is that stricture formation represents the final stage of gastroesophageal reflux with the esophagus undergoing scar formation. In dogs with lye-induced esophageal strictures, intralesional steroid injections increased stricture diameter in comparison to a control group.12 In addition, there have been numerous reports of humans with benign esophageal strictures successfully treated with intralesional steroid injections. 5 - 8 The majority of these strictures were caustic, radiation-induced, and anastomotic with only one stricture attributed to gastroesophageal influx. 6 In these cases, there was no uniformity with respect to the steroid dose or preparation, number of treatment VOLUME 37, NO.2, 1991
Figure 1. Barium esophagram of patient 2. A, Prior to steroid injections stricture diameter was 8.0 mm. B, At the conclusion of the study, stricture diameter was increased to 20.0 mm.
sessions, injection volume, or accompanying dilation therapy. Although several of these patients improved, this anecdotal evidence was never further tested in a controlled trial. Doses administered were as high as 200 mg of triamcinolone acetonide/session. 6 As intralesional steroid injections may cause skin atrophy,13 181
we selected a modest total dose of 20 mg of triamcinolone acetonide for our patients to minimize the chance that esophageal mucosal atrophy would result. Both of our patients had dramatic subjective and objective improvement after intralesional steroid injections of their strictures. Their chronic history of requiring regular esophageal dilations and the inclusion of a control period in the study make it extremely unlikely that their marked improvement was unrelated to the steroid treatment. In patient 1, there was no correlation between the measured diameter of the stricture by esophagography and the presence or extent of dysphagia. Others have similarly observed a poor correlation between stricture size measured by barium esophagography and dysphagia. 9 In contrast, patient 2 showed significant radiographic improvement at the conclusion of the study when he was asymptomatic. Previously cited reports have also shown dramatic radiographic resolution of strictures after treatment that included intralesional steroid injections.5, 7, 8 The mechanisms whereby steroid injections improve dysphagia are not clear. Intralesional steroid injections may increase stricture compliance allowing a bolus to pass more easily. It is conceivable, therefore, that intralesional steroid injections may be effective when applied without concomitant esophageal dilation, as has been reported in humans5 and experimental animals. 12 If intralesional steroid injection therapy is safe and effective, it could impact significantly on the treatment of peptic strictures. It could decrease the frequency of esophageal dilations and surgical repair of peptic strictures while improving the life-style and nutritional status of these patients. In addition, this simple treatment could reduce health care costs as the medication is inexpensive and fewer subsequent dilations would be needed. Importantly, patients would face a lower lifetime risk of the complications of esophagal dilations and surgery. We believe that intralesional steroid injections may
182
be more effective, safer, and less expensive therapy than standard esophageal dilations for treating refractory peptic esophageal strictures. We hope that our dramatic preliminary results will stimulate other investigators to further test this new treatment for peptic strictures in controlled clinical trials. ACKNOWLEDGMENTS
The authors are grateful for the assistance of Karen Izso. This article is dedicated to the memory of our friend and colleague, Mark Blue, MD.
REFERENCES 1. Williamson RCN. The management of peptic oesophageal stricture. Br J Surg 1975;62:448-54. 2. Wesdorp ICE, Bartelsman JFWM, den Hartog Jager FCA, Huibregtse K, Tytgat GNJ. Results of conservative treatment of benign esophageal strictures: a follow-up study on 100 patients. Gastroenterology 1982;82:487-93. 3. Lanza FL, Graham DY. Bougienage is effective therapy for most benign esophageal strictures. JAMA 1978;240:844-7. 4. Glick ME. Clinical course of esophageal stricture managed by bougienage. Dig Dis Sci 1982;27:884-8. 5. Holder TM, Ashcraft KW, Leape L. The treatment of patients with esophageal strictures by local steroid injections. J Pediatr Surg 1969;4:646-53. 6. Mendelsohn HJ, Maloney WHo The treatment of benign stricture of the esophagus with cortisone injection. Ann Otol Rhinol Laryngol 1970;79:900-4. 7. Nelson RS, Hernandez AJ, Goldstein HM, Saca A. Treatment of irradiation esophagitis. Am J GastroenteroI1979;71:17-23. 8. Gandhi RP, Cooper A, Barlow BA. Successful management of esophageal strictures without resection or replacement. J Pediatr Surg 1989;24:745-50. 9. Penagini R, Al Dabbagh M, Mesiewicz JJ, Evans PF, Trotman IF. Effect of dilatation of peptic esophageal strictures on gastroesophageal reflux, dysphagia, and stricture diameter. Dig Dis Sci 1988;33:389-92. 10. Ketchum LD, Smith J, Robinson DW, Masters FW. The treatment of hypertrophic scar, keloid, and scar contracture by triamcinolone acetonide. Plast Reconstr Surg 1966;38:209-18. 11. Kiil J. Keloids treated with topical injections of triamcinolone acetonide (Kenalog). Scand J Plast Reconstr Surg 1977;11:16972. 12. Ashcraft KW, Holder TM. The experimental treatment of esophageal strictures by intralesional steroid injections. J Thorac Cardiovasc Surg 1969;58:685-91. 13. Jemec GBE. Linear atrophy following intralesional steroid injections. J Dermatol Surg Oncol 1988;14:88-9.
GASTROINTESTINAL ENDOSCOPY
New Methods-New Materials Intralesional steroid injections for peptic esophageal strictures Michael Kirsch, Mark Blue, Robert K. Desai, Michael V. Sivak, Jr.,
MD MD MD MD
The majority of benign esophageal strictures are of peptic origin. t , 2 The clinical history typically includes chronic gastroesophageal reflux with progressive dysphagia. Medical management consists of reflux control measures and periodic mechanical esophageal dilations. Although some investigators have reported that the latter therapy is effective in treating benign esophageal strictures,2,3 others have demonstrated high recurrence rates with decreasing recurrence intervals after bougienage. 4 Clearly, some patients with benign strictures do not achieve acceptable symptom relief despite an intensive dilation schedule and gastroesophageal reflux therapy. These patients are often elderly with comorbid conditions that greatly increase the risk of surgical therapy. In addition, in our experience, some patients find bougienage uncomfortable and will delay needed dilation therapy despite the presence of symptoms. Successful treatment of benign esophageal strictures using intralesional steroid injections has been reported in uncontrolled studies. 5- s We report the results of a pilot study where two patients have demonstrated dramatic objective and subjective benefit after intralesional steroid injections of their strictures. METHODS
Two patients with benign peptic strictures of the esophagus were studied. Before entering the study, patient 1 underwent 10 esophageal dilation sessions in the preceding 14 months and patient 2 underwent 13 dilation sessions in the preceding 6 months. Both patients had very temporary symptomatic benefit after these dilations. Initially, both patients were assigned a dysphagia score from 0 to 21, similar to the method described by Penagini et al.,9 based on their ability to swallow certain foods easily. The following six foods, each with a different score value were given: water (1), applesauce (2), banana (3), unpeeled apple wedge (4), prunes (5), and white bread with the crust (6). Symptoms that developed after a test food was adminReceived May 30, 1990. For revision September 17, 1990. Accepted October 30, 1990. From The Cleveland Clinic Foundation, Cleveland, Ohio. Reprint requests: Michael V. Sivak, Jr., MD, The Cleveland Clinic Foundation, One Clinic Center, 9500 Euclid Avenue, Cleveland, Ohio 441955001.
180
istered were allowed to completely subside before continuing with subsequent test foods. A score of 0 indicates total dysphagia and a score of 21 indicates that all six foods were easily swallowed. Both patients had severe dysphagia upon entrance into the study. After a dysphagia score determination, each patient underwent a standard esophageal dilation using Savary-Gilliard dilators over a guidewire. This initial phase of the study was performed so that patients could serve as their own controls. When severe, persistent symptoms recurred, the dysphagia score determination was repeated. This was followed by a dilation to the same diameter as performed previously. During this dilation, patients received four injections of triamcinolone acetonide (Kenalog," 10 mg/ml; Squibb) in 0.5-ml aliquots into four quadrants of the most narrow region ofthe stricture using a standard sclerotherapy needle. For each patient, the study was concluded when the treatment phase was equal to the control phase. For example, in both patients studied, the control and treatment phases were each 3 weeks in duration as described below in Results. At the conclusion of the study, each patient returned for a final dysphagia score determination. Stricture size was assessed by barium esophagrams performed by an experienced gastrointestinal radiologist who was aware of the treatment schedule and study protocol. Esophagrams were performed before the initial endoscopy and repeated before the steroid injections and at the conclusion of the study. Stricture diameter was calculated by averaging two measurements taken from different views of the most narrow region of the stricture. During all follow-up visits, patients were questioned regarding their swallowing ability (improved, worse, or unchanged) and whether they believed they needed an esophageal dilation. Both patients were given standard treatment for gastroesophageal reflux with compliance stressed during telephone interviews and follow-up visits. At the conclusion of the study, data were analyzed for changes in the dysphagia score, subjective improvement, and stricture diameter. The study was approved by the Institutional Review Board of The Cleveland Clinic Foundation and informed consent was obtained.
RESULTS
Patient 1 initially experienced dysphagia characterized by sub-xyphoid pressure and eructation with all test foods except water and was assigned a dysphagia score of 1. At endoscopy, the 9.S-mm diameter endoscope could not be passed through the stricture and dilation to 15 mm was performed using a guidewire. After 3 weeks, he reported the complete return of symptoms and was assigned a dysphagia score of 3. After dilation to 15 mm, the steroid injections were performed as described. Three weeks later at the conclusion of the study, he was completely asymptomatic GASTROINTESTINAL ENDOSCOPY
eating all varieties of food including meat. At this time, he was assigned a dysphagia score of 21. Patient 2 initially experienced chest pressure after apple sauce and a banana, and vomited after the remaining foods were administered. He was assigned a dysphagia score of 1. The 9.8-mm diameter endoscope could not be passed through the stricture and dilation to 14 mm was performed. Symptoms returned after 10 days and in an additional 10 days he had an identical response to the test foods and was again assigned a dysphagia score of 1. After dilation to 14 mm, the steroid injections were performed. Three weeks later at the conclusion of the study, he was completely asymptomatic having no dietary restrictions. He swallowed all test foods without any difficulty and was assigned a dysphagia score of 21. In addition, both patients had dramatic subjective improvement after the steroid injections. Both patients felt that this was the longest asymptomatic period that they had ever experienced since they originally commenced dilation therapy. There were no adverse reactions to the treatment. After the study was completed, patient 1 ultimately required a standard esophageal dilation 3 months after the steroid injections. Remarkably, patient 2, who previously required dilation every 10 days, remained entirely asymptomatic until 2 months after the steroid injections at which time mild dysphagia returned. Both patients expressed interest in receiving additional steroid treatments. Stricture diameter in patient 1 was 3.0 mm initially and 3.5 mm before the steroid injections. At the conclusion of the study the diameter remained 3.5 mm despite the symptomatic improvement that occurred. Stricture diameter in patient 2 was 8.0 mm both initially and before the steroid injections. However, at the conclusion of the study when this patient was asymptomatic, the diameter was 20.0 mm (Fig. 1).
A
DISCUSSION
Intralesional steroid injections are effective in treating keloids, hypertrophic scars, and burn scars. lO, 11 The rationale for applying this therapy to peptic strictures is that stricture formation represents the final stage of gastroesophageal reflux with the esophagus undergoing scar formation. In dogs with lye-induced esophageal strictures, intralesional steroid injections increased stricture diameter in comparison to a control group.12 In addition, there have been numerous reports of humans with benign esophageal strictures successfully treated with intralesional steroid injections. 5 - 8 The majority of these strictures were caustic, radiation-induced, and anastomotic with only one stricture attributed to gastroesophageal influx. 6 In these cases, there was no uniformity with respect to the steroid dose or preparation, number of treatment VOLUME 37, NO.2, 1991
Figure 1. Barium esophagram of patient 2. A, Prior to steroid injections stricture diameter was 8.0 mm. B, At the conclusion of the study, stricture diameter was increased to 20.0 mm.
sessions, injection volume, or accompanying dilation therapy. Although several of these patients improved, this anecdotal evidence was never further tested in a controlled trial. Doses administered were as high as 200 mg of triamcinolone acetonide/session. 6 As intralesional steroid injections may cause skin atrophy,13 181
we selected a modest total dose of 20 mg of triamcinolone acetonide for our patients to minimize the chance that esophageal mucosal atrophy would result. Both of our patients had dramatic subjective and objective improvement after intralesional steroid injections of their strictures. Their chronic history of requiring regular esophageal dilations and the inclusion of a control period in the study make it extremely unlikely that their marked improvement was unrelated to the steroid treatment. In patient 1, there was no correlation between the measured diameter of the stricture by esophagography and the presence or extent of dysphagia. Others have similarly observed a poor correlation between stricture size measured by barium esophagography and dysphagia. 9 In contrast, patient 2 showed significant radiographic improvement at the conclusion of the study when he was asymptomatic. Previously cited reports have also shown dramatic radiographic resolution of strictures after treatment that included intralesional steroid injections.5, 7, 8 The mechanisms whereby steroid injections improve dysphagia are not clear. Intralesional steroid injections may increase stricture compliance allowing a bolus to pass more easily. It is conceivable, therefore, that intralesional steroid injections may be effective when applied without concomitant esophageal dilation, as has been reported in humans5 and experimental animals. 12 If intralesional steroid injection therapy is safe and effective, it could impact significantly on the treatment of peptic strictures. It could decrease the frequency of esophageal dilations and surgical repair of peptic strictures while improving the life-style and nutritional status of these patients. In addition, this simple treatment could reduce health care costs as the medication is inexpensive and fewer subsequent dilations would be needed. Importantly, patients would face a lower lifetime risk of the complications of esophagal dilations and surgery. We believe that intralesional steroid injections may
182
be more effective, safer, and less expensive therapy than standard esophageal dilations for treating refractory peptic esophageal strictures. We hope that our dramatic preliminary results will stimulate other investigators to further test this new treatment for peptic strictures in controlled clinical trials. ACKNOWLEDGMENTS
The authors are grateful for the assistance of Karen Izso. This article is dedicated to the memory of our friend and colleague, Mark Blue, MD.
REFERENCES 1. Williamson RCN. The management of peptic oesophageal stricture. Br J Surg 1975;62:448-54. 2. Wesdorp ICE, Bartelsman JFWM, den Hartog Jager FCA, Huibregtse K, Tytgat GNJ. Results of conservative treatment of benign esophageal strictures: a follow-up study on 100 patients. Gastroenterology 1982;82:487-93. 3. Lanza FL, Graham DY. Bougienage is effective therapy for most benign esophageal strictures. JAMA 1978;240:844-7. 4. Glick ME. Clinical course of esophageal stricture managed by bougienage. Dig Dis Sci 1982;27:884-8. 5. Holder TM, Ashcraft KW, Leape L. The treatment of patients with esophageal strictures by local steroid injections. J Pediatr Surg 1969;4:646-53. 6. Mendelsohn HJ, Maloney WHo The treatment of benign stricture of the esophagus with cortisone injection. Ann Otol Rhinol Laryngol 1970;79:900-4. 7. Nelson RS, Hernandez AJ, Goldstein HM, Saca A. Treatment of irradiation esophagitis. Am J GastroenteroI1979;71:17-23. 8. Gandhi RP, Cooper A, Barlow BA. Successful management of esophageal strictures without resection or replacement. J Pediatr Surg 1989;24:745-50. 9. Penagini R, Al Dabbagh M, Mesiewicz JJ, Evans PF, Trotman IF. Effect of dilatation of peptic esophageal strictures on gastroesophageal reflux, dysphagia, and stricture diameter. Dig Dis Sci 1988;33:389-92. 10. Ketchum LD, Smith J, Robinson DW, Masters FW. The treatment of hypertrophic scar, keloid, and scar contracture by triamcinolone acetonide. Plast Reconstr Surg 1966;38:209-18. 11. Kiil J. Keloids treated with topical injections of triamcinolone acetonide (Kenalog). Scand J Plast Reconstr Surg 1977;11:16972. 12. Ashcraft KW, Holder TM. The experimental treatment of esophageal strictures by intralesional steroid injections. J Thorac Cardiovasc Surg 1969;58:685-91. 13. Jemec GBE. Linear atrophy following intralesional steroid injections. J Dermatol Surg Oncol 1988;14:88-9.
GASTROINTESTINAL ENDOSCOPY
