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Endoscopy 2001; 33(12): 1007-1017
DOI: 10.1055/s-2001-18935
Original Article

© Georg Thieme Verlag Stuttgart · New York

Treatment of Achalasia: Botulinum Toxin Injection vs. Pneumatic Balloon Dilation. A Prospective Study with Long-Term Follow-Up

H. D. Allescher 1 , M. Storr 1 , M. Seige 1 , R. Gonzales-Donoso 1 , R. Ott 1 , P. Born 1 , E. Frimberger 1 , N. Weigert 1 , A. Stier 2 , M. Kurjak 1 , T. Rösch 1 , M. Classen 1
  • 1 Department of Internal Medicine II, Technical University of Munich, Munich, Germany
  • 2 Department of Surgery, Technical University of Munich, Munich, Germany
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Publication History

Publication Date:
07 December 2001 (online)

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Treatment of Achalasia: Botulinum Toxin Injection vs. Pneumatic Balloon Dilation. A Prospective Study with Long-Term Follow-UpEndoscopy 2004; 36(02): 1-1
DOI: 10.1055/s-2004-814189

Background and Study Aims: In patients with achalasia, intrasphincteric injection of botulinum toxin (BTX) has been suggested as an alternative regimen to balloon dilation and has been shown to be superior to placebo injection. The aim of the present study was to test the effectiveness, the long-term outcome and the cumulative costs of BTX injection in consecutive patients with symptomatic achalasia in comparison with pneumatic balloon dilation.

Patients and Methods: 37 patients, who presented with symptomatic achalasia between January 1994 and December 1996 were treated with either BTX injection (n = 23) or pneumatic dilation (n = 14). Patients with short-term or long-term symptomatic failures of the initial procedure were treated again, either with the same or with the alternative method, depending on the initial response and on the patient’s wish. Symptoms were assessed using a global symptom score (0 - 10) which was evaluated before treatment and 1 week, 1 month and then every 6 months after the treatment. In addition, body weight and recurrence of symptoms were noted and manometry was carried out before and after treatment. The patients were regularly contacted for the long-term follow-up.

Results: There were significant improvements in the global symptom scores of all patients treated, in both the BTX injection group (before 8.2 ± 1.3, after 3.0 ± 1.6) and the dilation group (before 8.3 ± 1.1, after 2.3 ± 1.9). There was also a significant decrease of lower esophageal sphincter pressure after treatment in the BTX group and the dilation group. There were no significant differences with regard to overall treatment failure and long-term outcome between patients who had or had not received previous treatment. No major complications were encountered in either group. An actuarial analysis over 48 months comparing patients receiving BTX injection or balloon dilation demonstrated that after 12 months neither therapy was significantly superior. After 24 months a single pneumatic dilation was superior to a single BTX injection, and after 48 months all patients treated by BTX injection had experienced a symptomatic relapse. In contrast, 35 % of all patients treated by dilation and 45 % of patients treated successfully by dilation were still symptom-free in an intention-to-treat analysis after 48 months. When the overall costs of treatment and further treatment after recurrence were compared, dilation and BTX injection showed a similar cost-effectiveness (costs per symptom-free day) after 48 months.

Conclusions: BTX injection, which can be performed in an outpatient setting, is as safe and cost-effective as balloon dilation in symptomatic achalasia. Taking into account the lower long-term efficacy of BTX injection therapy, however, it is an alternative only in a minority of older or high-risk patients.

References

  • 1 Cohen S, Fisher R, Tuch A F. The site of denervation in achalasia.  Gut. 1972;  13 556-558
    PubMedGoogle Scholar
  • 2 Guelrud M, Cohen D O. “Cardiospasm” in achalasia: demonstration of hypersensitivity of the lower esophageal sphincter.  Acta Gastroenterol Latinoam. 1972;  448 1-7
    PubMedGoogle Scholar
  • 3 Vantrappen G, Janssens H O, Hellemans J, et al. Achalasia, diffuse esophageal spasm and related motility disorders.  Gastroenterology. 1979;  76 450-457
    PubMedGoogle Scholar
  • 4 Aggestrup S, Uddman R, Sundler F, et al. Lack of vasoactive intestinal polypeptide in nerves in esophageal achalasia.  Gastroenterology. 1983;  84 924-927
    PubMedGoogle Scholar
  • 5 Tottrup A, Svane D, Forman A. Nitric oxide mediating NANC inhibition in opossum lower esophageal sphincter.  Am J Physiol. 1991;  260 G385-G389
    PubMedGoogle Scholar
  • 6 Tottrup A, Knudsen M, Gregersen H. The role of the L-arginine nitric oxide pathway in relaxation of the lower esophageal sphincter.  Br J Pharmacol. 1991;  104 113-116
    PubMedGoogle Scholar
  • 7 Vantrappen G, Hellemans J, Deloof W, et al. Treatment of achalasia with pneumatic dilatation.  Gut. 1971;  12 268-275
    CrossrefPubMedGoogle Scholar
  • 8 Vantrappen G, Hellemans J. Treatment of achalasia and related motor disorders.  Gastroenterology. 1980;  79 144-154
    PubMedGoogle Scholar
  • 9 Fellows I W, Ogilvie A W, Atkinson M. Pneumatic dilatation in achalasia.  Gut. 1983;  24 1020-1023
    PubMedGoogle Scholar
  • 10 Nair L A, Reynolds J C, Parkman H P, et al. Complications during pneumatic dilatation for achalasia or diffuse esophageal spasm. Analysis of risk factors, early clinical characteristics and outcome.  Dig Dis Sci. 1993;  38 1893-1904
    CrossrefPubMedGoogle Scholar
  • 11 Traube M, Dubovik S, Lange R C, et al. The role of nifedipine therapy in achalasia: results of a randomized, double-blind, placebo-controlled study.  Am J Gastroenterol. 1989;  84 1259-1262
    PubMedGoogle Scholar
  • 12 Feussner H, Kauer W, Siewert J R. The surgical management of motility disorders.  Dysphagia. 1993;  8 135-145
    PubMedGoogle Scholar
  • 13 Blasi J, Chapman E R, Link E, et al. Botulinum neurotoxin A selectively cleaves the synaptic protein SNAP-25.  Nature. 1993;  365 160-163
    CrossrefPubMedGoogle Scholar
  • 14 Jankovic J, Brin M F. Therapeutic uses of botulinum toxin.  N Engl J Med. 1991;  324 1186-1194
    PubMedGoogle Scholar
  • 15 Pasricha P J, Ravich W J, Kalloo A N. Effects of intrasphincteric botulinum toxin on the lower esophageal sphincter in piglets.  Gastroenterology. 1993;  105 1045-1049
    PubMedGoogle Scholar
  • 16 Pasricha P J, Ravich W J, Kalloo A N. Botulinum toxin for achalasia.  Lancet. 1993;  341 244-245
    PubMedGoogle Scholar
  • 17 Pasricha P J, Ravich W J, Hendrix T R, et al. Treatment of achalasia with intrasphincteric injection of botulinum toxin. A pilot trial.  Ann Intern Med. 1994;  121 590-591
    CrossrefPubMedGoogle Scholar
  • 18 Pasricha P J, Ravich W J, Hendrix T R, et al. Intrasphincteric botulinum toxin for the treatment of achalasia.  N Engl J Med. 1995;  332 774-778
    CrossrefPubMedGoogle Scholar
  • 19 Ferrari A P, Siqueira E S, Brant C Q. Treatment of achalasia in Chagas’ disease with botulinum toxin.  N Engl J Med. 1995;  332 824-825
    CrossrefPubMedGoogle Scholar
  • 20 Miller L S, Parkman H P, Schiano T D, et al. Treatment of symptomatic nonachalasia esophageal motor disorders with botulinum toxin injection at the lower esophageal sphincter.  Dig Dis Sci. 1996;  41 2025-2031
    CrossrefPubMedGoogle Scholar
  • 21 Storr M, Allescher H D, Rösch T, et al. Treatment of symptomatic diffuse esophageal spasm by injection of Botulinum toxin (BTX).  Gastroenterology. 2000;  118 A135
    PubMedGoogle Scholar
  • 22 Costa M, Furness J B, Humphreys C M. Apamin distinguishes two types of relaxation mediated by enteric nerves in the guinea-pig gastrointestinal tract.  Naunyn Schmiedebergs Arch Pharmacol. 1986;  332 79-88
    CrossrefPubMedGoogle Scholar
  • 23 Willis S, Allescher H D, Stoschus B, et al. Double blind placebo controlled study on the effect of the nitric oxide donor molsidomin and the 5-HT3 antagonist ondansetron on human esophageal motility.  Z Gastroenterol. 1994;  32 632-636
    PubMedGoogle Scholar
  • 24 Cox J, Buckton G K, Bennett J R. Balloon dilatation in achalasia: a new dilatator.  Gut. 1986;  27 986-989
    PubMedGoogle Scholar
  • 25 Wei L J, Glidden V. An overview over the statistical methods for multiple failure time data in clinical trials.  Stat Med. 1997;  16 833-839
    CrossrefPubMedGoogle Scholar
  • 26 Fishman V M, Parkman H P, Schiano T D, et al. Symptomatic improvement in achalasia after botulinum toxin injection of the lower esophageal sphincter.  Am J Gastroenterol. 1996;  91 1724-1730
    PubMedGoogle Scholar
  • 27 Al Karawi M A, Ahmed A M, Ghandour Z. Use of botulinum A toxin in achalasia.  Endoscopy. 1995;  27 217
    PubMedGoogle Scholar
  • 28 Rollan A, Gonzalez R, Carvajal S, et al. Endoscopic intrasphincteric injection of botulinum toxin for the treatment of achalasia.  J Clin Gastroenterol. 1995;  20 189-191
    PubMedGoogle Scholar
  • 29 Khoshoo V, LaGarde D C, Undall J N. Intrasphincteric injection of botulinum toxin for treating achalasia in children.  J Pediatr Gastroenterol Nutr. 1997;  24 439-441
    CrossrefPubMedGoogle Scholar
  • 30 Annese V, Basciani M, Lombardi G, et al. Perendoscopic injection of botulinum toxin is effective in achalasia after failure of myotomy or pneumatic dilation.  Gastrointest Endosc. 1996;  44 461-465
    PubMedGoogle Scholar
  • 31 Annese V, Basciani M, Perri F, et al. Controlled trial of botulinum toxin injection versus placebo and pneumatic dilation in achalasia.  Gastroenterology. 1996;  111 1418-1424
    CrossrefPubMedGoogle Scholar
  • 32 Pasricha P J, Rai R, Ravich W J, et al. Botulinum toxin for achalasia: long-term outcome and predictors of response.  Gastroenterology. 1996;  110 1410-1415
    CrossrefPubMedGoogle Scholar
  • 33 Culliere C, Ducrotte P, Zerbib F, et al. Achalasia: outcome of patients treated by intrasphincteric injection of botulinum toxin.  Gut. 1997;  41 87-92
    PubMedGoogle Scholar
  • 34 Annese V, Bassotti G, Coccia G, et al. Comparison of two different formulations of botulinum toxin A for the treatment of esophageal achalasia. The Gismad Achalasia Study Group.  Aliment Pharmacol Ther. 1999;  13 1347-1350
    CrossrefPubMedGoogle Scholar
  • 35 Kozarek R A, Gelfand M D, Patterson D J, et al. Randomized prospective trial of 50 vs. 100 IU BOTOX for achalasia - long-term-follow up.  Gastroenterology. 1997;  112 A184
    PubMedGoogle Scholar
  • 36 Annese V, Bassotti G, Coccia G, et al. A multicenter randomised study of intrasphincteric botulinum toxin in patients with esophageal achalasia. GISMAD Achalasia Study Group.  Gut. 2000;  46 597-600
    CrossrefPubMedGoogle Scholar
  • 37 Prakash C, Freedland K E, Chan M F, et al. Botulinum toxin injections for achalasia symptoms can approximate the short term efficacy of a single pneumatic dilatation: a survival analysis approach.  Am J Gastroenterol. 1999;  94 328-333
    CrossrefPubMedGoogle Scholar
  • 38 Katzka D A, Castell D O. Use of botulinum toxin as a diagnostic/therapeutic trial to help clarify an indication for definitive therapy in patients with achalasia.  Am J Gastroenterol. 1999;  94 637-642
    CrossrefPubMedGoogle Scholar
  • 39 Muehldorfer S M, Schneider T H, Hochberger J, et al. Esophageal achalasia: intrasphincteric injection of botulinum toxin A versus balloon dilatation.  Endoscopy. 1999;  31 517-521
    Article in Thieme ConnectPubMedGoogle Scholar
  • 40 Eaker J M, Gordon E Y. Esophageal botulinum toxin injection in high risk achalasia patients: a prospective trial.  Gastroenterology. 1996;  110 A991
    PubMedGoogle Scholar
  • 41 Eckardt V F, Aignherr C, Bernhard G. Predictors of outcome in patients with achalasia treated by pneumatic dilatation.  Gastroenterology. 1992;  103 1732-1738
    CrossrefPubMedGoogle Scholar
  • 42 Parkman H P, Reynolds J C, Ouyang A, et al. Pneumatic dilatation or esophagomyotomy treatment for idiopathic achalasia: clinical outcomes and cost analysis.  Dig Dis Sci. 1993;  38 75-85
    CrossrefPubMedGoogle Scholar
  • 43 Bansal R, Koshy S, Scheiman J M. Interim analysis of a randomized trial of Witzel pneumatic dilatation vs. intrasphincteric injection of botulinum toxin for achalasia.  Gastroenterology. 1996;  110 A561
    PubMedGoogle Scholar
  • 44 Fiorini A, Corti R E, Valero J L, et al. Botulinum toxin is effective in the short-term treatment of esophageal achalasia. Preliminary results of a randomized trial.  Acta Gastroenterol Latinoam.. 1996;  26 155-157
    PubMedGoogle Scholar
  • 45 Annese V, Basciani M, Borrelli O, et al. Intrasphincteric injection of botulinum toxin is effective in long-term treatment of esophageal achalasia.  Muscle Nerve. 1998;  21 1540-1542
    PubMedGoogle Scholar
  • 46 Vaezi M F, Richter J E. Current therapies for achalasia: comparison and efficacy.  J Clin Gastroenterol. 1998;  27 21-35
    CrossrefPubMedGoogle Scholar
  • 47 Malthaner R A, Tood T R, Miller L, et al. Long-term results in surgically managed esophageal achalasia.  Ann Thorac Surg. 1994;  58 1343-1346
    PubMedGoogle Scholar
  • 48 Vaezi M F, Richter J E, Wilcox C M, et al. Botulinum toxin versus pneumatic dilatation in the treatment of achalasia: a randomised trial.  Gut. 1999;  44 231-239
    CrossrefPubMedGoogle Scholar
  • 49 Panaccione R, Gregor J C, Reynolds R P, et al. Intrasphincteric botulinum toxin versus pneumatic dilatation for achalasia: a cost minimization analysis.  Gastrointest Endosc. 1999;  50 492-498
    PubMedGoogle Scholar
  • 50 Bhutani M S. Gastrointestinal uses of botulinum toxin.  Am J Gastroenterol. 1997;  92 929-933
    PubMedGoogle Scholar
  • 51 Storr M, Allescher H D. Esophageal pharmacology and treatment of primary motility disorders.  Dis Esophagus. 1999;  12 241-257
    CrossrefPubMedGoogle Scholar

H. D. Allescher, M.D.

Department of Internal Medicine II
Technical University of Munich
Klinikum rechts der Isar

Ismaninger Str. 22
81675 Munich
Germany


Fax: + 49-89-41404932

Email: hans.allescher@lrz.tum.de

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