RSS-Feed abonnieren
DOI: 10.1055/s-2003-38157
© Georg Thieme Verlag Stuttgart · New York
Botulinum Toxin for the Treatment of Upper Gastrointestinal Diseases: The Future or Already the Past?
Publikationsverlauf
Publikationsdatum:
27. März 2003 (online)
![](https://www.thieme-connect.de/media/endoscopy/200304/lookinside/thumbnails/10.1055-s-2003-38157-1.jpg)
Dear Sir,
Pasricha and colleagues, from Johns Hopkins Medical Center, presented the first results for treatment of achalasia using botulinum toxin that could be regarded as promising [1] [2]. Today, however, it might be said that botulinum toxin has not fulfilled all that was expected of it. Nevertheless, it is too early to decide whether botulinum toxin treatment in gastroenterology is in decline, even if only the upper part of the digestive system is taken into account.
We do not know what the outcome of the research of Allescher and colleagues, published recently in Endoscopy [3], would have been if those patients suffering from achalasia who did not show satisfactory improvement after botulinum toxin treatment had been given long-acting nitrates. It has been observed that topical nitrates heighten the effect of botulinum toxin in the treatment of patients with chronic anal fissure [4] [5]. It is also known that botulinum toxin induces nitric oxide synthase activity in motoneurons [6], and it is probable that an effect similar to that noticed in chronic anal fissure patients could be found in the case of achalasia. Nitric oxide is, in fact, one of the relaxing mediators for the lower esophageal sphincter (LES) [7], and exogenous nitric oxide donors induce esophageal relaxation [8].
Allescher et al. [3] also stated that they observed that 300 units of Dysport and 100 units of Botox were equally effective. Patients were given Dysport solution with a toxin concentration of 20 IE/ml and 60 IE/ml and, in the case of Botox, 20 IE/ml. One should bear in mind that there is a greater spread of toxin when either dose or volume injection is increased, and that a diffusion gradient spreads over a distance of 30 - 45 mm from the injection point [9] [10]. In general, a higher concentration of botulinum toxin allows for more accurate placement and therefore greater duration of effect [11]. It is not known whether, because of the high dilution of botulinum toxin used by Allescher et al. [3] (as also employed by neurologists who inject it into muscles much bigger than the LES [12] [13]), only a small amount of toxin got bound to the LES, as the botulinum toxin concentration decreased because of the increase of the area of diffusion.
It has not been ascertained whether a 50 IE/ml concentration of botulinum toxin would be as effective as the higher dilution of botulinum toxin applied in achalasia treatment, as has been described so far in reports on achalasia and botulinum toxin treatment.
Administration of such a small amount of Botox, e. g. 100 units of Botox diluted in 2.0 ml of physiological saline, could be a problem. Flushing the needle with 1 ml of saline would facilitate the injection of the final 1 ml of solution from the sclerotherapy needle. Then all the dose of botulinum toxin solution would be administered.
Even if it should transpire that the abovementioned doubts are not confirmed by any research, it is difficult to imagine a better method than local injection of botulinum toxin in the treatment of esophageal motility disorders other than achalasia, such as hypertensive LES [14] or diffuse esophageal spasm [15]. Because of the lack of pathophysiological knowledge, there is a scarcity of pharmacological options for treating any of these disorders of esophageal motor activity [15]. A similar situation obtains in the case of cricopharyngeal achalasia [16] and pyloric spasm [17].
Treatment of hypersalivation by local injection of botulinum toxin into the salivary glands of the head is a reliable and efficient therapy without side effects [18] [19]. It is of great importance to patients with head and neck carcinoma, tracheotomy, cerebral palsy, amyotrophic lateral sclerosis, or “idiopathic” hypersalivation disorder.
Injection of botulinum toxin can be used with good results in patients with diabetic gastroparesis or idiopathic gastroparesis [20] [21].
Intramuscular injections of botulinum toxin into the gastric antrum could also cause a reduction in food intake, and hence body weight, by inhibition of gastric emptying [22]. If, in the future, observations similar to those concerning rats are made with regard to people then, at a time of increasing occurrence of “diseases of civilization”, this could be the most frequent use for botulinum toxin in the digestive system (especially in obese patients awaiting cardiosurgery operations).
As yet we do not know what will be the role of botulinum toxin in gastroenterology. It is, however, worth considering the above questions and pursuing them by means of further research.
References
- 1 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
- 2 Pasricha P J, Ravich W J, Kalloo A N. Botulinum toxin for achalasia. Lancet. 1993; 341 244-245
- 3 Allescher H D, Storr M, Seige M. et al . Treatment of achalasia: botulinum toxin injection vs. pneumatic balloon dilatation. A prospective study with long-term follow-up. Endoscopy. 2001; 33 1007-1017
- 4 Lysy J, Israelit-Yatzkan Y, Sestiery-Ittah M. et al . Topical nitrates potentiate the effect of botulinum toxin in the treatment of patients with refractory anal fissure. Gut. 2001; 48 221-224
- 5 Madaliński M, Sławek J, Zbytek B. et al . Topical nitrates and the higher doses of botulinum toxin for chronic anal fissure. Hepatogastroenterology. 2001; 48 977-979
- 6 Mariotti R, Bentivoglio M. Botulinum toxin induces nitric oxide synthase activity in motoneurons. Neurosci Lett. 1996; 219 25-28
- 7 Rhee P L, Hyun J G, Lee J H. et al . The effect of sildenafil on lower esophageal sphincter and body motility in normal male adults. Am J Gastroenterol. 2001; 96 3251-3257
- 8 Gonzalez M, Mearin F, Vasconez C. et al . Oesophageal tone in patients with achalasia. Gut. 1997; 41 291-296
-
9 Shaari C hM, Sanders I.
Assessment of the biological activity of botulinum toxin. In: Jankovic J, Hallet M (eds) Therapy with botulinum toxin. New York; Dekker 1994: 159-170 - 10 Madaliński M. Nonsurgical treatment modalities for chronic anal fissure using botulinum toxin. Gastroenterology. 1999; 117 516-517
- 11 Klein A W. Dilution and storage of botulinum toxin. Dermatol Surg. 1998; 24 1179-1180
- 12 Munchau A, Bhatia K P. Uses of botulinum toxin injection in medicine today. BMJ. 2000; 320 161-165
- 13 Barnes M P. Experience of botulinum toxin in the management of spasticity. Eur J Neurol. 1997; 4 (Suppl. 2) S33-S36
- 14 Mathews S, Cohen H, Kline M. Botulinum toxin injection improves symptomatic hypertensive lower esophageal sphincter. New Orleans; Digestive Diseases Week 1998
- 15 Storr M, Allescher H D, Classen M. Current concepts on pathophysiology, diagnosis and treatment of diffuse oesophageal spasm. Drugs. 2001; 61 579-591
- 16 Blitzer A, Brin M F. Use of botulinum toxin for diagnosis and management of cricopharyngeal achalasia. Otolaryngol Head Neck Surg. 1997; 116 328-330
- 17 Wiesel P H, Schneider R, Dorta G. et al . Botulinum toxin for refractory postoperative pyloric spasm. Endoscopy. 1997; 29 132
- 18 Ellies M, Laskawi R, Rohrbach-Volland S. et al . Botulinum toxin to reduce saliva flow: selected indications for ultrasound-guided toxin application into salivary glands. Laryngoscope. 2002; 112 82-86
- 19 Suskind D L, Tilton A. Clinical study of botulinum-A toxin in the treatment of sialorrhea in children with cerebral palsy. Laryngoscope. 2002; 112 73-81
- 20 Ezzeddine D, Jit R, Katz N. et al . Pyloric injection of botulinum toxin for treatment of diabetic gastroparesis. Gastrointest Endosc. 2002; 55 920-923
- 21 Miller L S, Szych G A, Kantor S B. et al . Treatment of idiopathic gastroparesis with injection of botulinum toxin into the pyloric sphincter muscle. Am J Gastroenterol. 2002; 97 1653-1660
- 22 Gui D, De Gaetano A, Spada P L. et al . Botulinum toxin injected in the gastric wall reduces body weight and food intake in rats. Aliment Pharmacol Ther. 2000; 14 829-834
M. H. Madaliński, M.D., Ph.D.
Regional Centre for Pulmonary Diseases and Tuberculosis
ul. Kosciuszki 101/7 · 80-421 Gdańsk · Poland
Fax: + 48-58-3469972
eMail: m.h.madalinski@pro.onet.pl