Botulinum Toxin for the Treatment of Upper Gastrointestinal Diseases: The Future or Already the Past?

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

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