Mitomycin C – a potential therapy for refractory oesophageal strictures caused by caustic ingestion?

O Mukhtar1,2, DM Wood2,3, PI Dargan2,3. 1Clinical Pharmacology, King's College Hospital NHS Foundation Trust and King's Health Partners, London, UK, 2Clinical Toxicology, Guy's and St Thomas NHS Foundation Trust and King's Health Partners, London, UK, 3King's College London, London, UK

Background:

The oral ingestion of caustics (acids and alkalis) can cause significant gastro-oesophageal injury, ranging from mild oedema and hyperaemia (Grade I) to deep ulceration and necrosis (Grade III). Grade III injuries can culminate in chronic scarring which leads to stricture formation and dysphagia, whilst also resulting in nutritional deficiencies and an increased risk of gastro-oesophageal cancer. Corticosteroids have previously been used in an effort to attenuate both the inflammation and subsequent fibrosis - however prospective studies have shown that they are not effective in this setting. Once strictures have formed, standard treatment is repeated endoscopic dilatation. Mitomycin C has been used in the treatment of various fibrotic disorders ranging from childhood glaucoma to hypopharyngeal stricture. The first report of mitomycin C use for caustic related oesophageal stricture was published in 2002[1]. Here we review the published data to determine the role of mitomycin C in the management of caustic related oesophageal strictures.

Methods: A literature search using the terms “mitomycin, caustic” and “mitomycin, corrosive” was undertaken; we then hand searched the references of relevant papers to identify studies describing the use of mitomycin C in caustic oesophageal strictures [oesophageal strictures resulting from the ingestion of caustics, either accidentally or intentionally, in human subjects].

Results: We identified sixteen papers from the search; five did not relate to caustic ingestion, three were rodent studies, two were reviews and two were not available in English. One further paper was identified from the references of these papers. In total, five papers were analysed. All five were observational case reports/series; none were controlled studies. Two were case reports and three were case series. Two of the three case series described two cases; the third described ten cases of caustic oesophageal stricture [strictures secondary to other causes treated with mitomycin C were excluded]. Therefore we identified 16 individuals with caustic oesophageal stricture refractory to repeated endoscopic dilatation treated with mitomycin C. Patient age ranged from 13 months to 23 years; 75% were male and 25% female. Nine patients had complete remission of symptoms post mitomycin C such that they did not require further dilatations, five had an increase in dilatation interval, one required partial oesophageal resection and one had no improvement. Duration of follow up was not specified in 12 cases, but in the others was up to 60 months. Therefore, it is not possible to determine whether mitomycin C has an impact on the risk of gastro-oesophageal cancer.

Conclusion: This review of the published human literature suggests that mitomycin C is an effective treatment for caustic related refractory oesophageal stricture, although the results need to be interpreted with caution as there have been no controlled studies. It is not possible to determine whether mitomycin C has an impact on the risk of gastro-oesophageal cancer or to examine other factors that may influence efficacy such as the type of caustic causing stricture. We suggest that a case registry, integrating longer follow up, may be the best way to further examine the role of mitomycin C in caustic related oesophageal stricture.

References:

1. Afzal NA, Albert D, Thomas AL, Thomson M. A child with oesophageal strictures. Lancet 2002;359:1032.