Most patients were treated with meglumine diatrizoate (Gastrografin; Schering AG, Berlin, Germany) enema (33%), polyethylene glycol (PEG) lavage (20%), an enema with or without an oral laxative (22%), or oral laxatives (16%). Although the participating centres differed widely in the treatment of DIOS all were effective; only 2 patients (4%) needed surgery in the treatment of a DIOS episode (Table 6). One patient with pancreas insufficiency and a history of meconium ileus was treated surgically at age 2.9 years and experienced 2 more episodes of DIOS at age 3.3 and 3.6 years, whereas the other patient with pancreas insufficiency and without a history of meconium ileus was treated surgically at age 0.24 years and did not experience a relapse.
The present study found a higher frequency (44%) of meconium ileus at birth in patients with DIOS than the 15% to 28% found in other studies (1,17,21). This could be because of the stricter definition of DIOS in the present multicentre study compared with the reviewed studies (1,17,21). The relation between MI at birth and the subsequent development of DIOS is also corroborated by Blackman (22), who reported a significant correlation between these 2 entities. In 2 smaller studies a similar trend was observed, which did not reach statistical significance (23,24). Additionally, similar pathological defects, such as slow intestinal transit (25) and impaired intestinal secretion, may contribute both to the development of intestinal obstruction in DIOS and to meconium ileus.
Treatment with Gastrografin enema, PEG lavage, oral laxatives, or an enema with or without laxatives was effective in almost all of our patients with DIOS. Interestingly, although treatment schedules differed widely between centres, the preferred treatment in each centre was effective. This seems to indicate that removal of the sticky intestinal contents from the ileocaecum can be obtained effectively through different medical methods. In general, we prefer a step-up approach starting with oral laxatives with or without an enema: Treat the patient with PEG lavage, when this is not effective. Consider surgery if these conservative treatments are not successful.
The low frequency of mild genotype in patients with DIOS (3%) in our study is in concordance with the reported association between severe genotype and DIOS (17,22). This may indicate that a severely impaired intestinal chloride secretion, as a result of major CFTR dysfunction, plays an important role in this condition. However, the relation between severe genotype and DIOS is not absolute, because patients with a mild genotype may still develop DIOS. Genes other than the CFTR gene, modifier genes, may also influence the severity of the gastrointestinal phenotype of CF and thus DIOS (26,27), although the CF Twin and Sibling Study in the United States (22) reported no significant differences in concordance rates between monozygotic twins and siblings, indicating that genetic factors other than CFTR genotype do not play a major role in DIOS. Nevertheless, meconium ileus was clearly influenced by modifier genes, so DIOS, which is associated, may still have a small genetic component. Clearly, further studies are necessary to investigate the role of modifier genes in the gastrointestinal phenotype in patients with CF.
The authors thank Prof Dr Jacob Yahav from the Sheba Medical Centre, Tel Aviv-University, Tel Hashomer, Israel, for contribution of patients.
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