Efstratios Saliakellis

Efficacy of the neurokinin-1 receptor antagonist aprepitant in children with cyclical vomiting syndrome

Aprepitant (Emend, Merck Sharp & Dohme Ltd, Haarlem, the Netherlands), a neurokinin‐1 receptor antagonist, prevents vomiting in a range of conditions. No data are available on its use in children with cyclical vomiting syndrome (CVS).

Clinical relevance of esophageal baseline impedance measurement: just an innocent bystander.

Objective: The clinical relevance of esophageal baseline impedance (BI) remains to be determined. In the present study, we explored the impact of gastroesophageal reflux disease (GERD) and esophageal dysmotility on BI. Methods: A total of 18 children with esophageal atresia, 26 children with GERD, and 17 controls prospectively underwent esophagogastroduodenoscopy and pH–impedance monitoring. BI was measured in both proximal and distal esophagus. Gastroesophageal reflux (GER) and bolus transit indicators were defined according to published criteria. Results: Patients with esophageal atresia showed significantly lower proximal and distal BI values (952 [716–1811] &OHgr;; 895 [284–1189] &OHgr;; respectively) compared with those with GERD (3015 [2368–3975] &OHgr;; 2231 [1770–3032] &OHgr;, P < 0.001 and <0.001, respectively) and controls (3699 [3194–4358] &OHgr;; 3522 [2927–3994] &OHgr;, P < 0.001 and <0.001, respectively). Using linear regression, proximal BI strongly correlated with total bolus transit time (r2 = 0.61, P < 0.001) and bolus presence time (BPT; r2 = 0.63, P < 0.001). Distal BI weakly correlated with acid exposure time (r2 = 0.16, P < 0.01) and longstanding reflux episodes (r2 = 0.17, P < 0.01), and strongly correlated with total bolus transit time (r2 = 0.53, P < 0.001) and BPT (r2 = 0.58, P < 0.001). By logistic regression, BPT predicted low proximal BI values (odds ratio [OR] 1.052; P < 0.05), whereas both GER indicators (acid exposure time: OR 1.56, P < 0.05; longstanding reflux episodes: OR 2.8, P < 0.05) and BPT (OR 1.66, P < 0.01) predicted low distal BI values. Conclusions: Along the length of esophagus, both bolus transit variables and GER significantly affect BI. This suggests that BI may merely mirror phenomena occurring within the esophageal lumen or wall, limiting its value as a discrete clinical entity to replace variables already used for assessing both GERD and esophageal dysmotility.

Sequential incremental doses of bisacodyl increase the diagnostic accuracy of colonic manometry

Colonic manometry is the standard diagnostic modality for evaluating colonic motility in children. Intraluminal bisacodyl is routinely used to trigger high‐amplitude propagating contractions (HAPCs), a feature of normal colonic motility. Usually, only a single dose (0.2 mg/kg) is suggested. We retrospectively explored whether the use of an additional higher (0.4 mg/kg) dose of bisacodyl increases the yield of colonic manometry.

OP-24 ESOPHAGEAL BASELINE IMPEDANCE IN NEUROLOGICALLY IMPAIRED CHILDREN.

Introduction: Dysphagia, feeding difficulties and gastro-oesophageal reflux (GORD) are common complaints in neurologically impaired children. Motor pattern generators localised in the brain stem and CNS reflexes play a key role on controlling oesophageal peristalsis and lower oesophageal sphincter activity. Thus, it is not surprising that brain abnormalities may result in significant oesophageal motor dysfunction. In this prospective study we evaluated the differences in multichannel intraluminal impedance-pH monitoring (MII-pH monitoring) pattern between children with cerebral palsy (CP) and 2 groups of neurologically normal children with normal and abnormal MII-pH monitoring. We mainly focused our attention on oesophageal baseline impedance (BI), which has been proposed as useful parameter in predicting GORD severity. Methods: Twenty children with CP and 40 neurologically normal children with suspected GORD underwent MII-pH impedance. Classical MII-pH impedance parameters as well as BI values in both proximal and distal oesophagus were analysed. MII-pH monitoring was considered abnormal if acid exposure time (AET) was >5% and/or SAP was >95%. Results: Nine CP children had a diagnosis of GORD. Of neurologically normal children, 20 had an abnormal (GR-A) and 20 a normal MII-pH monitoring (GR-B). A significant difference in the proportion of children with abnormal AET was found between CP and GR-A (9/20 vs 17/20; p < 0.05). GR-A showed a significantly greater percentage of AET (15.97 [6.4–34.9]) than both CP (8.21 [0–31.9], p < 0.05) and GR-B (1.4, [0–4.5], p < 0.0001), whereas between the latter groups CP showed a greater AET (p < 0.05). Proximal BI values were significantly lower in CP (1759 [691–3133]&OHgr;) than GR-A (2396 [1080–3850]&OHgr;, p < 0.05) and GR-B (3385 [2249–4817]&OHgr;, p < 0.0001). No difference in distal BI was found between in CP (1106 [279–3098]&OHgr;) and GR-A (1152 [246–2526]&OHgr;), while was lower in CP than in GR-B (2965 [1986–3984]&OHgr;, p < 0.001). Considering all patients as a whole group, an inverse correlation was found between distal BI and AET (r-0.66; p < 0.001), whereas within groups an inverse correlation was only confirmed in GR-A pts (r-0.67; p < 0.001). Conclusions: Although an abnormal pH-impedance monitoring was detected in almost half of children with CP, no correlation was found between the AET and BI values, suggesting that the latter cannot be used as predictor of reflux severity in this group of patients. The presence of low impedance values in both proximal and distal oesophagus in children with CP supports the view that in neurologically impaired children BI mainly reflects oesophageal motor abnormalities, which have been previously reported.

Gastrointestinal Neuropathies: New Insights and Emerging Therapies

The bewildering complexity of the enteric nervous system makes it susceptible to develop a wide array of motility disorders, collectively called enteric neuropathies. These gastrointestinal conditions are among the most challenging to manage, mainly given poor characterization of their etiopathophysiology and outcomes. Not surprisingly, therefore, targeted or curative therapies for enteric neuropathies are lacking and management is largely symptomatic. Nonetheless, recent advances in neurogastroenterology have witnessed improvements in established strategies, such as intestinal transplantation and the emergence of new treatments including novel drugs, electrical pacing, and manipulation of fecal microbiota, as well as stem cell and gene therapy.

Gastroesophageal Reflux and the Neurologically Impaired Patient

Gastroesophageal reflux (GER) and its associated complications (gastroesophageal reflux disease—GERD) are very common in children with neurological impairment (NI) and correlate with the severity of neurodisability. A number of causative mechanisms underlie GERD in this population, many of which are inherent to the neurodisability and irreversible. Diagnosis is often difficult and compounded by a limited ability of NI children to communicate their symptoms, variable presentation and poor correlation with objective testing. Unfortunately, as a result, management is often misdirected and/or suboptimal. Overall, a high index of suspicion is needed for GERD when managing children with NI. A wide range of treatments are available for managing GER/GERD in this population of children, although the mainstay remains pharmacological therapy, namely, PPIs. A systematic approach is advised starting at simpler ‘conservative’ treatments through dietary manipulation, pharmacotherapy to surgical interventions. At each step there should be careful consideration of the benefits and risks and carers of NI children appropriately counselled about these. There is evidence to suggest that although there is a place for pharmacotherapy, consideration should also be given to diet both in terms of type and method of administration. In this respect there is emerging benefit for the use of post-pyloric feeding even as an alternative to surgery. Surgery, namely, anti-reflux procedures, should be considered the last resort although it appears to have a clear benefit in a highly selective group of NI children especially those with severe disability who have failed medical therapy. Overall, although there have been significant strides into understanding the management of NI children suffering problematic GER, there is a clear need for further robust studies in this challenging group.

Pediatric Chronic Intestinal Pseudo-obstruction

Chronic intestinal pseudo-obstruction (CIPO) represents the most severe end of the spectrum of gut motility disorders comprising a group of rare, heterogeneous, and disabling disorders of the gastrointestinal (GI) tract characterized by absent or ineffective intestinal peristalsis. Pediatric CIPO results from developmental and pathological processes, which affect, either singly or in combination, the intrinsic or extrinsic intestinal neurons (neuropathy) and/or smooth muscle fibers (myopathy) and/or interstitial cells of Cajal (ICC) (mesenchymopathy). These processes lead to an inability of the small intestine to propel its luminal contents normally, which manifests clinically as continuous or repetitive episodes of intestinal obstruction in the absence of a defined, fixed lumen-occluding lesion, hence the term “pseudo”-obstruction. The diagnosis of CIPO can be challenging and is based on a combination of clinical, radiological, manometric, and histopathologic findings. At the current time, therapeutic strategies are limited and largely supportive, designed to optimize nutrition and reduce the frequency and severity of pseudo-obstructive episodes. Overall management is focused on alleviating symptomatology and complications, preserving function of the GI tract, and improving patients’ quality of life. The therapeutic armamentarium includes pharmacotherapy to address reversible causes, e.g., inflammation, and to stimulate motility where possible, special means of alimentation (enteral, parenteral, and, where tolerated, oral) to provide nutrition while preserving gut function, as well as surgical interventions such as formation of ostomies (i.e., gastrostomy, ileostomy) to allow “venting” and decompression of the gut. A number of novel agents may hold future promise, but at the present time, small bowel transplantation provides the only option for definitive cure with improved outcomes and survival in centers with the relevant expertise.