High-resolution anorectal manometry in newborns: normative values and diagnostic utility in Hirschsprung disease.

BACKGROUND: Conventional methods of screening for Hirschsprung disease (HD) in newborns (barium enema, BE; anorectal manometry, ARM; rectal suction biopsy, RSB) have limitations and/or are invasive. High-resolution anorectal manometry (HR-ARM) is a minimally invasive technique that has potential to overcome most of these limitations, but normative data and performance characteristics have not been reported in newborns. The aims of our study were to assess anorectal sphincter metrics including resting pressure (RP), anal canal length (ACL), and rectoanal inhibitory reflex (RAIR) in healthy and asymptomatic newborns, and to explore the role of HR-ARM in the diagnosis of HD using these normal parameters. METHODS: All procedures were performed using solid state HR-ARM equipment (Medical Measurement Systems, Enchede, The Netherland) by a single operator. In the first phase, 180 asymptomatic newborns (term newborns 95, preterm newborns 85) were studied, and anal RP, ACL, and RAIR were measured. In the second phase, 16 newborns with clinical manifestations of HD were studied (9 of whom had histopathologic confirmation), and parameters compared to asymptomatic newborns. KEY RESULTS: Normative RP values were higher in term newborns compared with preterm newborns (p < 0.05), and correlated with age. Progressive maturation of the anal sphincter was evident with chronologic age, both in preterm and term newborns. RAIR was present in all normal subjects. Using absent RAIR as indicative of HD, HR-ARM had a sensitivity 89% and specificity of 83% compared to RSB; these performance characteristics were better than BE (sensitivity 78%, specificity 17%), with significantly higher diagnostic accuracy (80% vs 53%, respectively, p = 0.009). CONCLUSIONS & INFERENCES: Anorectal sphincter pressure progressively matures with incremental increase in RP during the first months of life. HR-ARM is an effective and safe method that complements the diagnosis of HD in newborns.

The impact of psychiatric and extraintestinal comorbidity on quality of life and bowel symptom burden in functional GI disorders.

BACKGROUND: Functional gastrointestinal disorders (FGID) patients report poor health-related quality of life (HRQOL) and experience high rates of psychiatric and extraintestinal functional disorder (EIFD) comorbidity. The independent influence of these comorbidities on HRQOL and symptom burden remains unknown. We sought to determine whether FGID with mood or EIFD comorbidity have poorer HRQOL and greater GI symptom burdens; to determine the influence of comorbidities on HRQOL in FGID independent of bowel symptoms. METHODS: Subjects reported on comorbidities (anxiety, depression, somatization, EIFD), FGID criteria (irritable bowel syndrome, IBS; functional dyspepsia, FD) using ROME III Research questionnaire, GI symptom burden, and HRQOL. Differences in measures were assessed between subjects with and without ROME III criteria. Multiple regression determined the relative contribution of comorbidities to HRQOL, and mediation analysis explored whether comorbidity influences HRQOL. KEY RESULTS: In a cohort of 912 GI outpatients (47.2 ± 1.5 years, 75.8% female), 606 (66.4%) met Rome III IBS and/or FD criteria. Comorbidities were common in FGID (≥1 in 77.4%), leading to lower HRQOL and greater GI symptom burden (each p < 0.05). Poorer HRQOL was predicted by both psychiatric and EIFD comorbidity (each p < 0.05) independent of GI symptoms (p < 0.001). Comorbidities together exerted a greater effect on predicted variation in HRQOL (70.9%) relative to GI symptoms (26.5%). CONCLUSIONS & INFERENCES: Psychiatric and EIFD comorbidities are common in FGID, decrease HRQOL and are associated with greater GI symptom burdens; these factors were stronger predictors of HRQOL than GI symptoms in FGID patients.

Botulinum toxin injection in dysphagia syndromes with preserved esophageal peristalsis and incomplete lower esophageal sphincter relaxation.

BACKGROUND: Botulinum toxin injection into the lower esophageal sphincter (LES) treats dysphagia syndromes with preserved peristalsis and incomplete LES relaxation (LESR). We evaluated clinical and esophageal motor characteristics predicting response, and compared duration of efficacy to similarly treated achalasia patients. METHODS: Thirty-six subjects (59 ± 2.2 years, 19F/17M) with incomplete LESR on high resolution manometry (HRM) treated with botulinum toxin injection were identified. Individual and composite symptom indices were calculated, and HRM characteristics extracted. Symptom resolution for 6 months was a primary outcome measure, and repeat botulinum toxin injection, dysphagia recurrence or employment of alternate therapeutic approaches were secondary outcome measures. Duration of response was compared using Kaplan-Meier survival curves to a historical cohort of similarly treated achalasia subjects. KEY RESULTS: Response lasted a mean of 12.8 ± 2.3 months. Symptom relief for >6 months was seen in 58.3%; short (<6 months) response was associated with younger age, higher chest pain index, and esophageal body spastic features (P ≤ 0.04). On multivariate logistic regression, chest pain, younger age and contraction amplitudes >180 mmHg independently predicted <6 months relief (P < 0.05 for each). On survival analysis, relief with a single injection extended to 1 year in 54.8% and 1.5 years in 49.8%, statistically equivalent to that reported by 42 similarly treated achalasia subjects (59 ± 3.2 years, 24F/18M). Symptom relief was more prolonged compared to achalasia when repeat injections were performed on demand (P = 0.003). CONCLUSIONS & INFERENCES: Botulinum toxin injections can provide lasting symptom relief in dysphagia syndromes with incomplete LESR. Prominent perceptive symptoms and non-specific spastic features may predict shorter relief.