Use of the functional luminal imaging probe in pediatrics: A comparison study of patients with achalasia before and after endoscopic dilation and non-achalasia controls.

BACKGROUND: Achalasia is an esophageal motility disorder characterized by esophagogastric junction (EGJ) dysfunction and impaired esophageal peristalsis with significant impact on quality of life. While the functional luminal imaging probe (FLIP) has been used to assess EGJ distensibility in achalasia, its clinical utility in pediatrics is limited due to absence of normative values and correlations with clinical outcomes in children. Thus, we sought to evaluate FLIP's use in a pediatric achalasia cohort undergoing dilations and non-achalasia controls. METHODS: We conducted a retrospective study of pediatric patients with achalasia who underwent FLIP before and immediately after balloon dilations and compared to a non-achalasia cohort. KEY RESULTS: Thirty patients with achalasia (mean age, 15.2 years; 40% female), including fourteen treatment-naïve and thirteen controls (mean age, 7.9 years; 61% female) were identified. Median EGJ distensibility index (EGJ-DI) 2.07 mm2  mmHg-1 and diameter (9.23 mm) in treatment-naïve patients were significantly lower compared to controls (EGJ-DI 6.8 mm2  mmHg-1 ; diameter 18.61 mm; (p < 0.001). Balloon dilations resulted in a significant increase in EGJ-DI immediately after the dilation, particularly in treatment-naïve patients (p < 0.001), and a significant improvement in Eckardt scores (p < 0.001). CONCLUSIONS & INFERENCES: Functional luminal imaging probe measurements of EGJ-DI in pediatric patients with achalasia are mostly consistent with adult findings. However, normal EGJ-DI is seen in symptomatic patients, including treatment-naive, highlighting the need for pediatric reference data. Balloon dilations achieve a significant increase in EGJ-DI with improvement in Eckardt scores, confirming the therapeutic value of dilations in achalasia management.

Protein-elongating mutations in MYH11 are implicated in a dominantly inherited smooth muscle dysmotility syndrome with severe esophageal, gastric, and intestinal disease.

Gastrointestinal motility disorders include a spectrum of mild to severe clinical phenotypes that are caused by smooth muscle dysfunction. We investigated the genetic etiology of severe esophageal, gastric, and colonic dysmotility in two unrelated families with autosomal dominant disease presentation. Using exome sequencing, we identified a 2 base pair insertion at the end of the myosin heavy chain 11 (MYH11) gene in all affected members of Family 1 [NM_001040113:c.5819_5820insCA(p.Gln1941Asnfs*91)] and a 1 base pair deletion at the same genetic locus in Proband 2 [NM_001040113:c.5819del(p.Pro1940Hisfs*91)]. Both variants are predicted to result in a similarly elongated protein product. Heterozygous dominant negative MYH11 pathogenic variants have been associated with thoracic aortic aneurysm and dissection while biallelic null alleles have been associated with megacystis microcolon intestinal hypoperistalsis syndrome. This report highlights heterozygous protein-elongating MYH11 variants affecting the SM2 isoforms of MYH11 as a cause for severe gastrointestinal dysmotility, and we hypothesize that the mechanistic pathogenesis of this disease, dominant hypercontractile loss-of-function, is distinct from those implicated in other diseases involving MYH11 dysfunction.

A rare presentation and diagnosis of juvenile polyposis syndrome and hereditary hemorrhagic telangiectasia overlap syndrome.

We present a unique case of juvenile polyposis and hereditary hemorrhagic telangiectasia overlap syndrome. The patient was found to have polyps on colonoscopy leading to genetic testing revealing an SMAD4 mutation. In children with SMAD4 mutation and juvenile polyposis, this overlap syndrome needs to be considered in the differential diagnosis and prompt the clinician to look for telangiectasias on examination and consider surveillance imaging to look for arteriovenous malformations. Our case highlights this clinical relationship and shows how nontraditional imaging using computed tomography colonography (CTC) can provide complimentary information along with colonoscopy. Despite low-dose techniques, CTC does add a radiation burden in the evaluation of these children who are at high risk for malignancy and should be used cautiously.

An unusual case of gastrointestinal bleeding.

A 10-year-old boy presented with a 3-day history of worsening abdominal pain, fever, emesis and melena. Abdominal ultrasound revealed a right upper quadrant mass that was confirmed by computed tomography angiogram (CTA), which showed an 8 cm well-defined retroperitoneal vascular mass. (123)Iodine metaiodobenzylguanidine ((123)MIBG) scan indicated uptake only in the abdominal mass. Subsequent biopsy revealed a paraganglioma that was treated with chemotherapy. This case represents an unusual presentation of a paraganglioma associated with gastrointestinal (GI) bleeding and highlights the utility of CTA and (123)MIBG in evaluation and treatment.

Changing indications for upper endoscopy in children during a 20-year period.

OBJECTIVES: In parallel with the increase in pediatric esophagogastroduodenoscopy (EGD) procedures since the 1970s, the incidence of disorders that require EGD for diagnosis in children has increased. The aim of this study was to identify changes in subject characteristics and endoscopic procedures during a 20-year interval in children undergoing EGD at a single center. PATIENTS AND METHODS: All of the children undergoing first EGD with biopsy in 1985, 1995, or 2005 were identified. Details of the clinical presentation and EGD were abstracted from medical records in a random sample of subjects within each time point. RESULTS: The number of first-time EGDs rose dramatically from 107 in 1985 to 1294 in 2005. The proportion of subjects that were younger than 1 year of age varied significantly from 13% in 1985 to 23% in 1995 and 8% in 2005 (P < 0.001). The proportion of subjects with gastrointestinal (GI) bleeding declined from 34% to 5% during the 20-year interval (P < 0.001), whereas the proportion with abdominal pain increased from 23% to 43% (P < 0.01). During the same interval, the proportion of subjects with complete EGD (biopsies from the esophagus, stomach, and duodenum) increased from 18% of EGDs in 1985 to 95% in 2005 (P < 0.001). CONCLUSIONS: This study of children undergoing first-time EGDs with biopsy during a 20-year interval demonstrated significant differences in subject characteristics and endoscopy practices. The inclusion of children with less severe clinical presentation and the collection of greater numbers of biopsies per procedure may contribute to the rising incidence rates of pediatric GI disorders.

Disease presentation and clinical course in black and white children with inflammatory bowel disease.

OBJECTIVES: To compare the disease presentation, disease phenotype, and clinical course between black and white children with inflammatory bowel disease (IBD). PATIENTS AND METHODS: A 10-year retrospective review was undertaken of the medical records of 245 pediatric patients with IBD studied at a tertiary care center. RESULTS: In this patient population 24% were black and 76% were white. There were no differences between black and white patients in terms of anatomic distribution of IBD, symptom presentation, and extraintestinal manifestations. A family history of IBD (36.4% vs 17.5%; P = 0.006) was more common in white children. Mean erythrocyte sedimentation rate of black patients with Crohn disease was higher at diagnosis compared with whites (P < 0.001) and a greater proportion of African Americans presented with a body mass index z-score less than -2 (P < 0.009). At 12 months following diagnosis 22.5% of African American children had a hemoglobin level lower than 10 g/dL compared with 4.3% of whites (P = 0.001). African Americans had evidence of more complicating stricturing and penetrating Crohn disease behavior (51.3% vs 27.4%; P = 0.006). African Americans received significantly more corticosteroids and infliximab to treat their IBD compared with whites (P < 0.04). CONCLUSIONS: This study suggests that for pediatric IBD, there may be racial differences in prevalence of family history and in disease phenotype.