Research Leaders

Core to the mission of the Suzi and Scott Lustgarten Center for GI Motility is the promotion of a coordinated, comprehensive research program, which empowers multidisciplinary collaboration and bridges science with care to better evaluate and treat functional GI and motility disorders.

A number of promising research developments have taken place over the last year, including the following:

Achalasia

A rare esophageal motility disease, achalasia results in the degeneration of the esophageal muscles and the nerves that control these muscles, leading to patients experiencing difficulty swallowing, chest pain, and regurgitation of foods and liquids.

Use of FLIP procedure for achalasia treatment

The most widely-used treatment for achalasia is pneumatic dilation (PD), which involves the endoscopic insertion and inflation of a cylinder-shaped balloon into the lower esophageal sphincter to expand the esophageal muscles enough to improve swallowing. This intervention is only effective if the balloon is inflated the proper amount, which varies considerably from patient to patient and cannot be determined intraoperatively in pediatric patients. To address this challenge, Alain Benitez, MD, and Kristin Fiorino, MD, assessed the role of the functional lumen imaging probe (FLIP) in determining adequate PD in pediatric achalasia patients. They determined that the FLIP procedure was an effective tool for determining the degree of sphincter release created by the dilation and immediately determining if there was a need for additional dilation. These findings increase the likelihood of an effective dilation, thus increasing the benefit of dilation and reducing the need for subsequent dilations in a short period of time.

Sedation protocols during FLIP

FLIP measurements are typically taken when patients are sedated; however, sedation protocols currently vary between adult and pediatric populations and across different institutions, and their effects on the functional properties of the esophagus during FLIP are unknown. The research team evaluated the effect of one sedative commonly used in children, Sevoflurane, on the functional properties of the esophagus during FLIP. They found that the use of this sedative may impact measurements taken by the FLIP, undermining the effectiveness of this procedure for accurate diagnosis of achalasia and other esophageal disorders.

Role of esophagogastric junction distensibility in pediatric EoE

Pediatric patients with eosinophilic esophagitis (EoE) typically experience upper abdominal pain, vomiting, and other symptoms overlapping with reflux. The research team determined that muscle tone and inflammation in EoE patients can reduce the ability of the esophagogastric junction to expand, potentially causing difficulty swallowing (dysphagia).

Gastroparesis

Gastroparesis affects the nerves and muscles of the stomach, delaying the emptying of food from the stomach to the small intestine, resulting in nausea, vomiting, and other symptoms similar to gastric reflux. Currently, the diagnosis of gastroparesis is accomplished through gastric emptying scintigraphy (GES), a four-hour exam for adults (two-hour exam for pediatric patients) during which pictures are taken of test meal passing through the stomach and GI tract.

Delayed gastric emptying

The research team set out to study the clinical factors predictive in delayed gastric emptying at four hours in pediatric patients. They determined that no clinical variables were associated with delayed gastric emptying in their study population, and that there was limited clinical benefit among participants of extending GES to four hours, if more than 80% emptying was achieved at three hours.

High resolution electrogastrography (HR-EGG)

In collaboration with Dr. Hayat Mousa from Rady Children’s Hospital, Drs. Fiorino and Benitez are seeking to determine the clinical benefit of HR-EGG in children with disorders of gastric origin including, gastroparesis and functional dyspepsia. The complexity of disorders such as gastroparesis poses a challenge in determining its origin and targeting therapies. With HR-EGG, the team will be able to determine if there is an ineffective gastric pacing in patients with gastroparesis and functional dyspepsia. This technology could also be expanded to other GI disorders that involve the stomach.

Pyloric function

Gastroparesis and its accompanying symptom of delayed gastric emptying is due in part to failure of the pyloric sphincter to adequately open and allow gastric contents to empty into the duodenum. Although a newly developed method to assess sphincter pressure and distensibility called impedance planimetry has enabled the evaluation of pyloric sphincter pressure and treatment response in adult patients with GP, the pyloric function and usefulness of this method for pediatric patients have not been previously analyzed. The research team has designed and received Institutional Review Board (IRB) approval to initiate a study to better understand the functional properties of the pyloric sphincter in pediatric patients with GP and the efficacy of impedance planimetry. The findings from this work will lead to improved methods for diagnosis, treatment and disease monitoring.

Irritable bowel syndrome (IBS)

Characterized by abdominal pain, bloating, and altered defecation patterns (constipation and diarrhea), irritable bowel syndrome is a functional GI motility disorder of brain-gut origin. According to one recently published study in North America, IBS impacts more than 14% of high-school age and 6% of middle-school age children. Current therapies used in the management of IBS are symptom-targeted and have a great degree of variability, especially in pediatric cases, since most medications have adult indications.

Microbiota and IBS

Because gut microbiota has been found to considerably influence IBS, many therapies are intended to alter the microbial composition of the gut using dietary modifications or antibiotics, including a popular non-absorbable antibiotic called Rifaximin. In February 2019, Dr. Alain Benitez submitted a proposal for a Penn-CHOP Microbiome Pilot grant to study the effect of Rifaximin on microbial composition and associated changes in IBS symptomology. We expect that this study will further confirm the importance of microbiota to the pathogenesis of IBS and aid clinicians in determining the most appropriate (and impactful) therapy for each patient by identifying early indicators of treatment response prior to the initiation of microbiota modulating therapies.

Myofascial release massage therapy for IBS-C

In April 2019, Dr. Maria Mascarenhas, Director of the Integrative Health at CHOP, and Dr. Alain Benitez presented an application for study funding to evaluate the use of abdominal wall targeted Myofascial Release Therapy (MRT), a hands-on technique that manipulates the muscle fascia, in reducing symptoms and improving quality of life in pediatric patients with constipation-predominant IBS. If proven effective, MRM will equip IBS-C pediatric patients and their families with an osteopathic tool that will aid them in reducing their symptoms and discomfort.

Rumination

Kari Barber, PhD, has launched our pilot program on rumination, an extraordinarily distressing upper-tract gastrointestinal disorder with a large behavioral component. Dr. Barber, who performs individual therapy for rumination, will be exploring with the assistance of two master’s student summer interns, the psychosocial consequences and healthcare utilization associated with rumination.

Cellie Coping Kit for functional GI and motility disorders

The diagnosis and treatment of functional gastrointestinal and motility disorders can be challenging, as they are initially focused on exclusion of underlying conditions with a wide range of less to more invasive procedures, a process that can be burdensome for children and their families. In response, Dr. Alain Benitez in collaboration with Dr. Nancy Kassam-Adams, PhD, and a multidisciplinary team of GI motility experts have created a Cellie Coping Kit for motility disorders, an innovative, cost-effective, child-friendly intervention modeled from a psychosocial therapy tool originally developed by CHOP for children with cancer (and later sickle cell disease). 

The Cellie Coping Kit comprises “Cellie,” a plush, stuffed toy which children are encouraged to use in a variety of ways as they implement coping strategies; age-appropriate coping cards with coping tools for children; as well as a book of instructions for parents offering tips for working with their children to identify and cope with stressors. Via a single-center, single-arm clinical trial, the research team is studying the effectiveness of the Cellie Coping Kit for functional and GI motility disorders in promoting the physical and emotional health of children and their families after a diagnosis of a gastrointestinal motility disorder.

Recent Publications

2018 Articles

Heuckeroth, RO: Even When You Know Everything, There Is Still More to Learn About Hirschsprung Disease. Gastroenterology 155(6): 1681-1684, December 2018

James P. White, Shanshan Xiong, Nicole P. Malvin, William Khoury-Hanold, Robert O. Heuckeroth, Thaddeus S. Stappenbeck and Michael S. Diamond: Intestinal Dysmotility Syndromes Following Systemic Infection by Flaviviruses. Cell November 2018

Sabine Schneider, Christina M. Wright, and Robert O. Heuckeroth: Unexpected Roles for the Second Brain: Enteric Nervous System as Master Regulator of Bowel Function. Annual Reviews of Physiology Page:  doi: 10.1146/annurev-physiol-021317-121515.  October 2018

Silvia Huerta Lopez, Marina Avetisyan, Christina Wright, Karim Mesbah, Robert Kelly, Anne Moon, Robert O. Heuckeroth: Loss of Tbx3 in murine neural crest reduces enteric glia and causes cleft palate, but does not influence heart development or bowel transit. Developmental Biology 444: Suppl 1:S337-S351.  October 2018 Notes: doi: 10.1016/j.ydbio.2018.09.017

Webster J, Lourie, E, Shaw, K, Huang, E: Implementation of a Constipation Action Plan in Primary Care Clinics to Decrease Referrals to Pediatric Gastroenterology: A Quality Improvement Initiative. Gastroenterology 155(1): e48-e49, 2018

2018 Books

Webster, J, Godwin, B: Clinical Approach to Esophageal and Gastric Disorders. Nelson's Pediatric Board Review. Elsevier, 2018.