ACG PERSPECTIVES

A FRESH LOOK at the INSIDES

THE CONTINUING JOURNEY OF A TRAINEE

Bhavana Bhagya Rao, MD Cleveland Clinic Foundation, Cleveland, OH

IT HAS BEEN AN EXCITING 16 MONTHS AS A GASTROENTEROLOGY

FELLOW. While at first training seemed daunting I have since slowly familiarized myself with and befriended all the cool gadgets and techniques that embellish the armamentarium of an endoscopist. Now, more than a year in as of the time of this writing, I dared to claim that I had a fair idea of what I was doing and felt under control during a procedure. But did I really know the inside scoop of performing a scope?

Recently, I had a unique opportunity to gain additional perspective on the actual impact of an endoscopic procedure on a human body. A middle-aged female patient with a new diagnosis of Peutz-Jegher’s syndrome was evaluated at our hereditary colon cancer clinic with the complaint of recurrent small bowel obstructions. Her history included a single abdominal surgery, performed when she was two years old, but she was unaware of further details. Abdominal computerized tomographic enterography was notable for multiple dilated small bowel polyps with scattered foci of intussusception,

which were suspected to be the etiology of her recurrent blockages. A push enteroscopy was pursued for polyp removal, which turned out to be technically challenging due to marked abdominal distension during the procedure. The scope could not be safely advanced beyond the mid-duodenum.

To ensure a complete “clean sweep of her small bowel,” the patient was scheduled for a laparoscopyassisted enteroscopy. This procedure would entail a joint collaboration by endoscopists and surgeons, who would help in advancing our intra-orally passed endoscope into the most distal regions of the small bowel, otherwise beyond reach, and there we would perform extensive polyp resection. As it turned out, during the laparoscopy the patient was noted to have extensive intra-abdominal adhesions and the surgeons switched from a laparoscopic approach to exploratory laparotomy and performed adhesiolysis while at the same time we proceeded with the push enteroscopy.

At this point in my training, I may well have performed upwards of 900 endoscopic procedures, but if I were being honest with myself, this felt as if it was my first because I saw the process in an entirely new light and discovered a whole new meaning. How fragile the intestinal tract seemed and how intrusive and foreign our five-foot-long scope appeared, invading her entrails through her mouth.

How different this was from our routine outpatient cases, where often during colonoscopies some patients are comfortably awake and talkative and even watch images of their insides along with us. Seeing her bowels quiver in the hands of the surgeon while our scope snaked through them was unnerving. It was anxiety provoking for me as we

“At this point in my training, I may well have performed upwards of 900 endoscopic procedures, but if I were being honest with myself, this felt as if it was my first because I saw the process in an entirely new light and discovered a whole new meaning.”

insufflated air into her bowels, and they ominously distended and glistened in the harsh operating room lights. The most nerve-wracking aspect of all was watching the sparks and glow within the bowel lumen as we cauterized more than 40 giant polyps from her jejunum and ileum. I realized how easy it is to forget in the operating room that the shiny bowels that spilled out of the gaping wound in her abdomen, the innumerable tubes and catheters that poked out from multiple sites, the scope that was jammed between three other tubes in the mouth, were all part of a whole, single, alive human being. She seemed so remote and distant— lost under all those layers of drape.

The next day, we went to check on her and, lo and behold, she was whole again, sitting up in a chair, beaming at us and profusely thankful. I had a quick flashback to the image I had of her from the previous day, and could not help but be impressed at the striking contrast in her circumstances. It was then time to move on to our scheduled procedures of the day, none of which was as exciting as her case or involved any operating room action. Yet something profound had changed for me: I looked at every patient and every esophagus and colon I examined in a new light. The screen still accurately displayed what the camera was seeing but, in the back of my mind, there was an added visual impression, a more holistic and comprehensive view of both the inside and outside milieu of the patient, that served to guide and caution me as an endoscopist.

It is easy for GI training to seem long and arduous, but medicine has provided me with several such experiences of clarity that have encouraged me to pause for introspection on even the so-called routine procedures we perform. Moments, often humbling, in which I am revitalized to continue seeking the “inside scoop” in all that we say and do, and to revel in the healing and care that we have the honor of being a part of everyday!

Funding Promising Careers in CLINICAL RESEARCH Nicholas J. Shaheen, MD, MPH, FACG, Director, ACG Institute for Clinical Research & Education

THE COLLEGE IS COMMITTED TO ADVANCING THE FIELD OF GI through the support of clinical research. This commitment is manifest in many ways, the most obvious being the clinical grants program of the ACG Institute. Through this program, the College annually awards substantial funds to promising researchers and projects, last year totaling $1,512,145. These awards are especially instrumental in the development of young clinical investigators.

2018 Junior Faculty Development Grants

Our Junior Faculty Development program has proven itself to be a significant incubator of young research talent in our field and, as it passes its 20th birthday, numbers multiple division chiefs, department chairs, deans and other significant contributors to academic medicine amongst its alumni. These research awards, which currently protect a substantial amount of time for research early in the careers of these recipients, are the “rocket fuel” that allows these careers to take off.

Clinical Research Awards & Pilot Awards

Our smaller awards, including ACG’s Clinical Research Awards and Pilot Awards, provide investigators not only external validation of the quality of their work, but also the seed money which often spurs other awards and further investigation. Given that the vast majority of our awards result in one or more peer-reviewed publications, members of the College can be proud of the performance of this program.

THIS YEAR, AS ALWAYS, the ACG Institute has invested in the future by having a large portion of the Institute’s research dollars go to promising young investigators whose Junior Faculty Development Awards are listed below. This three-year award of $100,000 per year protects time for clinical research.

Megan Adams, MD, JD, MSc

University of Michigan

Promoting High-Value Use of Endoscopic Sedation

“Balancing tests” are commonplace in American law, where the outcomes of legal disputes are often dependent on weighing counter-balanced interests, such as an inmate’s liberty interest versus the government’s interest in public safety. In my prior career as an attorney working for a state appeals court, it was my job to help the judges for whom I worked wrestle with these challenging balancing exercises across a range of legal contexts. I saw both the importance and difficulty in deciding questions regarding what values and interests should be taken into account and how these interests should be weighted. Indeed, I have continued to wrestle with these questions, albeit in a different context, since transitioning to a career in medicine.

As the US medical system shifts to valuebased health care delivery, we must learn how to balance complex and competing factors, including medical appropriateness, patient preferences, cost and access in a meaningful and equitable manner. This is particularly important in procedural fields such as GI in which the use of expensive, invasive interventions of sometimes marginal benefit is common. Now a general gastroenterologist,

attorney and health services researcher, my long-term goal is to build a successful career focused on improving the quality and delivery of health care for patients with gastrointestinal conditions by helping to define, measure and implement high-value care that effectively reconciles the inherent tradeoffs in health care delivery. The support provided through the 2018 ACG Junior Faculty Development Award will help me maximize the impact of my work and realize my goal of federal funding through an Agency for Healthcare Research and Quality or National Institutes of Health award.

Parakkal Deepak, MBBS, MS

Washington University School of Medicine in St. Louis

Triangular Phenotyping and Response Assessment in Small Bowel Crohn’s Disease Using MRE and Novel Proteomic Biomarkers

The small bowel is involved in ~70% of patients with Crohn’s disease. The assessment of Small Bowel Crohn’s Disease (SBCD) activity and response to therapy remains a major challenge in clinical management. Current serum biomarkers are inadequate for SBCD, and mucosal healing visualized during repeated ileocolonoscopies as a “treat-to-target” strategy is burdensome for the patient and carries inherent risks.

Thus, there is an unmet need for accurate and clinically meaningful methods to measure SBCD activity. This is particularly relevant as the field moves toward “treat-to-target” management strategies. Compared to colonoscopy, patients have reported greater preference for serial assessment of disease activity magnetic resonance enterography (MRE) and non-invasive serologic biomarkers. We recently demonstrated that treating to a target of radiological transmural response (TR) on CT enterography (CTE) or MRE was associated with reduction in hospitalization, surgery and corticosteroid use in a retrospective cohort study of SBCD patients. In this study, TR was assessed using a method that accounts for aggregated transmural inflammation and longitudinal disease burden.

The overall objective of this project is to establish that radiologic transmural response and a novel proteomic biomarker are accurate and clinically meaningful predictors of SBCD inflammatory activity and response to biologic therapy. To address this objective, we will establish a prospectively followed cohort of SBCD patients starting a new biologic therapy. These patients will be comprehensively phenotyped using state-of-the-art MRE imaging, proteomic profiling and clinical disease activity indices. We will use this innovative approach of triangular phenotyping to address our central hypothesis that “Corticosteroidfree remission at 52 weeks after biologic therapy initiation is predicted by short-term radiologic TR or early changes in serum proteomic biomarker profiles.”

Girish Hiremath, MD, MPH

Vanderbilt University Medical Center

Label Free Determination of Biomolecular and Biochemical Signatures in Eosinophilic Esophagitis: Bench to Bedside Application of Raman Spectroscopy

The long-term goal of this research is to develop an innovative, real-time, clinically applicable, minimally invasive approach to identify Eosinophilic Esophagitis (EoE) with molecular specificity.

At present, in the compatible clinical setting, identification of cellular, microstructural and tissue markers with hematoxylin and eosin staining (goldstandard) and immuno-histochemical analysis of esophageal biopsies is essential for identification of EoE and to distinguish it from overlapping conditions such as gastroesophageal reflux disease (GERD) and proton pump inhibitor (PPI) therapy responsive esophageal eosinophilia. This approach is expensive, time consuming, clinically burdensome and prone to subjective variability. Additionally, it allows identification of EoE only after tissue damage, oftentimes irreversible, has already set in. Therefore, a minimally invasive, efficient and real-time approach to identify EoE holds promise to advance the field, impact clinical care and promote patient outcomes. Raman spectroscopy-based applications are capable of providing labelfree, minimally invasive tools to discriminate tissue pathology in real-time with molecular specificity.

We have previously validated these applications in IBD. Our novel preliminary data suggest that Raman spectroscopy can precisely determine in vitro biochemical and molecular composition of the esophageal tissue affected by EoE and can distinguish EoE from GERD with 96% accuracy.

Also, for the first time in the pediatric age group we have demonstrated the safety and feasibility of a pediatric upper endoscope compatible fiberoptic Raman spectroscopy probe to acquire real-time, in vivo esophageal Raman spectra during esophagogastroduodenoscopy. Under the auspices of the ACG Junior Faculty Development Award, I propose to leverage our exciting preliminary results to test the hypothesis that identification of EoE-specific biochemical and molecular signatures will facilitate development of innovative and clinically applicable diagnostic strategies to identify EoE in children.

Rena Yadlapati, MD, MSHS

University of Colorado Anschutz Medical Campus

Determining Best Practices for Reflux Associated Laryngeal Symptoms

Inappropriate use of diagnostic and therapeutic strategies for Reflux Associated Laryngeal Symptoms (RALS) is a major problem, contributing to a high economic burden, increased patient risk, and failure to deliver effective personalized care. Identification of patient-centered and cost-effective clinical practices for RALS is a high priority. This study will address three crucial gaps impacting the clinical approach to RALS: (1) Paucity of diagnostic tests that predict clinically relevant outcomes; (2) Undefined clinical role of UES augmentation; and (3) Deficiency of personalized and costeffective approaches.

Central hypothesis: In a personalized, costeffective approach to RALS, a diagnostic screen (e.g., salivary pepsin) will guide a PPI trial. In the case of PPI non-response, physiologic testing (e.g., the multi-channel intraluminal impedance Z/2pH system, high-resolution impedance manometry) will elucidate mechanisms and personalize treatment.

This project leverages my background in health services research and esophageal physiology, and examines state-of-the-art clinical tools for a critically important and understudied field. The anticipated impact of this research is to lay the groundwork for future NIH K23 and R01 proposals aiming to: (1) Refine the diagnostic criteria for RALS; (2) Assess best practice strategies in a multicenter placebo- and shamcontrolled clinical trial; and (3) Implement and disseminate effective interventions. My long-term goal is to lead the national effort to improve the care of RALS through standardized implementation of guidelines.