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Unlocking the Genetic Mysteriesof JOHNS HOPKINS InsıdeTract SPRING 2017 NEWS FROM THE JOHNS HOPKINS DIVISION OF GASTROENTEROLOGY AND HEPATOLOGY 1 2 3 In this colocalization of a specimen taken from a patient with ileal Crohn’s disease, a green stain in image 1 illuminates zinc transporter genes within the instestinal crypt cells. Image 2 shows the cells’ teal-stained nuclei. Image 3 overlays the other two images and highlights in red a special type of crypt cell. “This tells us that the zinc transporter is present in some of the immune cells in the epithelia of both the terminal illium and the small bowel,” says researcher Joanna Melia, “and that there is even more of it in the presence of inflammation.” Unlocking the Genetic Mysteries of IBD oanna Melia’s patients with inflammatory bowel disease all ask her the same thing. “WE STILL DON’T UNDERSTAND WHAT “Every single one of them wants to know HAPPENS WHEN THIS GENE IS MUTATED, BUT Jwhat they should and shouldn’t eat,” she says. WE KNOW ZINC IS VERY IMPORTANT TO “Which seems reasonable, right? But there’s very little information on dietary recommendations for IMMUNITY AND GUT HEALTH.” patients” with Crohn’s disease and ulcerative colitis. —JOANNA MELIA Her research is driven by a desire to give those patients some answers. Melia, a gastroenterologist and researcher, says some patients tell her that certain foods trigger episodes while others report diet has no affect on or too little immune response in patients with IBD. the microbiome. their symptoms. Either can lead to intestinal inflammation. “There seems to be some competition among For example, for a long time, IBD patients were “Historically, we have divided up inflammatory the host and organisms in the gut for these encouraged to avoid foods containing fiber. “Now bowel disease into only two disease conditions, micronutrients in IBD,” she says. “For instance, the pendulum is swinging the other way,” she says. Crohn’s disease and ulcerative colitis,” says Melia. we and our collaborators have found that the “Newer studies say that fiber is good. So it’s really a “But there are likely many subtypes driven by many microorganisms in the intestines of patients with moving target.” different processes.” Crohn’s disease have more zinc transporters than the To better understand one aspect of diet and IBD, Using enteroids grown from intestinal tissue ones in healthy people.” Melia is researching a zinc transporting gene that samples, Melia and other Johns Hopkins researchers The role of diet in shaping the microbiome is has a mutation associated with increased risk of study intestinal transporters. undeniable, Melia says. But exactly what effects Crohn’s disease. The mutation has also turned up in She says that many of her Johns Hopkins various foods produce remains elusive. Still, she research of several other diseases, including obesity colleagues have produced important work in IBD believes there is hope to unlocking the puzzles of and schizophrenia, and it might hold clues to how genetics and in the area of dietary trace minerals, IBD, diet and the microbiome. micronutrients in the gut affect disease. such as copper, iron and zinc. Melia sees herself “We really want to learn how we can harness “We still don’t understand what happens when working in that tradition. micronutrients to improve gut health. I think we have this gene is mutated,” she says. “But we know zinc is Melia’s research also focuses on how new laboratory tools to begin to study these questions very important to immunity and gut health.” micronutrients, required by both humans and in new ways, and it is my hope we can provide more Melia says that it may produce either too much the microorganisms present in the gut, shape answers for patients,” she says. n DIRECTOR’S COLUMN GASTROPARESIS Myotomy Offers Relieffor Some Gastroparesis Patients he National Institutes "These were patients whose spastic lower esophageal sphincter of Health estimates that condition was debilitating," muscles have difficulty swallowing, as many as 5 million Khashab says. and food stays undigested in the TAmericans live with The endoscopist slides a stent esophagus. A myotomy of that gastroparesis. Johns Hopkins past the stomach and deploys it muscle brought many patients relief, gastroenterologist Mouen Khashab into the pyloric valve, holding the prompting Khashab to wonder if cites a 2008 American Journal of valve open and allowing nutrition gastroparesis patients might enjoy Gastroenterology study stating that to begin its journey through the similar benefits. Innovating for Others diagnoses of gastroparesis have intestines. Khashab says the stent "It's a sphincter muscle in a increased by more than 150 percent was successful more often than different place," he says. "Instead We’re proud of—and humbled by—our in the past 20 years. not, but that he never meant it as a of at the bottom of the esophagus, reputation for world-class research at the "It's becoming more common," permanent solution. it's at the bottom of the stomach. I Johns Hopkins University School of Medicine. he says. "We don't know why it's on "Stents migrate," he says. thought it might work." For 127 years, our institution has led such a steep rise." "Mucosa grows over them. There Khashab did a study on the advancements in the science of medicine. What's more, Khashab says are all sorts of reasons why it wasn't procedure and found that, in many But underlying our relentless pursuit of medical knowledge is a fundamental drive: there's no reliable medication or permanent." cases, myotomy did indeed relieve to help alleviate human suffering through the treatment for the condition, in Meanwhile, Khashab and other gastroparesis symptoms. He notes treatment of illness and disease. which the stomach cannot empty Johns Hopkins endoscopists (continued on back cover) This edition of Inside Tract showcases just properly, causing abdominal pain, were frequently a few of the ways that we do what we’ve nausea and vomiting. Ultimately, performing another dedicated our lives to—blending rigorous patients with persistent or chronic procedure for science with the compassionate care of patients. gastroparesis can suffer dehydration patients with The conditions you'll read about in this and malnutrition. achalasia. That issue are among today’s most widespread "No one has found a specific procedure, and pernicious: inflammatory bowel disease, cause," explains Khashab, "and the called peroral gastroparesis, diabetes, obesity and, of course, only medication for it has a black- endoscopic cancer. Though the conditions are common, our box warning for significant side myotomy teams’ approaches are often anything but. effects." (POEM), Saowanee Ngamruengphong, for example, Khashab has developed an involves spent last summer in Tokyo, studying advanced endoscopic procedure that snips the cutting the therapeutic endoscopy techniques for gastric pyloric sphincter to treat certain lower esophageal cancer. There, she learned from some of the sufferers of gastroparesis. He is sphincter muscle world’s foremost experts in the field, and she encouraged by the early results. to relieve spasms brings this expertise, scarcely available in the In 2012, he and several Johns that prevent it U.S., to our patients most in need. Hopkins colleagues began testing a from opening and Mouen Khashab says that about Mouen Khashab continues to advance metallic mesh stent to treat patients closing properly. two thirds of his patients who surgery-sparing, endoscopic solutions for have had pyloric myotomy report with severe, refractory gastroparesis. Patients with conditions of the GI tract. In this issue, we no more gastroparesis symptoms. delve into his efforts centered on the ubiquitous condition refractory gastroparesis. Equally innovative, Joanna Melia's research “IT'S A SPHINCTER MUSCLE IN A DIFFERENT into the genetics of IBD mines the origins of PLACE. I THOUGHT IT MIGHT WORK..” Crohn's disease and ulcerative colitis—teasing out clues that may one day lead to advanced —MOUEN KHASHAB treatments. And Ashish Nimgaonkar and colleagues are engineering a pill—based on prior research focused on weight loss—that may eliminate diabetes symptoms in patients who take it before meals. It is truly an honor to work with such colleagues—physicians and scientists who strive GASTRIC CANCER every day to improve the health and lives of our patients and people throughout the world. Should you have questions for me, anyone in this issue, or other members of our division, The Cutting Edge of Endoscopic Resection please don’t hesitate to contact us. Johns Hopkins among the few U.S. centers to offer innovative procedure Tony Kalloo, Director Division of Gastroenterology and Hepatology ooking at results from high-definition scopes, foremost facility for innovative endoscopic removal of Johns Hopkins University School of Medicine enhanced imaging, endoscopic ultrasound and gastric cancers. other advanced diagnostic tools, Johns Hopkins’ Gastric cancer is far less common in North Explore Our Online Resource for multidisciplinary teams work together on America than in Eastern Asia, which sees 50 percent Physicians: Clinical Connection L personalized care plans for patients with gastric cancer. of all new cases worldwide each year. The Japanese Connect with Johns Hopkins health care Most times, when resection is necessary, common center's faculty teaches the latest endoscopic resection professionals about the latest clinical endoscopic mucosal resection (EMR) is sufficient. techniques annually to only a few physicians from innovations and advances in patient care. But when patients require something more complex, around the world. gastroenterologist Saowanee Ngamruengphong and Ngamruengphong spent her time there learning Register for your free membership to colleagues offer other options. endoscopic submucosal dissection (ESD), as well as access videos, articles, clinical trials and For 10 weeks last summer, she studied advanced detection, evaluation and treatment of all kinds of early much more. endoscopic early-cancer removal techniques at the luminal cancers and precancers.
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