Office of Research & Development

VA research on

Gastrointestinal Health


Introduction

Gastroenterology is a medical specialty that deals with the diagnosis and treatment of disorders of the digestive system. Such disorders may involve the digestive tract, the pancreas, the liver, or the gallbladder.

Gastrointestinal problems are among the illnesses reported by many Gulf War Veterans following service in the 1990-1991 Persian Gulf War. Irritable bowel syndrome (IBS), which is marked by chronic, cramping, bloating, and diarrhea, was identified by the Institute of Medicine of the National Academy of Sciences as one of a range of illnesses Gulf War Veterans have incurred.

VA researchers have long worked to help Veterans with a number of digestive ailments. In 1955, Dr. Morton I. Grossman became chief of gastroenterology at the Greater Los Angeles VA Medical Center. Dr. Grossman is considered the father of modern gastrointestinal physiology.

The broad theme of his research was how nerves and hormonal influences control gastrointestinal secretions such as hormones, mucus, and acid, especially as this relates to peptic ulcers. He remained with VA as a senior medical investigator until his death in 1982.

Dr. Rosalyn S. Yalow, one of VA's three Nobel laureates, devoted much of her research work to the study of gastrointestinal hormones. (Gastrointestinal hormones are the secretion of an endocrine gland that is transmitted by the blood to the tissue on which it has a specific effect.)

Yalow received the Nobel Prize in Physiology or Medicine in 1977 for the development of the radioimmunoassay, a way to measure insulin and other gastrointestinal hormones in the blood.

Dr. Andrew V. Schally, another of VA's Nobel laureates, also studied gastrointestinal hormones. Schally has demonstrated that the hypothalamus, a part of the brain located just above the pituitary gland, regulated the endocrine system. The endocrine system includes the pituitary, thyroid, and adrenal glands; the pancreas; and the ovaries and testicles.

His findings have proved useful in treating diabetes, cancer, and peptic ulcers, in diagnosing and treating hormone-deficiency diseases, and in developing fertility treatments and contraceptives.

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Selected Major Accomplishments

  • 1950s: Greatly expanded, through the work of Dr. Morton I. Grossman, our understanding of the physiology and regulation of gastrointestinal secretions
  • 1977: Received the Nobel Prize in physiology or medicine (Dr. Rosalyn Yalow), for developing a new way to measure insulin and other hormones in the blood
  • 2004: Found that the open technique is superior to the laparoscopic technique for mesh repair of primary hernias
  • 2013
    • Learned that treatment with the drug infliximab and an immunomodulator significantly reduces the risk of hospitalization and surgery
    • Determined that weight is not a factor in whether or not proton-pump inhibitors can successfully treat gastroesophageal reflux disease
  • 2015: Found that giving spores of non-toxic Clostridium difficile (C. difficile) by mouth can stop repeated bouts of infection

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New, Ongoing, and Published Research

Areas of focus for VA researchers on gastrointestinal health include research on stomach ulcers, C. difficile infections, IBS, inflammatory bowel disease (IBD), colon cancer, gastroesophageal reflux disease, and other issues.

VA researchers are looking for potential drug therapies to help Veterans with these illnesses, exploring less invasive treatments, and seeking supportive strategies for Veterans during and after their treatment.

C. difficile infections

C. difficile is an intestinal bacterial infection that is difficult to treat using standard antibiotic treatment, because it has a very high recurrence rate. As many as 30 percent of patients experience recurrent episodes of the illness.

Treating C. difficile with nontoxic spores—Such infections can result in repeated hospitalizations, malnourishment, and dehydration and, occasionally, death. In 2015, an international team of researchers led by Dr. Dale Gerding of the Edward Hines, Jr. VA Hospital in Illinois found that giving spores of non-toxic C. difficile by mouth can stop repeated bouts of C. difficile infection.

The team randomly assigned 168 adult patients with C. difficile infections who had been treated for their infection to receive doses of either 10,000 or 10 million spores per day of non-toxic C. difficile in liquid form for 7 or 14 days, or to receive an identical placebo. Statistically significant reductions of relapses in infection were shown in those who received any dose of non-toxic C. difficile; the best results were shown in those who received 10 million spores a day for seven days.

Fecal transplantation—Also in 2015, VA researchers and researchers with the University of Minnesota looked at a procedure that dates back thousands of years and found it can be an effective method for battling C. difficile infections. The procedure, called fecal transplantation, involves removing stool containing healthy bacteria from a donor and inserting it into a sick patient.

The investigators' review looked at the results of studies involving data for more than 500 patients with C. difficile infections, and learned that fecal transplantation proved successful in treating 85 percent of patients with recurring infections. The researchers concluded that such transplantation is a safe and effective way to treat recurrent infections.

C. difficile rates and preoperative antibiotics—In December 2015, VA researchers published an analysis of information from the Veterans Affairs Surgical Quality Improvement Program's Database in JAMA Surgery. The database documents all non-cardiac operations at 134 VA medical centers each year.

They found that VA hospitals' rates of postoperative C. difficile infection are related to the number of preoperative antibiotics patients have taken, the complexity of their procedures, and the complexity of the hospital's surgical program—in addition to the already-known risk factors for the infection.

The researchers focused on 468,386 procedures performed during a four-year period, and documented that 1,833 cases of C. difficile infection were diagnosed within 30 days of surgery, an overall incidence of 0.4 percent. They found that patients who had taken three or more antibiotics before surgery were nearly six times more likely to develop C. difficile than patients who had taken only one or no antibiotics.

In addition, patients who underwent more complex surgical procedures were at increased risk of this complication, as were patients at hospitals that frequently handled complex procedures. Those who developed the infection had significantly higher rates of illness and death than those who did not, as well as longer postoperative hospital stays.

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➤ Inflammatory bowel disease (IBD)

More than 1 million Americans have inflammatory bowel disease (IBD), a term that includes Crohn's disease and ulcerative colitis. Crohn's disease is a chronic inflammatory condition of the entire gastrointestinal tract, and ulcerative colitis is an inflammation limited to the colon.

While IBD can affect anyone, it is more common in Caucasians and in younger people. Most people with IBD are diagnosed before age 30.

Drug combination to treat IBD—VA researchers and researchers from Baylor College of Medicine completed a study in 2013 using eight years of data from 176 VA facilities. The researchers found that taking the drug infliximab (sold as Remicade) together with an immunomodulator reduces the risk of hospitalization and surgery after one year in men with inflammatory bowel disease. This is especially true if the therapy is begun as soon as possible after IBD is diagnosed.

The study found that those who received nine months of both drugs had their risk of hospitalization for the condition decreased by 73 percent, and their risk of surgery decreased by 92 percent.

Immunomodulators affect the immune system, either by boosting it or suppressing it, in order to treat disease. Infliximab is a drug that has been approved for treating Crohn's disease since 1998.

IBD and colon cancer—IBD puts patients at a markedly increased risk of developing colon cancer. Researchers from three VA sites and other researchers throughout the world came together in 2014 to develop guidelines for how doctors should survey and manage dysplasia, which are areas of pre-cancerous cells, in patients with inflammatory bowel disease.

The new guidelines focus less on random biopsies to find potential trouble spots, and more on using available technology to identify and remove precancerous areas before cancer can develop. The researchers hope these guidelines will decrease the number of patients who develop colorectal cancer or require removal of their colon.

PTSD and autoimmune disorders—In 2015, a study of more than 666,000 Veterans of Iraq and Afghanistan found that those with PTSD were more likely to have autoimmune disorders such as IBD. The study, led by researchers at the San Francisco VA Medical Center, found a twofold increased risk of such disorders among those with PTSD, compared with those who had no psychiatric disorders, and an even greater risk compared with those who had psychiatric disorders other than PTSD.

Other autoimmune disorders these Veterans were at increased risk of developing included multiple sclerosis, lupus, inflammation of the thyroid, and rheumatoid arthritis. The study did not show that PTSD causes autoimmune disease, only that there is a relationship between the two conditions.

Oral therapy for ulcerative colitis—Also in 2015, a team from the Atlanta VA Medical Center, the Institute for Biomedical Sciences at Georgia State University, and Southwest University in China published the results of their study of an oral therapy to treat ulcerative colitis. The therapy, which consists of microparticles loaded with curcumin, an herbal anti-inflammatory agent, proved to be a promising drug carrier when tested on mice with the disease.

Previous studies had shown that curcumin can diminish inflammation in animals with colitis and can decrease the rate of relapse in the disease. The researchers also believe this new treatment will target damaged tissue more specifically and will reduce the side effects currently associated with ulcerative colitis treatment.

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➤ Gastroesophageal reflux disease

Frequent heartburn, or gastroesophageal reflux disease (GERD), is even more common than IBD. About 1 in 10 Americans experiences GERD symptoms at least once a week.

Smoking and obesity can contribute to GERD symptoms, and many foods—especially fatty, fried, citrus or tomato-based foods, chocolate, and caffeine—can worsen symptoms.

People who are obese are more likely to have GERD. Despite their higher risk, for the disorder, they are just as likely as normal-weight patients to be helped by proton-pump inhibitors, the strongest treatment available.

Weight not factor in proton-pump inhibitor treatment—A 2013 study of patients treated at the Kansas City, Missouri., VA Medical Center and the University of Kansas showed that weight was not a factor in the success of treatment with the proton-pump inhibitor esomeprazole (sold as Nexium and Essocam). People who were obese before treatment did tend to have more severe reflux symptoms, however.

Medical and surgical treatments for GERD—VA researchers are currently conducting a large cooperative study (CSP #573) to compare different medical and surgical treatments for patients with GERD. The treatments to be compared are antireflux surgery and two medical therapies (baclofen and desipramine.)

Fifteen VA medical centers are involved in this study, and researchers hope to enroll 393 GERD patients.

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➤ Ulcers

An ulcer is a small sore or lesion in the lining of the stomach or duodenum, the first part of the intestine. The sore is often aggravated by stomach acid, but is usually not caused by the acid itself. More likely, the cause is either a bacterium known as Helicobacter pylori (H. pylori) or the use of non-steroidal anti-inflammatory drugs (NSAIDs).

According to one VA researcher, Dr. David Graham of the Michael E. DeBakey VA Medical Center in Houston, the current antibiotic therapies to treat H. pylori bacteria are obsolete, because the bug is now resistant to certain common antibiotics.

In a 2014 article, Graham and two colleagues from National Taiwan University suggest instead that improving counseling and education for patients; taking the patient's personal history with antibiotics into account; and taking into account local patterns of antibiotic resistance can ensure that 9 in 10 patients who take antibiotics to remove H. pylori can get rid of the bug.

Graham and his colleagues also recommended doctors prescribe three antibiotics instead of two. While this stronger combination therapy slightly increases the risk of adverse side effects, most patients tolerate these drugs fairly well.

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➤ Hernias

A hernia occurs when an internal part of the body, such as the intestine, pushes through a weakness in the abdominal muscle or its surrounding tissue wall. An inguinal hernia occurs in the groin.

In 2004, a major VA cooperative study looked at two different methods of repairing inguinal hernias: open mesh surgery, in which a cut is made to allow the surgeon to push the bulge back into the abdomen, and laparoscopic mesh repair, where several smaller cuts are made allowing the surgeon to use special instruments to repair the hernia.

The researchers found that patients who had had the laparoscopic surgery were more likely to have a recurrence of the hernia, and had a higher rate of complications—although they also had less initial pain and returned to their normal activities one day earlier. Accordingly, the researchers determined that the open technique was superior to the laparoscopic technique for mesh repair of primary hernias.

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➤ Colon cancer

Colorectal, or colon, cancer refers to cancer that is found in either the colon or the rectum. According to the American Cancer Society, this type of cancer is the third most common cancer diagnosed in the United States.

VA has made it a priority to screen its patients aged 50 years and above for colorectal cancer. The American Cancer Society recently reported that the death rate from colon cancer has been dropping for the past 20 years, and there is good evidence that screening efforts have played an important role in this trend.

Colonoscopy vs. sigmoidoscopy—In In 2000, VA Cooperative Study #380 found that colonoscopy screening (a procedure in which a long, flexible, tubular instrument is used to view the entire inner lining of the colon) is more effective than sigmoidoscopy for early detection of cancer in adults with no symptoms of the disease.

Sigmoidoscopies also use a flexible tubular instrument, but they are partial examinations that cover only the left side of the colon. They are often used because, unlike colonoscopies, they do not usually require patients to be sedated, and the preparation before the examination is simpler.

Colonoscopy vs. fecal immunochemical testing—In 2010, VA researchers began conducting a large multisite study designed to compare the effectiveness of colonoscopies with that of fecal immunochemical testing (FIT) in reducing colon cancer deaths. FIT detects minute amounts of blood in the stool, which can be a warning sign of developing cancer.

The study's leaders are enrolling 50,000 Veterans in the test. Enrolled Veterans will either receive a one-time colonoscopy or an annual FIT test for 10 years. If the FIT test is positive, a follow-up colonoscopy will be recommended.

Length of colonoscopy procedure—A 2015 study by VA researchers and researchers from the University of Minnesota found that the longer doctors take to perform a colonoscopy, the lower the rates of cancer are in those patients who received them.

They studied 77,000 colonoscopies performed over six years by 51 gastroenterologists in a large Minnesota community practice. The average withdrawal time—the stage of the procedure during which the doctor carefully examines the colon—was about 8.6 minutes, but about 10 percent of the doctors had individual averages of under six minutes.

The patients who had been examined by doctors whose withdrawal times were shorter were more likely to have cancer—and the rate was more than twice as high for patients whose physicians' average times were under six minutes.

Gastrointestinal exam practices—A recent study by researchers at the Durham VA Medical Center and the University of North Carolina at Chapel Hill looked at whether VA physicians are recommending colonoscopies in accordance with existing guidelines.

The study, which was published in 2015, looked at the records of 1,466 Veterans who originally underwent colonoscopies between Oct. 2007 and Sept. 2008. They found that more than a quarter of those patients, who had been found at the time to have had low-risk benign tumors, received follow-up colonoscopies too early—and more than half of those who had been found to have had high-risk benign tumors received colonoscopies either too late, or not at all.

The researchers concluded that system-level improvements were needed so that Veterans would receive colonoscopies at the appropriate time, based on their individual risk of developing colon cancer.

A similar study, by researchers at the Minneapolis VA Health Care System, found that a substantial number of fecal occult blood tests (FOBT), a test for colon cancer, were potentially inappropriately done. They looked at the records of more than 900,000 Veterans, and found that 26.1 percent of the FOBTs these Veterans completed may have been inappropriate.

For some Veterans, the tests were inappropriate because they did not need to have them done at the time they were recommended; others were unnecessary because of the Veterans' limited life expectancy; and still others were completed when a colonoscopy should have been done instead.

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More on Our Website

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Selected Scientific Articles by our Researchers

Use of colonoscopy to screen asymptomatic adults for colorectal cancer. Veterans Affairs Cooperative Study Group 380. Lieberman DA, Weiss DG, Bond JH, Ahnen DJ, Garewal H, Chejfec G. Colonoscopic screening can detect advanced abnormal growths in the colon. Many of these growths would not be detected with sigmoidoscopies. Veterans Affairs Cooperative Study Group 380. N Engl J Med. 2000 Jul 20;343(3):162-8

Open mesh versus laparoscopic mesh repair of inguinal hernia. Neumayer L, Giobbie-Hurder A, Jonasson O, Fitzgibbons R Jr, Dunlop D, Gibbs J, Reda D, Henderson W: Veterans Affairs Cooperative Studies Program 456 Investigators. The open technique is superior to the laparoscopic technique for mesh repair of primary hernias. N Engl J Med. 2004 Apr 29;350(18):1819-27

Establishment of a minimally invasive program at a Veterans' Affairs Medical Center leads to improved care in colorectal cancer patients. Wilks JA, Balentine CJ, Berger DH, Anaya D, Awad S, Lee L, Haderxhanaj K, Albo D. Establishment of a minimally invasive colorectal cancer program in a Veterans Affairs Medical Center leads to increased access to laparoscopic colorectal resections and improved patient care while maintaining patient safety. Am J Surg. 2009 Nov;198(5):685-92.

Obesity does not affect treatment outcomes with proton pump inhibitors. Sharma P, Vakil N, Monyak JT, Silberg DG. In patients with GERD, high body mass index was associated with more severe erosive esophagitis at baseline. However, during proton pump inhibitor treatment, body mass index is not a significant independent predictor of heartburn resolution or erosive esophagitis healing. J Clin Gastroenterol. 2013 Sep;47(8):672-7.

Dual therapy with infliximab and immunomodulator reduces one-year rates of hospitalization and surgery among veterans with inflammatory bowel disease. Abraham NS, Richardson P, Castillo D, Kane SV. Dual therapy with infliximab and an immunomodulator for less than 8 months is associated with significant reductions in hospitalization and surgery within 1 year of the start of therapy. Clin Gastroenterol Hepatol, 2013 Oct;11(10):1281-7.

Multitarget stool DNA testing for colorectal-cancer screening. Imperiale TF, Ransohoff, DF, Itzkowitz S, Levin, TR, Lavin P, Lidgard GP, Ahlquist DA, Berger BM. A stool test combining altered human DNA and fecal hemoglobin showed higher single-application sensitivity than a commercial FIT for both colorectal cancer and advanced precancerous lesions, although with lower specificity. NEJM March 19, 2014/NEJMoa1311194.

Elevated risk for autoimmune disorders in Iraq and Afghanistan Veterans with posttraumatic stress disorder. O'Donovan A, Cohen BE, Seal KH, Bertenthal D, Margaretten M, Nishimi K, Neylan TC. Trauma exposure and PTSD may increase the risk of autoimmune disorders such as rheumatoid arthritis. Biol Psychiatry, 2015 Feb 15;77(4):365-74.

Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C. difficile infection: a randomized clinical trial. Gerding DN, Meyer T, Lee C, Cohen SH, Murthy UK, Poirier A, Van Schooneveld TC, Pardi DS, Ramos A, Barron MA, Chen H, Villano S. Nontoxigenic C. difficile strain M3 is safe and well-tolerated in patients with C. difficile infections, and can reduce recurrences of the infection. JAMA. 2015 May 5;313(17):1719-27.

Fecal microbiota transplantation for Clostridium difficile infection: a systematic review. Drekonja D, Reich J, Gezahegn S, Greer N, Shaukat A, MacDonald R, Rutks I, Wilt TJ. Fecal microbiota transplantation may have a substantial effect with few short-term adverse events for recurrent C. difficile infection. Ann Intern Med. 2015 May 5;162(9):630-8.

Rates and correlates of potentially inappropriate colorectal cancer screening in the Veterans Health Administration. Powell AA, Saini SD, Breitenstein MK Noorbaloochi S, Cutting A, Fisher DA, Bloomfield HE, Halek K, Partin MR. A substantial number of VHA colorectal cancer screening tests, especially fecal occult blood tests, are potentially inappropriate. J Gen Intern Med. 2015 Jun:30(6):732-41.

Oral administration of pH-sensitive curcumin-loaded microparticles for ulcerative colitis therapy. Xiao B, Zhang M, Merlin D. One step fabricated curcumin-loaded microparticles may hold promise as a readily scalable drug carrier for the efficient clinical treatment of ulcerative colitis. Colloids Surf B Biointerfaces, 2015 Aug 1:135:379-385.

Longer withdrawal time is associated with a reduced incidence of interval cancer after screening colonoscopy. Shaukat A, Rector TS, Church TR, Lederle FA, Kim AS, Rank JM, Allen JI. Shorter mean annual withdrawal times during screening colonoscopies were independently associated with lower adenoma detection rates and increased risk of interval colorectal cancer. Gastroenterology, 2015 Oct: 149(4):952-7.

Underuse and Overuse of Colonoscopy for Repeat Screening and Surveillance in the Veterans Health Administration. Murphy CC, Sandler RS, Grubber JM, Johnson MR, Fisher DA. In an analysis of VHA patients, more than one-fourth of patients with low-risk benign tumors received follow-up colonoscopies too early, and more than half of those with high-risk tumors did not undergo surveillance colonoscopies as recommended. Clin Gastroenterol Hepatol, 2015 Oct 19. Pii: S1542-3585(15)01404-4.

Analysis of morbidity and mortality outcomes in postoperative Clostridium difficile infection in the Veterans Health Administration. Li X, Wilson M, Nylander W, Smith T, Lynn M, Gunnar W. The number and class of antibiotics administered after surgery, preoperative length of stay, procedural characteristics, surgical program complexity, and patient comorbidities are associated with postoperative C. difficile infections in the VHA. JAMA Surg. 2015 Nov 25:1-9.

Veterans Affairs Office of Research and Development: Research Programs and Emerging Opportunities in Digestive Diseases Research. O'Leary TJ, Dominitz JA, Chang KM. This commentary highlights the impact of VA research on the understanding and treatment of digestive disease, provides insight into a few of the ongoing research efforts in digestive diseases, and considers emerging research opportunities. Gastroenterology. 2015 Dec: 149(7):1652-61.

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Gastrointestinal Health Fact Sheet


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