Chronic Gastrointestinal Research Articles

Looking Beyond Gastrointestinal Bleed to Diagnose Hereditary Hemorrhagic Telangiectasia (HHT)

A 60 year old male presented to our Gastroenterology clinic to establish care for history of recurrent upper gastrointestinal (GI) bleed over the past 12 years. The initial episode manifested as fatigue due to anemia. Evaluation with upper endoscopy had revealed several bleeding gastric Arteriovenous Malformations (AVMs) which were successfully cauterized. He had required repeated endoscopic therapy of the bleeding gastric AVMs every 18 to 24 months. Upon additional questioning, he reported repeated self-limiting epistaxis since the age of 3 years. A thorough physical exam revealed large telangiectases on his tongue, with multiple smaller ones on the inner margin of his lips and on the periungual fingertips. Laboratory testing revealed anemia and normal liver chemistries. He met clinical criteria (Curaçao criteria) for diagnosis of ‘definite’ HHT, which is diagnosed when at least 3 of the 4 clinical criteria (telangiectasias, epistaxis, visceral AVMs or family history of HHT) are present. Despite multiple previous endoscopic procedures and clinic visits, this was the first time he had been told he might have a genetic syndrome causing his illness. He was scheduled for deep enteroscopy which revealed AVMs in small intestine which were cauterized. Otolaryngology evaluation revealed telangiectases on nasal septal mucosa. He was offered genetic testing and also scheduled for screening with a brain MRA and Transthoracic contrast echocardiogram (TTCE).Figure 1Figure 2Figure 3HHT, also known as Osler-Weber Rendu disease, is an uncommon autosomal dominant disease caused by abnormal blood vessel development. HHT is a clinical diagnosis or can also be diagnosed by genetic testing. Chronic GI bleed is managed by iron supplementation, endoscopic therapy (argon plasma coagulation is preferred) and systemic hormonal or antifibrinolytic therapy in selected patients. Screening with brain MRA for Cerebrovascular malformations (CVMs) and TTCE for Pulmonary AVMs (PAVMs) is recommended. PAVMs can present as paradoxical embolization and CVMs may manifest as headaches, seizures or bleeding. Patients with documented PAVMs and those not yet screened must get antibiotic prophylaxis for dental procedures and avoid SCUBA diving. This case exemplifies Sir William Osler's best known saying, “Listen to your patient, he (she) is telling you the diagnosis”. HHT is underdiagnosed and a thorough history and exam will lead to timely diagnosis and prevention of complications.

Giardia lamblia infection increases risk of chronic gastrointestinal disorders.

Background Giardia lamblia is a common parasitic cause of infectious gastroenteritis in the United States and the world and may be linked to an increased risk of chronic gastrointestinal (GI) disorders. We sought to assess the risk of several chronic GI disorders following Giardia infection among active duty US military personnel.MethodsThis study was designed as a retrospective cohort study in which active duty military personnel with documented G. lamblia infection were assessed for the subsequent risk of developing a chronic GI disorder including irritable bowel syndrome (IBS), dyspepsia and gastroesophageal reflux disease (GERD). Post-giardia chronic GI disorder risk was compared to risk in uninfected personnel matched on several demographic characteristics and medical encounter information. Data were obtained from the Defense Medical Surveillance System and exposures (1998–2009) with outcomes identified based on documented medical encounters with specific medical billing codes. Modified Poisson regression was used to evaluate the relationship between G. lamblia infection and chronic GI disorders.ResultsA total of 80 Giardia cases were identified for an estimated incidence of 0.55 cases per 100,000 person-years. Cases were matched to 294 unexposed subjects. After adjusting for important covariates, there was an increased risk of IBS (relative risk: 2.1, p = 0.03) associated with antecedent Giardia infection.ConclusionThese data add to a growing body of literature and demonstrate an increased risk of IBS after infection with G. lamblia.

Mechanisms Involved in the Development of the Chronic Gastrointestinal Syndrome in Nonhuman Primates after Total-Body Irradiation with Bone Marrow Shielding.

In this study, nonhuman primates (NHPs) exposed to lethal doses of total body irradiation (TBI) within the gastrointestinal (GI) acute radiation syndrome range, sparing ∼5% of bone marrow (TBI-BM5), were used to evaluate the mechanisms involved in development of the chronic GI syndrome. TBI increased mucosal permeability in the jejunum (12-14 Gy) and proximal colon (13-14 Gy). TBI-BM5 also impaired mucosal barrier function at doses ranging from 10-12.5 Gy in both small intestine and colon. Timed necropsies of NHPs at 6-180 days after 10 Gy TBI-BM5 showed that changes in small intestine preceded those in the colon. Chronic GI syndrome in NHPs is characterized by continued weight loss and intermittent GI syndrome symptoms. There was a long-lasting decrease in jejunal glucose absorption coincident with reduced expression of the sodium-linked glucose transporter. The small intestine and colon showed a modest upregulation of several different pro-inflammatory mediators such as NOS-2. The persistent inflammation in the post-TBI-BM5 period was associated with a long-lasting impairment of mucosal restitution and a reduced expression of intestinal and serum levels of alkaline phosphatase (ALP). Mucosal healing in the postirradiation period is dependent on sparing of stem cell crypts and maturation of crypt cells into appropriate phenotypes. At 30 days after 10 Gy TBI-BM5, there was a significant downregulation in the gene and protein expression of the stem cell marker Lgr5 but no change in the gene expression of enterocyte or enteroendocrine lineage markers. These data indicate that even a threshold dose of 10 Gy TBI-BM5 induces a persistent impairment of both mucosal barrier function and restitution in the GI tract and that ALP may serve as a biomarker for these events. These findings have important therapeutic implications for the design of medical countermeasures.

Interleukin-8 in gastrointestinal inflammation and malignancy: induction and clinical consequences

Interleukin-8 in gastrointestinal inflammation and malignancy: induction and clinical consequences James A Cotton,1 Jaye M Platnich,1 Daniel A Muruve,1 Humberto B Jijon,1 Andre G Buret,2 Paul L Beck,1 1Department of Medicine, 2Department of Biological Sciences, University of Calgary, Calgary, AB, Canada Abstract: Owing to its immense surface area, the mucosal surface of the gastrointestinal (GI) tract is continually subject to numerous endogenous and exogenous antigens capable of inducing an inflammatory response in the appropriate setting. In certain individuals, these inflammatory responses may also become dysregulated and result in the development of chronic GI inflammation, such as inflammatory bowel disease. Furthermore, gastric and colonic malignant processes are extremely common and, to date, still have high mortality rates. As a result, continuing research has focused on elucidating potential molecular mechanisms involved in these processes in an attempt to understand the pathophysiology of these diseases and, potentially, aid in the development of novel therapeutics. Interleukin-8 (CXCL8) is a small molecular weight chemokine identified almost 30 years ago. Ongoing research has demonstrated that this factor contributes to a multitude of pathophysiological processes within the GI tract, including chronic GI inflammatory states, such as inflammatory bowel disease, and gastric and colonic carcinomas. This review highlights the role of CXCL8 in GI inflammation and malignancy. It describes molecular mechanisms involved in promoting and restraining CXCL8 production in GI cells and how CXCL8 contributes to the pathophysiology of a variety of GI inflammatory processes. Finally, this review describes a variety of mechanisms by which CXCL8–CXCL1/2 signaling may contribute to GI malignancy. Keywords: CXCL8, inflammatory bowel disease, IBD, colon cancer, IL-8, Crohn’s disease, ulcerative colitis

Predictors of radiation-induced gastrointestinal morbidity: A prospective, longitudinal study following radiotherapy for carcinoma of the prostate

Background Chronic gastrointestinal (GI) morbidity occurs in ≥50% of patients after external beam radiotherapy (EBRT) for carcinoma of prostate (CaP). This prospective, longitudinal study examines which baseline measurements of: 1) homocysteine and micronutrients in plasma; 2) chromosome damage/misrepair biomarkers; and 3) anal and rectal dose volume metrics predict GI morbidity after EBRT.Patients and methods In total, 106 patients with CaP had evaluations of GI symptoms (modified LENT-SOMA questionnaires) before EBRT and at one month, one, two and three years after its completion. Other variables measured before EBRT were: 1) plasma concentrations of homocysteine and micronutrients including caroteinoids and selenium; 2) chromosome damage/DNA misrepair (micronuclei/nucleoplasmic bridge) indices; and 3) mean anal and rectal wall doses and volumes of anal and rectal walls receiving ≥40 Gy and ≥60 Gy. Univariate and multivariate analyzes examined the relationships among: 1) plasma levels of homocysteine and micronutrients; 2) indices of chromosome damage/DNA misrepair; and 3) mean anal and rectal wall doses and volumes of anal and rectal walls receiving ≥40 Gy and ≥60 Gy and total GI symptom scores from one month to three years after EBRT.Results Increased frequency and urgency of defecation, rectal mucous discharge and bleeding after EBRT resulted in sustained rises in total GI symptom scores above baseline at three years. On univariate analysis, total GI symptom scores were significantly associated with: 1) plasma selenium and α tocopherol; 2) micronuclei indices of DNA damage; 3) mean anal and rectal wall doses; and 4) volumes of anal and rectal wall receiving ≥40 Gy and ≥60 Gy (p = 0.08–<0.001). On multivariate analysis, only volume of anal wall receiving ≥40 Gy was significant for increased GI symptoms after EBRT (p < 0.001).Conclusion The volume of anal wall receiving ≥40 Gy predicts chronic GI morbidity after EBRT for CaP.

Tracking gastrointestinal transit of solids in aged rats as pharmacological models of chronic dysmotility.

Dysmotility in the gastrointestinal (GI) tract often leads to impaired transit of luminal contents leading to symptoms of diarrhea or constipation. The aim of this research was to develop a technique using high resolution X-ray imaging to study pharmacologically induced aged rat models of chronic GI dysmotility that mimic accelerated transit (diarrhea) or constipation. The 5-hydroxytryptamine type 4 (5-HT4 ) receptor agonist prucalopride was used to accelerate transit, and the opioid agonist loperamide was used to delay transit. Male rats (18 months) were given 0, 1, 2, or 4 mg/kg/day prucalopride or loperamide (in dimethyl sulfoxide, DMSO) for 7 days by continuous 7-day dosing. To determine the GI region-specific effect, transit of six metallic beads was tracked over 12 h using high resolution X-ray imaging. An established rating scale was used to classify GI bead location in vivo and the distance beads had propagated from the caecum was confirmed postmortem. Loperamide (1 mg/kg) slowed stomach emptying and GI transit at 9 and 12 h. Prucalopride (4 mg/kg) did not significantly alter GI transit scores, but at a dose of 4 mg/kg beads had moved significantly more distal than the caecum in 12 h compared to controls. We report a novel high-resolution, non-invasive, X-ray imaging technique that provides new insights into GI transit rates in live rats. The results demonstrate that loperamide slowed overall transit in aged rats, while prucalopride increased stomach emptying and accelerates colonic transit.

Mast cells in gastrointestinal disorders

Mast cells are constitutively found in the gastrointestinal (GI) tract. The three major physiological functions of GI mast cells comprise of – as far as we know – regulation of GI functions, namely epithelial and endothelial functions, crosstalk with the enteric nervous system, and contribution to the host defense against bacterial, viral and parasitic agents. A number of chronic GI diseases, including inflammatory bowel disease (Crohn's disease, ulcerative colitis), celiac disease, irritable bowel syndrome, and food allergies, are thought to be associated with mast cell hyperplasia and humoral activity. Clinical conditions characterized by a decrease in mast cell functionality are not known so far. In the present review, we summarize current evidence which show that human mast cells play a central role at the GI barrier, both in health and disease.

Epidemiology of Uninvestigated Dyspepsia and Functional Dyspepsia in Asia

Functional dyspepsia (FD) is a group of gastrointestinal (GI) disorders that includes variable combinations of chronic or recurrent upper GI symptoms not explained by structural or biochemical abnormalities. FD accounts for a significant percentage of patients seen in primary care with abdominal symptoms. Although the criteria used to define FD can easily affect the prevalence in the general population, the prevalence of uninvestigated dyspepsia and FD diagnosed by the Rome III criteria is 5.3% to 20.4%, predominantly affecting females. The prevalence differs among geographical regions and races. Gene polymorphisms and early life events are also involved in the development of FD. The symptoms often alleviate and re‐appear in the course of these entities. This information may introduce physicians to the detailed background of these patients and strategies for treatment.

Ehlers Danlos syndrome and gastrointestinal manifestations: a 20-year experience at Mayo Clinic.

Gastrointestinal (GI) manifestations are found in Ehlers Danlos syndrome (EDS) hypermobility subtype (HM). We aimed to assess associations between EDS HM and other EDS subtypes with GI manifestations. We reviewed medical records of EDS patients evaluated at Mayo Clinic's Medical Genetics Clinic 1994-2013. We extracted information regarding EDS subtypes, GI manifestations, and treatments. We identified 687 patients; 378 (56%) had associated GI manifestations (female 86.8%, diagnosis mean age 29.6 years). Of the patients identified, 58.9% (43/73) had EDS classic, 57.5% (271/471) EDS HM, 47.3% (27/57) EDS vascular subtypes. In addition, 86 patients had EDS that could not be classified in any of those three subtypes. Commonest GI symptoms were: abdominal pain (56.1%), nausea (42.3%), constipation (38.6%), heartburn (37.6%), and irritable bowel syndrome-like symptoms (27.5%). Many GI symptoms were commoner in EDS HM than the other subtypes together. Among 37.8% of the 378 patients who underwent esophagogastroduodenoscopy, the commonest abnormalities were gastritis, hiatal hernia and reflux esophagitis. Abnormal gastric emptying was observed in 22.3% (17/76): 11.8% delayed and 10.5% accelerated. Colonic transit was abnormal in 28.3% (13/46): 19.6% delayed and 8.7% accelerated. Rectal evacuation disorder was confirmed in 18/30 patients who underwent anorectal manometry. Angiography showed aneurysms in abdominal vessels in EDS vascular type. Proton pump inhibitors (38%) and drugs for constipation (23%) were the most commonly used medications. A minority underwent colectomy (2.9%) or small bowel surgery (4%). EDS HM and other subtypes should be considered in patients with chronic functional GI symptoms and abdominal vascular lesions.

Intensity-modulated radiation therapy versus three-dimensional conformal radiation therapy with concurrent nedaplatin-based chemotherapy after radical hysterectomy for uterine cervical cancer: comparison of outcomes, complications, and dose-volume histogram parameters.

BackgroundThe purpose of this study is to report our clinical outcomes using intensity-modulated radiation therapy (IMRT) for adjuvant treatment of cervical cancer, compared with three-dimensional conformal radiation therapy (3DCRT), in terms of tumor control, complications and dose-volume histogram (DVH) parameters.MethodsBetween March 2008 and February 2014, 62 patients were treated with concurrent nedaplatin-based chemotherapy and whole-pelvic external beam radiation therapy (RT). Of these patients, 32 (52 %) received 3DCRT and 30 (48 %) received IMRT.ResultsThe median follow-up periods were 40 months (range 2–74 months). The 3-year overall survival rate (OS), locoregional control rate (LRC) and progression-free survival rate (PFS) were 92, 95 and 92 % in the IMRT group, and 85, 82 and 70 % in the 3DCRT group, respectively. A comparison of OS, LRC and PFS showed no significant differences between IMRT and 3DCRT. The 3-year cumulative incidences of grade 2 or higher chronic gastrointestinal (GI) complications were significantly lower with IMRT compared to 3DCRT (3 % vs. 45 %, p < .02) and in patients with V40 of the small bowel loops of ≤340 mL compared to those with >340 mL (3 % vs. 45 %, p < .001). Patients treated with IMRT had a higher incidence of grade 3 acute hematologic complications (p < .05). V40 and V45 of the small bowel loops or bowel bag were predictive for development of both acute and chronic GI complications.ConclusionsOur results suggest that IMRT for adjuvant treatment of cervical cancer is useful for decreasing GI complications without worsening outcomes.

Infectious Gastroenteritis as a Risk Factor for Tropical Sprue and Malabsorption: A Case–Control Study

Previous studies have linked an increase in functional and pathological gastrointestinal (GI) disorders following antecedent infectious gastroenteritis (IGE), yet studies of other chronic GI disorders such as tropical sprue (TS) and intestinal malabsorption (IM) are lacking. This study was performed to evaluate the association between documented IGE and the risk of TS and IM using a matched case-control study. The odds of IGE (exposure) among subjects with TS and IM were compared to the odds of exposure in matched controls. Data were obtained from the Defense Medical Surveillance System. Incidence was estimated based on the number of active duty military personnel, and conditional logistic regression models were used to evaluate the relationship between IGE and TS/IM while adjusting for potential confounders. The overall incidence of TS and IM was 0.24 and 1.98 per 100,000 person-years, respectively. After adjusting for important covariates, prior IGE was associated with an increase in the odds of TS (odds ratio (OR) 36.64) and IM (OR 3.93) (p < 0.001). Other covariates demonstrating an increased risk were being of Caucasian race, having greater than high school education, and service in military branches other than the Army. Overall, this study demonstrates the first significant estimates that a case of antecedent IGE is associated with an increased risk of TS and IM in an active duty military population. Ultimately, acquisition of TS or IM has the potential to decrease operational efficiency, which may have a significant impact on deployed military missions.

PTH-058 Long-term prognosis of patients presenting with gastrointestinal symptoms and abnormal calprotectin diagnosed with non-organic disease

<h3>Introduction</h3> Faecal calprotectin (fcal) is a non-invasive marker of intestinal inflammation that can assist physicians in investigating chronic gastrointestinal (GI) symptoms. Different cut-off values have been proposed, depending on the pre-test probability for organic disease, in order to improve diagnostic accuracy and to make the test more cost-effective. To support the use of a higher cut-off in clinical practice, we present data from a cohort of patients having been fully investigated for fcal levels above the lab reference cut-off. <h3>Method</h3> Retrospective observational study. <h3>Results</h3> We identified the patients who were referred to the Gastroenterology department at King’s College Hospital, London, UK between January 2002 and 2004 with chronic gastrointestinal symptoms and had a fcal test. During this period 367 patients were tested. Two hundred (200/367, 55%) were given a diagnosis of non-organic disease and were discharged to their primary care physician. Sixty one (61/200, 31%) with a median age of 48 years (range 21, 85) and 2:1 female: male ratio tested positive for fcal (&gt;60 μg/g, ELISA kit, Bühlmann). Thirty five (35/61, 57%) had presented initially with altered bowel habit, 15 (25%) with abdominal pain, 7 (12%) with bloating and 4 (6%) with diarrhoea. The median fcal was 113 μg/g (range 60, 850, &gt;150 μg/g in 18 [30%] patients). All had a normal ileocolonoscopy. The median follow up time from initial presentation to the initiation of this study was 10 years (range 9, 11). In this period 3 patients (3/61, 5%) were diagnosed with an organic condition. Two were diagnosed with Crohn’s disease (1 with terminal ileal [TI] and 1 with isolated perianal disease) after 7 years of their initial presentation and 1 with collagenous colitis after 5 years. The repeat fcal for the patient with TI disease increased from 80 μg/g to 1130 μg/g prior to diagnosis. The other two had normal fcal when retested. Four patients were found, in retrospect, to take NSAIDs regularly, three had a diagnosis of cystic fibrosis, two with liver cirrhosis and one had a diagnosis of HIV at the time of referral. None of the patients with a negative calprotectin developed organic disease during their follow-up. <h3>Conclusion</h3> In patients presenting with chronic GI symptoms, fcal in the range 60–150 μg/g is associated with a very low incidence of organic or significant pathology. Subsequent routine investigation of these patients after normal colonoscopy (other than perhaps repeating fcal to demonstrate a trend over time) is not recommended. <h3>Disclosure of interest</h3> None Declared.

Aging and the human gut microbiota-from correlation to causality.

The human gastrointestinal (GI) tract harbors the largest number and concentration of microbes found in the human body. Perturbations in the gut microbial ecosystem have also been associated with conditions as diverse as chronic GI diseases (e.g., Crohn's disease, ulcerative colitis), metabolic disorders (e.g., diabetes types 1 and 2, obesity) and antibiotic use (for a review see Sekirov et al., 2010). Metagenomic culture-independent methods have enabled the unraveling of the complexity of the gut microbiota (Rajilic-Stojanovic et al., 2009). Given the considerable inter-individual diversity in the actual composition of the microbiota, significant collaborative attempts have been made to systematize the available knowledge (Arumugam et al., 2011; Human Microbiome Project Consortium, 2012) and identify “core” microbiota that are conserved among humans to facilitate meaningful comparisons (Huse et al., 2012). Changes in the microbial composition also take place with age, with a high degree of variability at the two extremes of infancy and old age, punctuated by comparative stability during adulthood (for reviews, see Woodmansey, 2007; O'Toole and Claesson, 2010). Given that increases in life expectancy will likely result in an increase in the elderly population worldwide, analysis of the contribution of the microbiota to healthy aging assumes greater significance (for a recent review, see Tiihonen et al., 2010). Age-related spatio-temporal variations in the microbiota are best viewed within an ecological- evolutionary framework (see review by Costello et al., 2012). Diet is a major, controllable environmental factor influencing the composition of the host microbiome, with the high-fat, sugar-rich Western diet contributing to a Bacteroides-dominant microbiome and high-fiber diet to one dominated by Firmicutes with a strong correlation between long-term diet and enterotypes (Wu et al., 2011). In terms of ecological succession, the Bifidobacterium-dominated microbiota of the infant changes over time into the Bacteroidetes- and Firmicutes-dominated microbiota of the adult (Ottman et al., 2012), remaining fairly stable through adulthood in the absence of perturbations like long-term dietary changes or repeated antibiotic intervention. Pathogens may then be viewed as invasive species in the ecological sense, constantly testing the resilience of the native ecosystem, resulting in their elimination, low-level persistence (enabling future opportunism), or establishment causing disease.

Chronic inflammation and gastrointestinal cancer

Chronic inflammation has been identified as an important risk factor in the development of the gastrointestinal (GI) tract cancers, and the underlying molecular mechanisms have been studied extensively. Chronic inflammation is able to trigger cellular events to promote malignant transformation of normal epithelial cells in the GI tract to cancer. Host inflammation responses in carcinogenesis are through multiple mechanisms such as reactive oxygen and nitration species from mononuclear phagocytes and leukocytes, immune response and pro-inflammatory cytokines. Nuclear factor-κB (NF-κB) has been considered as the central mediator of the immune response. Activation of NF-κB by phosphorylation leads to translocation of NF-κB protein to the nucleus, and in turn regulates the transcription of several pro-inflammatory cytokines and chemokines. Furthermore, chronic inflammation creates an environment for genomic and epigenetic changes. In this review, we summarize the important molecular mechanisms that link chronic inflammation and GI tract cancer, including esophageal, gastric and colonic cancers, focusing on infective and noninfective agents such as gastroesophageal reflux disease, Helicobacter pylori gastritis and inflammatory bowel disease.

P-114 YI Long-Term Prognosis of Patients Presenting with Gastrointestinal Symptoms and Abnormal Calprotectin Diagnosed with Non-Organic Disease

Introduction Faecal calprotectin (fcal) is a non-invasive marker of intestinal inflammation that can assist physicians in investigating chronic gastrointestinal (GI) symptoms. Different cut-off values have been proposed, depending on the pre-test probability for organic disease, in order to improve diagnostic accuracy and to make the test more cost-effective. To support the use of a higher cut-off in clinical practice, we present data from a cohort of patients having been fully investigated for fcal levels above the lab reference cut-off. Method Retrospective observational study. Results We identified the patients who were referred to the Gastroenterology department at King’s College Hospital, London, UK between January 2002 and 2004 with chronic gastrointestinal symptoms and had a fcal test. During this period 367 patients were tested. Two hundred (200/367, 55%) were given a diagnosis of non-organic disease and were discharged to their primary care physician. Sixty one (61/200, 31%) with a median age of 48 years (range 21, 85) and 2:1 female: male ratio tested positive for fcal (>60 μg/g, ELISA kit, Buhlmann). Thirty five (35/61, 57%) had presented initially with altered bowel habit, 15 (25%) with abdominal pain, 7 (12%) with bloating and 4 (6%) with diarrhoea. The median fcal was 113 μg/g (range 60, 850, >150 μg/g in 18 [30%] patients). All had a normal ileocolonoscopy. The median follow up time from initial presentation to the initiation of this study was 10 years (range 9, 11). In this period 3 patients (3/61, 5%) were diagnosed with an organic condition. Two were diagnosed with Crohn’s disease (1 with terminal ileal [TI] and 1 with isolated perianal disease) after 7 years of their initial presentation and 1 with collagenous colitis after 5 years. The repeat fcal for the patient with TI disease increased from 80 μg/g to 1130 μg/g prior to diagnosis. The other two had normal fcal when retested. Four patients were found, in retrospect, to take NSAIDs regularly, three had a diagnosis of cystic fibrosis, two with liver cirrhosis and one had a diagnosis of HIV at the time of referral. None of the patients with a negative calprotectin developed organic disease during their follow-up. Conclusion In patients presenting with chronic GI symptoms, fcal in the range 60–150 μg/g is associated with a very low incidence of organic or significant pathology. Subsequent routine investigation of these patients after normal colonoscopy (other than perhaps repeating fcal to demonstrate a trend over time) is not recommended. Disclosure of interest None Declared.

P-158 Understanding how GATA3 Expression by Tregs Prevents Pathogenic Tregs

Although the etiology of inflammatory bowel disease is still unclear, current evidence suggests that dysregulated immune responses contribute to the disease state. One common approach to current and future therapies is to target mucosal inflammation by interfering with immune pathways. Regulatory T cells (Treg) are known to play a critical role in maintaining homeostasis of the gastrointestinal (GI) tract. While Tregs are critical for maintenance of the GI tract, their dysregulation, either through reduction in number and or function, has been associated with immunopathology. Furthermore, there is mounting evidence that human Treg can aberrantly secrete pro-inflammatory cytokines in settings of autoimmunity. Thus, understanding the factors that stabilize Treg function and survival in highly inflamed settings remains an outstanding question of high clinical relevance. We previously demonstrated that the canonical Th2 transcription factor GATA3 plays an integral role in promoting Treg physiology during inflammation within the gastrointestinal tract, and specifically in regulating inflammation during colitis. GATA3 does this through the dual role of promoting Treg accumulation at the site of inflammation and limiting excessive plasticity of Treg, namely the expression of Th1 (Tbet and IFNg) and Th17 (RORgt and IL-17A) factors. Thus GATA3 plays a multifaceted role in controlling the fate of Treg within inflamed tissues by enhancing both their stability and function. The overall aim of this proposal is to assess the contribution of Treg acquisition of effector function to immunopathology during gastrointestinal inflammation and the mechanism by which GATA3 limits dysregulation of Treg during colitis. Our studies include infection-induced inflammation of the gastrointestinal tract and the CD45RB T cell transfer model of colitis. We now show that Tregs can contribute to disease in infection-induced inflammation. Mice with Tregs that can maintain GATA3 expression have reduced immunopathology. Further, our work reveals a potential role for GATA3 in promoting IL-10 production by Treg during chronic GI infection. Taken together our studies show that Treg dysregulation can cause immunopathology directly. Future studies will examine mechanistically how GATA3 prevents pathogenic Tregs.

Gastrointestinal pathology in transplant patients.

The assessment of gastrointestinal (GI) specimens from transplant patients is complicated by the wide range of potentially rare pathologies that may be found in this clinical setting. Acute GI graft-versus-host disease (GvHD) is characterized by epithelial cell apoptosis, although there is increasing recognition that acute and/or chronic inflammation may also be present. By contrast, thus far there are no histological features known to be specific to chronic GI GvHD. Mycophenolate mofetil colitis may mimic both GvHD and inflammatory bowel disease, whereas both cytomegalovirus (CMV) and adenovirus infections can cause gland apoptosis. Post-transplant lymphoproliferative disorder should be considered if a Crohn's-like histological picture is seen, and granulomas in biopsies from umbilical cord blood recipients should raise a suspicion of cord colitis syndrome. Finally, the GI tract may be involved directly or indirectly by the disease that originally required haematopoietic stem cell or liver transplantation.

The Implications of Nonlocality

Chronic upper gastrointestinal (GI) symptoms of unclear etiology are frustrating to patients and physicians alike. The integrative medicine procedures of acupuncture and neural therapy may provide treatment options. Tongue piercing, which is prevalent in 5.6% of the adolescent population, may be a contributing factor in upper gastrointestinal symptoms. The objectives of the study were as follows: (1) To demonstrate the usefulness of an integrative medicine treatment approach in two cases of patients with chronic abdominal pain, nausea, and vomiting of unclear etiology who had failed standard medical management. (2) To identify scars from tongue piercings as a possible contributing factor in chronic upper GI symptoms of unclear etiology. Two retrospective case studies are presented of young adult females who were seen in a private multi-physician integrative medicine practice in the US. The patients were treated with neural therapy and acupuncture. The desired outcome was the cessation or reduction of the frequency of abdominal pain, nausea, and vomiting. Both patients had resolution of their symptoms. From this study, we have concluded the following: (1) Tongue scars from tongue rings may be causes of chronic upper gastrointestinal symptoms. (2) Neural therapy and acupuncture may be helpful in the treatment of chronic upper GI symptoms related to tongue scars.

Anti-TNF-α treatment for post-anastomotic ulcers and inflammatory bowel disease with Crohn's-like pathologic changes following intestinal surgery in pediatric patients.

To report a previously poorly recognized process of secondary formation of inflammatory bowel disease (IBD)-like process, specifically Crohn's-like changes in pediatric surgery patients who underwent major small bowel and colorectal surgery. We describe potential etiologies, presenting symptoms and treatment approaches. Retrospective chart review of patients with history of either chronic, partial gastrointestinal (GI) obstruction or Hirschsprung disease (HD) and subsequent histopathologic findings similar to IBD. Pathology and case histories were reviewed and treatments were compared. Over the last 20 years, a total of nine patients were identified that had the diagnoses of either HD (n = 3) or chronic GI partial obstruction (n = 6) with subsequent development of histopathologic changes similar to those seen in IBD. Overall meantime to diagnosis of IBD-like changes after intestinal resection was 7.70 ± 5.6 years. Half of the patients were also being managed for short bowel syndrome (SBS), and associated GI symptoms may have prolonged the time to identifying these IBD-like changes. When SBS patients were excluded, mean time to IBD changes after pull through for HD was 2.4 ± 0.24 years and after chronic GI partial obstruction was 6.3 ± 2.1 years. Two of the nine patients who underwent a resection of this IBD-like lesion developed a recurrence of this lesion. Anti-TNF-α treatment was used in three of the GI partial obstruction cases: two with complete relief and one with partial response that was supplemented with steroids. Two HD patients were treated with anti-TNF-α and both had marked improvement of symptoms. We describe IBD-like intestinal changes following intestinal resection in the pediatric age group. We also present the novel finding that these lesions are responsive to anti-IBD treatment, including anti-TNF-α, and recommend it as part of the medical treatment regiment offered for such patients.

Tongue Piercing and Chronic Abdominal Pain with Nausea and Vomiting—Two Cases

Chronic upper gastrointestinal (GI) symptoms of unclear etiology are frustrating to patients and physicians alike. The integrative medicine procedures of acupuncture and neural therapy may provide treatment options. Tongue piercing, which is prevalent in 5.6% of the adolescent population, may be a contributing factor in upper gastrointestinal symptoms. The objectives of the study were as follows: (1) To demonstrate the usefulness of an integrative medicine treatment approach in two cases of patients with chronic abdominal pain, nausea, and vomiting of unclear etiology who had failed standard medical management. (2) To identify scars from tongue piercings as a possible contributing factor in chronic upper GI symptoms of unclear etiology. Two retrospective case studies are presented of young adult females who were seen in a private multi-physician integrative medicine practice in the US. The patients were treated with neural therapy and acupuncture. The desired outcome was the cessation or reduction of the frequency of abdominal pain, nausea, and vomiting. Both patients had resolution of their symptoms. From this study, we have concluded the following: (1) Tongue scars from tongue rings may be causes of chronic upper gastrointestinal symptoms. (2) Neural therapy and acupuncture may be helpful in the treatment of chronic upper GI symptoms related to tongue scars.