Low-dose aspirin-induced gastrointestinal diseases: past,present, and future

Meta-analyses of randomized, placebo-controlled trials of low-dose aspirin indicate that aspirin approximately doubles the risk of major GI bleeding compared with placebo. The risk in Japanese may possibly be higher compared to Western populations, although the evidence is still lacking and prospective studies are required. Prior GI events, older age, and use of other injurious medicines such as NSAIDs, anticoagulants, and corticosteroids seem to be factors associated with an increased risk for upper GI bleeding among aspirin users. Prospective studies are needed to identify specific risk factors for upper GI bleeding in Japanese patients taking low-dose aspirin. There are many potential gastroprotective drugs available in Japan, and studies are needed to assess the relative effectiveness of various strategies including PPI use for the prevention of aspirin-related upper GI ulcer complications and whether any of these other agents also provide protection against small bowel or colonic damage. Aspirin-induced enteropathy is now increasingly being recognized and is presumably not uncommon, and the availability of new imaging techniques for the small intestine and noninvasive tests such as fecal calprotectin should allow rapid progress in this important area.     

Circumscribed intestinal protein loss with deficiency in CD4+ lymphocytes after the Fontan procedure

Protein-losing enteropathy is an important complication after right heart bypass operations (Fontan procedure). Laboratory examinations usually reveal hypoalbuminaemia, hypoproteinaemia, elevated α₁-antitrypsin clearance, and lymphocytopenia. A case of protein-losing enteropathy after Fontan procedure is reported with a circumscribed protein loss in the region of the terminal ileum despite good haemodynamics. The patient developed only mild hypoalbuminaemia and no diarrhoea but severe cellular and humoral immune abnormalities, namely a markedly decreased proportion of CD4+ lymphocytes but normal proportion of CD8+ lymphocytes (CD4+ 14%, CD8+ 23%) and decreased serum levels of immunoglobulin G. Intestinal biopsies revealed normal mucosa. This report is unique as it is the first to describe a ratio of CD4+ to CD8+ lymphocytes <1 due to an almost selective loss of CD4+ lymphocytes and a circumscribed intestinal protein loss in a patient who developed protein-losing enteropathy after Fontan operation. Conclusion There is a severe decrease of CD4+ lymphocytes of unknown origin in a patient with circumscribed intestinal protein loss after Fontan operation. Passive leakage of lymph fluid due to abnormal systemic venous pressure is not a sufficient explanation of the almost selective loss of CD4+ lymphocytes. Primary or secondary activation of the immune system may influence structural integrity and permeability of the intestinal wall and may play a triggering role in protein-losing enteropathy after the Fontan procedure. Received: 8 September 1998 / Accepted: 20 March 1999     

A new Amplatzer device to maintain patency of Fontan fenestrations and atrial septal defects.

This study evaluated use of Amplatzer fenestrated device to maintain patency of the Fontan fenestration and atrial septal defect. Fenestrations are routinely created in patients with lateral tunnel or extracardiac Fontan. Spontaneous closure of the fenestration can lead to Fontan circulation failure. Other patients without single-ventricle physiology may benefit from a small communication between the left and right atria for decompression if closure of the atrial septal defect leads to failure of a dysfunctional ventricle. Amplatzer septal occluder device was modified to create a fenestration through the disks. Three patients with modified Fontan and one patient with a large atrial septal defect underwent placement of the device by transcatheter technique. The device deployment was guided by transesophageal echocardiography. The procedure was successful in all patients. Contrast injection after placement revealed patent fenestration with free flow. Follow-up ranged from 3 months to 1 year. All devices were patent by transthoracic echocardiography. These preliminary results suggest that the Amplatzer fenestrated device can serve as a valuable tool in failing Fontan circulation and may help to avoid surgical intervention. More studies are needed to assess long-term efficacy of the device.     

Does the low FODMAP diet improve symptoms of radiation-induced enteropathy? A pilot study

Rationale: Patients with radiation-induced enteropathy (RE) after cancer treatment show similar symptoms as patients with irritable bowel syndrome (IBS). The low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet (LFD) is a widespread management strategy for IBS. We aimed to investigate if there may be a positive effect of LFD on symptoms and health-related quality of life (HRQOL) in patients with RE.

Methods: In an open non-controlled pilot study, 11 patients (all female) with RE-related IBS symptoms were recruited largely based on own initiative. All followed LFD for four weeks. IBS Severity Scoring System (IBS-SSS) and IBS Symptom Questionnaire (IBS-SQ) were used to assess symptoms. Short Form Nepean Dyspepsia Index (SF-NDI) and 12-item Short Form Health Survey (SF-12) evaluated HRQOL. A three day food record was used to estimate baseline intake of FODMAPs and to reveal dietary changes.

Results: FODMAP intake was successfully reduced, although LFD was found a burdensome intervention. IBS symptoms improved significantly based on mean total score of IBS-SSS and IBS-SQ, which changed from 310.2?±?60.7 to 171.4?±?107.2 (p?=?.001) and 27.4?±?4.1 to 15.7?±?10.1 (p?=?.002). HRQOL improved based on SF-NDI total score (30.5?±?9.4 to 18.3?±?8.2, p?=?.001) and based on mental (p?=?.047) and physical (p?=?.134) score of SF-12. Main additional dietary changes were reduced intake of energy, carbohydrates, and fiber.

Conclusion: Our findings from this small-scaled pilot study indicate that the LFD may alleviate symptoms and improve HRQOL in patients with RE. Further controlled studies with larger sample size should be conducted to verify our results and hopefully enable implementation of LFD as a future part of the management strategy for RE.     

Moving to tolerance: clinical application of T regulatory cells

Decreasing the incidence of chronic rejection and reducing the need for life-long immunosuppression remain important goals in clinical transplantation. In this article, we will review how regulatory T cells (Treg) came to be recognized as an attractive way to prevent or treat allograft rejection, the ways in which Treg can be manipulated or expanded in vivo, and the potential of in vitro expanded/generated Treg for cellular therapy. We will describe the first regulatory T cell therapies that have been or are in the process of being conducted in the clinic as well as the safety concerns of such therapies and how outcomes may be measured.     

Lawsonia intracellularis and Virulent Rhodococcus equi Infection in a Thoroughbred Colt

A 26-month-old thoroughbred colt with a 4-month history of continuous diarrhoea and weight loss was subject to necropsy examination. The small intestinal mucosa was thickened and this change particularly affected the terminal ileum. Microscopical examination revealed multifocal epithelial hyperplasia, with multifocal granulomas and marked lymphocytic infiltration of the lamina propria. Numerous gram-negative argyrophilic curved bacilli were observed within the cytoplasm of affected enterocytes. Macrophages and epithelioid cells forming the granulomas had abundant, lightly eosinophilic, foamy cytoplasm, with occasional large, clear vacuoles containing gram-positive coccobacilli. Immunohistochemical studies suggested that the argyrophilic bacilli were Lawsonia intracellularis and the gram-positive coccobacilli were Rhodococcus equi. L. intracellularis-specific DNA fragments were amplified from the affected ileocaecal mucosa by polymerase chain reaction. Virulent R. equi (VapA positive) was isolated in pure culture from the liver and mesenteric lymph nodes. These results suggested that the two intracytoplasmic organisms had induced multifocal proliferative and granulomatous enteritis accompanied by severe and extensive lymphocytic infiltration.     

Octreotide in Hennekam syndrome-associated intestinal lymphangiectasia

A number of disorders have been described to cause protein losing enteropathy (PLE) in children. Primary intestinal lymphangiectasia (PIL) is one mechanism leading to PLE. Few syndromes are associated with PIL; Hennekam syndrome (HS) is one of them. The principal treatment for PIL is a high protein, low fat diet with medium chain triglycerides supplementation. Supportive therapy includes albumin infusion. Few publications have supported the use of octreotide to diminish protein loss and minimize hypoalbuminemia seen in PIL. There are no publications on the treatment of PIL with octreotide in patients with HS. We report two children with HS and PLE in which we used octreotide to decrease intestinal protein loss. In one patient, octreotide increased serum albumin to an acceptable level without further need for albumin infusions. The other patient responded more dramatically with near normal serum albumin levels and cessation of albumin infusions. In achieving a good response to octreotide in both patients, we add to the publications supporting the use of octreotide in PIL and suggest that octreotide should be tried in patients with PIL secondary to HS. To the best of our knowledge, this is the first case report on the use of octreotide in HS-associated PIL.