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Current Opinion in Pharmacology Dec 2014The gastrointestinal mucosa is exposed to numerous chemical substances and microorganisms, including macronutrients, micronutrients, bacteria, endogenous ions, and... (Review)
Review
The gastrointestinal mucosa is exposed to numerous chemical substances and microorganisms, including macronutrients, micronutrients, bacteria, endogenous ions, and proteins. The regulation of mucosal protection, digestion, absorption and motility is signaled in part by luminal solutes. Therefore, luminal chemosensing is an important mechanism enabling the mucosa to monitor luminal conditions, such as pH, ion concentrations, nutrient quantity, and microflora. The duodenal mucosa shares luminal nutrient receptors with lingual taste receptors in order to detect the five basic tastes, in addition to essential nutrients, and unwanted chemicals. The recent 'de-orphanization' of nutrient sensing G protein-coupled receptors provides an essential component of the mechanism by which the mucosa senses luminal nutrients. In this review, we will update the mechanisms of and underlying physiological and pathological roles in luminal nutrient sensing, with a main focus on the duodenal mucosa.
Topics: Amino Acids; Animals; Carbohydrate Metabolism; Duodenum; Food; Humans; Intestinal Mucosa; Lipid Metabolism; Peptides
PubMed: 25113991
DOI: 10.1016/j.coph.2014.07.010 -
Archives of Pathology & Laboratory... Jan 2018- Patients who receive an upper gastrointestinal endoscopic examination frequently have biopsies taken from the duodenum. Accurate interpretation of duodenal biopsies is... (Review)
Review
CONTEXT
- Patients who receive an upper gastrointestinal endoscopic examination frequently have biopsies taken from the duodenum. Accurate interpretation of duodenal biopsies is essential for patient care. Celiac disease is a common clinical concern, but pathologists need to be aware of other conditions of the duodenum that mimic celiac disease.
OBJECTIVE
- To review the normal histologic features of duodenal mucosa and describe the clinical and histologic findings in celiac disease and its mimics, listing the differentiating features of biopsies with villous atrophy and epithelial lymphocytosis.
DATA SOURCES
- The study comprises a literature review of pertinent publications as of November 30, 2016.
CONCLUSIONS
- Celiac disease is a common cause of abnormal duodenal histology. However, many of the histologic features found in the duodenal biopsy of patients with celiac disease are also present in other conditions that affect the small bowel. Diagnostic precision may be enhanced by obtaining a careful patient history and by ancillary laboratory testing, particularly for the presence of antitissue transglutaminase antibodies.
Topics: Angiotensin II Type 1 Receptor Blockers; Anti-Inflammatory Agents, Non-Steroidal; Biopsy; Blind Loop Syndrome; Celiac Disease; Duodenitis; Graft vs Host Disease; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Intestinal Mucosa; Milk Hypersensitivity; Polyendocrinopathies, Autoimmune; Soybean Proteins
PubMed: 28758791
DOI: 10.5858/arpa.2016-0608-RA -
Journal For Immunotherapy of Cancer Jun 2020Rare cases of immune checkpoint inhibitor (ICI)-associated celiac disease (ICI-CeD) have been reported, suggesting that disruption of tolerance mechanisms by ICIs can...
BACKGROUND
Rare cases of immune checkpoint inhibitor (ICI)-associated celiac disease (ICI-CeD) have been reported, suggesting that disruption of tolerance mechanisms by ICIs can unmask celiac disease (CeD). This study aims to characterize the clinicopathological and immunophenotypic features of ICI-CeD in comparison to ICI-associated duodenitis (ICI-Duo) and usual CeD.
METHODS
A medical and pathological records search between 2015 and 2019 identified eight cases of ICI-CeD, confirmed by tTG-IgA. Nine cases of ICI-Duo, 28 cases of moderate CeD, as well as 5 normal controls were used as comparison groups. Clinical information was collected from the electronic medical records. Immunohistochemistry for CD3, CD8, T-cell receptor gamma/delta (γδ), programmed death ligand 1 (PD-L1), and programmed death 1 (PD-1) were performed, with quantification of intraepithelial lymphocyte (IEL) subsets in three well-oriented villi. CD68, PD-L1, and PD-1 were assessed as a percentage of lamina propria surface area infiltrated by positive cells. Statistical significance was calculated by the Student's t-test and Fisher's exact test.
RESULTS
The eight patients with ICI-CeD (F:M=1:3) and nine patients with ICI-Duo (F:M=5:4) presented similarly with diarrhea (13/17) and abdominal pain (11/17) after a median of 1.6 months on ICI therapy. In patients with ICI-CeD, tTG-IgA ranged from 104 to >300 IU/mL. Histological findings in ICI-CeD and ICI-Duo were similar and included expansion of the lamina propria, active neutrophilic duodenitis, variably increased IELs, and villous blunting. Immunohistochemistry showed that the average number of IELs per 100 enterocytes is comparable between ICI-CeD and ICI-Duo, with increased CD3 CD8 T cells compared with normal duodenum but decreased γδ T cells compared with CeD. Average PD-L1 percentage was 9% in ICI-CeD and 18% in ICI-Duo, in comparison to <1% in CeD and normal duodenum; average PD-1 percentage was very low to absent in all cases (<3%). On follow-up, five patients with ICI-CeD improved on a gluten-free diet (GFD) as the sole therapeutic intervention (with down-trending tTG-IgA) while the other three required immunosuppression. All patients who developed ICI-Duo received immunosuppression with variable improvement in symptoms.
CONCLUSIONS
ICI-CeD resembles ICI-Duo clinically and histologically but shares the serological features and response to gluten withdrawal with classic CeD. Immunophenotyping of IELs in ICI-CeD and ICI-Duo also shows similar CD3, CD8, γδ T cell subsets, and PD-L1 populations, all of which differed quantitatively from usual CeD. We conclude that ICI-CeD is biologically similar to ICI-Duo and is likely a variant of ICI-Duo, but treatment strategies differ, with ICI-CeD often improving with GFD alone, whereas ICI-Duo requires systemic immunosuppression.
Topics: Abdominal Pain; Adult; Aged; Biopsy; Celiac Disease; Diagnosis, Differential; Diarrhea; Duodenitis; Female; Humans; Immune Checkpoint Inhibitors; Immune Tolerance; Intestinal Mucosa; Intestine, Small; Male; Microvilli; Middle Aged; Retrospective Studies
PubMed: 32581063
DOI: 10.1136/jitc-2020-000958 -
Current Opinion in Gastroenterology Nov 2017We report recently published knowledge regarding gut chemosensory mechanisms focusing on nutrient-sensing G protein-coupled receptors (GPCRs) expressed on gut... (Review)
Review
PURPOSE OF REVIEW
We report recently published knowledge regarding gut chemosensory mechanisms focusing on nutrient-sensing G protein-coupled receptors (GPCRs) expressed on gut enteroendocrine cells (EECs), tuft cells, and in afferent nerves in the gastroduodenal mucosa and submucosa.
RECENT FINDINGS
Gene profiling of EECs and tuft cells have revealed expression of a variety of nutrient-sensing GPCRs. The density of EEC and tuft cells is altered by luminal environmental changes that may occur following bypass surgery or in the presence of mucosal inflammation. Some EECs and tuft cells are directly linked to sensory nerves in the subepithelial space. Vagal afferent neurons that innervate the intestinal villi express nutrient receptors, contributing to the regulation of duodenal anion secretion in response to luminal nutrients. Nutrients are also absorbed via specific epithelial transporters.
SUMMARY
Gastric and duodenal epithelial cells are continually exposed to submolar concentrations of nutrients that activate GPCRs expressed on EECs, tuft cells, and submucosal afferent nerves and are also absorbed through specific transporters, regulating epithelial cell proliferation, gastrointestinal physiological function, and metabolism. The chemical coding and distribution of EECs and tuft cells are keys to the development of GPCR-targeted therapies.
Topics: Afferent Pathways; Bariatric Surgery; Chemoreceptor Cells; Duodenum; Enteroendocrine Cells; Gastric Mucosa; Humans; Intestinal Mucosa; Receptors, G-Protein-Coupled
PubMed: 28806271
DOI: 10.1097/MOG.0000000000000396 -
The New England Journal of Medicine Jul 2020Environmental enteric dysfunction (EED) is an enigmatic disorder of the small intestine that is postulated to play a role in childhood undernutrition, a pressing global...
BACKGROUND
Environmental enteric dysfunction (EED) is an enigmatic disorder of the small intestine that is postulated to play a role in childhood undernutrition, a pressing global health problem. Defining the incidence of this disorder, its pathophysiological features, and its contribution to impaired linear and ponderal growth has been hampered by the difficulty in directly sampling the small intestinal mucosa and microbial community (microbiota).
METHODS
In this study, among 110 young children (mean age, 18 months) with linear growth stunting who were living in an urban slum in Dhaka, Bangladesh, and had not benefited from a nutritional intervention, we performed endoscopy in 80 children who had biopsy-confirmed EED and available plasma and duodenal samples. We quantified the levels of 4077 plasma proteins and 2619 proteins in duodenal biopsy samples obtained from these children. The levels of bacterial strains in microbiota recovered from duodenal aspirate from each child were determined with the use of culture-independent methods. In addition, we obtained 21 plasma samples and 27 fecal samples from age-matched healthy children living in the same area. Young germ-free mice that had been fed a Bangladeshi diet were colonized with bacterial strains cultured from the duodenal aspirates.
RESULTS
Of the bacterial strains that were obtained from the children, the absolute levels of a shared group of 14 taxa (which are not typically classified as enteropathogens) were negatively correlated with linear growth (length-for-age z score, r = -0.49; P = 0.003) and positively correlated with duodenal proteins involved in immunoinflammatory responses. The representation of these 14 duodenal taxa in fecal microbiota was significantly different from that in samples obtained from healthy children (P<0.001 by permutational multivariate analysis of variance). Enteropathy of the small intestine developed in gnotobiotic mice that had been colonized with cultured duodenal strains obtained from children with EED.
CONCLUSIONS
These results provide support for a causal relationship between growth stunting and components of the small intestinal microbiota and enteropathy and offer a rationale for developing therapies that target these microbial contributions to EED. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02812615.).
Topics: Animals; Bacteria; Bangladesh; Duodenoscopy; Duodenum; Environmental Illness; Feces; Female; Gastrointestinal Microbiome; Germ-Free Life; Growth; Growth Disorders; Humans; Infant; Infant Nutrition Disorders; Inflammatory Bowel Diseases; Insulin-Like Growth Factor I; Intestinal Diseases; Male; Mice; Mice, Inbred C57BL; Multivariate Analysis; Pancreatitis-Associated Proteins; Proteome
PubMed: 32706533
DOI: 10.1056/NEJMoa1916004 -
Journal of the International... 2017Helminthic infection and HIV have been reported to coexist, particularly in sub-Saharan African patients living with HIV. Strongyloidiasis is one of the most common...
Helminthic infection and HIV have been reported to coexist, particularly in sub-Saharan African patients living with HIV. Strongyloidiasis is one of the most common helminths, usually leading to cutaneous and gastrointestinal (GI) symptoms. In the immunocompromised host, this infection can lead to strongyloidiasis hyperinfection syndrome (SHS), not common in HIV-infected patients. Immune reconstitution inflammatory syndrome (IRIS) can follow the initiation of antiretroviral therapy (ART), with a variety of presentations. The authors present here a 32-year-old HIV-infected female who was recently diagnosed with AIDS, started ART, and recovered from SHS. Her upper endoscopy revealed severe duodenitis but no causal agent per biopsy or stool examination. After receiving symptomatic therapy, she showed improvement, a course of events that fit the diagnosis of GI-related IRIS.
Topics: AIDS-Related Opportunistic Infections; Adult; Anti-Retroviral Agents; Duodenum; Female; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Strongyloidiasis
PubMed: 27733639
DOI: 10.1177/2325957416673149 -
Singapore Medical Journal Jun 2018
Topics: Aged; Biopsy; Duodenal Diseases; Duodenum; Endoscopy; Gastric Fistula; Humans; Male; Pylorus
PubMed: 29974123
DOI: 10.11622/smedj.2018073 -
Journal of Pediatric Gastroenterology... Feb 2016Although gastritis and esophagitis are well studied in children, there is very limited literature on duodenitis in children. We aimed to assess the prevalence, etiology,...
OBJECTIVES
Although gastritis and esophagitis are well studied in children, there is very limited literature on duodenitis in children. We aimed to assess the prevalence, etiology, clinical, endoscopic, and pathological features in a large cohort of unselected children with duodenitis.
METHODS
We reviewed the pathology reports of all the upper endoscopies performed at our institution during 5 years to identify children with duodenitis. Biopsy sections were reviewed to confirm the diagnosis of duodenitis. Demographic, clinical, endoscopic data, and the presence of associated gastritis and esophagitis were noted in all of the children with duodenitis. The etiology of duodenitis was correlated with the patients' clinical diagnosis.
RESULTS
Out of 2772 children who had endoscopy, 352 had duodenitis with the prevalence rate of 12.7%. Gastritis was seen in 64% of children with duodenitis compared with 46% of children without duodenitis (P < 0.001). Common indications for endoscopy in children with duodenitis were abdominal pain, positive celiac serology, and diarrhea. The most common etiology was celiac disease (32%), followed by Crohn disease (13%), ulcerative colitis (3%), and Helicobacter pylori infection (6%). In 63% of cases, the endoscopic appearance of duodenum was normal. Cryptitis, villous changes, and cellular infiltration were noted on histology.
CONCLUSIONS
Prevalence of duodenitis is 12.7% in children undergoing endoscopy. Celiac disease and inflammatory bowel disease are common causes of duodenitis. Associated gastritis is common in children with duodenitis, and the correlation of endoscopic appearance with histology is poor.
Topics: Abdominal Pain; Adolescent; Celiac Disease; Child; Child, Preschool; Colitis, Ulcerative; Crohn Disease; Diarrhea; Duodenitis; Duodenum; Endoscopy; Female; Gastritis; Helicobacter Infections; Humans; Infant; Male; Prevalence
PubMed: 26252915
DOI: 10.1097/MPG.0000000000000942 -
World Journal of Emergency Surgery :... May 2023A common feature of external duodenal fistulae is the devastating effect of the duodenal content rich in bile and pancreatic juice on nearby tissues with...
INTRODUCTION
A common feature of external duodenal fistulae is the devastating effect of the duodenal content rich in bile and pancreatic juice on nearby tissues with therapy-resistant local and systemic complications. This study analyzes the results of different management options with emphasis on successful fistula closure rates.
METHODS
A retrospective single academic center study of adult patients treated for complex duodenal fistulas over a 17-year period with descriptive and univariate analyses was performed.
RESULTS
Fifty patients were identified. First line treatment was surgical in 38 (76%) cases and consisted of resuture or resection with anastomosis combined with duodenal decompression and periduodenal drainage in 36 cases, rectus muscle patch, and surgical decompression with T-tube in one each. Fistula closure rate was 29/38 (76%). In 12 cases, the initial management was nonoperative with or without percutaneous drainage. The fistula was closed without surgery in 5/6 patients (1 patient died with persistent fistula). Among the remaining 6 patients eventually operated, fistula closure was achieved in 4 cases. There was no difference in successful fistula closure rates among initially operatively versus nonoperatively managed patients (29/38 vs. 9/12, p = 1.000). However, when considering eventually failed nonoperative management in 7/12 patients, there was a significant difference in the fistula closure rate (29/38 vs. 5/12, p = 0.036). The overall in-hospital mortality rate was 20/50 (40%).
CONCLUSIONS
Surgical closure combined with duodenal decompression in complex duodenal leaks offers the best chance of successful outcome. In selected cases, nonoperative management can be tried, accepting that some patients may require surgery later.
Topics: Adult; Humans; Retrospective Studies; Duodenal Diseases; Duodenum; Intestinal Fistula; Anastomosis, Surgical
PubMed: 37208716
DOI: 10.1186/s13017-023-00503-w -
Archives of Pathology & Laboratory... Sep 2023Eosinophilic diseases of the gastrointestinal tract (EGIDs), eosinophilic gastritis (EoG), and eosinophilic duodenitis (EoD) are rarely suspected clinically and...
CONTEXT.—
Eosinophilic diseases of the gastrointestinal tract (EGIDs), eosinophilic gastritis (EoG), and eosinophilic duodenitis (EoD) are rarely suspected clinically and infrequently detected by pathologists.
OBJECTIVE.—
To determine whether histories of allergic or eosinophilic disorders and requests to rule out EoG and EoD affect pathologists' awareness of eosinophils in gastrointestinal biopsies.
DESIGN.—
Thirty-one community-based pathologists were given 16 sets of biopsies from gastric and duodenal mucosa with elevated eosinophils, Helicobacter pylori gastritis, atrophic gastritis, normal stomach and duodenum, lymphocytosis, and celiac disease. Participants were assigned to 3 groups: group A did not receive histories of allergic or eosinophilic conditions; group B received similar histories plus a clue of possible allergic or eosinophilic conditions; and group C received the same histories as B and was asked to rule out EoG/EoD. A list of gastric and duodenal diagnoses and a space for comments were provided. Results were analyzed descriptively.
RESULTS.—
Pathologists correctly diagnosed most noneosinophilic gastrointestinal disorders, indicating competence in gastrointestinal pathology. With respect to EoG and EoD, pathologists in group C performed significantly better that those in groups A and B. The combined odds ratio with 95% CI was 12.34 (2.87-53.04), P < .001, for A versus C and 4.02 (1.60-10.09), P < .02, for B versus C.
CONCLUSIONS.—
Most pathologists neither reported gastric/duodenal eosinophilia nor diagnosed EoG/EoD, even when provided histories of eosinophilic disorders. Requests to rule out EoG/EoD resulted in only 4 of 11 participants evaluating and counting eosinophils in some cases. Simple evidence-based histopathologic criteria are needed before pathologists can be expected to consider and diagnose EGIDs.
Topics: Humans; Pathologists; Eosinophilia; Gastritis; Duodenum; Duodenitis
PubMed: 36399607
DOI: 10.5858/arpa.2022-0204-OA