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Clinical Gastroenterology and... Mar 2022Eosinophilic gastritis (EG) and eosinophilic duodenitis (EoD), characterized by chronic gastrointestinal (GI) symptoms and increased numbers or activation of eosinophils... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
Eosinophilic gastritis (EG) and eosinophilic duodenitis (EoD), characterized by chronic gastrointestinal (GI) symptoms and increased numbers or activation of eosinophils and mast cells in the GI tract, are likely underdiagnosed. We aimed to determine rates of EG and EoD and number of biopsies required to optimize detection using screening data from a randomized trial of lirentelimab (AK002), an antibody against siglec-8 that depletes eosinophils and inhibits mast cells. We also characterized endoscopic features and symptoms of EG and EoD.
METHODS
Subjects with moderate-to-severe GI symptoms, assessed daily through a validated patient-reported outcome questionnaire, underwent endoscopy with a systematic gastric and duodenal biopsy protocol and histopathologic evaluation. EG diagnosis required presence of ≥30 eosinophils/high-power field (eos/hpf) in ≥5 hpfs and EoD required ≥30 eos/hpf in ≥3 hpfs. We analyzed diagnostic yields for EG and EoD and histologic, endoscopic, and clinical findings.
RESULTS
Of 88 subjects meeting symptom criteria, 72 were found to have EG and/or EoD (EG/EoD), including patients with no prior diagnosis of EG/EoD. We found that GI eosinophilia was patchy and that examination of multiple biopsies was required for diagnosis-an average of only 2.6 per 8 gastric biopsies and 2.2 per 4 duodenal biopsies per subject met thresholds for EG/EoD. Evaluation of multiple nonoverlapping hpfs in each of 8 gastric and 4 duodenal biopsies was required to capture 100% of EG/EoD cases. Neither endoscopic findings nor symptom severity correlated with eosinophil counts.
CONCLUSIONS
In an analysis of patients with moderate-to-severe GI symptoms participating in a clinical trial of lirentelimab for EG/EoD, we found eosinophilia to be patchy in gastric and duodenal biopsies. Counting eosinophils in at least 8 gastric and 4 duodenal biopsies is required to identify patients with EG/EoD, so they can receive appropriate treatment. (ClinicalTrials.gov, Number: NCT03496571).
Topics: Biopsy; Duodenitis; Enteritis; Eosinophilia; Eosinophilic Esophagitis; Eosinophils; Gastritis; Humans
PubMed: 34089846
DOI: 10.1016/j.cgh.2021.05.053 -
Journal of Veterinary Internal Medicine Jan 2017Duodenitis-proximal jejunitis (DPJ) is an acute sporadic gastrointestinal disorder of horses of unknown cause.
BACKGROUND
Duodenitis-proximal jejunitis (DPJ) is an acute sporadic gastrointestinal disorder of horses of unknown cause.
HYPOTHESIS/OBJECTIVES
We hypothesize that Clostridium difficile toxins are involved in the pathogenesis of DPJ in horses. The objective of this study was to determine whether experimentally delivered C. difficile toxins cause clinical signs and histologic lesions similar to those of naturally occurring DPJ.
ANIMALS
Six healthy mature mixed breed horses.
METHODS
Experimental study: animal model of animal disease. Fasted horses were administered crude C. difficile toxins via gastroscopy and monitored for up to 48 hour. Blood was collected for complete blood cell count, biochemistry profile, and plasma fibrinogen assay, and abdominal fluid was collected for cytologic analysis and total solids before and after toxin administration. Physical examination and abdominal ultrasonography were performed throughout the study period. Tissues were collected from the gastrointestinal tract and processed for routine histologic analysis, and lesions were scored.
RESULTS
Clinical signs were observed in 2 of 6 horses that are typical although not specific for horses with naturally occurring DPJ. Histopathologic lesions were observed in 6 of 6 horses and were similar to those reported in horses with naturally occurring DPJ. Two horses were severely affected.
CONCLUSIONS AND CLINICAL IMPORTANCE
Duodenitis-proximal jejunitis is likely a syndrome with multiple causes that result in the same clinical and pathologic findings, and our data suggest that the toxins of C. difficile represent one cause of this syndrome. Toxin dose and variation in individual animal susceptibility might affect the clinical signs and lesions after administration of C. difficile toxins.
Topics: Animals; Clostridioides difficile; Clostridium Infections; Duodenitis; Female; Horse Diseases; Horses; Jejunal Diseases; Male
PubMed: 27906466
DOI: 10.1111/jvim.14624 -
The Journal of Physiology Feb 2015Luminal lipid in the duodenum modulates gastroduodenal functions via the release of gut hormones and mediators such as cholecystokinin and 5-HT. The effects of luminal...
KEY POINTS
Luminal lipid in the duodenum modulates gastroduodenal functions via the release of gut hormones and mediators such as cholecystokinin and 5-HT. The effects of luminal short-chain fatty acids (SCFAs) in the foregut are unknown. Free fatty acid receptors (FFARs) for long-chain fatty acids (LCFAs) and SCFAs are expressed in enteroendocrine cells. SCFA receptors, termed FFA2 and FFA3, are expressed in duodenal enterochromaffin cells and L cells, respectively. Activation of LCFA receptor (FFA1) and presumed FFA3 stimulates duodenal HCO3(-) secretion via a glucagon-like peptide (GLP)-2 pathway, whereas FFA2 activation induces HCO3(-) secretion via muscarinic and 5-HT4 receptor activation. The presence of SCFA sensing in the duodenum with GLP-2 and 5-HT signals further supports the hypothesis that luminal SCFA in the foregut may contribute towards the generation of functional symptoms.
ABSTRACT
Intraduodenal fatty acids (FA) and bacterial overgrowth, which generate short-chain FAs (SCFAs), have been implicated in the generation of functional dyspepsia symptoms. We studied the mechanisms by which luminal SCFA perfusion affects duodenal HCO3(-) secretion (DBS), a measure of mucosal neurohumoral activation. Free fatty acid receptor (FFAR) 1 (FFA1), which binds long-chain FA (LCFA), and SCFA receptors FFA2 and FFA3 were immunolocalised to duodenal enteroendocrine cells. FFA3 colocalised with glucagon-like peptide (GLP)-1, whereas FFA2 colocalised with 5-HT. Luminal perfusion of the SCFA acetate or propionate increased DBS, enhanced by dipeptidyl peptidase-IV (DPPIV) inhibition, at the same time as increasing GLP-2 portal blood concentrations. Acetate-induced DBS was partially inhibited by monocarboxylate/HCO3(-) exchanger inhibition without affecting GLP-2 release, implicating acetate absorption in the partial mediation of DBS. A selective FFA2 agonist dose-dependently increased DBS, unaffected by DPPIV inhibition or by cholecystokinin or 5-HT3 receptor antagonists, but was inhibited by atropine and a 5-HT4 antagonist. By contrast, a selective FFA1 agonist increased DBS accompanied by GLP-2 release, enhanced by DPPIV inhibition and inhibited by a GLP-2 receptor antagonist. Activation of FFA1 by LCFA and presumably FFA3 by SCFA increased DBS via GLP-2 release, whereas FFA2 activation stimulated DBS via muscarinic and 5-HT4 receptor activation. SCFA/HCO3(-) exchange also appears to be present in the duodenum. The presence of duodenal fatty acid sensing receptors that signal hormone release and possibly signal neural activation may be implicated in the pathogenesis of functional dyspepsia.
Topics: Animals; Cholecystokinin; Chromaffin Cells; Duodenum; Fatty Acids, Volatile; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Rats; Receptors, G-Protein-Coupled; Serotonin; Signal Transduction
PubMed: 25433076
DOI: 10.1113/jphysiol.2014.280792 -
The Journal of International Medical... Jan 2020Congenital duodenal obstruction is typically treated by duodenoduodenostomy. Tapering of the dilated segment has been indicated to reduce duodenal dysmotility. The...
OBJECTIVE
Congenital duodenal obstruction is typically treated by duodenoduodenostomy. Tapering of the dilated segment has been indicated to reduce duodenal dysmotility. The purpose of this study was to review the outcomes between these two approaches.
METHODS
We retrospectively reviewed cases of duodenal obstruction repair performed at a quaternary care referral pediatric hospital from 2007 to 2017. The length of stay, time to full enteral feeding, and complications were compared between patients who underwent duodenoduodenostomy with and without tapering duodenoplasty (n=4 and n=35, respectively).
RESULTS
Both groups had similar times to initial enteral feeding (7 days) and full enteral feeding (14 vs. 15 days). Among the 35 patients who underwent duodenoduodenostomy alone, 6 (17%) required a return to the operating room; in contrast, no patients who underwent tapering required a return to the operating room. Of those who returned to the operating room, two underwent tapering at that time because of duodenal dilation and feeding intolerance.
CONCLUSIONS
Although limited by the small sample size, this study suggests that patients undergoing tapering duodenoplasty may have a slightly shorter time to full enteral feeding and a lower rate of complications than patients undergoing duodenoduodenostomy alone.
Topics: Duodenal Obstruction; Duodenostomy; Duodenum; Female; Humans; Infant, Newborn; Male; Postoperative Complications; Prognosis; Retrospective Studies
PubMed: 31353994
DOI: 10.1177/0300060519862109 -
Clinical and Translational... Mar 2020The diagnostic value of different noninvasive diagnostic modalities and the endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) reliability of duodenal...
OBJECTIVES
The diagnostic value of different noninvasive diagnostic modalities and the endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) reliability of duodenal gastrointestinal stromal tumors (GISTs) are ambiguous in the present studies.
METHODS
Patients with a histopathological diagnosis of the primary duodenal GISTs between the years 2008 and 2018 were analyzed. Data on the treatment and clinicopathological features were recorded. Furthermore, the computed tomography (CT)/magnetic resonance imaging (MRI), EUS, and EUS-FNA results were collected and compared.
RESULTS
A total of 142 patients were enrolled into the study. In all patients, the most common symptom was gastrointestinal bleeding (44.4%), followed by abdominal pain and bloating (27.5%). Duodenal GISTs were mostly located in the second duodenal portion (52.1%), followed by the first portion (19.0%). EUS had significantly higher sensitivity and positive predictive values than CT or MRI (P = 0.047 and P = 0.005, respectively). The EUS-FNA sensitivity of duodenal GISTs was also significantly higher than the conventional endoscopic biopsy (73.3% vs 33.3%, P = 0.006). A total of 131 patients underwent surgery, including limited resection or pancreaticoduodenectomy. The tumor size and postoperative complication rates were higher in patients who underwent pancreaticoduodenectomy (P = 0.001 and P < 0.001, respectively).
DISCUSSION
The diagnostic value of EUS is significantly higher than that of CT and MRI for duodenal GISTs. The EUS-FNA can provide a histological diagnosis of duodenal GISTs in most cases.
Topics: Adult; Aged; Diagnostic Errors; Duodenal Neoplasms; Duodenum; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Endoscopy; Gastrointestinal Stromal Tumors; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pancreaticoduodenectomy; Predictive Value of Tests; Reproducibility of Results; Retrospective Studies; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 32352716
DOI: 10.14309/ctg.0000000000000156 -
Laboratory Investigation; a Journal of... Mar 2020Intestinal Na-nutrient cotransport depends on claudin-2 and claudin-15 mediated Na recycling. Expression of these proteins is coordinately regulated during postnatal...
Intestinal Na-nutrient cotransport depends on claudin-2 and claudin-15 mediated Na recycling. Expression of these proteins is coordinately regulated during postnatal development. While expression of claudin-2 and claudin-15 has been studied in inflammatory bowel disease (IBD) and celiac disease (CD), it has not been assessed in other malabsorptive diseases, and no reports have compared expression in children and adults. We used quantitative immunofluorescence microscopy to assess claudin-2 and claudin-15 expression in duodenal biopsies from children and adults with malabsorptive disease and healthy controls. Consistent with previous work in rodents, claudin-2 expression in healthy children was markedly greater, and claudin-15 expression was less, than that in adults. Claudin-2 expression was increased in adults with CD and downregulated in children with graft-versus-host disease (GVHD). In contrast, claudin-15 expression was reduced in adults with GVHD and common variable immunodeficiency (CVID). These data show that one of the two Na/water pore-forming claudins is upregulated in CD and downregulated in GVHD and CVID. The specific claudin whose expression changes, however, reflects the age of the patient (child or adult). We conclude that contributions of claudin-2 and claudin-15 to pathophysiology of and responses to diarrhea in children and adults with GVHD and CVID differ from those in CD and IBD.
Topics: Adult; Aged; Aged, 80 and over; Child, Preschool; Claudin-2; Claudins; Duodenum; Female; Humans; Infant; Malabsorption Syndromes; Male; Middle Aged
PubMed: 31605016
DOI: 10.1038/s41374-019-0324-8 -
World Journal of Gastroenterology Feb 2015Geographically the prevalence of duodenal ulceration is related to the staple foods in the diet in regions of developing countries where the diet is stable. It is higher... (Review)
Review
Geographically the prevalence of duodenal ulceration is related to the staple foods in the diet in regions of developing countries where the diet is stable. It is higher in regions where the diet is based on milled rice, refined wheat or maize, yams, cassava, sweet potato, or green bananas, and is lower in regions where the staple diet is based on unrefined wheat or maize, soya, certain millets or certain pulses. Experiments on rat gastric and duodenal ulcer models showed that it was the lipid fraction in staple foods from low prevalence areas that was protective against both gastric and duodenal ulceration, including ulceration due to non-steroidal anti-inflammatory drugs (NSAIDs). It also promoted ulcer healing. The lipid from the pulse, Dolichos biflorus, horse gram which was highly protective was used to identify the fractions with protective activity in the lipid. The protective activity lay in the phospholipid, sterol and sterol ester fractions. In the phospholipid fraction phosphatidyl choline (lethicin) and phosphatidyl ethanolamine (cephalin) were predominant. In the sterol fraction the sub-fractions showing protective activity contained β-sitosterol, stigmasterol, and an unidentified isomer of β-sitosterol. The evidence from animal models shows that certain dietary phospholipids and phytosterols have a protective action against gastroduodenal ulceration, both singly and in combination. This supports the protective role of staple diets in areas of low duodenal ulcer prevalence and may prove to be of importance in the prevention and treatment of duodenal ulceration and management of recurrent ulcers. A combination of phospholipids and phytosterols could also play an important role in protection against ulceration due to NSAIDs.
Topics: Animals; Cytoprotection; Diet; Dietary Fats; Dietary Fiber; Disease Models, Animal; Duodenal Ulcer; Duodenum; Gastric Mucosa; Phospholipids; Phytosterols; Plant Oils; Rats; Stomach; Stomach Ulcer
PubMed: 25663757
DOI: 10.3748/wjg.v21.i5.1377 -
Internal Medicine (Tokyo, Japan) Oct 2023
Topics: Humans; Duodenum; Intestinal Mucosa; Lymphadenopathy; Lymphoid Tissue; Carcinoma
PubMed: 36889708
DOI: 10.2169/internalmedicine.1225-22 -
Journal of Radiology Case Reports Mar 2020The underlying etiologies of paediatric bowel obstruction are wide ranging. It can be divided into proximal and distal bowel obstruction. Amongst the different...
The underlying etiologies of paediatric bowel obstruction are wide ranging. It can be divided into proximal and distal bowel obstruction. Amongst the different etiologies of the proximal bowel obstructions at the level of the duodenum, there are a few etiologies including duodenal atresia, internal hernias, intestinal malrotation, annular pancreas etc. Superior mesenteric artery syndrome is amongst one of these differential diagnoses which is more prevalent in the adolescent age group. We describe the imaging features of this entity and its demographics, imaging characteristics, treatment and prognosis.
Topics: Adolescent; Diagnosis, Differential; Duodenal Obstruction; Duodenum; Humans; Intestinal Atresia; Superior Mesenteric Artery Syndrome
PubMed: 33082917
DOI: 10.3941/jrcr.v14i3.3830 -
Turk Patoloji Dergisi 2020Endoscopic resections are increasingly being used for superficial gastrointestinal lesions. However, application of these techniques in the duodenum remains challenging,...
OBJECTIVE
Endoscopic resections are increasingly being used for superficial gastrointestinal lesions. However, application of these techniques in the duodenum remains challenging, due to the technical difficulties and high complication rates. This study projects a western tertiary center's experience in the endoscopic treatment and diagnostic workup of 19 cases of non-ampullary duodenal lesions.
MATERIAL AND METHOD
Specimens (12 endoscopic mucosal resections, 6 endoscopic submucosal dissections, and one endoscopic full-thickness resection) were processed following a strict protocol (photographed, mapped digitally and submitted totally) for histopathologic examination. Clinicopathologic characteristics, margin status and follow-up information were analyzed.
RESULTS
The mean age of the 16 patients was 52 years (range: 22-81). Mean lesion size was 1.4 cm (range: 0.3-3.6 cm) for all cases, 2 cm for endoscopic submucosal dissections and 1.1 cm for endoscopic mucosal resections. Mean number of blocks submitted was 4/case. Seven neuroendocrine tumors, 3 tubulovillous adenomas were diagnosed along with nine benign lesions. For endoscopic submucosal dissections, en-bloc and R0 resection rates were 100% (n=6/6) and 83% (n=5/6); for endoscopic mucosal resections, they were 92% (n=11/12) and 83% (n=10/12), respectively. Only one patient had procedure-related late perforation that was managed endoscopically. No mortality was encountered.
CONCLUSION
Duodenal endoscopic resections proved successful, safe and feasible methods in a tertiary center. The pathologist's role is to designate the accurate diagnosis, related histopathologic parameters and margin status. The gross protocol was found to be essential in evaluating specimen margins and orientation, as well as in size measurement. We recommend following a standardized approach including gross photography and digital mapping when handling these specimens, for both diagnostic and data collection purposes.
Topics: Adult; Aged; Aged, 80 and over; Duodenum; Endoscopic Mucosal Resection; Female; Humans; Intestinal Polyps; Male; Middle Aged; Young Adult
PubMed: 31825518
DOI: 10.5146/tjpath.2019.01474