Gastroduodenitis Associated with Active Ulcerative Colitis Treated with Infliximab: Different Clinical Course in the Colon and Gastroduodenal Lesions.

A 29-year-old man with severe ulcerative colitis and gastroduodenitis was initially treated with oral mesalamine and high-dose intravenous steroid therapy; however, his epigastralgia and vomiting did not improve. After initiating infliximab, the patient experienced prompt improvement in symptoms and inflammation. Although steroids were effective for the colon, they proved ineffective for gastroduodenal lesions, highlighting the necessity for molecular-targeted agents, such as infliximab, in these cases. The timing for administering such agents should be carefully considered.

Determination of Optimal Eosinophil Thresholds for Diagnosis of Eosinophilic Gastritis and Duodenitis: A Pooled Analysis of 4 Prospective Studies.

INTRODUCTION: Consensus is lacking regarding the number of eosinophils (eos) required for the diagnosis of eosinophilic gastritis (EoG) and eosinophilic duodenitis (EoD). In addition, thresholds that require multiple high-power fields (HPFs) may not be practical for clinical use, resulting in delayed or missed diagnoses. This pooled analysis of 4 prospective studies assessed thresholds for multiple and single HPFs used to diagnose EoG and EoD. METHODS: Studies included the phase 2 ENIGMA1, the phase 3 ENIGMA2, an EoG/EoD prevalence study and a healthy volunteer study. Eos were quantified in the epithelium and lamina propria for controls and symptomatic participants. Symptomatic participants were further divided by histologic diagnosis of EoG/EoD. Peak eos counts were assessed, and the area under the receiver operating characteristic curve was analyzed to identify eos cutoffs for detection of EoG/EoD using the Youden index and sensitivity and specificity equality approaches. RESULTS: Based on the highest specificity analysis in 740 patients, the optimal eos threshold was determined to be 20 eos/HPF in 5 gastric HPFs for EoG (71% sensitivity and 94% specificity) and 33 eos/HPF in 3 duodenal HPFs for EoD (49% sensitivity and 100% specificity). For single-field analysis, the optimal eos thresholds were 33 eos/HPF (EoG) and 37 eos/HPF (EoD), both corresponding to 93% sensitivity and 93% specificity. DISCUSSION: Highly specific single gastric and duodenal HPF thresholds may have more clinical applicability than thresholds requiring multiple HPFs and could better facilitate development of practical histopathologic guidelines to aid pathologists and clinicians in the detection and diagnosis of EoG and/or EoD.

Environmental enteric dysfunction and small intestinal histomorphology of stunted children in Bangladesh.

There is lack of information on the histological characteristics of the intestinal mucosa in Bangladeshi children. Collection of intestinal biopsy samples and assessment of the histomorphological features is considered to be the traditional gold standard for diagnosis of environmental enteric dysfunction (EED). The purpose of the study was to evaluate the intestinal histological characteristics of stunted children aged between 12-18 months with possible EED. 110 children with chronic malnutrition (52 stunted with length-for-age Z score, LAZ<-2 and 58 at risk of stunting with LAZ <-1 to -2) from the Bangladesh Environmental Enteric Dysfunction (BEED) study protocol who underwent upper gastrointestinal (GI) endoscopy were selected for this study. To explore the association of EED with childhood stunting, upper GI endoscopy was done and the biopsy specimens were studied for histopathology. Villous height and crypt depth were measured and the presence and intensity of inflammatory infiltrates in the lamina propria was investigated. Bivariate analysis was performed to examine the relationship between stunting and histologic morphology. More than 90% children irrespective of nutritional status were diagnosed to have chronic non-specific duodenitis on histopathology. Half of the children from both groups had villous atrophy as well as crypt hyperplasia and lymphocytic infiltration was present in more than 90% children, irrespective of groups. However, no statistically significant difference was observed when compared between the groups. The prevalence of chronic non-specific duodenitis in Bangladeshi children, irrespective of nutritional status, was high. A significant number of these children had abnormal findings in intestinal histomorphology. Trial registration number: ClinicalTrials.gov ID: NCT02812615 Date of first registration: 24/06/2016. https://clinicaltrials.gov/ct2/results?cond=NCT02812615&term=&cntry=&state=&city=&dist.

Automated analysis of small intestinal lamina propria to distinguish normal, Celiac Disease, and Non-Celiac Duodenitis biopsy images.

BACKGROUND AND OBJECTIVE: Celiac Disease (CD) is characterized by gluten intolerance in genetically predisposed individuals. High disease prevalence, absence of a cure, and low diagnosis rates make this disease a public health problem. The diagnosis of CD predominantly relies on recognizing characteristic mucosal alterations of the small intestine, such as villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. However, these changes are not entirely specific to CD and overlap with Non-Celiac Duodenitis (NCD) due to various etiologies. We investigated whether Artificial Intelligence (AI) models could assist in distinguishing normal, CD, and NCD (and unaffected individuals) based on the characteristics of small intestinal lamina propria (LP). METHODS: Our method was developed using a dataset comprising high magnification biopsy images of the duodenal LP compartment of CD patients with different clinical stages of CD, those with NCD, and individuals lacking an intestinal inflammatory disorder (controls). A pre-processing step was used to standardize and enhance the acquired images. RESULTS: For the normal controls versus CD use case, a Support Vector Machine (SVM) achieved an Accuracy (ACC) of 98.53%. For a second use case, we investigated the ability of the classification algorithm to differentiate between normal controls and NCD. In this use case, the SVM algorithm with linear kernel outperformed all the tested classifiers by achieving 98.55% ACC. CONCLUSIONS: To the best of our knowledge, this is the first study that documents automated differentiation between normal, NCD, and CD biopsy images. These findings are a stepping stone toward automated biopsy image analysis that can significantly benefit patients and healthcare providers.

Cytomegalovirus Graft Duodenitis Diagnosed by Transanal Double-Balloon Endoscopy Technique in an Enteric-Drained Pancreas Transplant Recipient: A Case Report.

Duodenal graft complications are not uncommon after pancreas transplant (PTx). Although direct visualization and biopsy of the duodenal graft are important for accurate diagnosis and management, endoscopic access is often limited in cases of enteric-drained PTx. Herein, we present a case of cytomegalovirus (CMV) graft duodenitis that was successfully diagnosed by transanal endoscopy using the double-balloon technique. The patient was a 54-year-old woman who underwent simultaneous pancreas and kidney transplant for type 1 diabetes mellitus and end-stage kidney disease. Enteric drainage was established by anastomosing the graft duodenum to her ileum. One month after the transplant, she developed fever and complained of lower abdominal pain. Graft duodenitis was suspected by laboratory test and imaging study results. Transanal double-balloon endoscopy was performed, and the biopsy specimen of the mucosa of the graft duodenum revealed CMV duodenitis without histopathologic findings of acute rejection. The postendoscopy course was uneventful. Treatment with ganciclovir was promptly initiated, and the CMV duodenitis was resolved with good function of the pancreas graft. In patients who undergo PTx with establishment of exocrine drainage by enteroanastomosis to the recipient ileum, transanal double-balloon endoscopy might be a feasible and safe technique for the surveillance of duodenal graft complications, including CMV duodenitis.

Pattern-based approach to duodenitis and duodenopathy.

Duodenum is currently the most popular site to obtain samples of intestinal mucosa for recognition of a disorder leading to malabsorption. Although there are significant overlaps between histological findings described in various non-neoplastic diseases of the duodenum, recognition of one of the six basic morphologic patterns, namely coeliac disease-like pattern, active chronic duodenitis, acute GvHD-like pattern, enteritis with predominant eosinophilic infiltration, enteritis with predominant infiltration by macrophages, and non-inflammatory enteropathy, usually allows diagnostic separation, especially if subtle histological details, clinical setting and serological investigation are taken into account.

Clinical Profile and Prevalence of H Pylori, Iga-Ttg, and Spectrum of Duodenal Abnormalities in Non Ulcer Dyspepsia.

The Rome IV criterion for a diagnosis of NUD is chronic or recurrent epigastric pain within the last 3 months and an onset of symptoms at least 6 months prior to presentation. The term functional Dyspepsia and idiopathic dyspepsia are often used as well. Symptoms include ulcer-like dyspepsia; gastroparetic-like (nausea, early satiety, and post-prandial pain), and undifferentiated. Pathogenesis of NUD is not completely known yet. Several mechanisms have been proposed to be responsible for these symptoms. Although there is strong evidence of an association between H. pylori infection and NUD, Celiac Disease and NUD. Being a tropical country, the prevalence of infections is parasitic cause. Dyspepsia is likely to be more in India. However, the present data from India as scares in literature. Hence the present study was planned to decipher the clinical profile, prevalence of H. pylori, IgA tTG, spectrum of duodenal biopsy abnormalities in NUD patients. MATERIAL: This Descriptive Observational study was carried out in the Gastro Enterology center in GOI research institute from August 2020 to March 2021. Initially, 200 dyspepsia patients were selected. 50 patients were excluded due to various reasons. Finally, 150 patients who met the Rome 4 criteria for NUD/Functional Dyspepsia were recruited. The inclusion criteria were patients above 18 years of age, dyspepsia for >/- 6 months, and no evidence of underlying malignancy, pan gastritis, previous gastric ulcers, and pancreatitis. The patients underwent routine blood investigations like haemogram and biochemistry, Rapid Urease Test (RUT), Upper Gastro-Intestinal Endoscopy, Duodenal Biopsy, and Serum IgA-tTG antibody. OBSERVATION: The mean age was 46.3 yrs. +/- 14.12 yrs, of which 49.3% were females and 50.70% were males. The prevalence of Epigastric Pain Syndrome (EPS) was found in 37.3%, Post Prandial Distress Syndrome (PDS) in 30.7%, and 32% had both EPS+PDS. 38% of the NUD patients were positive on Rapid Urease Test (RUT) suggesting H. pylori infection. 88.7% of NUD patients were IgA-tTG antibody negative and 11.3% serologically positive. The Duodenal biopsy was normal in 48% of patients, 21.3% had mild inflammation/duodenitis, 8% chronic duodenitis and 22.7% had various grades of Celiac Disease (as per Marsh Grading). These 22.7% showing evidence of Celiac Disease on histopathological examination showed Marsh Grade 1 in 12.7%, Grade-2 in 2%, Grade 3A in 6.7%, and Grade 3B in 1.3%. Only 17.6% of biopsy positive had IgA-tTG antibody positivity but only 4% of total cases were positive for both biopsy and IgA-tTG antibody (p-value 0.05). Eosinophilic infiltration in duodenum common in NUD patients. It was observed that 17.33% (26/150) NUD patients had duodenal eosinophilia. Further, look for the association of duodenal eosinophilia with various diseases. 33.33% (19/57) H. pylori patients had duodenal eosinophilia with p-value < 0.001. It was also observed that 7.52% (7/93) others like normal individual, Chronic duodenitis, mild inflammation/ duodenitis had Duodenal eosinophilia. CONCLUSION: The prevalence of H. pylori and IgA-tTG antibodies in non-ulcer dyspepsia patients was 38% and 11.3% respectively. The spectrum of Duodenum biopsy abnormalities in NUD patients included mild inflammation/ duodenitis, Chronic duodenitis, and Celiac Disease. 22.7% of NUD patients had various degrees of celiac disease morphology on D2 biopsy and only 17.6% of these biopsy positive patients were positive for IgA-tTG. Only 4% of total NUD patients were positive for both biopsy and IgA-tTG antibody labeled as Celiac Disease (CeD). There is a significant association between H. pylori and duodenal eosinophilia.

CLINICAL, ENDOSCOPIC, AND HISTOLOGICAL CHARACTERISTICS OF HELICOBACTER PYLORI POSITIVE AND NEGATIVE ARMENIAN CHILDREN WITH RECURRENT ABDOMINAL PAIN AND/OR DYSPEPSIA.

Recurrent abdominal pain (RAP) and dyspepsia are common complaints in children. These symptoms are often associated with Helicobacter pylori (Hp) infection. The aim of the present study was to prospectively analyze clinical, endoscopic, and histological characteristics of Hp+ and Hp- children with RAP and/or dyspepsia. Patients aged 2-18 years with RAP and/or dyspepsia, referred for an upper endoscopy to Arabkir Medical Center - Institute of Child and Adolescent Health (Arabkir MC-ICAH) from November 2015 to December 2017, were involved in the study. Histology was assessed according to the updated Sydney system. Gastric and duodenal specimens were stained by modified Giemsa staining for Hp infection. One antral biopsy was cultured in Hp selective media. 150 patients were included into the study: 70.7% Hp+, 29.3% Hp-. Nausea and vomiting were significantly more common in Hp+ patients (p<0.05). Gastric nodularity (p=0.02), erosions in the stomach (p=0.056), and duodenal erosions (p=0.019) were more common in Hp+. Chronic active (p=0.027) and non-active gastritis (p=0.002), cumulative findings of metaplasia/dysplasia/atrophy in the stomach (p=0.014) and chronic non-active duodenitis (p=0.016), were significantly more common in Hp+ patients. Hp infection prevalence is high in Armenian children with dyspepsia and/or RAP. Clinical symptoms, endoscopic findings, and histopathological findings were significantly different in Hp+ patients as compared to Hp- patients.

Endoscopic findings unrelated to portal hypertension in patients with liver cirrhosis undergoing a varicose vein screening programme. / Hallazgos endoscópicos no relacionados con hipertensión portal en pacientes con cirrosis hepática sometidos a un programa de cribado de varices.

AIM: To determine the prevalence of endoscopic lesions unrelated with portal hypertension in patients with cirrhosis. PATIENTS AND METHODS: Cross-sectional study including a consecutive cohort of patients with liver cirrhosis enrolled in a screening program of oesophageal varices who underwent an upper gastrointestinal endoscopy from November, 2013, to November, 2018. Clinical predictors of endoscopic lesions unrelated to portal hypertension were analyzed by univariate and multivariate logistic regression. RESULTS: A total of 379 patients were included. The most frequent aetiology of liver disease was alcohol consumption (60.4%). The prevalence of endoscopic lesions unrelated with portal hypertension was 39.6% (n=150). Among 96 patients with peptic lesions, urease was obtained in 56.2% of patients (positive in 44.4% of them). The prevalence of endoscopic lesions unrelated to portal hypertension was not associated with age, gender, liver function or ultrasound findings of portal hypertension. The prevalence of endoscopic lesions unrelated to portal hypertension was not associated with age, gender, liver function or ultrasound findings of portal hypertension. Smokers had a trend to increased prevalence of endoscopic lesions unrelated to portal hypertension (43.2% vs. 34.6%; p=0.09), particularly peptic ulcer (6.4% vs. 0.6%; p=0.05) and peptic duodenitis (17.3% vs. 6.3%; p=0.002). Active smoking was the only independent predictor of peptic ulcer or duodenitis (OR=2.56; p=0.017). CONCLUSION: Active smoking is a risk factor for endoscopic lesions unrelated to portal hypertension. This finding should be further investigated to reassess endoscopic screening programs in cirrhotic smokers.

Determination of Biopsy Yield That Optimally Detects Eosinophilic Gastritis and/or Duodenitis in a Randomized Trial of Lirentelimab.

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).

Quantification of Mucosal Eosinophils for the Histopathologic Diagnosis of Eosinophilic Gastritis and Duodenitis: A Primer for Practicing Pathologists.

Eosinophilic gastrointestinal diseases, specifically eosinophilic gastritis and duodenitis, are chronic inflammatory conditions characterized by persistent gastrointestinal (GI) symptoms and elevated levels of activated eosinophils in the GI tract. Both clinical and endoscopic findings are nonspecific, no clinical or histopathologic diagnostic guidelines are published, and disease awareness is low, both among clinicians and amongst pathologists, who tend to overlook mild or moderate increases in the density of eosinophils in GI biopsy specimens. Yet, evaluating and, at times, counting eosinophils in GI biopsies may have important clinical implications: the numbers of tissue eosinophils correlate with clinical manifestations, can be used as determinants of effective management, and are used to assess the effects of treatment. A most persuasive argument for providing a count rather than a value judgment is that patients read reports, understand numbers, and use them to help to understand the course of their disease. The objective of this primer is to provide pathologists with the tools to incorporate a quantitative assessment of eosinophilia in the diagnosis of gastric and duodenal biopsy specimens and to develop a systematic approach to their evaluation, counting, and reporting. To achieve this aim, we present our general approach to the biopsy (where to count), followed by details on the characteristics of a countable eosinophil (what to count), and provide with a set of suggestions on the counting methods (how to count). We conclude with suggestions on how to report GI tissue eosinophilia in a manner that alerts clinicians and prompts pertinent management steps.

Alterations in the histological features of the intestinal mucosa in malnourished adults of Bangladesh.

There is paucity of knowledge on the histological features of the intestinal mucosa in malnourished adults of Bangladesh. The purpose of the study was to explore the histological features of the intestinal mucosa in malnourished adults of Bangladesh and to compare the findings with their well-nourished counterparts. 64 adults (37 malnourished with body mass index, BMI < 18.5 kg/m2 and 27 controls with BMI > 18.5 kg/m2) from the Bangladesh Environmental Enteric Dysfunction (BEED) study, who underwent upper-gastrointestinal endoscopy, were selected for this study. With a view to address the association of environmental enteric dysfunction (EED) with malnutrition, upper-gastrointestinal endoscopy was performed and mucosal biopsies from the distal duodenum were studied for histopathology. Villous height, crypt depth, and presence of inflammatory infiltrates in lamina propria were investigated. Bivariate analysis was performed to quantify the relation between malnutrition and the histological features. About 95% adults, irrespective of nutritional status, were diagnosed to have chronic non-specific duodenitis on histopathology. Malnourished adults suffered significantly more from chronic active duodenitis compared to their well-nourished counterparts (p = 0.003). Malnourished adults also had significantly higher frequency of subtotal villous atrophy, crypt hyperplasia and marked cellular infiltration in the lamina propria than the healthy controls (p < 0.05).

Celiac disease: histology-differential diagnosis-complications. A practical approach.

Celiac disease is a multi-factorial chronic inflammatory intestinal disease, characterized by malabsorption resulting from mucosal injury after ingestion of wheat gluten or related rye and barley proteins. Inappropriate T-cell-mediated immune response against ingested gluten in genetically predisposed people, leads to characteristic histological lesions, as villous atrophy and intraepithelial lymphocytosis. Nevertheless, celiac disease is a comprehensive diagnosis with clinical, serological and genetic characteristics integrated with histological features. Biopsy of duodenal mucosa remains the gold standard in the diagnosis of celiac disease with the recognition of the spectrum of histological changes and classification of mucosa damage based on updated Corazza-Villanacci system. Appropriate differential diagnosis evaluation and clinical context also for the diagnosis of complications is, moreover, needed for correct histological features interpretation and clinical management.

Upper Gastrointestinal Manifestations of Inflammatory Bowel Disease.

Although the features of lower gastrointestinal tract inflammation associated with ulcerative colitis and Crohn disease are generally familiar to pathologists, there is less awareness of and familiarity with the manifestations of inflammatory bowel disease in the esophagus, stomach, and duodenum. Nonetheless, their diagnosis has therapeutic and possibly prognostic implications, potentially foretelling severe complications. The recognition that ulcerative colitis can affect gastrointestinal organs proximal to the large intestine and terminal ileum represents a revision of concepts ingrained among generations of physicians. This article reviews the pathologic features and clinical significance of esophagitis, gastritis, and duodenitis associated with inflammatory bowel disease.

Distribution of duodenal tuft cells is altered in pediatric patients with acute and chronic enteropathy.

Clinical interest into the function of tuft cells in human intestine has increased in recent years. However, no quantitative study has examined intestinal tuft cells in pathological specimens from patients. This study quantified tuft cell density by using a recently identified marker, specific for tyrosine phosphorylation (pY1798) of girdin (also known as CCDC88A or GIV) in the duodenum of pediatric patients. Deidentified sections with pathological diagnosis of acute duodenitis, ulcer, or celiac disease, and age-matched normal control were analyzed under double-blind conditions. Immunostaining for pY1798-girdin demonstrated the distinct shape of tuft cells with and filopodia-like basolateral membrane structure and a small apical area, which densely expressed gamma-actin. As compared to normal tissues, the specimens diagnosed as celiac disease and duodenal ulcer had significantly fewer tuft cell numbers. In contrast, acute duodenitis showed varied population of tuft cells. The mucosa with severe inflammation showed lower tuft cell numbers than the specimens with none to mild inflammation. These results suggest that loss of tuft cells may be involved in prolonged inflammation in the duodenal mucosa and disrupted mucosal integrity. pY1798-girdin and gamma-actin are useful markers for investigating the distribution and morphologies of human intestinal tuft cells under healthy and pathological conditions.

Iron pill-induced duodenitis: A distinct pattern of duodenal mucosal injury in a patient with a duodenal mass.

Ferrous sulfate is an oral iron supplement commonly used to treat iron deficiency anemia. Upper gastrointestinal (GI) tract mucosal damage with associated tissue iron accumulation can sometimes occur with therapeutic dosages of oral iron-containing medications. A distinct histologic pattern of iron deposition with associated inflammatory and reactive changes caused by mucosal injury from oral iron-containing medications has been most commonly described within gastric biopsies and has been referred to as "iron-pill gastritis". There have only been very rare reports of duodenal mucosa biopsies demonstrating predominantly extracellular crystalline iron deposits with surrounding tissue inflammation and injury analogous to the "iron-pill gastritis" pattern. Here we report a case of "iron pill-induced duodenitis", an uncommon histologic pattern of duodenal iron deposition and mucosal injury seen in a female in her 50 s with clinical findings of a duodenal mass.

Nod2 Protects the Gut From Experimental Colitis Spreading to Small Intestine.

BACKGROUND AND AIMS: Nucleotide oligomerization domain 2 [NOD2] mutations are key risk factors for Crohn's disease [CD]. NOD2 contributes to intestinal homeostasis by regulating innate and adaptive immunity together with intestinal epithelial function. However, the exact roles of NOD2 in CD and other NOD2-associated disorders remain poorly known. METHODS: We initially observed that NOD2 expression was increased in epithelial cells away from inflamed areas in CD patients. To explore this finding, Nod2 mRNA expression, inflammation, and cytokines expression were examined in the small bowel of wild-type [WT], Nod2 knockout and Nod2 mutant mice after rectal instillation of 2,4,6-trinitrobenzene sulphonic acid [TNBS]. RESULTS: In WT mice, Nod2 upregulation upstream to rectal injury was associated with pro-inflammatory cytokine expression but no overt histological inflammatory lesions. Conversely, in Nod2-deficient mice the inflammation spread from colitis to ileum and duodenum. CONCLUSIONS: Nod2 protects the gut from colitis spreading to small intestine.