Bulb Biopsy Research Articles

Diagnostic Yield of the Number of Duodenal Biopsies in Celiac Disease

Abstract Background The diagnosis of celiac disease relies on a combination of clinical evaluation, serological testing, and histopathological examination of duodenal biopsies. However, there is ongoing debate regarding the optimal number of duodenal biopsies required for an accurate diagnosis, as well as the isolated yield of water interface directed biopsy. Aim The primary objective is to determine the cumulative benefit of multiple duodenal biopsies, establishing the specificity and sensitivity of each biopsy separately with focus on the isolated yield of water interface directed biopsy. Methods A Cross-sectional study conducted on 22 children with symptoms and signs suggestive of celiac disease (CD) and positive serology with antitissue transglutaminase antibodies at the pediatric gastrointestinal endoscopy Unit at EL Demerdash Hospital, Ain Shams University for 6 months. four biopsies were taken, one from duodenal bulb, and 2 from rest of duodenum and the fourth one using water immersion technique visualizing the most affected area. Results Among the 22 enrolled children, 18 patients were histopathologically positive for celiac disease and 4 children were negative. The bulb, duodenal, and water interface biopsies were positive in 94.4%, 88.8%, and 66.7% respectively, of those positively diagnosed as celiac disease by Marsh criteria. In addition, bulb, and duodenal biopsies have the highest sensitivity of 94.4%, and 88.9%, respectively, also, they have the highest accuracy. Duodenal bulb biopsies were capable alone to diagnose 17 out of 18 definite cases. The missed case diagnosis was reached either by water interface or any random duodenal biopsy. Conclusion Bulb biopsy showed to be the most accurate in diagnosing celiac disease, on the contrary, water interface biopsy was not sensitive in diagnoses, so the celiac diagnostic efficacy can be reached by assessment of 2 duodenal biopsies, one of them from the duodenal bulb.

The Characteristics of Isolated Bulb Celiac Disease in Children.

Mucosal injury in celiac disease (CD) patients can be patchy, and up to 12% of CD patients can have mucosal changes limited to the duodenal bulb. Hence, recent guidelines recommend obtaining bulb biopsies in addition to distal duodenum. This study aimed to describe a cohort of children with isolated bulb CD and assess the benefit of separating bulb biopsies. A retrospective chart review between January 2011 and January 2022 at 2 medical centers was conducted. We included children with CD who underwent endoscopy with separated biopsies from the bulb and distal duodenum. A blinded pathologist performed Marsh-Oberhuber grading on selected cases. We identified 224 CD patients, of which 33 (15%) had histologically confirmed isolated bulb CD. Patients with isolated bulb CD were older at diagnosis (10 vs 8 years; P = 0.03). Median anti-tissue transglutaminase immunoglobulin A (TTG IgA) level was lower in isolate bulb CD (2.8 vs 16.7 times the upper limit of normal [ULN], P < 0.001). Almost 88% (29/33) of isolated bulb CD patients had an anti-TTG IgA value of less than 10 times the ULN. Time to anti-TTG IgA normalization (mean 14 months) was similar between the 2 groups. A pathologist review of diagnostic biopsies could not distinguish between the bulb and distal duodenum biopsies in approximately one-third of the reviewed samples. Separating bulb from distal duodenum biopsies can be considered during CD diagnosis, particularly in children with anti-TTG IgA levels less than 10 times the ULN. Larger prospective cohorts are needed to decide whether isolated bulb CD is a unique cohort or an early stage of the conventional CD.

Celiac Disease Diagnosis Via Histopathological Correlation of Duodenal Biopsies in Children

Aim: The purpose of this study is to compare the diagnostic accuracy of duodenal bulb biopsies to distal duodenal biopsies in patients suspected of having celiac disease. Study Design: Cross-sectional study Place and Duration: This study was conducted at Department of Pathology, The children's hospital &amp; The institute of child health, Multan during the period from April, 2022 to September, 2022. Methods: Total 86 children of celiac disease were presented in this study. Informed written consent provided by parents of children for the collection of detailed demographic data. Under general anaesthesia, a duodenal bulb sample and four distal duodenum samples were collected during an upper gastrointestinal endoscopy. Histological alterations indicative with CD were identified. Histological diagnosis and grading were performed using a modification of the Marsh-Oberhuber classification. The entire data set was analyzed by using SPSS 20.0. Results: Forty nine (56.97%) patients were females and 37 (43.03%) cases were males. Children’s mean age was 6.4±3.27 years with mean weight 15.9±6.19 kg. Mean height of the cases was 94.7±10.42 cm. There were 51 (59.3%) children had urban residency. According to marsh grading, 50 (58.1%) cases had grade IIIC. We found that frequency of crypt hyperplasia, influx of immune cells in lamina propria and enterocytes change in both duodenal bulb and distal part biopsies were equal while only frequency of villous atrophy and intraepithelial lymphocytes were different in both biopsies. 96.5% patients reported a high level of correlation, while only 3.5% reported no correlation. Conclusion: Both biopsy sites agree strongly. We may now suggest duodenal bulb biopsy alone. Since the endoscopic method of distal duodenum is laborious and requires more knowledge and time, obtaining biopsies from the proximal section is easier and requires less experience, therefore this strategy may be used even at facilities with junior paediatric gastroenterologists. Keywords: Celiac disease, Children, Histopathology, Duodenal bulb, Distal duodenum

An Unusual Cause of Acute Gastroenteritis, Ascites, and Eosinophilia in a 29-Year-Old Woman

An Unusual Cause of Acute Gastroenteritis, Ascites, and Eosinophilia in a 29-Year-Old Woman

A Multicenter Cross Sectional Study to Evaluate the Role of Duodenal Bulb Biopsy in the Diagnosis of Celiac Disease

Background and Aim: A systemic immune disorder elicited by dietary gluten in people who are genetically predisposed to it is referred to as a celiac disease. D1 had been ruled out as a biopsy site due to concerns about Brunner's glands, peptic duodenitis, gastric metaplasia, and presumed reduced villous height. Due to histological confounding factors, the duodenal bulb (D1) as a biopsy site was traditionally avoided. The present study aimed to assess the duodenal bulb biopsy role in the diagnosis of celiac disease. Methodology: This multicenter cross sectional study was conducted on 108 celiac disease patients in the department of Gastroenterology, Bacha Khan Medical Complex, Swabi, North West General hospital Peshawar and Pir Abdul Qadir Shah Jilani Institute of Medical Science Gambat Khairpur, Sindh from September 2020 to July 2021. All the celiac disease patients were clinically symptomatic and had anti-tissue transglutaminase (anti TTG IgA) positive antibodies. Endoscopically, six mucosal biopsies were taken from each patient, four each from the distal duodenum and two additional biopsy separately labelled was taken from bulb. Modified Marsh grading was used for morphological grading. Results: Of the total 108 Celiac disease patients, 60 (55.6%) were females and 48 (44.4%) were male patients. the overall mean age was 32.62±6.4 years. Prior to diagnosis of Celiac disease, symptoms median duration was 5.4 years with a range of 6 months to 40 years. The most prevalent clinical presentation were iron deficiency anemia 43% (n=46) and chronic diarrhea 32% (n=35) respectively. Other clinical presentation were chronic pain abdomen, infertility, short stature, and cirrhosis. Elevated TTG of 117.1 ± 49.82 U/ml was measured in all the patients with a range of 20 to 250 U/ml. The incidence of similar and different modified Marsh grade was in 66 (61.1%) and 42 (58.9%) respectively at both site. Out of 42 different modified March grade patients, higher mucosal atrophy in bulb and descending duodenum showed higher grade in 16 and 26 patients respectively. Isolated bulb involvement was seen in nine patients. Due to bulb biopsy, Celiac disease diagnosis was correctly done in these patients. Conclusion: The present study supported the villous atrophy and intraepithelial lymphocytosis patchy nature in biopsy specimens of celiac disease. The diagnosis of celiac disease improved with inclusion of duodenal bulb biopsies in our sampling protocol. Celiac disease patchy nature and distribution demonstrated different Marsh grades in different biopsy sites. The celiac disease diagnostic yield is increased by combining the bulb and the descending duodenum biopsy. Keywords: Celiac Disease, Duodenal bulb biopsy, Modified Marsh grade

S1354 Modification of the Tight Junctional Barrier in Human Duodenal Mucosal by Oral Zinc Administration in a Patient-Based Study: RNA-Seq and Western Immunoblot Analyses

Introduction: Mucosal barrier function is targeted in a wide variety of GI disease. Celiac disease, IBD, GI malignancies, sepsis and a wide variety of GI microbial infectious diseases all compromise the GI barrier. The tight junctional (TJ) complex is pivotal in this regard. The ability to safely modify the TJ complex and reduce its leakiness could be prophylactically and/or therapeutically useful. Methods: Patients 18-80 years of age presenting for endoscopic medical surveillance of gastroesophageal disorders but free of current small bowel disease were recruited for study. Patients were instructed to administer orally either a zinc-gluconate medication (12 patients) (26 mg elemental zinc) or a sodium gluconate placebo (11 patients), BID, for 14 days immediately prior to their EGD. During their EGD, standard duodenal bulb biopsies were taken for Western immunoblot analysis and for mRNA analysis. Biopsies were immediately flash frozen on dry ice in the procedures room and stored at -195oC for subsequent extraction. For protein studies, biopsies were homogenized in lysis buffer, sonicated and then analyzed by PAGE and Western immunoblot using a variety of antibodies to TJ proteins. Analysis of the biopsy transcriptome was performed by high-throughput RNA-seq. Results: Transcriptome analysis of over 20,000 genes revealed upregulation of many known zinc-regulated genes such as metallothioneins A, B, F, G, H, L, and M. The TJ barrier gene, occludin (OCLN), was also upregulated. Enrichment analysis using GSEA showed zinc upregulating several gene ontology (GO) biological processes as well as cellular components and pathways (Reactome). These included Zinc Ion Homeostasis (GO), Response to Zinc Ion (GO), Cell Junction Organization (Reactome), Cell-Cell Junction Assembly (GO), and Tight Junction (GO). Western immunoblot analyses showed statistically significant upregulation (two-tailed t-test) of the TJ proteins, claudin-2 and tricellulin, in mucosal biopsies of the zinc-treated group. Claudins -3 and -5 showed significant upregulations, and claudin-7, a significant down regulation, in a one-tailed t-test. Claudins -1, -4 and -18 showed no trend regarding a zinc-induced change. Conclusion: This is the first evidence of intended modification of TJ complexes in humans in situ. The results follow on a large body of published literature showing zinc-induced TJ changes and improved barrier function in a variety of human epithelial cell culture and animal models.

What is the Optimal Method Assessing for Persistent Villous Atrophy in Adult Coeliac Disease?

Methods of assessing gluten-free diet (GFD) adherence in adults with coeliac disease (CD) include serological testing, dietitian evaluation, questionnaires and repeat duodenal biopsies. Persisting villous atrophy (VA) is associated with CD complications, however gastroscopy with biopsies is expensive and invasive. This study aimed to assess the abilities of a duodenal bulb (D1) biopsy and the Celiac Dietary Adherence Test (CDAT) to detect persisting VA in adults with CD. A prospective observational study of adult CD patients referred for follow-up duodenal biopsies was performed. Quadrantic biopsies were taken from the second part of the duodenum (D2), in addition to a D1 biopsy. Patients underwent follow-up serological testing, and completed the CDAT and Biagi Score. These non-invasive adherence markers were compared against duodenal histology. 368 patients (mean age 51.0 years, 70.1% female) had D1 and D2 biopsies taken at follow-up gastroscopy. Compared to D2 biopsies alone, additional D1 biopsies increased detection of VA by 10.4% (p<0.0001). 201 patients (mean age 50.3 years, 67.7% female) completed adherence questionnaires and serology. When detecting VA, sensitivities and specificities of these markers were 39.7% and 94.2% for IgA- tTG, 38.1% and 96.4% for IgA-EMA, 55.6% and 52.2% for CDAT and 20.6% and 96.4% for the Biagi score. Bulbar biopsies increase detection of persisting VA by 10.4%. Serology, CDAT and Biagi performed poorly when predicting VA. The gold standard for predicting persisting VA remains repeat biopsy.

Morphological evaluation of bulb and distal duodenal biopsies in pediatric celiac disease with clinical and serological correlation.

An early correct diagnosis of celiac disease (CD) is fundamental to reversal of symptoms and prevention of complications in pediatric patients. Our aim was to evaluate the role of duodenal bulb biopsy by studying the degree of mucosal damage in the duodenal bulb (D1) and second part of the duodenum (D2) and correlating the findings with serum IgA anti-tTG levels. Pediatric patients (age <18 years) with clinical suspicion of CD and positive IgA anti-tTG titers were consecutively enrolled over a period of one year. Demographic variables, anthropometry, clinical history, laboratory values and endoscopic findings were studied. Endoscopic biopsies obtained from D1 and D2 were evaluated and assigned histopathologic grades that were correlated with serology. Descriptive statistics were employed. A total of 37 clinically suspected cases of pediatric CD were studied. The mean age was 6.7 years and the M:F ratio was 1:1.3. Thirty-two (32) children had varying degrees of growth impairment. Eight (8) children had only extra-intestinal symptoms. Thirty (30) children were anemic, hypoalbuminemia was seen in five (5) children while transaminitis was seen in two (2) children. IgA anti-tTG >300 U/ml was associated with Marsh-Oberhuber Grade 3 morphology at atleast one site. Low positive serology values should be confirmed by histopathology. Biopsies should be taken even in the absence of endoscopic abnormality. Additional D1 biopsies placed in a separate container can increase the diagnostic yield.

Diagnostic utility of multiple site duodenal biopsies in celiac disease.

Celiac Disease involves the small intestine patchily affecting more frequently the proximal small bowel but the histological changes have been observed till terminal ileum. Of late in addition to D2, the duodenal bulb (D1 region) biopsies have been found helpful in identifying a small group of patients with CD. Therefore, multiple site biopsies are recommended as histological changes are not uniform throughout small intestine. During this present 1.5 years prospective study, we evaluated 84 cases of suspected celiac disease with respect to the light microscopy (D1, D2, and D3 biopsy) and serology (anti tTg and or EMA). Histological examination was done according to Modified Marsh grading system. Out of 84 cases with raised anti tTg, the segmental biopsies significantly increased the diagnostic accuracy from 39/44 cases (88.6%) to 43/44 cases (97.7%) and 44/44 cases (100%) when D2 alone, D1 + D2 and D1 + D2 + D3 biopsies were evaluated, respectively. Of the suspected cases of celiac disease patients (tTg > 10 ULN and associated weight loss, diarrhea), additional D3 biopsy increased the diagnostic yield by 2.1%, compared to D1, D2 region biopsy and 6.38% compared to standard D2 biopsy alone. Of the 28 cases (tTg > 10 times ULN + EMA positive and associated weight loss, diarrhea), the potential celiac disease (histologically Type 1/Normal) cases reduced from 28.5% (standard D2 region alone) to 21.4% and 17.8% when additional biopsies were taken from D1 region and D3 region, respectively, and additional D3 biopsy increased the diagnostic yield by 10.8% (compared to standard D2 biopsy alone) and 3.7% (compared to D1 and D2 biopsy). We believe multiple sites duodenal biopsies including D3 region biopsies might increase the diagnostic accuracy of adult celiac disease in addition to sensitive and specific serologic tests.

Mucosal microbiome dysbiosis associated with duodenum bulb inflammation

BackgroundThere is high morbidity in clinical patients with duodenum bulb inflammation. Mucosa-associated microbiota, which are closely related to inflammatory processes, may have a pathogenic role, but the duodenum bulb microbial signature is poorly studied. ObjectiveThis study aimed to characterize microbial changes associated with duodenum bulb inflammation. MethodsMucosal biopsy is commonly used to assess microbial communities associated with the intestinal mucosa. Sixteen patients (8 with duodenum bulb inflammation and 8 controls) underwent gastroscopy, and duodenal bulb biopsies were obtained. Diagnoses were based on both endoscopic and histological findings. To determine microbiota composition and diversity, 454 pyrosequencing of bacterial 16S rRNA and multiple bioinformatics analyses were performed. OTU-level alpha diversity indices, such as the Chao1 richness estimator, abundance-based coverage estimator (ACE) metric, Shannon diversity index, and Simpson index, were calculated using the OTU table in QIIME. ResultsMore OTUs were identified in the normal samples (781) than in the inflammatory samples (553). Metastats analysis identified 19 phyla and 97 genera that were significantly different between the two groups, and the beta diversity was significantly different between the two groups (unweighted UniFrac: P = 0.001; weighted UniFrac: P = 0.001). For all individuals, composition analyses showed that the most abundant phyla in the duodenal bulb samples were Fusobacteria, Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria. The phylogenetic diversity of the microbiota in the duodenal bulbs of healthy volunteers was higher than that in volunteers with inflammation. Dominant microbes differed between the DN samples and DI samples. The most frequently represented genera in the DN samples were Cetobacterium, Aeromonadaceae, and Clostridium (accounting for 58.4%, 8.5%, and 4.8% of the total, respectively), and the dominant genera in the DI samples were Cetobacterium, Cupriavidus, and Helicobacter (accounting for 43.6%, 13.1%, 4.5% of the total, respectively). Significant differences in the microbiota were observed between those exhibiting an inflammatory state and the controls. ConclusionsThese results confirm that the dominant species in duodenum bulbs differ between healthy subjects and patients with inflammation and that mucosal microbiome dysbiosis is involved in the development of duodenum bulb inflammation.

Duodenal bulb biopsy in the diagnostic work-up of coeliac disease.

Coeliac disease (CD) is an autoimmune enteropathy which can present with patchy mucosal lesions. The aim of the present study is to investigate the significance of duodenal bulb biopsy in the diagnostic work-up of CD in both pediatric and adult patients, and to highlight the key points for pathologists. D1 (duodenal bulb) and D2 (distal duodenum) biopsies of 153 newly diagnosed serology-positive CD patients were evaluated for villous/crypt ratio and intraepithelial lymphocyte (IEL) counts on CD3-stained slides and were classified according to Marsh. Mucosal pathology was patchy in 15% (13% only D1 and 2% only D2) of patients, and 85% of patients had diffuse mucosal pathology involving both D1 and D2 biopsies which showed concordant histology in 60% and discordant in 25% of the cases. Though majority of the patients (75%) with only D1 involvement were pediatric cases, no significant difference was found between pediatric and adult patients when all cases were considered (17 vs 14%). Our results clearly indicate that without D1 sampling, diagnosis of CD would have been missed in a significant number of cases (13%), thereby highlighting the importance of taking duodenal biopsies from multiple sites in the diagnostic work-up of CD. We, therefore, conclude that every biopsy piece from both D1 and D2 should be carefully evaluated for the whole spectrum of mucosal changes caused by gluten ingestion and classified using a scheme based on Marsh to allow recognition of mild lesions.

The INSPIRE Bio-Resource Research Platform for Healthy Aging and Geroscience: Focus on the Human Translational Research Cohort (The INSPIRE-T Cohort)

BackgroundThe Geroscience field focuses on the core biological mechanisms of aging, which are involved in the onset of age-related diseases, as well as declines in intrinsic capacity (IC) (body functions) leading to dependency. A better understanding on how to measure the true age of an individual or biological aging is an essential step that may lead to the definition of putative markers capable of predicting healthy aging.ObjectivesThe main objective of the INStitute for Prevention healthy aging and medicine Rejuvenative (INSPIRE) Platform initiative is to build a program for Geroscience and healthy aging research going from animal models to humans and the health care system. The specific aim of the INSPIRE human translational cohort (INSPIRE-T cohort) is to gather clinical, digital and imaging data, and perform relevant and extensive biobanking to allow basic and translational research on humans.MethodsThe INSPIRE-T cohort consists in a population study comprising 1000 individuals in Toulouse and surrounding areas (France) of different ages (20 years or over — no upper limit for age) and functional capacity levels (from robustness to frailty, and even dependency) with follow-up over 10 years. Diversified data are collected annually in research facilities or at home according to standardized procedures. Between two annual visits, IC domains are monitored every 4-month by using the ICOPE Monitor app developed in collaboration with WHO. Once IC decline is confirmed, participants will have a clinical assessment and blood sampling to investigate markers of aging at the time IC declines are detected. Biospecimens include blood, urine, saliva, and dental plaque that are collected from all subjects at baseline and then, annually. Nasopharyngeal swabs and cutaneous surface samples are collected in a large subgroup of subjects every two years. Feces, hair bulb and skin biopsy are collected optionally at the baseline visit and will be performed again during the longitudinal follow up.Expected ResultsRecruitment started on October 2019 and is expected to last for two years. Bio-resources collected and explored in the INSPIRE-T cohort will be available for academic and industry partners aiming to identify robust (set of) markers of aging, age-related diseases and IC evolution that could be pharmacologically or non-pharmacologically targetable. The INSPIRE-T will also aim to develop an integrative approach to explore the use of innovative technologies and a new, function and person-centered health care pathway that will promote a healthy aging.

Duodenal Bulb Histology in Paediatric Celiac Disease: A Case-Control Study.

BackgroundControversy exists about optimal methods for duodenal biopsy in diagnosis of celiac disease (CD), in terms of both number of samples and anatomic location. The reliability of duodenal bulb biopsy has been questioned given that normal bulb architecture may mimic disease. However, multiple studies have reported patients with CD have histopathological lesions limited to proximal changes in the duodenal bulb alone.MethodsWe retrospectively compared duodenal and duodenal bulb histology in a population of paediatric patients with CD and compared with a population of nonceliac controls at Stollery Children’s Hospital, 2010 to 2012.ResultsFifty-seven paediatric patients diagnosed with CD and 16 nonceliac controls were included in the study. Fifty-three celiac patients (93.0%) had histopathology consistent with CD (modified Marsh score of 3A, 3B or 3C) in the duodenal bulb. The modified Marsh classification differed significantly between duodenum and duodenal bulb in nine celiac patients (15.8%). Of these, five (8.8%) had Marsh 3 in the bulb and Marsh 0 in the distal duodenum. Among controls, no patients had villous atrophy in either the distal duodenum or duodenal bulb, and all patients had a modified Marsh score of 0 at both sites.ConclusionsThe results of this study reinforce that duodenal bulb samples are critically important for diagnosing CD in paediatric patients. We suggest that duodenal bulb samples be submitted in separate containers from distal duodenal samples to facilitate accurate interpretation. In contrast to prior reports, we found villous blunting and intraepithelial lymphocytosis are actually uncommon findings in paediatric patients with nonceliac gastrointestinal disorders.

Clinicopathological features of duodenal bulb biopsies and their relationship with upper gastrointestinal diseases

AimTo assess the prevalence of the lesions in duodenal bulb mucosa and the relationship between duodenal lesions and upper gastrointestinal diseases, including helicobacter pylori infection. MethodsClinical, endoscopic and pathological data of the cases with duodenal bulb and gastric mucosal biopsy from January 2005 to May 2017 were analyzed retrospectively. ResultsA total of 3540 patients were enrolled. The biopsy from protuberant lesions with endoscopic morphology are mostly duodenal gastric heterotopia or adenoma. The biopsy from duodenal ulcers are often observed in inflammatory changes and gastric metaplasia.Patients with gastric heterotopia had a significantly lower prevalence of chronic atrophic gastritis, intestinal metaplasia, and gastric ulcer; and much higher prevalence of gastroesophageal reflux disease and gastric fundic polyps.Patients with gastric metaplasia had been positively associated with gastroesophageal reflux disease, and negatively associated with gastric fundic polyps.There were positive correlation between helicobacter pylori infection and duodenal active inflammation, Brunner gland hyperplasia, gastric metaplasia and duodenal ulcer. However, Patients with gastric heterotopia in bulb had been negatively associated with helicobacter pylori infection. ConclusionsThe mucosa lesions in duodenal bulb were associated with concurrent gastric fundic gland polyps, gastroesophageal reflux disease, duodenal ulcer, and helicobacter pylori infection.

Efficacy of duodenal bulb biopsy for diagnosis of celiac disease: a systematic review and meta-analysis.

Background and study aims Although duodenal biopsy is considered the “gold standard” for diagnosis of celiac disease, the optimal location of biopsy within the small bowel for diagnosis remains unclear. The primary aim of this study was to perform a structured systematic review and meta-analysis to evaluate the diagnostic utility of endoscopic duodenal bulb biopsy for celiac disease. Patients and methods Searches of PubMed, EMBASE, Web of Science, and Cochrane Library databases were performed from 2000 through December 2017. Review of titles/abstracts, full review of potentially relevant studies, and data abstraction was performed. Measured outcomes of adult and pediatric patients included location of biopsy, mean number of biopsies performed, and diagnosis of celiac disease as defined by the modified Marsh-Oberhuber classification. Results A total of 17 studies (n = 4050) were included. Seven studies evaluated adults and 11 studies assessed pediatric populations. Mean age of adults and pediatric patients was 46.70 ± 2.69 and 6.33 ± 1.26 years, respectively. Overall, sampling from the duodenal bulb demonstrated a 5 % (95 % CI 3 – 9; P < 0.001) increase in the diagnostic yield of celiac disease. When stratified by pediatric and adult populations, duodenal bulb biopsy demonstrated a 4 % (95 % CI: 1 to 9; P < 0.001) and 8 % (95 % CI: 6 to 10; P < 0.001) increase in the diagnostic yield of celiac disease. Non-celiac histologic diagnoses including Brunner gland hyperplasia and peptic duodenitis were reported more commonly in the duodenal bulb as compared to the distal duodenum with an increase in diagnostic yield of 4 % (95 % CI 3 – 5; P < 0.001) and 1 % (95 % CI 1 – 2; P < 0.001), respectively. Conclusions Based upon our results, biopsy and histologic examination of duodenal bulb during routine upper endoscopy increases the diagnostic yield of celiac disease.

A prospective study to evaluate the role of duodenal bulb biopsy in the diagnosis of celiac disease.

Celiac disease (CeD) requires a biopsy from the small intestine to confirm the diagnosis. Conventionally, duodenal bulb (D1) was avoided as a biopsy site due to histological confounding factors at this site. However, sometimes, the bulb mucosa is the only affected site. The aim of the present study was to assess changes in duodenal bulb histology and compare it to distal duodenal histology and to analyze whether the addition of duodenal bulb biopsy increases the diagnostic yield of the CeD. It was a prospective study comprising of 98 patients of CeD who were symptomatic clinically and had positive anti tissue transglutaminase (tTG) antibody. Endoscopically four mucosal biopsies were taken, two each from the bulb and distal duodenum, and morphology was graded as per modified Marsh grade. Iron deficiency anemia (40%) was a most common clinical presentation followed by chronic diarrhea (30%). Sixty patients showed same Marsh grade and 38 showed different Marsh grade at both sites. Patients who were showing the difference in the Marsh grade at the two biopsy sites, in place of; descending duodenum showed higher grade in 24 patients while higher mucosal atrophy was documented in the bulb in 14 patients. No patient of CeD had isolated D1 involvement. In eight patients, the correct diagnosis of CeD could be made only because of bulb biopsy. Majority of the patients had no classical symptoms. Different Marsh grade at the two biopsy sites was documented demonstrating the patchy distribution of CeD. Combining biopsy from both bulb and descending duodenum maximizes the diagnostic yield of the CeD.

Partial Recovery of Proprioception in Rats with Dorsal Root Injury after Human Olfactory Bulb Cell Transplantation.

Transplanted human olfactory ensheathing cells (hOECs) were mixed with collagen into a unilateral transection of four dorsal roots (C6-T1) in a rat model. By mixing with collagen, the limited numbers of hOEC were maximized from an olfactory bulb biopsy and optimize cavity filling. Cyclosporine was administered daily to prevent immune rejection. Forelimb proprioception was assessed weekly in a vertical climb task. Half of the rats receiving hOEC transplants showed some functional improvement ("responders") over six weeks of the study while the other half did not ("nonresponders") and performed similarly to "injured only" rats. Transplanted cells were seen at both one week and six weeks after the surgical procedure; many were concentrated within the lesion cavity, but others were found with elongated processes in the overlying connective tissue. There were some fibers in the injury area associated with transplanted cells that were immunostained for neurofilament and TUJ1. Responder and nonresponder rats were compared with regard to microglial activation within the deep dorsal horn of cervical levels C7, C8 and also axon loss within the cuneate fasciculus at cervical level C3. Little difference was seen in microglial activation or axonal loss that could account for the improved proprioception in the responders group. This preliminary study is the first to transplant human olfactory bulb cells into a rat model of dorsal root injury; by refining each component part of the procedure, the repair potential of OECs can be maximized in a clinical setting.

Is it Celiac Disease or CVID-Associated “Celiac-Like Disease”?

Common Variable Immunodeficiency (CVID) is the most common primary immunodeficiency in adults. Gastrointestinal (GI) symptoms are common in CVID patients, and up to 50% of patients have chronic diarrhea with malabsorption. CVID is commonly associated with intestinal villous atrophy mimicking Celiac Disease (CD). The prevalence of true CD in CVID remains unknown. We present a case of gluten-free diet (GFD) responsive CD in a patient with CVID. A 67 year old Caucasian female with long standing history of CVID on IgG replacement therapy, chronic kidney disease, and severe iron deficiency presented for evaluation of persistent nausea, anorexia, weight loss and non-healing chronic leg ulcer. She underwent EGD after initial anti tissue transglutaminase (anti-TTG) was found to be 17 U/mL, which showed marked villous blunting and mild lymphocytic infiltration with inflammatory pathology. Enteral access was obtained for nutritional supplementation in a setting of ongoing weight loss. An EGD 1 month after high fidelity enteral GFD showed resolution of inflammatory changes and improvement in villous blunting. (Table 1) The ensuing 3 months of strict diet adherence resulted in removal of the feeding tube with resolution of anorexia and nausea, as well as a 35 pound weight gain with return to healthy baseline weight. A dramatic improvement in her chronic leg wound was observed that had previously been resistant to all therapies. Anti-TTG levels at 4 month mark improved to 8 U/mL. Common variable immunodeficiency (CVID) with an estimated prevalence of 1/100,000 to 1/50,000 is the most common symptomatic primary antibody deficient syndrome. Up to 50% of CVID patients have chronic diarrhea with malabsorption. CVID is commonly associated with intestinal villous atrophy mimicking Celiac Disease (CD). Due to unreliable antibody testing and inconsistent response to GFD making a diagnosis of CD in CVID remains a challenge. Based on a few recent studies, the only criterion to confirm CD in CVID population is histological response to GFD. Our patient had significant improvement in symptoms and showed a histological response with GFD. CVID and CD can co-exist, hence a high level of clinical suspicion is warranted to diagnose CD in the CVID population.Table: Table. Sequential Duodenal Bulb Biopsies

Rospective Study of the Role of Duodenal Bulb Biopsies in the Diagnosis of Celiac Disease

Background and Aim: Celiac disease is a systemic immune mediated disorder triggered by dietary gluten in genetically susceptible persons. D1 had been avoided as a possible biopsy site because of concerns over presence of Brunner's glands, gastric metaplasia, peptic duodenitis, and presumed reduced villous height. Prospective data from small studies has suggested that D1 may be the only site of villous atrophy in newly diagnosed celiac disease (ultra-short celiac disease). We wanted to verify this concept that whether the addition of duodenal bulb biopsy increase the diagnostic yield of celiac disease and was there any difference in histological grading between the two sites. Methods: We studied 50 cases of celiac disease those who were symptomatic clinically and positive for celiac serology. Endoscopically four mucosal biopsies each, were taken from the bulb and distal duodenum of each patient and morphology graded as per Modified Marsh grade. Results: In our study of 50 patients, out of 100 biopsies, 60 biopsies (30 patients) showed same Marsh grade in the bulb and descending duodenum and 40 biopsies (20 patients) showed different Marsh grade at both the sites. Patients those have different Marsh grade, descending duodenum showed higher grade than the bulb part in 13 patients while 7 patients showed higher mucosal atrophy in bulb than descending duodenum. Although there was a difference in morphological grade at both the sites, in none of the cases, the bulb biopsy was positive with negative distal duodenal biopsy for celiac disease or vice versa. Conclusion: Biopsy from both sites are mutually exclusive. Taking biopsy samples from both sites maximize the diagnostic yield. Diagnostic yield from bulb biopsy is as good as distal duodenum and could substitute D2 biopsy in paediatric patients. The authors have none to declare.

Optimizing the diagnosis of celiac disease.

The diagnostic approach in celiac disease is continuously evolving as our understanding of its pathophysiology improves. This review aims to provide a summary of contemporary work that supports optimization of the diagnosis of this common yet underdiagnosed condition. The recently updated National Institute of Clinical Excellence and European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines and the contentious biopsy-free diagnostic approach will be discussed. We will review the evidence advocating optimal biopsy techniques such as single bite biopsy and controversial bulb biopsy sampling to increase diagnostic yield. Recent data providing phenotypical characterization and clinical outcomes of celiac subtypes such as potential celiac disease, seronegative celiac disease and ultrashort celiac disease will be covered. We will present emerging evidence on novel case finding strategies with point of care tests. Promising novel markers for celiac disease such as serum intestinal fatty acid binding protein and in-vitro gluten challenge will be included. Recent work has demonstrated the clinical significance of the celiac disease subtypes, emphasizing the importance of careful diagnosis and recognition. There is a move toward a less invasive and perhaps more cost-effective diagnostic approach in celiac disease, but duodenal biopsy remains the gold standard at present for all adults and the majority of pediatric patients.