Duodenal Bulb Biopsy Research Articles

The Role of Duodenal Bulb Biopsy in the Diagnosis of Celiac Disease in Children

It is suggested that for celiac disease (CD) diagnosis, biopsies should also be taken from the duodenal bulb. Whether bulb biopsies suggestive of CD can be found on upper gastrointestinal endoscopy (EGD) done for reasons other than CD diagnosis is not clear. The aim of our study was to evaluate the contribution of routine bulb biopsies to the diagnosis of CD, when taken regardless of prior suspicion of CD. The study included 96 children who underwent EGD for suspected CD and a control group of 69 children who underwent EGD for reasons other than CD. The mucosal changes were evaluated using the Marsh-Oberhuber classification. Among the 87 children diagnosed with CD, we identified 6 patients (7%) with typical histologic findings only in the bulb (Marsh 3), but also 1 patient (1.1%) with findings only in the distal duodenum (Marsh 2). In 20 patients (23%) the histological changes were more severe in the bulb. One patient had more prominent findings in the second part of the duodenum. None of the control patients had histological changes compatible with CD in the bulb or the second part of the duodenum. Our findings suggest that when CD is suspected, biopsies should be taken from both locations (bulb and second part) as mucosal changes may emerge only at one site. Nevertheless, the presence of characteristic histology on duodenal bulb biopsies might be sufficient for the diagnosis of CD.

Prospective study of the role of duodenal bulb biopsies in the diagnosis of celiac disease

Studies have demonstrated that villous atrophy in celiac disease is patchy and have suggested that duodenal bulb biopsies aid in diagnosis. To determine the role of the addition of duodenal bulb biopsies to distal duodenum (D2) biopsies in the diagnosis of celiac disease. Prospective, case-control study. Tertiary referral hospital. Patients undergoing upper endoscopy with biopsy for diagnosis or follow-up of celiac disease and control patients. Blinded review of duodenal biopsy samples. Increasing the yield as well as accuracy of the histologic diagnosis of celiac disease with the addition of bulb biopsies. Of 128 patients enrolled in the study, 67 had celiac disease. Of 1079 biopsy specimens, only 319 (30%) were adequate for complete histologic analysis, resulting in 40 celiac patients and 40 control patients for analysis. Of the 40 celiac patients, 35 (87.5%) had atrophy in either the bulb or D2, 30 (75%) exhibited atrophy at both sites with an identical grade of atrophy seen in 18 patients (45%). Fourteen patients (35%) had identical types of Marsh lesions in both biopsy sites. Twelve patients (30%) had atrophy detected in the bulb, D2, or both, but lacked intraepithelial lymphocytes and thus could not be assigned a Marsh grade. Five patients (13%) had a diagnosis of celiac disease based on findings in the bulb biopsy only. Small sample size and study performed in an academic medical center. Our study confirms the patchy nature of villous atrophy as well as intraepithelial lymphocytosis in biopsy specimens from individuals with celiac disease. Adding duodenal bulb biopsies to our sampling regimen increased the diagnostic yield of celiac disease.

Bulb biopsies for the diagnosis of celiac disease in pediatric patients

Celiac disease (CD) is a gluten-dependent enteropathy. The current standard for diagnosing CD involves obtaining 4 biopsy samples from the descending duodenum. It has been suggested that duodenal bulb biopsies may also be useful. To assess the utility of bulbar biopsies for the diagnosis of CD in pediatric patients. Prospective study. Single center. Forty-seven consecutively enrolled pediatric patients with celiac serologies and a clinical suspicion of CD. All patients underwent EGD, and 4 biopsy samples were obtained from the duodenal bulb and 4 from the descending duodenum of each child. The pathologist blindly reported the Marsh histological grade for the diagnosis of CD of the bulb and descending duodenum. The diagnosis of CD was histologically confirmed in 89.4% (42/47) of the cases of biopsy samples obtained from the descending duodenum and in all 47 obtained from the bulb. In 35 patients (74.5%), histology was the same in the bulb and duodenum; in 11 (23.4%) cases, the grade of atrophy was higher in the bulb than in the descending duodenum, and 5 (10.6%) had bulb histology positive for CD but negative duodenal findings. One child (2.1%) had a higher histological grade in the duodenum than in the bulb. The diagnostic gain with bulbar biopsies was 10.6%. Small sample and absence of a comparison group (asymptomatic children with normal CD antibodies). We suggest examining 4 biopsy samples from the duodenal bulb and 4 from the descending duodenum to improve diagnostic accuracy of CD.

PTH-087 Routine duodenal bulb biopsy in coeliac disease: a paradigm shift in our clinical practice?: Abstract PTH-087

<h3>Introduction</h3> Historically Brunner9s glands were thought to interfere with interpretation of duodenal bulb biopsies. Recent reports suggest that the duodenal bulb may be the only site to demonstrate villous atrophy (VA) in coeliac disease (CD). There are few data on the prevalence of lesions in non-coeliac patients. <h3>Methods</h3> We aimed to compare the histological findings in the duodenal bulb and distal duodenum of patients with CD against controls having gastroscopy with duodenal biopsy. Indications included positive coeliac serology, family history, diarrhoea, and iron deficiency anaemia. A total of 215 patients were prospectively accrued. Biopsies were graded using the Marsh criteria by a single pathologist. <h3>Results</h3> 215 patients, (150 female, 65 male) median age 48 years (range 16-89) were analysed. 17 patients demonstrated VA in the bulb only. 1 had VA in distal duodenum only. 1 control patient with HIV enteropathy had VA in the bulb and distal duodenum. Both new diagnosis CD (8%, p&lt;0.05) and CD in remission (15%, p&lt;0.001) were more likely than controls to have VA in the bulb alone. When comparing the Marsh grade score for the bulb and the duodenum, 24/59 of patients in remission had a discrepancy of at least 1 Marsh grade compared with only 8/91 new diagnosis CD (p&lt;0.0001), and 4/65 controls (p&lt;0.0001). 21/24 of the patients in remission with a discrepancy had the more severe lesion in the bulb (Abstract 087). <h3>Conclusion</h3> Villous atrophy may be present only in the duodenal bulb. In this study 7/91 (8%) of new diagnosis CD and 9/59 (15%) of CD in remission demonstrated VA in the bulb alone. When looking at CD in remission, 41% of patients have a discrepancy in severity of the histological lesion between the bulb and the duodenum; in this group the most severe lesion is nearly always in the bulb. This is the first study to demonstrate that optimal assessment of both new diagnosis CD and those in remission requires a duodenal bulb biopsy in addition to distal duodenal biopsies.

Celiac disease

To summarize recent advances in celiac disease published between August 2008 and July 2009. Celiac disease affects nearly 1% of most populations but remains largely unrecognized. In the last year, work has shown that the prevalence of celiac disease has increased dramatically, not simply due to increased detection. Also, undiagnosed celiac disease may be associated with increased mortality. Significant progress has been made in understanding how gliadin peptides can cross the intestinal border and access the immune system. New genetic loci and candidate genes that may contribute to the risk of celiac disease and its overlap with type 1 diabetes mellitus have been identified. Novel deamidated gliadin peptides antibodies have better diagnostic accuracy over native gliadin-based tests. The inclusion of duodenal bulb biopsy specimens may increase the rate of celiac disease detection. The spectrum of celiac disease likely includes a minority of patients with mild enteropathy. A practical seven-item instrument may facilitate standardized evaluation of gluten-free diet adherence. Finally, refractory celiac disease, although rare, is associated with a poor prognosis. Celiac disease is a global health problem that requires a multidisciplinary and increasingly cooperative multinational research effort.

Importance of duodenal bulb biopsies in children for diagnosis of celiac disease in clinical practice

BackgroundThe patchy nature of villous lesion in celiac disease is increasingly being recognized. Current guidelines recommend four endoscopic duodenal mucosal biopsies from the second or more distal part of the duodenum to confirm the diagnosis of celiac disease. The purpose of the study was to investigate the usefulness of duodenal bulb mucosal biopsies in confirming the diagnosis of celiac disease in everyday clinical practice.MethodsAll patients with a positive tissue-transglutaminase antibody requiring biopsy-confirmation of celiac disease over a two-year period were studied. Two endoscopic biopsies were taken from the duodenal bulb and four biopsies from the second (or distal) part of the duodenum.ResultsThirty-five patients were included, mean age 8.1 (± 4.7) years. Thirty-one (88.6%) patients had abnormal distal duodenal biopsies, one had Marsh type 1, one had Marsh type 2 and twenty-nine had Marsh type 3 lesion. All but two patients with abnormal distal duodenal biopsies also had abnormal bulb biopsies. Four (11.4%) patients had normal distal duodenal biopsies but abnormal bulb biopsies. Of these, one patient had Marsh type 2 and three had Marsh type 3 lesion. The distal duodenum was also grossly normal in these four patients. The histological diagnosis of celiac disease would not have been possible in these four cases with distal duodenal biopsies only.ConclusionThe lesion in celiac disease in children can be patchy with duodenal bulb mucosa being the only area showing histological changes. The recommendations regarding the site of biopsies should be revised to include biopsies not only from distal duodenum but also from bulb to improve the diagnostic yield.

Variability of Histopathological Changes in Childhood Celiac Disease

Adult studies of celiac disease (CD) have shown that duodenal mucosal histopathological changes may be patchy, and the diagnostic utility of duodenal bulb biopsies is believed to be limited. Few related pediatric data exist. We assessed the prevalence of variable biopsy findings and duodenal bulb involvement in children with CD, as well as its association with clinical parameters. A total of 198 consecutive cases of CD diagnosed at the Children's Hospital during 2001-2005 were analyzed. All biopsies were scored by a pathologist blinded to the clinical data using the Marsh criteria. Mucosal changes were classified as focal if changes consistent with CD and normal mucosa were found within a single biopsy fragment. Patchiness was defined as variation of at least one Marsh grade between separate fragments in a biopsy set. The median age was 9.3 years; 62% were female. An average of 3.6 biopsy samples was obtained per case. In 101 cases, biopsy samples were obtained from the duodenal bulb and the second portion of the duodenum. Focality was present in biopsy samples collected from 36 (18%) cases. Patchiness was found in 105 (53%) cases, and at least 1 normal biopsy fragment was present in 71 (36%) cases. In 10 cases, only the bulb biopsies were diagnostic of CD. There was no association with the clinical features examined. Duodenal involvement in pediatric CD is frequently patchy and may show variable severity even within a single biopsy fragment. Variability cannot be predicted by clinical characteristics. Multiple endoscopic biopsies, including the duodenal bulb, should be obtained in suspected pediatric CD cases to maximize diagnostic yield.

The Duodenal Bulb Biopsy “Myth”: Is There Now Enough Evidence to Change Clinical Practice?

Department of Gastroenterology and Hepatology, Royal Hallamshire Hospital, Sheffield, UK There are no external funding grants or support. No conflicts of interest exist.

Is There Any Value in Performing Duodenal Bulb Biopsies for Diagnosing Celiac Disease?

Is There Any Value in Performing Duodenal Bulb Biopsies for Diagnosing Celiac Disease?

Diagnostic value of duodenal bulb biopsy in patients with celiac disease

Aims Multiple endoscopic biopsies from the descending duodenum are usually recognised as the standardised method for the evaluation of mucosal changes in celiac disease. Generally, the duodenal bulb is not considered a useful site for biopsies, due to some difficulties in histological evaluation. We wanted to verify if duodenal bulb histology established a correct diagnosis of celiac disease. Methods Fifty-two consecutive children with suspicion of celiac disease and positive anti-tissue transglutaminase (tTG) antibodies were enrolled in a prospective fashion. During upper gastrointestinal (GI) endoscopy, two of four biopsies each were taken from descending duodenum distal to the papilla of Vater (D 2 ) and duodenal bulb (B). The histological lesions were classified according to the modified Oberhuber classification by a single pathologist who was blinded to the site of biopsy. Results A total of 52 children had a final diagnosis of CD. The main presenting symptoms were diarrhea 43/52 (82.7%), anaemia 40/52 (76.9%) and failure to thrive 32/52 (61.5%). All had type 3 lesion– (a) mild, (b) moderate, or (c) severe– in at least one site. There were 45/52 (86.5%) CD patients with lesions of identical type (2 or 3) in both biopsy sites. The number of intraepithelial lymphocytes was not significantly different in the descending part of the duodenum as compared to the duodenal bulb. Conclusions The biopsies from the duodenal bulb and second part of the duodenum in celiac disease can be equally representative of the underlying disease. The diagnosis of celiac disease can reliably be made even if biopsies are taken from the duodenal bulb rather than distal duodenum or jejunum.

Duodenal Bulb Biopsies in Celiac Disease: A Multicenter Study

Celiac disease (CD)-related lesions have been reported in duodenal bulb biopsies, sometimes the bulb mucosa being the only one affected. The aim was to verify in a significant series whether histological lesions are always present in the bulb of celiac patients, what is the prevalence of lesions when isolated to the bulb, and if similar lesions are present in nonceliac subjects. We studied 665 children with CD (241 males, range 9 months-15 years, 8 months), at diagnosis on a gluten-containing diet, and 348 age- and sex-matched gastroenterological controls submitted to upper endoscopy for gastroenterological complaints. During endoscopy, multiple biopsies (1 bulb and 4 distal duodenum samples) were taken. Anti-endomysium antibodies were evaluated by immunofluorescence method, anti-human tissue-transglutaminase antibodies by an enzyme-linked immunosorbent assay or radioimmunoassay. Human leukocyte antigen-DRB1, -DQA1, and -DQB1 genes were typed by polymerase chain reaction sequence-specific primers repeat method. In all of the patients with CD, histological lesions were present in the bulb sample; in 16 of them, the lesions were present only in the bulb. Patchy villous atrophy was found in 20 children. All of the patients with CD were anti-endomysium and/or antitransglutaminase positive. The controls showed neither autoantibody positivity nor mucosal changes compatible with CD. This study demonstrated that CD-related histological lesions are always present in the bulb; sometimes this specific site is the only one affected. Therefore, we suggest taking 2 biopsies from the bulb and 2 from the distal duodenum for CD diagnosis.

Diagnostic duodenal bulb biopsy in children with celiac disease

Background. The gold standard of Celiac Disease (CD) diagnosis is up to now based on characteristic histological features, according to Marsh criteria modified by Oberhuber (M/O). The biopsies are usually performed in descending duodenum, 1 for each quadrant (Seattle's criteria). Only few papers focused on the role of duodenal biopsies in diagnosis of CD.

Patchy villous atrophy in adult patients with suspected gluten-sensitive enteropathy: is a multiple duodenal biopsy strategy appropriate?

The current internationally accepted gold standard for diagnosing celiac disease is a small-bowel biopsy demonstrating villous atrophy. However, it has been suggested that the diagnosis might not be considered as confirmed if the villous atrophy is patchy. Our aim was to assess whether there is an optimal duodenal biopsy strategy for detecting villous atrophy in adult patients with suspected gluten-sensitive enteropathy. Patients who had positive endomysial or tissue transglutaminase antibodies were prospectively recruited. Nine biopsies were taken from the duodenum: one from the duodenal bulb, four from the proximal duodenum, and four from the distal duodenum. Each biopsy was graded according to the Marsh criteria. All possible biopsy regimes were evaluated for their ability to detect the presence and severity of villous atrophy. A total of 56 patients were recruited (23 men [41 %], 33 women [59 %]; mean age 47, range 16 - 85): 53/56 patients had villous atrophy present in at least one biopsy; 10/53 patients had biopsy specimens that showed "patchy" villous atrophy. In all 53 patients with villous atrophy this was detected by taking a minimum of three biopsies (sensitivity 100 %, 95 % confidence interval [CI] 93.2 % - 100 %). However, this strategy always incorporated a duodenal bulb biopsy. The most severe degree of villous atrophy in all 56 patients was only detected by using a five-biopsy regime (sensitivity 100 %, 95 % CI 93.6 % - 100 %). In this study we observed that villous atrophy in adult patients with suspected gluten-sensitive enteropathy (antibody-positive) is patchy. For this reason we would suggest a minimum of three biopsies, incorporating a duodenal bulb biopsy, to ensure that villous atrophy is detected. However, a five-biopsy regime is required for recognition of the most severe lesion.

3 P Duodenal bulb biopsy in diagnosis of childhood coeliac disease

3 P Duodenal bulb biopsy in diagnosis of childhood coeliac disease

Prevalence of gastric metaplasia in the duodenal bulb is low in Helicobacter pylori positive non-ulcer dyspepsia patients.

Gastric metaplasia in duodenum is a common phenomena in duodenal ulcer patients. However, the role of gastric metaplasia in patients with non-ulcer dyspepsia is not clear. It is not known either whether Helicobacter pylori infected non-ulcer patients who are CagA-seropositive have gastric metaplasia in duodenum more often than CagA-negative patients. To compare prevalence of gastric metaplasia in duodenum in non-ulcer dyspepsia patients according to Helicobacter pylori status. A series of 400 unselected dyspeptic patients in primary care were investigated. Patients with no endoscopic evidence of organic disease (n=236) were enrolled in the study. Duodenal bulb and gastric biopsies were collected, as well as blood samples for Helicobacter pylori determination. There were no differences between CagA-seropositive and -seronegative Helicobacter pylori infected patients as far as concerns gastric metaplasia in duodenal bulb (20% vs 25%). Helicobacter pylori negative non-ulcer patients more often had gastric metaplastic changes (46%, p<0.0001) in duodenum. Helicobacter pylori infection has no major role in development of gastric metaplasia in duodenal bulb in non-ulcer dyspeptic patients. Furthermore, it does not result in positive CagA-serology, an increased risk for gastric metaplasia compared with CagA-seronegative cases.

Utility of endoscopic biopsy samples to quantitate human duodenal ion transport

Duodenal mucosal bicarbonate secretion (DMBS) prevents acid-peptic damage and facilitates nutrient absorption. DMBS is diminished in patients with duodenal ulcers and is normalized after Helicobacter pylori eradication. The measurement of DMBS in human patients in vivo requires intubation with a multi-lumen balloon tube and permits limited testing with putative agonists and antagonists. Our purpose was to develop a means to investigate transport events in human duodenal biopsy samples in vitro. After validation studies in a modified mini-Ussing chamber were performed, duodenal transport events were examined in proximal endoscopic biopsy samples from normal volunteers (n = 17). Tissues were mounted in modified mini-Ussing chambers (volume 2.5 ml, surface area 3.8 mm 2). Short circuit current (I sc), potential difference (PD), and bicarbonate secretion were determined under basal conditions and after stimulation with graded doses of prostaglandin E 2 (PGE 2)(10 −8 to 10 −4 mol/L) and dibutyryl cAMP (db-cAMP)(10 −4 to 10 −2 mol/L). Duodenal tissues remained viable for at least 2 hours and exhibited stable basal HCO 3-secretion and electrical parameters. Stimulation with PGE 2 and db-cAMP resulted in dose-related increases in both I SC and HCO 3-secretion ( P < .05) that were abolished by ouabain and anoxia. It is concluded (1) that human duodenal bulb biopsy samples maintain their inherent transport function in mini-Ussing chambers and (2) that by using this novel method it will be possible to define the transport events that modulate human duodenal secretion, in particular bicarbonate secretion, in both health and disease.

Relation between gastric acid output, Helicobacter pylori, and gastric metaplasia in the duodenal bulb.

Factors that determine gastric metaplasia in the duodenal bulb are ill defined. It is more common and extensive in the presence of high acid output and possibly in the presence of Helicobacter pylori. However, no quantitative relation between acid output and the extent of gastric metaplasia has been demonstrated and its relation to H pylori is uncertain. To determine the relation between H pylori infection and acid output and the presence and extent of gastric metaplasia in the duodenal bulb. subjects: H pylori positive and negative patients with duodenal ulcer and healthy controls were studied. Quadrantic duodenal bulb biopsy specimens were taken and the presence and extent of gastric metaplasia determined using a computer enhanced image intensifier. Basal and stimulated acid outputs were measured. gastric metaplasia was significantly (p < 0.05 more common and significantly (p < 0.05) greater in extent in patients with duodenal ulcer than in controls. Neither the prevalence or extent of gastric metaplasia was affected by H pylori status. There were significant (p < 0.01) direct correlations between acid output and extent of gastric metaplasia. Prevalence and extent of gastric metaplasia are not related to H pylori in controls, or in patients with duodenal ulcer. Rather, high acid response to gastrin may be more important.

Expression of trefoil peptides pS2 and human spasmolytic polypeptide in gastric metaplasia at the margin of duodenal ulcers.

Duodenal ulcers are associated with gastric metaplasia in the duodenum, both at the ulcer margin and at more distant sites in the duodenal bulb. pS2 and human spasmolytic polypeptide (hSP) are secretory peptides expressed in gastric epithelial cells and in gastric metaplasia. As these peptides may be important in ulcer healing, this study investigated the possibility that the expression of pS2 and hSP is increased in gastric metaplasia at the margin of duodenal ulcers. Duodenal bulb biopsy specimens from 12 duodenal ulcer patients were assessed. Sections were immunostained with monoclonal antibodies for pS2 and hSP. Cytoplasmic stain intensities were measured by an image analysis system and expressed as integrated optical density (IOD) units, In situ hybridisation for pS2 and hSP mRNA was carried out on parallel sections. Duodenal sections were also stained with diatase periodic acid Schiff/alcian blue to localise areas of gastric metaplasia. pS2 antigen staining in the duodenum was restricted to surface epithelial cells, and hSP to acinar and ductular components of Brunner's gland. mRNA localisation corresponded to immunostaining cells. In gastric metaplasia, pS2 expression was greater at the ulcer margin than away from the ulcer, as judged by the intensity of antibody staining (mean IOD units (SEM), 20.6 (3.3) v 9.5 (3.0); p < 0.001). There was a trend towards greater hSP staining at the ulcer margin but this did not achieve statistical significance. These findings support the putative role of pS2 and possible hSP in mucosal healing and providy further evidence for an autocrine 'ulcer-gastric metaplasia-repair' loop involving these trefoil peptides.

Effect of Helicobacter pylori eradication on gastric metaplasia of the duodenum.

Helicobacter pylori associated duodenal ulcers occur in patches of gastric metaplasia. The pathogenesis of gastric metaplasia is unclear, but it has been produced in experimental animals by acute injury and has been shown to be present to a greater extent of H pylori positive subjects. This study aimed to discover if gastric metaplasia regressed with eradication of H pylori or healing of duodenal ulcers, or both. Thirty two duodenal ulcer patients with H pylori infection confirmed by biopsy urease test and by antral histological examination were studied. Patients were treated with triple therapy (deNol 240 mg twice daily, amoxycillin 500 mg three times daily, and metronidazole 400 mg three times daily) for two weeks after the first endoscopy and were subsequently re-endoscoped. Three duodenal bulb biopsy specimens were obtained per patient at each endoscopy. Biopsy sections were stained with haematoxylin and eosin to determine the severity of duodenitis, and with diastase periodic acid-Schiff/alcian blue to assess the extent of gastric metaplasia. Slides were assessed by two histopathologists unaware of treatment status. H pylori was eradicated in 63% of subjects and all ulcers were healed at follow up. The median extent of gastric metaplasia at the start of treatment and 6-18 months (median 10) after treatment was compared in the two groups. Gastric metaplasia declined in eradicators from 16% to 8% (p < 0.05) while in non-eradicators there was no significant change (25% initially and at follow up). A positive relation between extent of gastric metaplasia and duodenal inflammation score was present before treatment (r(s) = 0.74, p < 0.001) and was unchanged after treatment in the non-eradicator group (r(s) = 0.89, p < 0.001). In the eradicator group, however, the inflammation score had significantly declined (p < 0.02) and the close relation with gastric metaplasia was no longer present. These results suggest that H pylori itself is at least in part responsible for producing gastric metaplasia of the duodenum.

Localization of infection by the microsporidian Enterocytozoon bieneusi in the gastrointestinal tract of AIDS patients with diarrhea.

We compared the level of Enterocytozoon bieneusi infection at different sites within the small intestine among patients with AIDS. The level of E. bieneusi infection of each patient biopsy was determined and compared using semi-thin plastic section light microscopy and transmission electron microscopy (TEM). Nine subjects with chronic diarrhea who had endoscopic biopsies of either proximal (bulb) or distal (fourth portion) duodenum plus proximal jejunum (just past ligament of Treitz), either simultaneously or within a few months of each other were studied. All patients had TEM-confirmed diagnoses of E. bieneusi intestinal microsporidiosis. The intensity of infection was always greater in biopsies taken from the patients' jejunum compared with those taken from the duodenal bulb. In one patient, the duodenal bulb biopsy was negative while the jejunal biopsy, taken at the same time, was positive. The distal duodenum was usually, but not always, equal to the jejunum in terms of parasite burden. Esophageal, gastric, and colorectal biopsies from these and other patients were negative for E. bieneusi. For the diagnosis of E. bieneusi to evaluate chronic diarrhea in AIDS patients, upper intestinal endoscopy biopsies should be taken at the most distal site possible.