Clinical Case Summary

Small bowel bleeding can pose a diagnostic and therapeutic challenge.
We present an interesting case involving the use of different endoscopic modalities in jejunal diverticular bleeding. A 66-year-old male with gout and intermittent Naproxen use presented to the Emergency Department with melena. Oesophagogastroduodenoscopy (OGD) and colonoscopy did not reveal any source of bleeding. A Computed Tomography Mesenteric Angiography scan showed evidence of recent hemorrhage within the small bowel loops without active blush seen. Subsequent video capsule endoscopy (VCE) revealed blood pooling in the distal small bowel. He underwent a retrograde double balloon enteroscopy showing only coffee-ground stains in the distal jejunum. Further review of VCE images showed another small ‘dark spot’ in the proximal jejunum. Thus, he underwent an antegrade motorised spiral enteroscopy (MSE) which showed fresh blood clots in the proximal jejunum with multiple large diverticula. Active bleeding was identified from one of the diverticula but difficulty was encountered in manoeuvring the MSE into the jejunal diverticulum. The MSE was switched to a cap-fitted paediatric colonoscope which made it easier to advance into the proximal jejunal diverticulum to address the pulsating vessel. Hemostasis was achieved with adrenaline injection and application of hemostatic clips.
MSE can locate pathology that lies coaxial to the axis of the scope but it can be difficult to reach the culprit lesion due to its off axis location and acute angulation within the diverticulum. Push enteroscopy or balloon-assisted enteroscopy (BAE) maintains its benefit of having a more flexible shaft/tip and can safely enter a jejunal diverticulum for hemostasis even if located off axis compared to MSE. Although MSE represents an innovation, conventional push enteroscopy or BAE still remains an important tool in the endoscopic armamentarium.

References

Illustrative material

1. VCE image with ‘dark spot’
2. Endoscopic image of large diverticulum
3. Hemostasis was achieved with adrenaline injection and application of hemostatic clips
   

Introduction

H.pylori infection is common in developing countries leading to of high prevalences of peptic ulcers and gastric cancer. However, the diagnostic tests such as rapid urease test or urease breath test requires facilities and patients need to go to medical sites, which raise a more and more need for non-invasive and convenient tests appropriate to community.

Aims & Methods

A cross-sectional study was conducted at the Institute of Gastroenterology and Hepatology, Hanoi, Vietnam to compare the H.pylori determination results of the qualitative detection of 2 antibodies specific to FliD and CagA with the rapid urease test and urease breath test in Vietnamese patients with upper gastrointestinal symptoms. Patients over 18 years old with upper GI symptoms and no prior history of treated peptic ulcers or H.pylori eradication were invited to participate in the study. Patients were indicated with upper GI endoscopy and three methods to diagnose H.pylori infection: Rapid Urease Test (RUT), Urease Breath Test (UBT), and qualitative detection of 2 antibodies specific to FliD and CagA (Pylori Duotect). Pylori Duotect is considered positive if either antibody for FliD and CagA are positive. The parameters for evaluating the diagnostic accuracy of Pylori Duotect include sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV). Patients are considered H.pylori positive if both RUT and UBT are positive.

Results

From December 1, 2023, to April 20, 2024, 189 patients were recruited for the research. The mean age were 45.8 years old (min-max: 18-76 years old), 40.7% were female. The most common symptom of patients was epigastric pain (46.6%). There were 172 patients (91%) with gastritis, 27 patients (14.3%) with gastric ulcers and 16 (8.5%) with duodenal ulcers. Using the Pylori Duotect test, 50.8% of the patients were positive, in which 39.6% were positive with FliD and 86.5% were positive with CagA. Based on RUT and UBT results, 31.2% of patients were diagnosed with H. pylori infection. Pylori DuoTect’s sensitivity, specificity, PPV, and NPV were 81.4%, 63.8%, 50.5%, and 88.3%, respectively.

Conclusion

The Pylori DuoTect test had low sensitivity and specificity in diagnosis H. pylori infection in patients with upper gastrointestinal symptoms.

Introduction

Digestive hemorrhage is a frequent complication in advanced chronic kidney disease. Patients with end-stage renal disease (ESRD) are more likely to have gastrointestinal (GI) problems, including digestive bleeding of high or low origin.

Aims & Methods

The aim of our work is to study the particularities of HD in CKD patients.
This is a monocentric prospective analytical study over a period of 28 months: April 2020 to August 2022, including patients with HD with CKD at the dialysis stage or not, including renal transplant patients.
In order to be able to compare patients with ESRD with patients without ESRD, a control group of patients admitted for HD who had a GI endoscopy during the study period and with normal renal function were identified and grouped. In this group of patients, we took into account age, sex, indications, GI endoscopy results and ICU stay.
We also assessed all-cause mortality between the groups of CKD patients with HD versus the control group.

Results

A total of 378 patients underwent digestive exploration for HD. In this population, 46 (12.16%) patients with CKD were compared with 332 patients without RI.
70% (n=32) of the patients with RI were on chronic hemodialysis, 26% (n=12) had a GFR<60ml/min/1.73m2 but were managed without the aid of dialysis or transplantation, and 4% (n=2) patients were renal transplant recipients.
The most common etiologies in CKD patients were ulcer disease 65.2% (n=30); vascular ectasia 28.2% (n=13), gastritis 26% (n=12), esophagitis 10.8% (n=5); and tumors in 8.6% (n=4).
After statistical analysis patients with CKD had:
A higher risk of hemodynamic instability 69.5% (n=32) compared to the control group 11.14% (n=37) with p=0.002,
A higher rate of recurrence 26% (n=12) CKD patients compared to 9.6% (n=32) of the control group with a p=0.00.
A higher mortality rate 4.34% (n=2) in CKD patients compared to the control group 1.2% (n=4) with p=0.00.

Conclusion

GI bleeding in advanced chronic kidney disease is more severe it is accompanied by a higher risk of recurrence of ICU stay and mortality, hence the interest of prompt management and close monitoring. The main causes are peptic ulcer and vascular ectasia.

Introduction

This study assessed typical symptoms (abdominal pain, bloating, diarrhoea, nausea, tiredness) in patients with celiac disease (CeD) following a gluten-free diet (GFD) and evaluated the association between symptom severity and quality of life (QoL) to address limited data in this area.

Aims & Methods

In the Virtual Celiac Symptoms Study (NCT05309330), patients reported daily symptoms using the Celiac Disease Symptom Diary 2.1^© (CDSD 2.1^©) over 12 weeks and completed patient-reported outcome measures (PROMs), with 7-day look-back, at specified timepoints, including the Impact of Celiac Disease Symptoms Questionnaire (ICDSQ) and the Patient Global Impression of Severity (PGI-S) measure. Spearman’s correlation coefficient (SCC) and generalized linear regression evaluated associations between symptom severity and QoL PROM scores and mean differences were adjusted for key demographics.

Results

In total, 480 participants completed the study (mean [standard deviation] age: 31 [15] years, 81.7% female, 93.8% White). For all CeD symptoms measured, there was a positive linear association between CDSD 2.1^© symptom severity and PROM scores (p <0.001). The SCC between symptom severity and PROMs was 0.45–0.62 (PGI-S) and 0.33–0.56 (ICDSQ). The strongest correlations between gastrointestinal symptom severity (abdominal pain, bloating, diarrhoea, and nausea) and PROMs were between PGI-S score and abdominal pain (SCC: 0.62) and bloating (SCC: 0.59). Patients with severe/very severe abdominal pain versus none had mean (95% confidence interval [CI]) 63.1% (53.2–73.6) and 217.5% (165.1–280.2) greater PGI-S and ICDSQ scores, respectively.

Conclusion

The results indicate that higher symptom severity is strongly associated with worse QoL in patients with CeD following a GFD and that CDSD 2.1^© assesses patient-relevant symptom severity in CeD.

Disclosure

MA, NC, DAL, SG and RS are employees and shareholders of Takeda. LMM was an employee of Takeda at the time of the study. JRM and SS are employees of Analysis Group, Inc., which received research support from Takeda Development Center Americas, Inc. DA has served as a consultant for Takeda Pharmaceuticals and Ironwood Pharmaceuticals. MG is an employee of the Celiac Disease Foundation, which received financial support from Takeda Development Center Americas, Inc. EL serves as a consultant for Takeda Pharmaceuticals and is an author for UpToDate (celiac section) for which he receives royalties.

Introduction

Clinical trials in coeliac disease require reliable histological metrics to quantify mucosal damage and demonstrate improvement with treatment. Regulatory agencies are recognizing this and expect some form of histological assessment in coeliac disease trials. Qualitative scoring systems are highly variable among readers. It has been suggested that quantitative scoring provides better consistency among different readers.

Aims & Methods

This study aimed to assess the variability that occurs when quantifying villus height (Vh), crypt depth (Cd) and the Vh:Cd ratio, and identified approaches to improve correlation among observers at different institutions. A set of 236 slides stained with haematoxylin and eosin from 28 patients with coeliac disease on a gluten-free diet (NCT03738475) were used. Quantitative scoring of Vh, Cd, Vh:Cd ratio and the sum of Vh and Cd were initially compared between different institutions that prioritized ocular microscopy or digital pathology. Additionally, the change from baseline with gluten ingestion for each of these measurements was compared between institutions. Improvements to inter-reader correlations were assessed by implementing a common digital pathology software and using agreed upon criteria for making quantitative measurements. Data sets were subjected to statistical analysis to understand correlation and significance. Regression slopes were calculated and the coefficient of determination, R², was derived as a measure of linearity. The concordance correlation coefficient was calculated as an index of agreement beyond linearity. Pairwise Pearson correlation coefficients between readers from different institutions were calculated to demonstrate the degree of association between readers.

Results

Initial inter-reader analysis found that Vh:Cd ratios had a similar, linear trend between readers, regardless of ocular or digital pathology usage, but that there was a consistent systematic difference partially due to differences in reader assessment of the location of the crypt–villus border. Use of a common digital pathology platform and clear scoring criteria greatly improved inter-reader correlations, even when scoring was done by a non-pathologist. Importantly, the assessment of change from baseline in the quantitative measurements after gluten exposure was also highly concordant (Table). The software also enabled visual comparison of readers’ individual measurements of the crypt and villous lengths allowing potential reasons for differences in these measurements to be identified.

Table 1. Changes from baseline in Vh and Cd metrics obtained via ocular microscopy and digital pathology after gluten challenge.

Conclusion

The results suggest that quantitative histology in coeliac disease is reliable and can be improved through digital pathology, software measurement aids and attention to selecting optimally oriented sections. Given the ease with which pathologists without training in the use of quantitative histology software can produce results similar to those from experienced central laboratories, quantitative histology may be feasible outside the clinical trial setting.

Disclosure

AV has nothing to disclose. DAL, DR, DC, GS, JM and QL are employees of Takeda Development Center Americas, Inc. and receive stock or stock options. JI is the founder and owner of Jilab, Inc.; is a Full Professor at Tampere University, Medical Faculty; and has a consulting agreement with Takeda. JAM has grants from Nexpep/ImmusanT, National Institutes of Health, Immunogenix, Takeda Pharmaceutical, Allakos, Oberkotter, Cour; and has received consultancy fees from Bionix, Lilly Research Laboratory, Johnson & Johnson, Dr. Schar USA, UCB Biopharma, Celimmune, Intrexon Corporation, Dren Bio, Reistone Pharma, Chugai Pharma, Kanyos, Boehringer Ingelheim, Equillium and Torax Medical. MR is a consultant for Takeda and Bristol Myers Squibb. MZC has nothing to disclose. TTW has nothing to disclose.
Funding statement: This study was sponsored by Takeda Development Center Americas, Inc. Medical writing support was provided by Oxford PharmaGenesis, Oxford, UK and was funded by Takeda Pharmaceuticals.