Clinical Case Summary

Introduction: The diagnosis of abdominal pain is usually difficult (1).Celiac artery compression syndrome (CACS) is an extremely rare cause of mesenteric ischemia. CACS was first described by Harjola in a young woman (2).The classic description is an abdominal pain that often develops a few minutes after eating and is gradually relieved after the next hours and weight loss (3).A high index of suspicion for this condition is crucial as none of the laboratory investigations is diagnostic.
Case presentation: We present the case of a 29-year-old heavy smoker man who presented to our clinic with 4 months history of severe abdominal pain. The pain was generalized and sometimes localized at left side. He described it as burning and constant. It was aggravated by food and was not relieved by over- the-counter medications. He rated the pain as 7 out of 10. It was associated with nausea and constipation. He was diagnosed as having indigestion. He reported that he had reduced appetite and lost more than 15 kg. The past medical history was unremarkable.Upon examination, the patient appeared in pain. His vital signs were normal. Abdominal examination revealed a soft abdomen with generalized tenderness. The initial laboratory findings were within the normal range.Considering the severity and character of the pain, the initial differential diagnosis was mesenteric ischemia. Hence, the patient underwent a contrast-enhanced computed tomography scan of the abdomen. The scan demonstrated indentation of median crus of the diaphragm upon the proximal celiac trunk close to its origin with relative post stenotic dilatation . In light of the clinical and radiological findings, the diagnosis of celiac artery compression syndrome was made.
Subsequently, the patient was prepared for surgical intervention. Careful dissection of the ligament was performed and the celiac artery was decompressed successfully. Postoperatively, the patient was able to tolerate oral feeding with no postprandial pain.

References

(1) Clouse RE, mayer EA, Aziz Q et al.functional abdominal pain syndrome.Gastroenterology 130:1492-1497,2006.
(2) Hariola PT. Arare obstruction of celiac artery. Amnaks chirurgiae at Gynecologiae Femniae 1963;52:547-93.
(3) Kuczyńska M, Światłowski Ł, Sojka M, Pyra K, Drelich-Zbroja A, Jargiełło T: Abdominal angina: an underrecognized cause of alarming symptoms. Pol Arch Intern Med. 2020, 130:898-900. 10.20452/pamw.15485

Introduction

Autonomic neuropathy affecting multiple organs is a common and severe complication of diabetes¹. Neuropathy of the enteric nervous system and the regulatory autonomic nerve fibers can affect the entire gastrointestinal tract, causing mild to severe gastrointestinal symptoms². The correlation between gastrointestinal symptoms and underlying pathophysiology is generally weak, so objective assessment is important to guide treatment^3-5. Methods for direct evaluation of enteric neuropathy are not yet available in clinical practice. Hence, gastrointestinal transit times and contractile activity are used as proxies for enteric autonomic dysfunction^6,7. Panenteric gastrointestinal assessment is considered essential, yet suitable methods are generally inaccessible, and diagnosing diabetic gastroenteropathy often causes significant challenges^4,8. It is unknown whether measures of extraintestinal autonomic function can reflect diabetic gastroenteropathy and whether these measures could serve as supplementary diagnostic tools.

Aims & Methods

We aimed to assess 1) whether gastrointestinal symptoms are associated with motility measures and 2) whether gastrointestinal symptoms/motility measures are associated with extraintestinal autonomic markers. We included 81 persons with type 1 or type 2 diabetes (65% female, mean age 54) with gastrointestinal symptoms and either symptoms or signs of autonomic neuropathy. The Gastroparesis Cardinal Symptom Index (GCSI) and the Gastrointestinal Symptom Rating Scale (GSRS) were used to assess gastrointestinal symptoms. The wireless motility capsule assessed panenteric transit times and motility indices. Cardiovascular reflex tests performed with the VAGUS device and the cardiac vagal tone assessed with the eMotion Faros device estimated cardiovascular autonomic neuropathy, while the SUDOSCAN evaluated sudomotor function.

Results

Proximal gastrointestinal symptoms were positively associated with the gastric motility index (GCSI: 1.18 (1.04 - 1.35), p=0.01; GSRS: 1.15 (1.03 - 1.29), p=0.02; median ratio (95%CI)), while only satiety reflected gastric emptying time (1.24 (1.03 - 1.49), p=0.02). Diarrhea was associated with decreased small bowel transit time (0.93 (0.89 - 0.98), p=0.005), while constipation was associated with prolonged colonic transit time (1.16 (1.03 - 1.31), p=0.02). Gastrointestinal symptoms increased with the degree of abnormal cardiovascular reflex tests (GCSI: 0.67 (0.16 - 1.19), p=0.03; GSRS: 0.87 (0.30 - 1.45), p=0.01; mean difference (95%CI)) but not with motility measures. Cardiac vagal tone and sudomotor function were not associated with gastrointestinal markers.

Conclusion

Gastrointestinal and extraintestinal autonomic measures were not associated. However, proximal gastrointestinal symptoms were associated with the gastric motility index and cardiovascular reflex tests. Hence, the latter may contribute to evaluating whether proximal gastrointestinal symptoms are autonomically derived.

References

1. Verrotti A, Prezioso G, Scattoni R, Chiarelli F. Autonomic neuropathy in diabetes mellitus. Front Endocrinol (Lausanne). 2014;5:205.
2. Azpiroz F, Malagelada C. Diabetic neuropathy in the gut: pathogenesis and diagnosis. Diabetologia. 2016;59(3):404-408.
3. Arora Z, Parungao JM, Lopez R, Heinlein C, Santisi J, Birgisson S. Clinical utility of wireless motility capsule in patients with suspected multiregional gastrointestinal dysmotility. Dig Dis Sci. 2015;60(5):1350-1357.
4. Kuo B, Maneerattanaporn M, Lee AA, et al. Generalized transit delay on wireless motility capsule testing in patients with clinical suspicion of gastroparesis, small intestinal dysmotility, or slow transit constipation. Dig Dis Sci. 2011;56(10):2928-2938.
5. Rouphael C, Arora Z, Thota PN, et al. Role of wireless motility capsule in the assessment and management of gastrointestinal dysmotility in patients with diabetes mellitus. Neurogastroenterol Motil. 2017;29(9).
6. Kempler P, Amarenco G, Freeman R, et al. Management strategies for gastrointestinal, erectile, bladder, and sudomotor dysfunction in patients with diabetes. Diabetes Metab Res Rev. 2011;27(7):665-677.
7. Camilleri M, Chedid V, Ford AC, et al. Gastroparesis. Nat Rev Dis Primers. 2018;4(1):41.
8. Bertoli D, Mark EB, Liao D, et al. MRI-Based Quantification of Pan-Alimentary Function and Motility in Subjects with Diabetes and Gastrointestinal Symptoms. J Clin Med. 2023;12(18).

Introduction

Celiac disease is an autoimmune disorder where the intake of gluten (a protein found in wheat, barley, and rye) causes damage to the small intestine and impairs nutrient absorption. Studies have shown that individuals with celiac disease have reduced quality of life and higher levels of anxiety and depression. However, this has not been studied in the general population, among individuals with newly discovered, untreated celiac disease.

Aims & Methods

The aim of this study was to investigate anxiety, depression, mental health, and subjective well-being in individuals with newly diagnosed and untreated celiac disease, compared with the general population. This study used data from the fourth Trøndelag health study (HUNT4), conducted between 2017 and 2019 with over 56,000 adult participants from 20 years of age. Previously undiagnosed celiac disease was identified among the participants by analyses of blood samples from all participants and confirmed with endoscopy and duodenal biopsies. The participants in HUNT4 also answered questionnaires measuring levels of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS), mental distress using the Cohort of Norway Medical Health Index (Conor-MHI), and subjective well-being using a three-part questionnaire. Differences in mental health among individuals with newly diagnosed celiac disease and the remaining HUNT4 participants were compared.

Results

Celiac disease was diagnosed in 454 HUNT4 participants by March 2022. The celiac group had a lower median age (53 vs. 56 years) compared to the remaining HUNT4 population. The celiac group had significantly lower mean scores on the HADS anxiety subscale (4.0 vs. 4.4), depression subscale (2.8 vs. 3.3), and total scale (6.8 vs. 7.7) compared to the reference population. On the CONOR-MHI scale, the celiac disease group had a lower total mean score (1.4 vs. 1.5) with lower scores in the categories of "secure and calm", "irritable", "happy and optimistic", "sad/depressed", and "lonely" compared to the reference population. Finally, the celiac disease group had a lower mean score on the question “Do you feel mostly strong and clear, or tired and fatigued?” (3.3 vs. 3.4) and a higher mean score on the question “How is your health now?” (3.0 vs. 2.9) compared to the reference population. No significant difference was observed in the HADS or CONOR-MHI scores by Marsh grades at diagnosis among the celiac disease group.

Conclusion

The study suggests that individuals with undiagnosed celiac disease have lower levels of anxiety, depression, and mental distress compared to the general population, while also reporting slightly better subjective well-being. These findings contradict other studies on psychological health in celiac disease.

Disclosure

No con

Introduction

Vonoprazan (VPZ)-based regimens are an effective first-line therapy for Helicobacter pylori infection. However, their value as a rescue therapy needs to be explored.

Aims & Methods

We assessed a VPZ-based regimen as a H. pylori rescue therapy.
Patients with a history of H. pylori treatment failure were administered 20 mg VPZ twice daily, 750 mg amoxicillin 3 times daily, and 250 mg Saccharomyces boulardii twice daily for 14 days. ¹³C-urea breath tests were used to assess H. pylori status; adverse events were recorded using a questionnaire.

Results

We enrolled 68 patients with 1–3 previous eradication failures. The overall eradication rates calculated using intention-to-treat and per-protocol analyses were 92.6% (63/68) and 92.3% (60/65), respectively. The eradication rate did not differ with the number of treatment failures. The rates of clarithromycin, metronidazole, and levofloxacin resistance were 91.3% (21/23), 100% (23/23), and 60.9% (14/23), respectively. In 60.9% (14/23) patients, the H. pylori isolate was resistant to all 3 antibiotics. The eradication rate was higher among patients without anxiety (96.8%) than among patients with anxiety (60.0%, P = 0.025). No severe adverse events occurred; 95.6% (65/68) patients showed good compliance. Serological examination showed no significant changes in liver and kidney function.

Conclusion

Vonoprazan and amoxicillin dual regimen with S. boulardii supplementation is a safe and effective H. pylori rescue therapy, with an acceptable eradication rate (>90%), regardless of the number of prior treatment failures. Anxiety was associated with eradication failure, and the regimen may need to be adjusted for patients with anxiety.

Clinical Case Summary

A 64-year-old women, without known family history of colorectal cancer (CRC), underwent a colonoscopy due to iron deficiency anemia. In the colonoscopy, with an adequate bowel preparation, an ulcerated lesion in the ascending colon was identified. Multiple biopsies were performed, and the colon was tattooed distally to the lesion. Histology confirmed adenocarcinoma. Staging was performed and the CT-scan identified parietal thickening of the distal ascending colon and multiple infracentrimetric nodules at the root of the mesentery, without description of other suspicious lesions. After a multidisciplinary team meeting, a right hemicolectomy was proposed, which occurred 12 weeks after endoscopic diagnosis. Macroscopic evaluation of the surgical specimen didn’t identify lesions compatible with the described neoplasia, despite the colic tattoo being observed. Also, in the anatomopathological evaluation, there was no evidence of tumor. The resected nodes were negative for neoplasia. The colonoscopy was repeated 8 weeks after surgery, with no identifiable lesions. The list of patients who underwent colonoscopy on the same day was reviewed, and the hypothesis of misidentification of the patient was excluded. Finally, biopsies of the neoplasia and the colectomy specimen were compared by capillary electrophoresis, confirming the compatibility of the genetic profile between them.
We present a rare case of a spontaneous remission of CRC. This phenomenon has been described in several neoplasms, but is rare in CRC, corresponding to <2% of all cases. The pathophysiology is not well understood, with several etiologic mechanisms proposed. With this exemplary case, we emphasize the measures to avoid identification errors, how to investigate cases of disagreement between pre- and post-operative diagnoses and the importance of recognizing that spontaneous remission of CRC is not synonymous of cure, being necessary to maintain the recommended follow-up.

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.