Introduction

Gastroesophageal reflux disease (GERD) is the most common foregut disease, affecting about 20% of the adult population. It is characterized by a constant exposure of the mucosal cells to gastric acid and enzymes, which results in modification of the mucosal tissue integrity and persistent symptoms such as heartburn and regurgitation. Although GERD is associated with an esophageal epithelial barrier dysfunction, pharmacological therapies mainly aim to reduce the acidity of the gastroesophageal environment rather than protect the integrity of the esophageal tissue. Therefore, restoring the esophageal epithelium integrity, together with controlling gastric acidity, may represent an efficient approach to improve symptoms and prolong remission periods.

Aims & Methods

This study aims to evaluate the efficacy of an oral solution containing xyloglucan and pea proteins (XP) in reestablishing the integrity of gastroesophageal tissues and decreasing gastric pain in a GERD murine model.
To induce GERD, C57BL/6 mice were alternatively overfed and fasted for 56 days. Mice were then treated with XP, sodium alginate, omeprazole or omeprazole+XP twice daily for 7 days. Gastric pain and inflammatory markers were evaluated after 3 and 7 days of treatment. At day 7, after sacrifice, esophagi and stomachs were surgically removed and evaluated for macroscopic and histological examination.

Results

XP, omeprazole and omeprazole+XP were equally effective in reducing gastric pain at day 3 and 7, while alginates were ineffective at day 3. XP significantly reduced gastric macroscopic damage and demonstrated the same efficacy as omeprazole in reducing esophageal damage (p<0.001). XP was significantly able to reduce histological damage (p<0.001), with an efficacy comparable to that of omeprazole, but superior to that of alginates. Inflammatory and GERD-related markers such as iNOS and IL6 among others, were significantly reduced by XP at day 3 and 7, with a superior efficacy compared to alginates at day 7 (p<0.001). Furthermore, XP was able to significantly increase gastric pH (p<0.01).

Conclusion

Disruption of the esophageal epithelial barrier plays a fundamental role in initiating the pathophysiology of GERD. This study demonstrated that XP can effectively restore gastric homeostasis, improve esophageal integrity and decrease inflammation and pain in vivo, with a similar efficacy to that of omeprazole. Moreover, XP improves tissue integrity with a superior efficacy to alginates. Given the results, the mucoprotective properties of XP could represent a safe and effective alternative approach to manage GERD-related tissue damage. Future studies should confirm the beneficial effects of XP on esophageal mucosa to provide symptoms relief in patients suffering from GERD.

Introduction

Accurate and timely identification and treatment of celiac disease (CeD) by clinicians is increasingly recognized to be an important issue. This study aimed to identify educational needs of healthcare providers (HCPs) in diagnosing and managing CeD by surveying HCPs across Europe (EU) and the United States (US).

Aims & Methods

A survey focused on practices, knowledge, experience, and attitudes towards CeD was conducted among gastroenterology (GI) physicians (EU and US), nurse practitioners (NPs), and physician associates (PAs); primary care physicians (PCPs), NPs, and PAs; and dietitians (US only) who see patients with CeD. The survey used a simulated patient case for decision-making context and was distributed from August to September 2023.

Results

Respondents included 378 HCPs (75 EU, 303 US); most were physicians in group practices, with significant representation from community settings. After reviewing the case, most GIs (76%-88%) included CeD in their top 3 differential diagnosis versus 65% of PCPs. 83% of PCPs recommended starting a gluten-free diet (GFD) before endoscopy vs 36%-37% for GIs. Most dietitians were comfortable providing dietary guidance for CeD but the majority would also recommend initiation of a GFD prior to endoscopy. 87%-93% of GIs would order an endoscopy to confirm diagnosis, but many are not obtaining a guideline-recommended number of biopsies, particularly from the distal duodenum.

Conclusion

This study highlights a significant need for targeted interventions to enhance the identification and evidence-based diagnosis of CeD across various healthcare specialties. In particular, the practice of initiating a GFD prior to diagnosis should be addressed.

Disclosure

NC, SC, AS, MA and DL are employees and shareholders of Takeda.

Introduction

Anorectal manometry (ARM) is the most widely established diagnostic tool for studying defecation disorders. The London protocol and classification provide a standardized format for performing and interpreting High Resolution ARM. However, these are not based on clinical evidence, but only on expert consensus.

Aims & Methods

The aims of our study were to assess the impact of protocol modification on diagnostic agreement, focusing on resting pressure and push using the High Definition-ARM (HD-ARM) probe. A retrospective analysis was conducted of HD-ARM recordings performed in patients with chronic constipation at our digestive pathophysiology laboratory from January to October 2022. Evaluation of recordings was performed by applying both the London protocol and the proposed changes, as reported below. Resting pressure was assessed by combining modifications in both the baseline rest period (60, 50, 40, 30, 20 and 10 s) and stabilization period (3, 2 and 1 min). Each of the pushes was evaluated for 10 s, selecting the most qualitatively normal one for analysis. The diagnostic agreement between the standard protocol and the proposed modifications was compared by using Cohen's Kappa (k).

Results

	Mean anal pressure, (SD) mmHg	Mean rectal pressure, (SD) mmHg	Abnormal expulsion with dyssynergia, n	Abnormal expulsion with poor propulsion, n	Abnormal expulsion with poor propulsion and dyssynergia, n	Abnormal expulsion with normal manometric pattern of rectoanal coordination, n	Normal expulsion with abnormal manometric pattern of rectoanal coordination, n	No disorder of rectoanal coordination, n	Cohen's Kappa
Push 15 s	79.7 (40.5)	43.3 (26.6)	24	8	15	5	13	4	/
Push 10 s	82.7 (43.0)	44.2 (27.4)	24	8	15	5	13	4	1.000

Recordings of 69 patients with chronic constipation (53 F, mean age 53 [SD: ± 17]) were analyzed. At resting pressure assessment, performed according to the London protocol and classification, 30% and 27% of patients presented with anal hypotonia and hypertonia, respectively. As recording periods gradually changed, there was a concomitant change in some diagnoses; up to a stabilization period of 2 min and a baseline rest period of 30 s, a strong agreement with the standard protocol was maintained (κ = 0.823). Correlation was perfect between pushes assessed at 15 and 10 s (k = 1.000), respectively.

Conclusion

A 2-min stabilization period, 30-s baseline rest period, and 10-s push analysis allow a reduction of 105 s in study duration, thus obtaining very good diagnostic accuracy compared to the London protocol. In conclusion, we provide the first evidence-based study of a modified HD-ARM probe protocol (focusing on resting pressure and push) by analyzing recordings of patients with chronic constipation.

Introduction

Chronic intestinal pseudo-obstruction (CIPO) is a rare syndrome characterized by severe gastrointestinal (GI) dysmotility that mimics a GI obstruction in the absence of any detectable mechanical cause [1]. CIPO can be classified as primary (e.g. linked to a genetic disorder), secondary (to a wide array of conditions) or idiopathic. We recently demonstrated that jejunal longitudinal muscle layer abnormalities associated to vascular changes can contribute to GI dysfunction in a genetically driven form of CIPO [2].

Aims & Methods

The aim of this study was to investigate the presence of jejunal longitudinal muscle layer atrophy and vascular alterations in idiopathic forms of CIPO. Full thickness jejunal biopsies were collected from n=27 well characterized patients and n=10 controls. Formalin fixed-paraffin embedded (FFPE) tissue sections were stained with Sirius Red/Fast Green-collagen-assay to measure longitudinal muscle layer thickness and to spectrophotometrically determine fibrosis. FFPE full thickness jejunal sections were also stained with orcein to quantify and measure blood vessel size. The blood vessels were subdivided in >300µm (large), 300-101µm (medium), 100-51µm (small) and <50µm (very small). Frozen full-thickness tissue was used to assess by western blot the expression of HIF-1α as marker of hypoxia and of thymidine phosphorylase (TP), as this enzyme is involved in the pathophysiology of angiogenesis and is found absent in previously documented CIPO secondary to a genetic disorder [3]. Finally, jejunal muscle thickness was correlated with patients’ clinical data.

Results

Idiopathic CIPO patients showed 1.87 times (431.9±192.2 vs. 837.2±446.4 µm; P=0.0026) decreased thickness of the jejunal longitudinal muscle layer and a higher fibrosis index compared to controls. Idiopathic CIPO patients displayed a lower vascular area with more submucosal vessels/mm²vs. controls; vessels <50 µm increased at the expense of medium and large vessels. Moreover, the jejunum of idiopathic CIPO patients presented an increased HIF-1α expression indicative of hypoxia and a lower TP enzyme expression suggesting alterations in local angiogenesis. Finally, from a clinical standpoint, the jejunal muscle thickness was inversely correlated to the number of sub-obstructive episodes, abdominal distension and pain.

Conclusion

In addition to genetic CIPO, also idiopathic forms of this syndrome exhibit significant changes, i.e. muscular atrophy and fibrosis associated with major vascular remodeling likely dependent to hypoxia and a lower local TP protein expression. These data are clinically relevant as reduced muscular thickness correlates with worse clinical phenotypes of idiopathic CIPO.

References

[1] Downes, T.J.; Cheruvu, M.S.; Karunaratne, T.B.; De Giorgio, R.; Farmer, A.D. Pathophysiology, Diagnosis, and Management of Chronic Intestinal Pseudo-Obstruction. J Clin Gastroenterol 2018, 52, 477-489, doi:10.1097/MCG.0000000000001047.
[2] Boschetti, E.; D'Angelo, R.; Tardio, M.L.; Costa, R.; Giordano, C.; Accarino, A.; Malagelada, C.; Clavenzani, P.; Tugnoli, V.; Caio, G.; et al. Evidence of enteric angiopathy and neuromuscular hypoxia in patients with mitochondrial neurogastrointestinal encephalomyopathy. Am J Physiol Gastrointest Liver Physiol 2021, 320, G768-G779, doi:10.1152/ajpgi.00047.2021.
[3] Hirano, M.; Carelli, V.; De Giorgio, R.; Pironi, L.; Accarino, A.; Cenacchi, G.; D'Alessandro, R.; Filosto, M.; Martí, R.; Nonino, F.; et al. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Position paper on diagnosis, prognosis, and treatment by the MNGIE International Network. J Inherit Metab Dis 2021, 44, 376-387, doi:10.1002/jimd.12300.

Introduction

Endoscopic mucosal resection has been associated with lesion recurrence in 16%-27% of cases. Guidelines recommend endoscopic follow-up but it is unclear if endoscopic assessment has to include biopsies.

Aims & Methods

This study aims to evaluate the recurrence prediction of white light endoscopy (WLE) and narrow band imaging (NBI) in the assessment of colorectal mucosal resection scar. We performed a systematic review in PubMed, Embase, Cochrane and Web of Science databases, searching for studies comparing WLE and NBI. Statistical analysis included data pooling and heterogeneity testing. Quality of the included studies was assessed by Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2).

Results

The meta-analysis included 5 studies and 798 mucosal resections. The pooled sensitivity and specificity and AUC for WLE were 80.9% (95% CI 71.8% to 87.5%), 95.6% (95% CI 92.0% to 97.6%) and 0.917 (95% CI 0.885 to 0.972), respectively. The pooled sensitivity and specificity and AUC for NBI were 92.1% (95% CI 87.3 to 95.2%), 94.1% (95% CI 91.9% to 95.7%) and 0.935 (95% CI 0.772 to 0.972), respectively. There was no difference in AUC of WLE and NBI (p=0.633).

Conclusion

Our study demonstrates a high sensitivity, specificity and accuracy for endoscopic diagnosis of recurrent lesions after colorectal mucosal resection, specially with NBI. In all cases of low confidence assessment, biopsy is required.

References

1. Desomer L, Tutticci N, Tate D, Williams S, McLeod D, Bourke M. A standardized imaging protocol is accurate in detecting recurrence after EMR. Gastrointest Endosc. 2017 Mar;85(3):518–26.
2. Kandel P, Brand EC, Pelt J, Ball CT, Chen WC, Bouras EP, et al. Endoscopic scar assessment after colorectal endoscopic mucosal resection scars: when is biopsy necessary (EMR Scar Assessment Project for Endoscope (ESCAPE) trial). Gut. 2019 Sep;68(9):1633–41.
3. Pu L, Chiam K, Yamamura T, Nakamura M, Berzin T, Mir F, et al. Narrow-band imaging for scar (NBI-SCAR) classification: From conception to multicenter validation. J Gastroenterol Hepatol. 2019 Sep;34:227–8.
4. Riu Pons F, Andreu M, Gimeno Beltran J, Álvarez-Gonzalez MA, Seoane Urgorri A, Dedeu JM, et al. Narrow band imaging and white light endoscopy in the characterization of a polypectomy scar: A single-blind observational study. World J Gastroenterol. 2018 Dec 7;24(45):5179–88.