Introduction

Ischemic damage, caused by the compression of vascular structures in the neck of diverticular task has been proposed as one of the pathogenetic mechanisms diverticular disease (DD). However, as suggested for other gastrointestinal chronic diseases, another factor that can contribute to ischemia might be the activated platelet-dependent thrombosis through an oxidative imbalance mediated by arachidonic acid (AA) metabolism. The dominant oxidative imbalance described ex vivo in colonic wall human models of diverticulosis and diverticular disease supports this ischemic hypothesis.

Aims & Methods

Aim of the study was to assess the presence of relative circulating biomarkers that could be potentially useful to clarify DD pathogenesis and to highlight possible new target therapies. A cross-sectional study including 30 patients (Male=15; age:60.5±2.4years) referred to the DD outpatient clinic and sex- and age-matched healthy subjects (HS) (n=10) has been designed. Patients were subdivided in asymptomatic diverticulosis (DIV), symptomatic uncomplicated and complicated DD (SUDD and cDD) (n=10 per group). Circulating oxidative stress markers such as soluble Nox2-derived peptide (sNox2-dp), a direct marker of NADPH oxidase activation, hydrogen peroxide (H₂O₂) and isoprostanes production, together with antioxidant capacity (HBA) were evaluated by ELISA and colorimetric assay. Moreover, thromboxane B (2) (TxB2), generated as isoprostanes, upon arachidonic acid (AA) metabolism-derived platelet activation, as well as TNF-α and LPS were determined using the ELISA method. Gut permeability was assessed by evaluation of circulating levels of zonulin. Data (mean±SE) were expressed as fold variations from HS, p<0.05 was considered significant.

Results

The analysis of circulating biomarkers reflected the oxidative imbalance observed in DD colonic tissues. In respect to HS, a significant progressive increase from asymptomatic to symptomatic DD was observed both for H₂O₂ (DIV:1.68±0.26, SUDD:2.48±0.35, cDD:2.99±0.21) and isoprostanes (DIV: 2.53±0.35, SUDD: 3.46±0.21, cDD: 3.57±0.2), counteracted by a significant progressive decrease in HBA (DIV:0.74±0.04, SUDD:0.63±0.04, cDD:0.57±0.03). The AA-driven metabolites isoprostanes and TxB2 resulted significantly correlated to the progressive increase in sNox2-dp levels (DIV:1.69±0.13, SUDD:2.68±0.22, cDD:2.92±0.18) (r=0.61, 95%CI:0.37-0.77; r=0.73, 95%CI:0.55-0.85 respectively) supporting the involvement of platelet activation. TxB2, similarly to isoprostanes, progressively increased from asymptomatic (2.42±0.13) to symptomatic DD (SUDD: 4.44±0.13 and cDD:4.25±0.52). A significant progressive increase was also observed in the known platelet activators TNF-α (DIV: 1.39±0.08, SUDD:2.04±0.19, cDD:2.03±0.11) and LPS (DIV:1.59±0.17, SUDD:2.59±0.14, cDD:2.78±0.13). LPS increase correlated to that of zonulin (r=0.59, 95%CI:0.35-0.76, p<0.0001) highlighting the presence of low-grade endotoxemia related to increased permeability.

Conclusion

These preliminary results showed a progressive increase of circulating oxidative biomarkers from asymptomatic to symptomatic DD opening a new pathogenic scenario in diverticular disease. The evidence of a pathogenic role of platelet activation and increased intestinal permeability in DD oxidative imbalance deserves further studies. Circulating oxidative biomarkers might represent a useful clinical tool in the management of this disease.

Introduction

Psychiatric comorbidity, most commonly measured as severity of anxiety and depression symptoms, has been found to be associated with IBS symptom severity. However, available studies have rarely assessed the importance of formal psychiatric diagnoses on disease burden in IBS. In this analysis from a pan-European project (DISCOvERIE) focusing on the relevance of comorbid mental (anxiety, depression) and/or somatic (fibromyalgia, chronic fatigue syndrome) diagnoses in patients with IBS, we aimed to assess whether presence of psychiatric diagnoses according to the DSM-5 criteria has an impact on overall symptom severity in IBS.

Aims & Methods

We included patients with IBS according to the Rome IV criteria from nine different European centers. Exclusion criteria included the presence of severe psychiatric disease (i.e. bipolar disorder, schizophrenia, autism spectrum disorder, schizoaffective disorder, or organic psychiatric disorder demanding psychopharmacotherapy, psychiatric day-care or inpatient treatment). The patients underwent The Mini International Neuropsychiatric Interview (MINI) to diagnose major psychiatric diagnoses (a total of 17). Fibromyalgia and chronic fatigue were diagnosed by current diagnostic criteria. They also filled in questionnaires assessing Severity of IBS symptoms (IBS-SSS), depression (PHQ-9), anxiety (GAD-7), somatic symptoms (PHQ-15), and fibromyalgia symptoms (FIQ). Severity of symptoms were compared between groups with increasing number of psychiatric diagnoses using One-Way Between-Groups ANOVA with linear trend analysis.

Results

In total, 617 patients with IBS (median age 44 years, 80% females) were included. Among the IBS patients, 269 (44%) had none of the mental (anxiety, depression) or somatic (fibromyalgia, chronic fatigue syndrome) comorbidities (median age 44 y, 75% females), whereas 174 (28%) had comorbid mental disorder only (median age 38 y, 82% females), 49 (8%) had comorbid somatic disorder only (median age 50 y, 86% females) and 124 patients (20%) had mental and somatic comorbidities (median age 47 y, 86% females). The most common psychiatric diagnoses among the IBS patients were depression (n=284), generalized anxiety disorder (n=145) and panic disorder (n=38) followed by agoraphobia (n=23) and social anxiety (n=19). Participants were divided into four groups according to the number of psychiatric diagnoses (0, 1, 2, and ≥3). The severity of IBS, depression, anxiety, somatic, and fibromyalgia symptoms all increased gradually with increasing number of psychiatric diagnoses. The effect sizes (partial eta squared) were small for IBS symptoms, medium for somatic symptoms and large for the other severity measures (Table 1).

Table 1: Symptom severity in groups with increasing number of psychiatric diagnoses

Conclusion

This multicenter pan-European study shows that psychiatric diagnoses are common among IBS patients and that the overall disease burden in IBS is associated with psychiatric comorbidity. These findings highlight the importance of taking psychiatric comorbidity into consideration and to acknowledge the relevance of gut-brain axis interactions when managing patients with IBS.

Disclosure

Hans Törnblom: Consultant or advisory board member for Allergan, Cinclus Pharma, Medifactia, and VIPUN and as a speaker for Tillotts, Takeda, and Shire.
Daisy Jonkers: Part of the work of DJ, outside the submitted work has been financed by public-private partnership grants of Top Knowledge Institute (TKI) Agri&Food and Health Holland, by the Carbokinetics program as part of the NWO-CCC Partnership Program, by Organic A2BV/Mothersfinest BV.

Introduction

There are several reports about the diagnosis of early gastric cancers (EGCs) using artificial intelligence (AI) systems, but satisfactory data for sensitivity and specificity are not yet available. Linked color imaging (LCI) produces high color contrast between malignant lesions and surrounding mucosa compared to white light imaging (WLI). Therefore, LCI combined with AI (LCI-AI) has the potential to further improve the diagnosis of gastric cancer compared with WLI combined with AI (WLI-AI). We developed three new LCI-AI models to determine their sensitivity and specificity for the diagnosis of EGCs.

Aims & Methods

Three models including a convolutional neural network (CNN) model (high resolution net (HRNet)), a transformer model (Segformer) and a hybrid (combined CNN and transformer) model (Uniformer), were based on MMSegmentation. When each model recognized a gastric cancer lesion from test image data, it was shown with the existing position as a blue area on WLI images and green area on LCI images. Non-neoplastic mucosa was shown as a black area on both images. Endoscopic images using WLI and LCI (LASEREO 7000 system series and scopes of EG-L600ZW and EG-L600ZW7, Fujifilm Corporation, Tokyo, Japan) were collected from patients with EGCs from January 2015 to December 2018 at Jichi Medical University Hospital. A total of 1970 images including 1179 WLI and 791 LCI images of 236 EGCs were used for training the three LCI-AI models. Another set of 414 EGC images was selected for validation from 43 cases. Primary and secondary endpoints were the sensitivity and specificity of each AI model, respectively.
The image-based performance metric was based on Dice loss, calculated by subtracting the mean Dice similarity score. A Dice score >20% was defined as the correct diagnosis of cancer because EGCs sometimes have unclear demarcation lines. The correct diagnosis of a non-malignant lesion was defined as no reactive black areas in surrounding mucosae. Each case had from four to 21 images. Therefore, the median Dice score was used as a representative value in each case to evaluate performance. All three models’ programming and data analysis were supported by AI Medical Service Inc. (Tokyo, Japan).

Results

Analysis of lesions in all EGC images showed both sensitivity (82.8%) and specificity (83.4%) with LCI-AI to be high and similar to those with WLI-AI (83.1% and 84.3%, respectively). Sensitivities of LCI-AI/ WLI-AI among HRNet, SegFormer and UniFormer were 80.9%/81.6% (p=0.625), 83.8%/83.8% (p=0.224) and 83.8%/83.8% (p=0.450), respectively and specificities were 80.0%/86.0% (p=0.120), 86.4%/84.8% (p=0.672) and 86.8%82.0%/ (p=0.214), respectively. Representative Dice values among cases with EGCs showed sensitivities for LCI-AI using HRNet, SegFormer and UniFormer to be extremely high, at 92.7% 90.9% and 93.0%, respectively, although not significantly different when compared to those using WLI-AI, 84.6% (p=0.67), 85.4% (p=0.15) and 80.5% (p=0.19), respectively. Higher sensitivities were found regardless of lesion size, morphology, and Helicobacter pylori status. All sensitivities using LCI-AI were higher than 80% whereas those using WLI-AI varied from 64% to 89%.

Conclusion

LCI-AI showed high sensitivity and specificity for the diagnosis of EGCs using all three models tested, suggesting potential for practical clinical use in the near future.

Disclosure

Hiroyuki Osawa and Hironori Yamamoto have consultant relationships with Fujifilm Corporation and have received honoraria, grants and royalties from the company. Hiroyuki Osawa has a consultant relationship with AI Medical survice inc. and has recieved honoraria.This study received no funding from Fujifilm Corporation and AI Medical survice inc. nor any other funding source.

Introduction

The enteric nervous system (ENS) is situated deep in the intestinal wall. Full-thickness biopsies may be used to assess damage to the neurons, i.e., enteric neuropathy. The ENS is difficult to examine in conventional histological sections of 3-5 µm, due to the complex spatial organization and large size of neurons.

Aims & Methods

The aim of the present study was to assess the volume and thickness of the ENS in human ileum full-thickness biopsies using X-ray phase-contrast micro-computed tomography. Full-thickness ileum biopsies from five controls and six patients clinically diagnosed with gastrointestinal dysmotility and neuropathy were included. Punch biopsies of 1-mm diameter (up to 1 cm in length), centered on the myenteric plexus, were extracted from the paraffin blocks, placed into a polyimide tube, and subsequently scanned with x-ray phase-contrast micro-CT. Quantitative volumetric analysis was performed from the reconstructed data.

Results

The architecture of both ganglia and fascicles was well visible. The connections between different parts of the ENS could be followed. The volume and thickness of the neural tissue could be determined in 3D in all samples. The neural tissue volume/total tissue volume was higher in controls (4.57 (3.61-5.26)) compared with the patients with enteric neuropathy (3.07 (2.57-3.76)) (p=0.013). The patient with the longest disease duration had the lowest ratio overall (2.51).

Conclusion

3D analysis may be used to determine the thickness and volume of the ENS over larger areas of the gastrointestinal tract than available in light microscopy. The assessment can be performed in an objective, standardized way, without prior staining or preparaiton, to ensure reproducibility and comparison between health and disease. Further evaluation is needed to examine the role of this method in the diagnosis of enteric neuropathy.

References

Peruzzi N, et al. 3D analysis of the myenteric plexus of the human bowel by X-ray phase-contrast tomography - a future method? Scand J Gastroenterol 2020;55:1261–1267.

Introduction

Systemic sclerosis (SSc) is a rare autoimmune disease of the connective tissue that can affect multiple organs. The esophagus is the most affected gastrointestinal tract, while interstitial lung disease (ILD) is a main feature associated with SSc.

Aims & Methods

The aim of the present study was to evaluate the association and prognostic implication between motor esophageal disorders and pulmonary involvement in SSc patients. We retrospectively assessed patients with SSc who underwent both the high resolution manometry with the new Chicago Classification 4.0 and pulmonary evaluation comprehensive of function tests and high-resolution computer tomography (HrCT) with the use of Warrick score. A total Warrick score≥7 was considered predictive of ILD, while a score≥10 in a HrCT acquired prospectively from baseline evaluation was considered to establish significant interstitial involvement.

Results

Forty-two patients were included. We found a score≥7 in 11 patients with aperistalsis, in 6 subjects with ineffective esophageal motility and in 6 patients with a normal manometry. Otherwise, a Warrick score<7 was observed in 3 patients with aperistalsis, and in 2 and 14 patients with ineffective esophageal motility disorder and with a normal contractility, respectively. Higher scores were observed in subjects with absent contractility or ineffective esophageal motility than subjects with normal motility, indeed DCI and HrCT score were inversely correlated in linear and logarithmic regression analysis. Prospectively, lower baseline pressure of lower esophageal sphincter and greater HrCT scores at follow-up evaluation were significantly associated.

Conclusion

This study shows an association between motor esophageal disorder and pulmonary involvement in SSc patients: more severe is the esophageal involvement, more critical is the pulmonary disease.