Introduction

Patients with diabetes mellitus (DM) are at an increased risk of developing cardiovascular disease (CVD). Hepatic steatosis is common among patients with DM, but its impact on CVD risk remains unclear.

Aims & Methods

This study aimed to prospectively assess the association between a reduction in hepatic steatosis and a lower risk of CVD in patients with DM.
A total of 323 patients with DM were prospectively enrolled from January 2022, after excluding those with viral hepatitis, overt cirrhosis, and cancer. Clinical measurements and CVD history were recorded. The following parameters were assessed: body weight (BW), body mass index (BMI), waist circumference (WC), laboratory data (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, platelet count, hemoglobin A1C, cholesterol, and triglycerides), presence of hypertension (HTN), dyslipidemia, alcohol consumption, smoking status, liver stiffness measurement (LSM by FibroScan®), and current anti-DM medications. Hepatic steatosis was quantified using the controlled attenuation parameter (CAP) measured by FibroScan® at baseline and after two years. CVD was defined as ischemic heart disease or ischemic/hemorrhagic stroke.

Results

A total of 277 patients completed the two-year follow-up and underwent repeat CAP assessment. The mean age was 57±12 years, and 56.3% were male. The baseline mean CAP was 274±18 dB/m. A history of CVD was present in 86 (31%) patients, while 6 (3.2%) developed new CVD events during follow-up. Among the new CVD cases, 3 were cardiac events, and 3 were neurovascular events. CAP scores decreased in 176 patients (d-CAP group) and increased in 101 patients (i-CAP group). The mean CAP change was -33±29 dB/m in the d-CAP group and +24±18 dB/m in the i-CAP group. The mean age was higher in the d-CAP group than in the i-CAP group (58±12 vs. 55±12 years, p=0.012). The baseline mean CAP was higher in the d-CAP group than in the i-CAP group (284±50 vs. 255±47 dB/m, p<0.001). There were no significant differences in male proportion (58% vs. 53.5%, p=0.468), BW (71±14 vs. 73±17 kg, p=0.258), BMI (26.1±4.2 vs. 27±4.9 kg/m², p=0.14), WC (89±10 vs. 90±12 cm, p=0.397), laboratory data, HTN (56.8% vs. 48.5%, p=0.182), dyslipidemia (66.5% vs. 64.4%, p=0.72), alcohol consumption (24.4% vs. 21.8%, p=0.616), smoking status (48.9% vs. 43.6%, p=0.395), or baseline LSM (6.9±3.8 vs. 6.9±3.5 kPa, p=0.988) between the two groups. The use of metformin (93.2% vs. 93.1%, p=0.972) and pioglitazone (2.3% vs. 2%, p=1.0) did not differ significantly, but insulin use was lower in the d-CAP group than in the i-CAP group (5.1% vs. 12.9%, p=0.022). When stratified by CAP change, the incidence of new CVD was 0% (0/55) in patients with CAP reduction of ≤-40 dB/m, 2% (4/201) in those with changes between -40 and +40 dB/m, and 9.5% (2/21) in those with CAP increases of ≥+40 dB/m (p=0.037).

Conclusion

Hepatic steatosis, as measured by CAP, can change dynamically in patients with DM. Although this was an observational study, a marked decrease in CAP score was associated with a lower risk of CVD in patients with DM. Therefore, CAP monitoring may be a valuable tool for assessing CVD risk. Efforts to reduce hepatic steatosis, as reflected by CAP reduction, may contribute to CVD prevention in this population.

Introduction

In the carcinogenic pathway of colorectal cancer, the first concept is the "adenoma-carcinoma sequence" and the second concept is the " serrated pathway ". In these concepts, adenomas and serrated lesions gradually progress to cancer. The third concept is the "de novo pathway," in which cancer develops without adenomas or serrated lesions and is also characterized by high malignancy and rapid progression. We have endoscopically characterized depressed colorectal cancers considered to be of the "de novo pathway" and validated the usefulness of pit pattern and EC classification.

Aims & Methods

A total of 54819 colorectal neoplasms were resected endoscopically or surgically in our institution from April 2001 to December 2024. They were subjects of this study. Advanced cancers were excluded. Of these, 1694 lesions were submucosally invasive (T1) carcinomas, 7330 lesions were classified as high-grade dysplasia and 39977 lesions as low-grade dysplasia. Morphologically, they were divided into 3 types: depressed, flat, and protruded type comprising 1.0 (%), 46.4 (%),and 52.6（%), respectively. Specifically, the distinctive features of depressed type neoplasms concerning their pit pattern and EC classification were examined. EC classification is a classification for an endocytoscopy that can evaluate pathology, such as nuclear atypia and glandular structure, by magnifying stained cells. EC1a is diagnosed as normal mucosa, EC1b is diagnosed as hyperplastic polyps, and if slit-like glandular ducts or spindle-shaped nuclei are present, it is classified as EC2 and diagnosed as an adenoma or intramucosal carcinoma. If irregularly shaped glandular ducts or nuclei with a high N/C ratio are found, it is classified as EC3a, and diagnosed as intramucosal carcinoma or SM lightly invasive carcinoma. If the glandular ducts are indistinct and the nucleus is irregularly shaped and darkly stained, it is classified as EC3b and diagnosed as SM highly invasive carcinoma.

Results

Most of the flat (91.5%) and protruded type (94.9%) lesions showed type IIIL or IV pit pattern, which are common findings in adenomas. On the other hand, most of the depressed type lesions (92.6%) classified as type IIIs, VI or VN pit patterns, are typically seen in carcinomas. As for endocytoscopy, most of flat and protruded type lesions were identified as EC2 corresponding to adenomas. In contrast, relatively high rates of depressed type lesions were categorized as EC3a (40.3%) and EC3b (52.4%), consistent with invasive carcinomas.
The proportion of T1 carcinomas in depressed type lesions was 58.7%, whereas in flat and protruded type lesions it was 2.5% and 2.5%, respectively. Additionally, 12.0% of depressed type lesions less than 5mm in diameter were T1 carcinomas, whereas flat and protruded type lesions were 0.01% and 0%, respectively.

Conclusion

This study revealed that depressed lesions were classified as type IIIs, VI or VN pit patterns on magnifying endoscopy and as type EC3a or EC3b on endocytoscopy. Lesions with these features or pit patterns tend to invade the submucosal layer even if they are small size. Despite their high potential for malignancy, depressed lesions are often ignored. However, it is critical to recognize their features and accurately diagnose lesions based on morphology, pit pattern, and EC classification.

Disclosure

Shin-ei Kudo and Masashi Misawa received speaking honoraria from Olympus Corporation and have an ownership interest of the products of Cybernet Systems. Tetsuo Nemoto received a research grant from Olympus Corporation for other studies. Other authors have nothing to declare.

Introduction

Gastroparesis is a disorder characterized by delayed gastric emptying without mechanical obstruction, leading to symptoms such as nausea, vomiting, abdominal pain, and bloating. Cannabis and its active compounds are thought to interact with the gastrointestinal system through cannabinoid receptors, influencing motility, sensation, and inflammation. Nevertheless, data pertaining to the interactions between cannabis use, gastric motility and gastrointestinal (GI) symptoms is still scant¹.

Aims & Methods

The aim of the current study was to compare GI symptoms and gastric motility in a cohort of patients referred for gastric emptying breath test (GEBT). In this prospective study, all consecutive patients referred for motility testing in a tertiary hospital were recruited. Following obtaining written informed consent, questionnaires, including ROME, SCL-90-R and SF36 were filled out by the patients. Carbon-13 spirulina GEBT was done performed according to protocol, following consumption of a standardized meal. Patients with ongoing (regular or occasional) cannabis use were compared with non-cannabis users for all symptoms, quality of life and GEBT testing results. An additional healthy cohort of volunteers was recruited for validation of GEBT cut-off values and comparison to the symptomatic cohort.

Results

A total of 88 patients and 14 healthy volunteers were included in the current study. Among patients, 15 (17%) were identified as cannabis users, and these were compared with 73 non-users. Mean age and gender did not differ between users and non-users (52.4 vs 43.0, and 21% vs 33% males, respectively, p=NS). Gastric emptying breath test results did not significantly differ between groups, both in terms of mean values (t^1/2 127.2 vs 129.2 minutes, users versus non-users, respectively; p=NS) and in the proportion of delayed gastric emptying (26.7% versus 32.9%, users versus non-users, respectively; p=NS). None of the healthy volunteers displayed delayed gastric emptying results. Cannabis users demonstrated a higher gastrointestinal symptom burden and a greater number of diagnosed disorders of gut-brain interaction (DGBI) compared to non-users.

Conclusion

In our cohort of patients referred for gastric emptying breath tests, gastric emptying was similar between cannabis users and non-users. This is in line with previous studies suggesting that cannabis does not improve delayed gastric emptying. Nevertheless, previous studies suggested that cannabis may alleviate gastroparesis-associated symptoms². In this context, our results show that cannabis use was rather associated a more severe and systemic symptomatic manifestation of gut-brain disorders, in contrast to a more localized upper gastrointestinal involvement seen in non-users. Although causality cannot be established, we do note that despite ongoing cannabis use, treatment response was sub-optimal in the user patient group. Factors contributing to these differences, such as physiological or psychological constructs, should be further explored.

References

¹Parkman HP et al. Marijuana Use in Patients with Symptoms of Gastroparesis: Prevalence, Patient Characteristics, and Perceived Benefit. Dig Dis Sci. 2020
²Barbash, B et al. Cannabinoids Lead to Significant Improvement in Gastroparesis—Related Abdominal Pain: 1204. American Journal of Gastroenterology 2018.

Clinical Case Summary

A 75-year-old male under follow-up for chronic anemia secondary to multiple gastrointestinal angiodysplasias. He required transfusions every two weeks and maintained a baseline hemoglobin level of around 7–8 g/dL despite repeated therapeutic endoscopy with argon plasma coagulation. In light of this, he began daily treatment with oral Thalidomide 50 mg, with a good response for three years. At that point, he developed persistent melena and also experienced a deep vein thrombosis attributed to the treatment, leading to its discontinuation. The regimen was then changed to subcutaneous Octreotide 10 mg monthly, later intensified to 30 mg per month. Despite this, he continued to have recurrent gastrointestinal bleeding and multiple hospital admissions due to anemia-related symptoms. With no other treatment options available, a weekly dose of 30 mg was prescribed, achieving a good response for two years. Eventually, due to loss of efficacy and refractoriness to other treatments, compassionate use of Bevacizumab was initiated at a dose of 7.5 mg/kg monthly. From the beginning and after three doses, the patient became asymptomatic and experienced no further bleeding episodes, maintaining hemoglobin levels around 12–13 g/dL.
Gastrointestinal angiodysplasias are a common and significant condition due to the increased demand they place on healthcare services. Their management is complex, and treatment options are limited, particularly in cases that are refractory to standardized therapies. In such patients, the use of Bevacizumab can be considered. Although evidence is limited, it shows promising results, as demonstrated in our case.

References

Figure 1. Enteroscopy image showing angiodysplasia in the small intestine
Figure 2. Therapeutic enteroscopy, image prior to argon plasma coagulation therapy
Figure 3. Capsule endoscopy image showing angiodysplasia in the small intestine
Figure 4. Another capsule endoscopy image showing active bleeding secondary to one of the angiodysplasias

Introduction

Besides analgesia, opioids affect gastrointestinal (GI) motility, including decreased bowel peristalsis and delayed gastric emptying. Peripherally acting mu-opioid receptor antagonists, like naloxegol, are approved for treating opioid-induced constipation.

Aims & Methods

We aimed to evaluate the effects of naloxegol on opioid-induced lower GI tract dysfunction using magnetic resonance imaging (MRI) to assess changes in colonic volumes in healthy volunteers (HV).
In this double-blind, randomised, three-way crossover study, 15 HV complete three study visits, separated by ≥1 week washout, with administration of 25 mg naloxegol + 60 mg codeine, 60 mg codeine + placebo, or double placebo. During each visit, five abdominal MRI scans (each 20 min.) are obtained at 30 min intervals, at baseline, after drug intake, after a standardized 44 g oatmeal and 100 mL Nutridrink (313 kCal) meal, after a second drug dose, and after a bisacodyl 10 mg suppository administration. Colonic segmental volumes were quantified from all MRI scans using Entrolytics (Motilent, London, UK) in the ascending, transverse, descending, and rectosigmoid colon. We recorded the passage of stool during the study visit. Results are presented as medians with min. and max. P-values <0.05 are considered statistically significant. Adjusted p-values are used in case of post-hoc analysis.

Results

Interim analysis on 8 HVs (mean age 36±5y, 75% females) revealed that two subjects made stool on 2 mornings before the study visit. Four subjects passed stool in the double placebo group (2 postprandial, 2 post-bisacodyl), and 2 of them passed stool in the other 2 groups as well, around the same time. A significant scan x group effect was found for the whole colon volumes (p<0.05). More specifically, there was a significant difference in median ascending colon volumes between the scans (p=0.03), and especially in the double placebo group (Table). Although there was no significant difference in the median transverse colon volumes, bisacodyl led to a significant decrease in descending colon volume (p<0.0001), more specifically in the naloxegol+codein group and the double placebo group (ps<0.05), but not in the codein+placebo group. No significant differences in volumes of the rectosigmoid were detected.

Conclusion

Interim MRI analysis of 8 HVs suggests different colonic motility responses across groups and timepoints. Toilet visits were suppressed in both codeine groups. Different responses to drug and food intake were found in the ascending and descending colon between the naloxegol+codein and double placebo group on one hand compared to the codein+placebo group. Expansion and analysis of the full number of subjects will further clarify insights into the acute colonic responses to opioids and potential reversal by naloxegol.

Introduction

Although traditionally regarded as a vestigial organ, the appendix is increasingly recognized for its potential role in modulating gut immunity and contributing to the development of significant inflammatory or neoplastic intestinal diseases [1]. However, the underlying mechanisms linking the appendix to these immune and pathological processes remain poorly understood. This study aimed to investigate the relationship between the local immune microenvironment and the mutational landscape of rectal carcinomas in the context of prior or progressive appendectomy status.

Aims & Methods

This study aimed to investigate the relationship between the local immune microenvironment and the mutational landscape of rectal carcinomas in the context of prior or progressive appendectomy status.
Patients enrolled in the IMMUNOREACT 1 and 2 studies (NCT04915326 and NCT04917263, respectively) were stratified according to appendectomy status. Immunohistochemical analysis was performed to assess a range of immune markers, including CD3, CD4, CD8, CD8β, Tbet, FoxP3, PD-L1, MSH6, PMS2, and CD80. Additionally, flow cytometry was employed to evaluate the percentage of epithelial cells expressing CD80, CD86, CD40, HLA-ABC, or HLA-DR, as well as to quantify activated CD8+ T cells, CD4+ Th1 cells, and regulatory T cells (Tregs). Non-parametric tests were used.

Results

In this cohort, 41 patients out of 163 underwent appendectomy for other causes (e.g. appendicitis) before having been diagnosed with a rectal cancer. When the two groups were compared for microenvironmental features, in the normal mucosa of patients who had a previous appendectomy there was a higher rate of epithelial cells expressing HLA-abc (p=0,04) and a higher expression of CTLA4 on CD3+ T cells (p=0,03) when compared to appendectomy-naive patients. Within the rectal cancer tissue, a higher expression of CD86 on epithelial (cancer) cells expression was found in patients who already had an appendectomy (p=0,03). In therapy naïve patients, previous appendectomy was associated to a higher activation of CD4+ T helpers (expression of CD25), (p=0.04), and to tendency of higher rate of epithelial cells expressing HLA-abc (p=0,06) and of T cells expressing CTLA-4 (p=0.08). In patients who had neoadjuvant therapy, lower level of PD-L1 on the leukocyte surface were observed in patients who had a previous appendectomy (p=0.039).

Conclusion

Our findings suggest that prior appendectomy may be associated with distinct alterations in the local immune microenvironment of rectal carcinomas, including increased expression of antigen-presenting and immune-regulatory molecules such as HLA-BC, CTLA4, and CD86. In therapy naïve patients, appendectomy seem to increase the activation of T helper cells counterbalanced by an increase of the number of T cells expressing CTLA-4. These immune shifts in both tumour tissue and adjacent healthy mucosa support the hypothesis that the appendectomy may in somehow alter the interaction between epithelia cells and intraepithelial T cells. Further trancriptomic ​analysis will shed light on the effect of appendectomy on mucosal microevironment of ​rectal cancer patients.

References

1. Collard MK, Tourneur-Marsille J, Uzzan M, Albuquerque M, Roy M, Dumay A, Freund JN, Hugot JP, Guedj N, Treton X, Panis Y, Ogier-Denis E. The Appendix Orchestrates T-Cell Mediated Immunosurveillance in Colitis-Associated Cancer. Cell Mol Gastroenterol Hepatol. 2023;15(3):665-687.

Clinical Case Summary

Introduction: Eating disorders are often overlooked in the management of inflammatory bowel disease (IBD), despite their potential to aggravate malnutrition and reduce treatment effectiveness.
Aims & Methods: This case report aims to raise awareness of the possible coexistence of binge eating disorder (BED) and IBD. A female Crohn’s disease patient with persistent malnutrition and therapeutic resistance disclosed binge eating behavior and was referred for psychiatric care.
Results: Despite clinical remission with infliximab, the patient maintained a BMI of 13.8. After BED diagnosis and psychiatric intervention, her BMI increased to 16.6 with notable emotional improvement.
Conclusion: BED can mimic or worsen IBD complications. Screening for eating disorders and implementing multidisciplinary care—including mental health support—are crucial to optimize outcomes.

References

1) Inflammatory Bowel Disease and Eating Disorders: A systematized review of comorbidity
L Ilzarbe et al. J Psychosom Res. 2017 Nov.
2)Celiac Disease and Inflammatory Bowel Disease Are Associated With Increased Risk of Eating Disorders: An Ontario Health Administrative Database Study
Lakshmimathy Subramanian et al. Clin Transl Gastroenterol. 2024.
3)Shared genetic influences between eating disorders and gastrointestinal disease in a large, population-based sample of adult women and men
Laura A Pascoe et al. Psychol Med. 2024 Apr.
4) Prevalence and Characteristics of Avoidant/Restrictive Food Intake Disorder in Adult Neurogastroenterology Patients
Helen Burton Murray et al. Clin Gastroenterol Hepatol. 2020 Aug.