Introduction

Blueberry ingestion resulted in significant abdominal symptom relief, improved Gastrointestinal Symptom Rating (GSRS) and quality-of-life and life functioning scores by Outcome Questionnaire (OQ 45.2) in patients with DGBI¹. It is unclear via which mechanisms blueberries exert their beneficial effect in DGBI².

Aims & Methods

We explored the associations between symptomatic responses to blueberry ingestion, faecal microbiota composition, clinical phenotypes and tests of disease mechanisms in DGBI.
Male and female patients aged 18-60 years with DGBI (irritable bowel syndrome or functional dyspepsia, Rome 4), were randomised to blueberries (30g freeze-dried powder = 180g fresh blueberries) or placebo daily for 6 weeks in a double-blind, cross-over study. GSRS and OQ-45.2 were assessed before and in week 6 of each treatment period. Responders were defined by improved GSRS or OQ-45.2. Demographics, lifestyle and symptom details were documented at baseline³. Further variables were gathered before and in week 6 of treatment: Bristol Stool Scale, breath H_2, CH₄ and symptoms after fructose 35g, cognitive tests (CANTAB®), skin fluorescence for advanced glycation end-products and serum tight junction proteins (claudin-3 and -5, zonula occludens-1). Stool microbiome analysis was performed by DNA extraction and sequencing for shotgun metagenomics. Nonmetric multidimensional scaling ordination plots based on Bray-Curtis dissimilarity were generated at the species level with clinical covariates. Spearman association of microbial species with demographics, clinical phenotype and mechanistic tests at baseline and during treatment were analysed by stratifying data into pre- and post-treatment groups, as well as responders and non-responders by GSRS and OQ-45.2.

Results

In 43 DGBI patients there were significant associations between faecal microbiota composition, clinical phenotypes and tests relating to disease mechanisms that were distinct between blueberry responders and non-responders. Examples of prominent baseline associations were breath gases after fructose with Ruminococcus sp AF41_9 in GSRS responders and with Eggerthella lenta, Lachnospiraceae bacterium AM48_27BH, Phocaeicola vulgatus, Ruminococcus callidus, Mediterraneibacter glycyrrhiznilyticus in non-responders. Cognitive skills were associated with Clostridium sp AF34_13 and Clostridiaceae bacterium Marseille_Q4149 in responders, and with Blautia glucerasea, Eggerthella lenta and Ruminococcus callidus in non-responders. Tight junction protein levels correlated with Clostridiaceae bacterium Marseille_Q4149, Anaerobutyricum hallii and Bacteroides intestinalis in responders and with Anaerostipes hadrus, Blautia faecicola, Blautia glucerasea, Clostridia bacterium UC5_1_1D1 and Ruminococcus gnavus in non-responders. During blueberry ingestion new associations between bacterial taxa and GSRS, breath gases after fructose, tight junction protein levels emerged, which were largely distinct between responder groups. Responders by OQ-45.2 showed associations between bacterial taxa, demographics and mechanistic tests both at baseline and during blueberry dosing that were largely distinct from those of GSRS responders.

Conclusion

In patients with DGBI, GI and general symptom relief with blueberry ingestion were characterised by specific, distinct associations between faecal microbiota, clinical phenotype and tests of disease mechanisms at baseline and during treatment. This first longitudinal blueberry treatment study in DGBI patients suggests an important role of the intestinal microbiota in symptom genesis warranting further study.

References

¹Wilder-Smith CH, Materna A, Olesen SS. Blueberries Improve Abdominal Symptoms, Well-Being and Functioning in Patients with Functional Gastrointestinal Disorders. Nutrients. 2023 May 20;15(10):2396.
²Kalt W, Cassidy A, Howard LR, Krikorian R, Stull AJ, Tremblay F, Zamora-Ros R. Recent Research on the Health Benefits of Blueberries and Their Anthocyanins. Adv Nutr. 2020 Mar 1;11(2):224-236.
³Wilder-Smith CH, Drewes AM, Materna A, Olesen SS. Extragastrointestinal Symptoms and Sensory Responses During Breath Tests Distinguish Patients With Functional Gastrointestinal Disorders. Clin Transl Gastroenterol. 2020 Aug;11(8):e00192.

Disclosure

This study was supported by a research grant from the US Highbush Blueberry Council.

Introduction

Accurate prediction of lymph node metastasis (LNM) in submucosal invasive (T1) colorectal cancer (CRC) is essential for determining the need for additional surgery following endoscopic resection. Conventional histopathological assessments, however, are limited by interobserver variability. This study aimed to develop and externally validate a stacking-based artificial intelligence (AI) model integrating histopathological whole slide images (WSIs) and clinical parameters to predict the risk of LNM in T1 CRC.

Aims & Methods

This retrospective study included 1,056 patients with histologically confirmed T1 CRC treated at Showa Medical University Northern Yokohama Hospital. Of these, 593 cases were used for model training and 100 for internal testing. External validation was conducted on 25 cases from two independent institutions.
The proposed stacking ensemble model incorporated the Multiple Instance Self-Training (MIST) score derived from WSIs, patient sex, and tumor location (colon vs. rectum). Base learners included logistic regression, XGBoost, and random forest, with a meta-learner synthesizing their outputs to generate the final LNM prediction. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) in both internal and external cohorts.

Results

LNM was observed in 69 (11.6%) training cases, 15 (15.0%) test cases, and 2 (8.0%) external validation cases. The model achieved an AUC of 0.6965 in the internal test cohort and 0.7500 in the external validation cohort, demonstrating stable and generalizable predictive performance.
A representative case involved a 64-year-old man with a 16-mm type 0-Is lesion in the sigmoid colon resected via endoscopic mucosal resection (EMR). Histopathology showed well-differentiated tubular adenocarcinoma (tub1 > tub2), submucosal invasion depth of 3,300 µm (T1b), tumor budding grade BD1, Ly0, V1a, and negative resection margins (HM0, VM0). Despite guideline-based recommendations prompting additional surgical resection, no LNM was found (N0, 0/16), and the patient remained recurrence-free five years postoperatively—consistent with the AI model’s prediction.

Conclusion

The stacking-based AI model exhibited robust and generalizable performance in predicting LNM in T1 CRC, both internally and across external institutions. This approach offers a complementary tool to conventional pathology and may enhance individualized decision-making regarding the necessity of additional surgical intervention.

Introduction

The management of malignant hilar biliary obstruction can be done by endoscopic biliary stenting, which is a well-established palliative treatment, improving the quality of life by relieving symptoms.

Aims & Methods

This systematic review and meta-analysis aimed to compare the use of stents placed above and across the sphincter of Oddi in patients with malignant hilar biliary obstruction. We performed a systematic search of the PubMed, Embase, and Cochrane Library databases in April 2025. Article screening was conducted independently by two authors using Rayyan software. Inclusion criteria were randomized controlled trials (RCTs) comparing stent placement above and across the sphincter of Oddi for malignant hilar biliary obstruction, evaluating at least one of the outcomes of interest. The outcomes were stent migration, stent patency, cholangitis, stent occlusion, and successful placement of the stent. RStudio software was used for statistical analysis, applying a random-effects model to calculate the risk ratio (RR) in binary outcomes and mean differences (MD) in continuous outcomes.

Results

We included three RCTs comprising 161 patients. There was no significant difference between the transpapillary and suprapapillary stents regarding the rates of stent migration (RR 2.03; 95% CI 0.41–10.16; p=0.39; I²=55%), cholangitis (RR 0.65; 95% CI 0.08–5.07; p=0.68; I²=0%), technical success (RR 0.99; 95% CI 0.95–1.04; p=0.80; I²=0%), and stent occlusion (MD 89.20; 95% CI 16.30–162.10; p=0.02; I²=78%). However, the mean number of patent stents was significantly lower in the suprapapillary stent group.

Conclusion

The two types of stent seem similar in terms of technique, efficacy, and safety, although the suprapapillary stent seems superior in terms of stent patency.

References

Ko SW, Joo HD, Song TJ, Kim S, Choi SJ, Oh CH, Oh D, Park JS, Yoon SB, Yoon JH, Seo DW, Lee SK. Impact of the suprapapillary method on patency in distal malignant biliary obstruction: a multicenter randomized controlled trial. Gastrointest Endosc. 2024 Oct;100(4):679-687.e1. doi: 10.1016/j.gie.2024.03.024. Epub 2024 Mar 21. PMID: 38521477.
Kurita A, Uza N, Asada M, Yoshimura K, Takemura T, Yazumi S, Kodama Y, Seno H. Stent placement above the sphincter of Oddi is a useful option for patients with inoperable malignant hilar biliary obstruction. Surg Endosc. 2022 May;36(5):2869-2878. doi: 10.1007/s00464-021-08576-x. Epub 2021 Jun 2. PMID: 34076770.
Finn Møller Pedersen, MD, Annmarie Touborg Lassen, Ove B. Schaffalitzky de Muckadell. Finn Møller Pedersen, MD, Annmarie Touborg Lassen, Ove B. Schaffalitzky de Muckadell. Gastroint Endosc. 1998;48(6):574-579.

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.

Clinical Case Summary

A 46-year-old male with stenosing colonic Crohn’s disease (CD) and perianal fistulas, treated with Infliximab and Azathioprine, achieved clinical and endoscopic remission (CDAI 35, fecal calprotectin 73 µg/g, and SES-CD 1) after 36 months of therapy. Following three years of immunosuppression, he developed dysphagia, weight loss, fever and night sweats – no respiratory symptoms were present. The patient was hospitalized for further evaluation and nutritional support. Infectious screening ruled out bacterial infections, CMV, EBV, HIV, HBV, HCV, tuberculosis, toxoplasmosis, and syphilis. Upper gastrointestinal endoscopy revealed active, ill-defined ulcers in the larynx and pharynx [1] ; two well-defined, clean-based ulcers with non-erythematous edges in the distal esophagus; and elevated, reddened, non-friable post-bulbar lesions. Pharyngeal biopsies collected by the otolaryngology team demonstrated a marked inflammatory response with loose granulomas. Fungal testing revealed numerous fungi consistent with Histoplasma capsulatum (Figure 3B). CT scans indicated adrenal thickening and enlarged para-aortic lymph nodes, supporting the diagnosis of disseminated histoplasmosis. The patient was treated with liposomal amphotericin B, followed by oral itraconazole, resulting in clinical improvement. Given the remission of CD and the confirmed disseminated granulomatous infection, immunosuppressive therapy was discontinued. This case highlights the risk of opportunistic infections in patients with inflammatory bowel disease (IBD) undergoing long-term immunosuppression, particularly when in anti-TNF combination therapy. Gastrointestinal histoplasmosis, especially in the absence of pulmonary symptoms, is a rare infection that is often misdiagnosed due to symptom overlap with IBD. Clinicians must maintain a high index of suspicion to ensure early diagnosis and appropriate management, as delayed treatment is potentially life-threatening.

References

Castro HM, Fullana MP, Canale HL. Disseminated histoplasmosis in immunosuppressed patient. Med Clin (Barc). 2021 Jan 8;156(1):48. English, Spanish. doi: 10.1016/j.medcli.2019.10.002. Epub 2019 Nov 26. PMID: 31784112.

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.