Introduction

Gastric cancer remains a major health challenge globally, with Helicobacter pylori (H. pylori) infection being a well-known risk factor. Despite significant advances in understanding the pathological mechanisms of gastric cancer, the specific interactions between H. pylori and the host immune system within the tumor microenvironment are not fully elucidated. This study leverages cutting-edge spatial transcriptomic technologies to explore these interactions in gastric cancer samples.

Aims & Methods

This research aims to elucidate the mechanisms through which H. pylori contributes to immune evasion in the gastric cancer microenvironment. We utilized spatial transcriptomics on 71 gastric cancer samples, supplemented by single-cell transcriptomics on 10 of these samples to achieve a high-resolution view of cellular interactions. Advanced analytical techniques, including cell interaction networks, neighborhood analysis, and deconvolution mapping, were employed to dissect the complex interplay between tumor cells, immune cells, and H. pylori.

Results

Our results reveal a sophisticated mechanism by which H. pylori induces the recruitment and activation of cancer-associated fibroblasts (CAFs) and regulatory T cells (Tregs), facilitating an immunosuppressive tumor microenvironment. Spatial transcriptomics highlighted significant alterations in gene expression patterns conducive to immune evasion, primarily mediated by the interaction between H. pylori, CAFs, and Tregs. The integration of single-cell and spatial data provided a detailed map of the immune landscape, revealing key nodes and pathways involved in this process.

Conclusion

The findings of this study provide compelling evidence of H. pylori’s role in shaping the immune landscape of gastric cancer towards immunosuppression through the modulation of CAFs and Tregs. These insights underscore the potential benefits of immunotherapeutic strategies tailored for H. pylori-positive gastric cancer patients. Future therapeutic interventions could focus on targeting these specific interactions to enhance the efficacy of cancer immunotherapy in this cohort.

Disclosure

Introduction

Combination with an advanced therapy (AT) and immunomodulator (IMM) is commonly used to optimise outcomes in Crohn’s disease (CD) and ulcerative colitis (UC). However, the comparative benefit of IMM co-therapy with different ATs and optimal duration of IMM co-therapy are unclear.

Aims & Methods

We aimed to determine the impact of IMM co-therapy on AT persistence.
We interrogated the Persistence Australian National IBD Cohort (PANIC5) registry of CD and UC patients from 2007-2021. The PANIC registry includes 100% of AT prescribing data in Australia. Non-persistence was defined as failure to dispense prescriptions for over six months. Co-therapy with IMM was defined as concurrent dispensing of a thiopurine (azathioprine or mercaptopurine) or methotrexate during AT use. Kaplan-Meier survival curves were generated and compared using the log-rank test. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI).

Results

31,967 CD patients and 13,492 UC patients were included. 44.2% of CD and 37.9% of UC patients had received co-therapy with IMM. IMM co-therapy increased persistence of infliximab in both CD (median Kaplan Meier survival time 50.0 [95% CI 47.3-52.7] vs 27.0 months [95% CI 24.5-29.5], HR=0.68, p<0.001) and UC (35.0 [95% CI 31.4-38.6] vs 18.0 [95% CI 16.2-19.8], HR=0.71, p<0.001). Similarly, IMM co-therapy increased persistence of adalimumab in both CD (48.0 [95% CI 45.6-50.4] vs 25.0 [95% CI 23.3-26.7], HR=0.67, p<0.001) and UC (25.0 [95% CI 19.2-30.8] vs 17.0 [95% CI 14.2-19.8], HR=0.77, p<0.001). IMM co-therapy did not significantly affect persistence of vedolizumab in CD (33.0 [95% CI 27.0-39.0] vs 36.0 [95% CI 31.1-40.9], p=0.43), vedolizumab in UC (45.0 [95% CI 38.7-51.3] vs 48.0 [95% CI 41.8-54.2], p=0.11) or ustekinumab in CD (median survival and 95% CI unable to be calculated as event rate >50%; p=0.13). Ustekinumab was not approved for UC in Australia before 2021; thus no UC data were available.
Subgroup analysis showed a significant difference in anti-tumour necrosis factor inhibitor (TNFi) persistence across CD patients based on IMM timing during TNFi therapy (Table 1; p<0.001). CD patients who had at least three months of IMM before de-escalation had better persistence compared to those who stopped IMM within the first three months of TNFi (96.0 vs 19.0 months, p<0.001). Continuous IMM use during TNFi therapy had intermediate persistence (37.0 months, 95%CI 33.1-40.8). Patients who were not treated with IMM initially but started IMM in the last three months of therapy had the worst persistence (4.0 months, 95%CI 2.7-5.3). A similar pattern was seen in UC (Table 1). There was no difference between thiopurine and methotrexate co-therapy in either CD (p=0.41) or UC (p=0.45).

Table 1 – Median Kaplan Meyer persistence, stratified by timing of immunomodulator usage during anti-tumour necrosis alpha inhibitor (TNFi) therapy

Conclusion

IMM co-therapy significantly improved persistence of TNFi, but not vedolizumab or ustekinumab in both CD and UC. Discontinuing IMM within three months of commencing TNFi was associated with reduced persistence compared to continuing initial co-therapy for longer before de-escalation.

Disclosure

RWL has served as an advisory board member for AbbVie, Aspen, BMS, Celgene, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences and Takeda, and has received research funding from Joanna Tiddy USYD, McCusker Charitable Foundation, Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer and MRFF.

Introduction

Methotrexate (MTX) remains the cornerstone of treatment for rheumatoid arthritis (RA) and psoriatic arthritis (PsA), yet concerns about hepatotoxicity often lead to premature discontinuation.

Aims & Methods

This study aimed to reassess the risk of liver fibrosis in long-term methotrexate therapy and to identify clinical, metabolic, and treatment-related factors associated with hepatic changes. This was a prospective cohort study including 201 patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) undergoing MTX therapy for ≥6 months. Liver stiffness was assessed using transient elastography (Fibroscan®) and acoustic radiation force impulse (ARFI). Hepatic steatosis was evaluated using the controlled attenuation parameter (CAP). Serum-based indices (FIB-4, APRI) were calculated. Clinical and metabolic data—including BMI, waist/hip circumference, lipid profile, glucose, comorbidities, and alcohol use (B-peth)—were collected. Associations with liver parameters were analyzed using Spearman correlation and multivariable linear regression adjusted for age, sex, and diagnosis.

Results

Liver stiffness values were generally low, with minimal fibrosis detected by Fibroscan (median 4.7 kPa) and ARFI (median 2.85 kPa). ARFI and Fibroscan values showed weak but significant correlation (ρ = 0.19, p = 0.03). APRI, but not FIB-4, modestly correlated with both imaging modalities. Multivariable regression identified no independent predictors of increased liver stiffness. In contrast, CAP-measured steatosis was significantly associated with higher BMI (p = 0.002) and waist circumference (p = 0.001), while MTX dose, duration, and alcohol intake (B-peth) showed no associations. Principal component analysis confirmed that steatosis clustered with metabolic rather than pharmacologic variables.

Conclusion

In this real-world cohort, significant liver fibrosis was rare despite prolonged MTX exposure. Hepatic steatosis, rather than fibrosis, emerged as the dominant hepatic alteration, driven primarily by modifiable metabolic risk factors. These findings support the use of targeted metabolic assessment and intervention in MTX-treated patients rather than routine discontinuation based on fibrosis concern.

Clinical Case Summary

Bouveret syndrome is a rare type of ileus caused by the impaction of large gallstones that pass through a cholecystoenteric fistula in the duodenum.Although endoscopic treatment is preferable over surgery for patients with Bouveret,1 some difficulties in endoscopic procedures must be overcome.2 Herein, we describe the usefulness of combined endoscopic procedures of electrohydraulic lithotripsy (EHL) and new technique by using the guide wire as a snare (Figure1).72 years old female patient known chronic liver disease and splenomegaly came to the emergency department by progressive abdominal pain, persistent vomiting, and weight loss two months ago. Upper Endoscopy was arranged next day and showed hugely dilated stomach with remnant food (signs of Gastric outlet obstruction) down to large stone at second part of duodenum totally obstructing lumen and a fistulous opening. MRCP was done and revealed: dilated Common Bile Duct about 10 mm down to its lower with extensive air in the biliary tree, dilated IHBRs with extensive pneumobilia, collapsed thick-walled gall bladder with air inside and large 35x55 mm impacted stone in the second part of the duodenum. An attempt using Biliary Electrohydraulic lithotripsy (EHL) was done, EHL over 3 hours was with minimal effect as the stone was hard and decreased the stone size to about 4 cm but it is still lodged in the angle, and we couldn’t grasp it by snare.We used Boston scientific guidewire 0.035 to create an open snare which overlapped the stone in its place then gradually pulled to the stomach. Over another 4 hours we used EHL and Lithotripsy stone extractor to destroy the stone into small fragments less than 1 cm.The stone was destroyed. The duodenum was reevaluated and circumferential ulcerations was noted with complete healing of fistula. The patient started oral intake 24 hours after the procedure with no abdominal pain or vomiting. Long term follow up of the patient showed marked weight gain with no adverse effects.

References

1. Cappell MS, Davis M. Characterization of Bouveret’s syndrome: A comprehensive review of 128 cases. A m J G a s t r o e n t e r o l 2006;
101: 2139–46.
2. Caldwell KM, Lee SJ, Leggett PL, Bajwa KS, Mehta SS, Shah SK. Bouveret syndrome: Current management strategies. C l i n E x p
69–75.

Clinical Case Summary

A 45 y/o female patient complained from fatigue and dyspnea, her CBC showed MHA (Hb 6.5 g/dl, MCV 62 fl/cell) with normal WBCs and PLTs and she denied any apparent bleeding or menstrual abnormalities. Upon investigating, her virology profile was negative, she had +ve FOB, low levels of iron (25.6 ug/dl), low ferritin (10.3 ng/ml) and high Reticulocyte count (3.5%). She underwent upper and lower GI endoscopies without significant findings. She received packed RBCs to correct her general condition but the symptoms recurred. Repeated upper and lower endoscopies didn’t show any source of bleeding. Capsule enteroscopy was ordered and showed multiple red spots, dilated vessels and small varices. We thought of angiodysplasia so we ordered CT enterography but the scan couldn’t detect vascular abnormalities in small intestinal wall and showed an aneurismal dilation at portal vein confluence (3x3.7cm) along with dilated both portal vein and splenic vein. The interventional radiology team described the aneurysm as fusiform not saccular, so it wasn’t suitable for coiling and embolization.
Portal vein aneurysm (PVA) was discovered incidentally in this case. The turbulence of the portal blood flow is believed to be causing congestion in the drained intestinal segments. As a result, we found the described spots and dilated vessels in the jejunum. DBE was suggested to apply APC to the telangiectatic spots, but this won’t address the dilated veins that’s why we preferred consulting intervention radiology to deal with both the intestinal lesions and the aneurysm itself as the main cause of this condition, but unfortunately no definitive intestinal lesions were seen in the angiography CT and the aneurysmal anatomy wasn’t suitable for intervention, also endovascular surgical consultation declined the portal vein reconstruction possibilities due to the difficulty and procedural risks. We advised the patient to continue on supportive treatment and blood transfusion when needed.

References

Kurtcehajic, A., Zerem, E., Alibegovic, E., Kunosic, S., Hujdurovic, A. and Fejzic, J.A., 2023. Portal vein aneurysm-etiology, multimodal imaging and current management. World Journal of Clinical Cases, 11(4), p.725.

Introduction

Esophageal motility disorders are common in the clinical practice, with impact in patient’s quality of life. High-resolution esophageal manometry (HREM) is the gold standard for evaluation of patients with functional esophageal disorders. The Chicago Classification offers a standardized approach HREM, reducing bias and enabling a precise diagnosis of these disorders. Despite these, HREM remains a complex exam, both in data analysis and in accessibility. This proof-of-concept study aims to develop and validate an artificial intelligence model for identification of motility disorders in HREM according to the Chicago Classification.

Aims & Methods

618 HREM exams from two different devices and three centers from Spain and the United States of America were used for model development. Several machine learning models were trained and evaluated for detection of motility disorders. The exams were classified according to the Chicago Classification 4.0, based on a consensus reached by two independent HREM experts. The training and testing dataset were divided in a 80%/20% patient split design based on label frequency. Models’ performance was evaluated through their accuracy and area under the receiver-operating characteristic curve (AUC-ROC).

Results

The GradientBoostingClassifier model outperformed the remaining machine learning models with an accuracy of 94.2% and an AUCROC of 0.921 for identifying disorders of esophagogastric junction outflow. The xGBClassifier model detected disorders of peristalsis with an accuracy of 80.9% and an AUC-ROC of 0.871.

Conclusion

In this pilot study with integration of exams from different devices and demographic contexts, several machine learning models accurately identified disorders of the esophagogastric junction outflow and peristalsis in HREM according to Chicago Classification.
The integration of AI into the study of esophageal motility disorders through HREM-driven diagnosis is expected to revolutionize the way these conditions are managed, optimizing both exam accuracy and accessibility, transforming patient management.