Introduction

The composition of the gut microbiota differs between individuals with (advanced) adenomas (AA) and colorectal cancer (CRC) compared to controls, suggesting its importance in the adenoma–carcinoma sequence and highlighting its potential as a non-invasive biomarker. While 16S ribosomal RNA sequencing (16S rRNA) is a commonly used method for microbiome research, metaproteomic (MP) analysis of faecal samples is an emerging alternative. MP is generally used to study human and bacterial proteomes, but additionally allows for microbiota profiling. However, a direct comparison between MP and 16S is lacking.

Aims & Methods

This study aims to evaluate the comparability between faecal microbiota composition profiles derived from bacterial MP and 16S rRNA gene sequencing in patients with colorectal neoplasia.
Subjects scheduled for colonoscopy, regardless of indication, were eligible to provide a faecal sample prior to bowel cleansing. Based on endoscopic and histological findings, patients were divided into subgroups. Both 16S rRNA sequencing and MP analysis by liquid chromatography–tandem mass spectrometry were performed on all faecal samples. Only proteins with a unique peptide were quantified and taxonomically annotated using the Human Microbiome NIH project. For 16S, the SILVA 132 99% OTUs database was used.

Results

Faecal samples from 12 CRC, 10 AA, 11 non-advanced adenoma patients, and 20 controls were included in this study. No significant differences in alpha or beta diversity were observed for either technique. After taxonomic annotation, 225 operational taxonomic units (OTUs) were obtained for 16S consisting of 10 different phyla, 53 families, 180 genera, 14 species and no subspecies. Taxonomic annotation of the bacterial proteins resulted in 354 OTUs across 7 different phyla, 45 families, 81 genera, 261 species and 250 subspecies. At phylum level, Bacteroidetes and Firmicutes accounted for the majority of the relative abundance in both analytical strategies. In total, 5 phyla, 27 families, 44 genera and 4 species were detected with both techniques, including CRC-associated genera such as Bacteroides, Parvimonas, and Prevotella. However, CRC-associated Fusobacterium was detected exclusively with MP, and Peptostreptococcus with 16S. Among CRC-associated species, Ruminococcus torques was detected with both methods, while Fusobacterium nucleatum, Parvimonas micra, and Bacteroides fragilis were detected exclusively with MP. The top 12 most abundant families and genera account for over half of the relative abundance in both methods. For these most abundant taxa, overlap was found for 9 families and 5 genera. The distribution among individuals in the various study groups was subsequently examined at family and genus level. Notably, 16S exhibited a higher inter-individual variability and a higher number of outliers compared to MP.

Conclusion

Metaproteomics had a more limited range for detecting bacterial diversity at genus level but offered higher resolution for identifying bacteria at the (sub)species level. In contrast, the highest resolution for 16S rRNA sequencing is typically achieved up to genus-level, resulting in undetected species. There was considerable overlap between 16S and MP analyses at family level regarding the top 12 most prevalent bacteria, but less overlap at genus level between the two analytical methods. This underscores the value of combining both methods for a more complete analysis of bacterial diversity.

Introduction

While the clinical trial (JCOG1009/1010) evaluating the efficacy and safety of endoscopic submucosal dissection (ESD) for intramucosal (T1a(M)) undifferentiated early gastric cancer (UD-EGC) of the predominant type measuring <2 cm not associated with ulceration showed a favorable 5-year survival outcome (99.3% (95% confidence interval: 97.1-99.8 )), the 10-year prognosis is still uncertain. We have followed the patients for 10 years.

Aims & Methods

Main eligibility criteria were endoscopically diagnosed cT1a/N0/M0, single primary lesion, size ≤2 cm, no ulceration, and histological components of undifferentiated adenocarcinoma in biopsy. Based on the histologic findings after ESD, additional gastrectomy was indicated if the histopathologic examination did not meet the criteria for curative resection. The primary endpoint was 5-year overall survival (OS) of the undifferentiated-predominant type group, and 10-years follow-up of patients was planned.

Results

Of a total of 346 patients enrolled between February 2011 and May 2013 from 49 institutions, 337 were eligible and all eligible patients underwent ESD. Histopathologic findings of the resected specimens showed undifferentiated predominant cancer in 275 patients while one patient could not be evaluated due to emergent surgery for a perforation during ESD. Of the 275 patients, 195 whose ESD was judged to result in a curative resection were followed up without additional treatment, and 73 of the remaining 79 patients whose ESD was judged to result in a non-curative resection received additional gastrectomy. Among the 275 patients with UD-EGC, one patient experienced a metastatic recurrence 3,034 days after ESD. The 10-year OS and relapse-free survival (RFS) of patients with undifferentiated-predominant type were 96.2% (95% confidence interval: 93.1-97.9) and 95.7% (95% confidence interval: 92.4-97.6), respectively, while the 10-year OS and RFS for all 346 enrolled patients were 95.1 % and 94.7 %, respectively.

Conclusion

ESD for UD-EGC with tumor size of 2 cm or less is the standard treatment, with excellent 10-year survival results as well as in the 5-year period.

Introduction

EUS-guided hepaticogastrostomy (EUS-HGS) is a novel technique that allows internal drainage of the biliary system via the stomach. This approach may be of value in patients with duodenal obstruction, surgically altered anatomy, or in hilar strictures with inadequate drainage of the left hepatic duct by other techniques (1, 2). However, this procedure has a high technical complexity and until recently no dedicated stents were available exposing the patient to adverse events such as the risk of biliary leakage and stent migration (3). A partially covered self-expanding metallic stent (pcSEMS) with anti-migration flaps may overcome these risks. So far, the available data on the use of this specific stent is limited, and prospective studies are particularly missing.

Aims & Methods

Aim of this study was to assess the safety and feasibility of EUS-HGS in patients with an inoperable malignant biliary obstruction, with the use of this dedicated stent. This prospective single-center study included patients with inoperable malignant biliary obstruction that underwent an EUS-HGS. Patients were ineligible in case of uncontrolled coagulopathy, tumor infiltration in the gastric wall, intervening blood vessels or extensive amount of ascites. Procedure was performed with a 10cmx10mm pcSEMS (Giobor stent, Taewoong Medical). Primary outcome was safety, defined as rate of procedural related adverse events (AEs) and mortality <30 days. Technical and clinical success rate were evaluated as secondary endpoints, defined as successful deployment of the stent in the intended location and at least 50% decrease of bilirubin <14 days.

Results

Between January 2022 and July 2024, 25 patients (14 female [56%], median age 70 years [IQR 64-76]) were included. Reason to perform EUS-HGS included duodenal obstruction (n=12), altered anatomy (n=6) or failed drainage of the left hepatic duct by ERCP (n=7). In 21/25 patients EUS-HGS was technically successful (84%). In one patient the procedure was aborted due to a self-limiting bleeding after puncture of the bile duct, in one patient due to unsuccessful cannulation of the central bile duct and in two patients the cholangiogram showed previously unidentified intrahepatic strictures that precluded adequate drainage by EUS-HGS. No severe periprocedural AEs occurred. Three patients (14%) were re-admitted with presumed cholangitis <30 days after the procedure; two with undrained right-sided bile ducts for which a percutaneous drain was placed, and one patient due to obstruction of the bile duct branches by the covered part of the stent, for which an endoscopic re-intervention was performed replacing the Giobor stent by a fully covered and uncovered SEMS. Five patients died within 30 days due to fulminant disease progression. None of these patients experienced procedural related AEs. Clinical success was achieved in 18/19 (95%) patients with technical success and follow-up of at least two weeks. Six out of the 18 patients with clinical success developed recurrent biliary obstruction after a mean of 105 days (SD 80). Obstruction was caused by hyperplasia at the uncovered portion of the stent (n=3) and due to sludge obstructing the stent (n=3). Successful re-intervention was performed in all patients.

Conclusion

This prospective study shows that EUS-HGS with a dedicated partially covered stent is feasible and safe. Tissue hyperplasia in the uncovered part of the stent and sludge obstruction may compromise long-term stent patency. Larger, comparative studies addressing stent design and timing of EUS-HGS are eagerly awaited.

References

1. Pawa, S., et al., American Society for Gastrointestinal Endoscopy guideline on the role of therapeutic EUS in the management of biliary tract disorders: summary and recommendations. Gastrointest Endosc, 2024.
2. van der Merwe, S.W., et al., Therapeutic endoscopic ultrasound: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy, 2022. 54(2): p. 185-205.
3. Binda, C., et al., Efficacy and safety of endoscopic ultrasound-guided hepaticogastrostomy: a meta-regression analysis. Endoscopy, 2024. 56(9): p. 694-705

Clinical Case Summary

We report a case of a 71-year-old male, former heavy smoker with obesity and obstructive sleep apnea, admitted with headache, fatigue, anorexia, and persistent cough. Initial blood tests showed hemoglobin 12.7 g/dL and elevated C-reactive protein (145.4 mg/L). Chest CT revealed a spiculated lingular nodule (37×28 mm) with pulmonary and mediastinal lymphadenopathy. Bronchoscopy confirmed non-small cell lung carcinoma (adenosquamous subtype). Staging PET-CT demonstrated widespread metastases (lungs, liver, adrenals, bones, peritoneum, muscles), and brain MRI identified cerebral involvement.
During hospitalization, the patient developed melena with hemoglobin dropping to 7.1 g/dL. Upper GI endoscopy was negative. Ileocolonoscopy revealed multiple clots and a friable, infiltrative lesion in the terminal ileum (25 cm from ileocecal valve) with active low-grade bleeding. Hemostasis was successfully achieved using argon plasma coagulation (APC).
The final diagnosis was mid-gastrointestinal bleeding due to small bowel metastasis from lung cancer. Given the extent of disease, palliative care and oncology follow-up were arranged. No further bleeding episodes occurred post-intervention.
This case highlights the diagnostic challenge of small bowel metastases as a rare cause of GI bleeding. It emphasizes the role of endoscopic therapy as an effective, minimally invasive palliative strategy to control bleeding and improve patient quality of life, avoiding surgical intervention in advanced oncologic settings.
Points toiscuss:
• Recognition of small bowel metastasis in patients with known malignancy presenting with GI bleeding.
• The utility of ileocolonoscopy in diagnosing mid-GI bleeding sources.
• Endoscopic management (APC) as a palliative tool in metastatic disease.
Illustrative Material:
• Ileocolonoscopy image of terminal ileum metastatic lesion.
• PET-CT scan showing metastatic spread.

Introduction

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized by esophageal dysfunction and eosinophilic inflammation of the esophageal mucosa. In this study, we investigated the bacterial flora in saliva and esophageal mucus in patients with EoE and examined the relationship between EoE disease activity and mucosal cytokine expression.

Aims & Methods

Cases consisted of patients with active and inactive EoE (A-EoE and I-EoE, respectively). A-EoE was defined as a peak eosinophil count > 15/high-power field, according to the 2025 consensus guidelines. Saliva samples were collected from the patients before the endoscopic examination. Brushing samples were collected from the distal esophagus of patients with EoE during endoscopic procedures. The degree of EoE inflammation was assessed using the EoE endoscopic reference score (EREFS). The samples were profiled using the Illumina MiSeq platform. The V3–V4 regions of the 16S rRNA gene (460 bp) were amplified by using tailed PCR.

Results

Fifty-nine patients were enrolled, including 8 with I-EoE, 17 with A-EoE, and 28 non-EoE controls. Major bacterial genera, such as Streptococcus, Prevotella, Veillonella, and Alloprevotera, were detected in both the oral cavity and esophagus. Compared with the control group, the active EoE group had significantly more Prevotella spp. in the saliva and esophageal mucosa. Conversely, significantly fewer Neisseria spp. were found in the saliva and Streptococcus spp. in the esophageal mucosa of patients with active EoE. The EREFS of EoE and Streptococcus were inversely correlated.

Conclusion

In this study, we clarified the characteristics of the bacterial flora in the saliva and esophageal mucosa of patients with eosinophilic esophagitis.

Introduction

Recent studies have revealed that liquid-liquid phase separation (LLPS) plays a critical role in tumorigenesis. Myotilin (MYOT), a key component of actin cross-linking protein complexes, is involved in regulating myofibril assembly and maintaining the structural integrity of Z-discs in muscle cells. Intriguingly, MYOT contains intrinsically disordered regions (IDRs) and has been implicated in the migration of gastric cancer. However, whether MYOT undergoes LLPS and whether this process contributes to gastric cancer progression remains unexplored.

Aims & Methods

We aimed to investigate whether MYOT undergoes LLPS and its potential role in gastric cancer progression.
Differential gene expression analysis was performed on gastric cancer samples from our sequencing data and validated using public databases. The Disprot, Database of Protein Disorder was used to predict the IDRs of MYOT. Fluorescence recovery after photobleaching (FRAP) and cellular immunofluorescence were explored to assess MYOT’s ability to undergo LLPS. Cell proliferation, apoptosis and migration assay were conducted to investigate the potential role of MYOT in gastric cancer. Actin polymerization assays were performed to evaluate the qualitative effects of purified MYOT on actin polymerization.

Results

Differential gene expression analysis revealed that MYOT was significantly downregulated in gastric cancer tissues compared to adjacent normal tissues, a finding further confirmed by RT-qPCR. In the prediction of protein structure, it can be found that MYOT contains extensive IDRs. FRAP analysis demonstrated rapid fluorescence recovery in GFP-MYOT droplets within minutes, suggesting dynamic LLPS behavior. Similarly, purified GFP-MYOT exhibited fusion behaviors, further supporting its capacity for LLPS in vitro. Overexpression of MYOT did not significantly affect gastric cancer cell proliferation or apoptosis, but reduced cell migration. Actin polymerization failed to occur both in the GFP-MYOT and GFP control samples.

Conclusion

Our findings demonstrate that MYOT suppresses gastric cancer cell migration and purified GFP-MYOT does not directly promote on actin polymerization, implicating its potential role as a tumor suppressor. Additionally, MYOT undergoes LLPS both in vitro and in vivo, as evidenced by FRAP. We propose that MYOT may exert its anti-tumor effects through LLPS-mediated mechanisms, offering a novel perspective on its function in gastric cancer progression.

Introduction

Contemporary studies suggest there are racial disparities in the outcomes of acute presentations. This study aimed to investigate the impact of sex and race on the management and outcomes of patients presenting with upper gastrointestinal bleeding (UGIB).

Aims & Methods

Using International Classification of Diseases 10th Revision Codes, all adults >18 admitted from 2016–2020 with a discharge diagnosis of UGIB were extracted from the National Inpatient Sample.

Results

In over 900,000 hospitalisations for UGIB, 69.4%, 14.1%, 9.6%, 3.6%, 0.9% and 2.4% were for admissions in white, black, Hispanic, Asian/pacific islander, native American and ‘other’ patients respectively. Comorbidity burden varied between racial groups (p<0.001). White patients had higher crude rates of endoscopy, and comparable rates of surgery or interventional radiology to control blood loss, in comparison to other racial groups. Adjusted analysis revealed that black and Asian/pacific islander racial group patients had lower odds of in-hospital all cause mortality compared to white patients, but ‘other’ racial group patients had higher odds of mortality (p<0.001). There was no difference for Hispanic or native American patients. For non-variceal bleeding, these outcomes persisted. However, for variceal bleeds, there were no significant differences in outcomes between each racial group.

Conclusion

There are racial disparities in the management and outcomes of admissions for UGIB. These difference persist despite the aetiology of bleeding. Underlying reasons for differences in outcomes must be investigated to ensure improved outcomes across high-risk patient groups.