Introduction

There is a lack of standardized routines for endoscopy training. Most training is delivered locally without a predefined curriculum. Access to simulated environments is often lacking, potentially impeding skill development. While simulator training is known to enhance endoscopic proficiency, gender differences in learning styles and outcomes remain underexplored. Research suggests males may excel in speed-based tasks, possibly due to visuospatial advantages from video gaming experience, while females often underestimating their abilities yet achieving comparable results with practice.
This study investigates whether an introductory endoscopy course in a simulated setting for trainee physicians is perceived as meaningful by the participants and evaluates technical improvements in a simulated environment, with focus on how gender influences learning outcomes in quality metrics.

Aims & Methods

The aims of the study were to assess technical skill improvements in a simulated environment, highlighting gender differences in performance, and to determine whether surgical and gastroenterology trainees find the course valuable for their training.
In this observational study, 19 surgical and gastroenterology trainees participated in the 4-day introductory endoscopy course. The course combined theoretical instruction with supervised simulator training using the GI-Mentor II (gastroscopy case and Endo Bubble exercise 1) and Thompson Endoscopic Skills Trainer (polyp snaring exercise). Pre- and post-course performance was assessed for rapidity (completion times) and quality (efficiency of screening, mucosa inspected) metrics, with data collected via simulator outputs and manual timing. Two questionnaires evaluated baseline characteristics and perceived course value. Paired t-tests compared performance changes, with outcomes stratified by gender to explore differences in skill acquisition.

Results

Table 1: Showing the results of the box trainer and virtual gastroscopy.

Conclusion

The introductory endoscopy course significantly improved trainees’ technical skills and quality performance in simulator-based exercises, validating its effectiveness. Gender differences were notable: Females significantly enhanced quality metrics (efficiency of screening: +11%, mucosa inspected: +6%), while males improved rapidity in technically demanding tasks (box-trainer, balloon test). Future curricula and practical skills training might be tailored to address these gender differences to better optimise training outcomes.

Clinical Case Summary

A 52-year-old man with myelodysplastic syndrome (MDS-IB2) underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from a mismatched unrelated donor. Prophylaxis included post-transplant cyclophosphamide, cyclosporine A, and mycophenolate mofetil. On day +54, the patient developed watery diarrhea and weight loss. Rectosigmoidoscopy and histology revealed grade 2 intestinal acute graft-versus-host disease (aGVHD). Systemic corticosteroids and Ruxolitinib were initiated due to steroid-refractoriness. After initial improvement, on day +101, he was hospitalized for severe bloody diarrhea, fever, and abdominal pain. Abdominal CT showed thickening and hyperemia of the terminal ileum and ascites (Figure 2). Intestinal ultrasound confirmed marked wall thickening, increased vascularization, and luminal distension (Figure 3). Colonoscopy revealed extensive ulcerations with mucosal denudation in the terminal ileum (Figure 1) and cecum, and superficial ulcers in the colon. Histology showed fibrino-leukocytic debris without glandular structures and few epithelial cell apoptosis, making GVHD assessment inconclusive (Figure 4). Immunohistochemical stains for CMV, HSV, and HHV8 were negative. PCR testing on biopsy tissue detected 363 copies/ml of human herpesvirus 6 (HHV-6) DNA, confirming HHV-6 enteritis. Ruxolitinib was discontinued and Ganciclovir initiated, resulting in rapid apyrexia, reduced diarrhea, and clinical stabilization. Follow-up intestinal ultrasound at one month demonstrated marked reduction in bowel wall thickness, supporting resolution (Figure 5). This case highlights the importance of considering HHV-6 reactivation in apparent steroid-refractory aGVHD. Early imaging, endoscopy, and molecular diagnostics on tissue are crucial to guide targeted therapy.

References

• Figure 1: Endoscopic image of terminal ileum with mucosal denudation

• Figure 2: CT scan showing ileal wall thickening and mucosal contrast enhancement

• Figure 3: Intestinal ultrasound showing extensive wall thickening and hypervascularization

• Figure 4: Ileal histology with fibrino-leukocytic debris

• Figure 5: Intestinal ultrasound showing reduction in wall thickening

Introduction

Emerging experimental and clinical data suggest that the gut microbiome can significantly influence the antitumor efficacy of key chemotherapy agents, including 5-fluorouracil, oxaliplatin, and docetaxel. These agents form the backbone of the neoadjuvant chemotherapy (NAC) regimen, FLOT, which is widely used for the treatment of locally advanced gastric cancer (GC). However, despite growing evidence from preclinical models, clinical studies investigating the direct association between gut microbiome composition and the response to NAC in GC patients remain scarce.

Aims & Methods

This study aims to address this gap in knowledge by exploring the relationship between the gut microbiome and therapeutic outcomes in this clinical context. In this longitudinal observational study, we explored the association between pre-treatment fecal microbiome composition analyzed via 16S rRNA gene sequencing and histological tumor regression, as assessed by the Becker score, in GC patients undergoing NAC with the FLOT regimen, followed by gastrectomy.

Results

Among the 38 enrolled patients, 19 (50%) achieved a Becker score of 1–2 and were classified as ‘Responders,’ while the other 19 (50%) were classified as ‘Non-responders’. Responders exhibited a higher abundance of Parabacteroides distasonis, Alistipes sp. AL-1, and Bacteroides plebeius. A combined biomarker of these species demonstrated robust predictive accuracy for a favorable response to NAC, with sensitivity of 89%, specificity of 63%, and an AUC of 0.8 (95% CI: 0.66–0.94). In contrast, non-responders showed a predominance of bacterial genera, including Ruminococcaceae UCG-014, Ruminococcus 1, Ruminococcaceae UCG-005, and the [Eubacterium] eligens group. The combined biomarker of these genera demonstrated excellent predictive performance for poor NAC response, with sensitivity of 89%, specificity of 95%, and an AUC of 0.93 (95% CI: 0.85–1.0).

Conclusion

The results of our study support the hypothesis that the pre-treatment gut microbiome composition can serve as a reliable biomarker for predicting both positive and negative responses to NAC in GC patients. By identifying specific microbial signatures associated with chemotherapy outcomes, this research provides critical insights into how microbiome-based strategies might enhance personalized treatment regimens for GC. Future studies are needed to validate these findings and explore potential therapeutic interventions targeting the microbiome to improve clinical outcomes in GC patients.

Introduction

Gastric cancers (GCs) are histologically classified into differentiated and undifferentiated types. Mixed histological type is considered more aggressive clinical behavior compared to pure histological type. However, no reports of large-scale prospective studies regarding the long-term prognosis of mixed histological type cured in patients by endoscopic resection (ER).

Aims & Methods

We aimed to determine the long-term prognosis of mixed histological-type GCs in patients cured by ER. We used data from the J-WEB EGC study, a nationwide, multicenter, prospective cohort that enrolled 9,715 patients with 10,926 lesions treated by ER between 2010 and 2012 across 41 institutions in Japan. For this analysis, we included patients classified as eCura A or B, according to the Japanese gastric cancer treatment guidelines, represent pathological criteria for curative resection following ER. eCura A included: differentiated-type, pT1a, without ulceration (UL0), negative horizontal and vertical margins (HM0, VM0) (A-1), and no lymphovascular invasion (Ly0, V0); differentiated-type, ≤30 mm, pT1a, with ulceration (UL1), HM0, VM0, Ly0, V0 (A-2); and undifferentiated-type, ≤20 mm, pT1a, UL0, HM0, VM0, Ly0, V0 (A-3). eCura B included differentiated-type, pT1b with submucosal invasion <500 μm, HM0, VM0, Ly0, and V0. We excluded patients with multiple lesion and those with lesions containing unusual type. Each patient was followed up for 5 years. The primary endpoints were 5-year overall survival (OS) and 5-year primary disease-specific survival (pDSS) to primary GC. Patients were divided into pure and histological types. OS and pDSS were assessed using the Kaplan–Meier method, and hazard ratios (HRs) for all-cause mortality was estimated using the Cox proportional hazards regression model with death as the event. After stratification into eCuraA-1, eCuraA-2, eCuraA-3, and eCura B, the 5-year OS and pDSS were compared between the pure and mixed histological types.

Results

A total of 7,242 patients with 8,187 GC lesions were classified as eCura A or B. After excluding 646 patients with multiple GC lesions and one patient with an GC lesion containing a neuroendocrine tumor component, 6,595 patients with a single GC lesion were included in the analysis. Of these, 6,434 were pure histological type and 161 mixed histological type. There was no difference in OS between pure and mixed histological types in all patients (92.5%, 95% confidence interval [CI]: 87.4–95.7 vs. 90.5%, 95% CI: 89.7–91.2; p = 0.415, respectively). Additionally, mixed histological type was not an independent factor in adjusted HRs for OS all-cause mortality (0.93, 95% CI: 0.52–1.64). The 5-year pDSS of the mixed histological-type GCs was significantly lower than that of the pure histological-type GCs (99.4%, 95% CI: 96.6–99.9 vs 99.96%, 95% CI: 99.9–100, p = 0.003, respectively). Among eCura A-2 patients, pDSS of the mixed histological-type GCs was significantly lower than that of the pure histological-type GCs (94.4%, 95% CI: 74.2–99.0 vs. 100%, 95% CI: 99.3–100; p < 0.001, respectively).

Conclusion

The long-term prognosis of curative ER patients, including those with mixed histological-type GCs, was favorable. However, the stratification analysis showed that mixed histological-type GCs in eCura A with ulcers was more likely to cause primary GC death than pure histological-type and might need careful surveillance.

Introduction

Spontaneous bacterial peritonitis(SBP) is the most common type of infection in patients with cirrhosis, with high mortality and recurrence rates^[1]. The intestinal immune barrier is an important link in blocking intestinal bacterial translocation^[2-3], but the mechanism of immune barrier changes in SBP in cirrhosis is unclear. The gut microbiota influences antitumor immunity by producing immunomodulatory metabolites^[4]. However, microbial consumption of multiple metabolites may also influence host immune responses^[5]. Here, we investigated the role of Stenotrophomonas maltophilia and its metabolites in the development of SBP.

Aims & Methods

We detected the bacterial composition of ascites and stool in patients with spontaneous bacterial peritonitis by 16S sequencing. The Stenotrophomonas maltophilia-SBP rat model was established by oral administration of carbon tetrachloride and Stenotrophomonas maltophilia. Metabolomics analysis was performed by liquid chromatography-mass spectrometry and single-cell sequencing was used to analyze changes in intestinal cell composition and gene expression. The biological functions of Stenotrophomonas maltophilia-conditioned medium and metabolites were determined in rat CD8⁺T cells.

Results

16S sequencing found that the abundance of Stenotrophomonas maltophilia in SBP ascites samples was high and positively correlated with inflammatory indicators. Among 1876 patients with cirrhosis and ascites, patients infected with Stenotrophomonas maltophilia had significantly increased levels of procalcitonin, C-reactive protein, ascites lactate dehydrogenase, and polymorphonuclear leucocytes count. Animal experiments showed that Stenotrophomonas maltophilia derived from human ascites can promote the occurrence of SBP in rats. Single-cell sequencing results showed that it significantly increased CD8⁺T cell exhaustion in the ileum and reduced memory T cells. Metabolomics analysis revealed that arginine was a significantly decreased metabolite in the supernatant of Stenotrophomonas maltophilia, and its downregulation was verified in rat serum and intestinal tissue. Mechanistically, Stenotrophomonas maltophilia degrades arginine through arginine decarboxylase, inhibits mTORC1 activity, thereby reducing CD8⁺T cell effector function and ultimately promoting the progression of SBP. Arginine supplementation significantly inhibited the formation of SBP and improved intestinal barrier function.

Conclusion

Stenotrophomonas maltophilia has been shown to promote SBP in rats by degrading arginine. Arginine supplementation is a potential preventive measure for SBP.

References

[1] Serper M, Tang H, Zhang S, et al. Clinical outcomes and care for spontaneous bacterial peritonitis: A national
cohort study. Hepatology. 2025.

• [2] Piano S, Singh V, Caraceni P, et al. Epidemiology and Effects of Bacterial Infections in Patients With Cirrhosis Worldwide. Gastroenterology. 2019. 156(5): 1368-1380.e10.
• [3] Pabst O, Hornef MW, Schaap FG, Cerovic V, Clavel T, Bruns T. Gut-liver axis: barriers and functional circuits. Nat Rev Gastroenterol Hepatol. 2023. 20(7): 447-461.
• [4] Cong J, Liu P, Han Z, et al. Bile acids modified by the intestinal microbiota promote colorectal cancer growth by suppressing CD8(+) T cell effector functions. Immunity. 2024. 57(4): 876-889.e11.
• [5] Meza-Perez S, Liu M, Silva-Sanchez A, et al. Proteobacteria impair anti-tumor immunity in the omentum by consuming arginine. Cell Host Microbe. 2024. 32(7): 1177-1191.e7.

Clinical Case Summary

The patient was a 39-year-old man admitted to the emergency department for sudden onset of diffuse abdominal pain. The patient had a pathological history of chronic smoking. The clinical history dates back 10 hours to the onset of abdominal pain, initially localized to the epigastrium and rapidly generalized to the entire abdomen, unrelieved by usual treatment and without other associated signs. The patient was conscious, normocardiac, normotensive, slightly tachypneic and apyretic. A diffuse abdominal tenderness was noted, with no other particular pathological signs. Biological work-up revealed hyperleukocytosis at 20430/mm3 , C-reactive protein (CRP) at 5.80 mg/L , no hydroelectrolytic disorders, and the rest of the biological work-up returned normal. Abdominal CT revealed pneumo bubbles with infiltration of mesenteric fat, predominantly at the supra-mesocolic level, in favor of a hollow organ perforation. The patient underwent surgery, which revealed a pre-pyloric gastric perforation measuring approximately 1 cm with a clean edge and the presence of 2 hepatic nodules measuring 0.25 and 0.5 cm in segment II. The rest of the exploration was without anomalies, and the gastric perforation was sutured, with biopsy of the edges of the gastric perforation and biopsy of the hepatic nodules. Histopathological examination revealed the presence of subacute and chronic nonspecific inflammatory remodeling in the gastric margin biopsy, whereas the liver biopsy showed epithelial and gigantocellular granulomatous inflammation with caseous necrosis consistent with tuberculosis.The diagnosis of hepatic tuberculosis was made.The patient was put on standard anti-tuberculosis treatment for 6 months.

Clinical Case Summary

A 36-year-old man with a history of chronic diarrhea was admitted with isolated oedemato-ascitic syndrome and general deterioration.On examination,he had conjunctival subicterus bilateral lower limb edema, thoracoabdominal collateral venous circulation and ascites.As part of the etiological work-up of the oedemato-ascitic syndrome,Cardiac and renal causes were ruled out.Chest X-ray showed a hilar opacity with tracheal retraction.GeneXpert test on sputum confirmed pulmonary tuberculosis.Paracentesis showed non-infected transudate ascites with a serum-ascites albumin gradient at 11 g/L.Blood tests showed microcytic hypochromic anemia,normal platelet count,and elevated liver tests with AST at 18 times the upper limit of normal (ULN), ALT at 11× ULN, alkaline phosphatase at 3.3× ULN,normal GGT,prothrombin time at 25%,and a direct hyperbilirubinemia of 24 mg/L.Viral serologies were negative.Serum protein electrophoresis showed a beta-gamma bridging pattern with hypergammaglobulinemia.Antinuclear antibodies were positive, while the remaining autoimmune panel and Wilson's disease screening were negative.Abdominal CT angiography showed hepatomegaly with hypertrophy of the caudate lobe,a “flip-flop” pattern,stenosis of the intrahepatic inferior vena cava, and non visualization of the hepatic veins confirming Budd-Chiari syndrome(BDS).The etiological work-up of the chronic diarrhea revealed negative HIV serology,normal TSH,and elevated IgA anti-transglutaminase antibodies.Ileocolonoscopy showed partial villous atrophy in the ileum,supporting the diagnosis of coeliac disease (CD).Given the radiological features suggestive of BDS,a thrombophilia work-up was performed and was negative.An autoimmune etiology related to CD was retained as the most likely cause of BDS.A gluten-free diet resolved the diarrhea.Anticoagulation was started, but persistent portal hypertension and difficulty maintaining therapeutic anticoagulation led to referral for a portosystemic shunt.

References

An actual image of the thoracoabdominal collateral venous circulation of the patient, and his abdominal CT angiography.