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

A 62-year-old woman with hypothyroidism and multiple sclerosis presented to our care to underwent outpatient esophagogastroduodenoscopy (EGD) after one episode of hematemesis, which had occurred 20 days earlier following the use of Naproxen (440 mg/day) for low back pain. Proton pump inhibitor (PPI) therapy had been initiated afterward. EGD revealed a 20 mm ulcer in the gastric body with an adherent clot. Upon gastric distension, oozing bleeding from the ulcer was observed and treated with adrenaline injection and endoscopic clips. Diffuse oozing from the gastric mucosa and multiple suction-related hematomas were also noted. The patient was hospitalized and started on high-dose intravenous PPI therapy and fasting. H. pylori serology was negative. Physical exam showed hepatomegaly and lower limb edema. Lab tests revealed elevated cholestatic enzymes, proteinuria, leukocytosis, hypoalbuminemia, mild anemia, and a monoclonal spike on serum protein electrophoresis. Abdominal ultrasound confirmed hepatomegaly. Autoimmune, viral, and metabolic liver diseases were excluded. Liver magnetic resonance raised suspicion of a storage disorder. Liver biopsy confirmed AL-type amyloid deposits. A follow-up EGD was performed, in absence of further GI bleeding, to obtain gastric biopsies. It showed a 1 cm ulcer with an adherent clot in the fundus. Again, insufflation triggered diffuse oozing from the ulcer and gastric mucosa with suction-related hematomas. Histology confirmed amyloid deposits. Suspecting multiple myeloma, immunofixation identified Bence-Jones proteinuria and hypergammaglobulinemia. Spinal MRI showed vertebral collapse at D12–L1; cardiac MRI excluded cardiac involvement. MM with secondary AL amyloidosis was diagnosed. Treatment with targeted therapy led to symptom resolution.This case highlights the importance of considering rare systemic diseases in atypical GI bleeding, especially when triggered by minimal stimuli such as gastric distension.

References

1. Histological images of liver and stomach with amyloid deposits.
2. Endoscopic images of gastrointestinal bleeding manifestations in patients with gastric amyloidosis

Introduction

Assessment of liver fibrosis is a key element in the management of patients with hepatitis B virus (HBV) infection, whether in the active, inactive, or occult phase. Among the non-invasive tools currently available, the FIB-4 score, based on biological parameters and FibroScan, using vibration-controlled transient elastography (VCTE) are widely used.

Aims & Methods

This retrospective, descriptive, and analytical study was conducted in a university hospital between 2017 and 2025. All patients followed for chronic HBV infection in the department of hepatogastroenterology were included. Clinical and biological data, along with fibrosis assessment results (FIB-4 score and FibroScan), were collected from patients medical records. The aim of this study was to compare the diagnostic performance and concordance of these two modalities in assessing liver fibrosis in a heterogeneous population of HBV-infected patients.

Results

A total of 100 HBV-infected patients were included, consisting of 54 males (54%) and 46 females (46%), with a median age of 55 years [42.5; 60]. Among them, 70% of patients had an active chronic hepatitis B (n=70), 29% were in the inactive phase (n=29), and 1 patient had an occult HBV infection.
Regarding comorbidities, 14% had arterial hypertension, 13% had metabolic dysfunction-associated steatotic liver disease (MASLD), and 5% had type 2 diabetes mellitus. Alcohol consumption was reported in 4% (n=4), and 5% were smokers (n=5). A family history of liver disease was documented in 12% of cases (n=12).
Concerning virological parameters, HBe antigen was positive in 13% (n=13) and negative in 87% (n=87). HBV DNA levels were <2,000 IU/mL in 48% of patients (n=48), between 2,000 and 20,000 IU/mL in 25% (n=25), and >20,000 IU/mL in 27% (n=27).
Evaluation of liver fibrosis using both the FIB-4 score and FibroScan revealed that 40% of patients had a FIB-4 score >3.25, indicating advanced fibrosis, while 60% had a score <1.45, suggesting minimal fibrosis. These findings were consistent with those obtained by FibroScan. To assess the diagnostic performance of the FIB-4 score in detecting advanced fibrosis (F3–F4) according to FibroScan, a receiver operating characteristic (ROC) analysis was conducted. The FIB-4 score demonstrated an area under the curve (AUC) of 0.96 using a cutoff value of 1.96, with a sensitivity of 93.75%, specificity of 84.52%, and a negative predictive value (NPV) of 98.61%.

Conclusion

The FIB-4 score demonstrated excellent diagnostic accuracy for identifying advanced liver fibrosis in patients with HBV infection, with a performance comparable to that of FibroScan. Given its simplicity, accessibility, and cost-effectiveness, the FIB-4 index represents a reliable first-line tool for fibrosis screening, particularly in settings where elastography is unavailable or limited.

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.

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.

Clinical Case Summary

The syndrome of buried lumen-apposing metal stents (LAMS) occurs in 4.7% of cases and is caused by a foreign body reaction characterised by tissue overgrowth embedded in the stent. This complication often requires surgery or "stent-in-stent" endoscopic procedures (1). Stent in a stent safely and effectively recanalises LAMS placed as esophagogastric anastomosis (2), gallbladder drainage (3), and endoscopic ultrasound (EUS)-directed transgastric ERCP (EDGE) (4). We report the first EUS-directed transenteric ERCP (EDEE) case using this approach. In 2023 a patient with Roux-en-Y hepaticojejunostomy (HJ) substenosis and recurrent cholangitis was admitted to our institution. The first attempt to perform an EUS-guided gastrojejunostomy (GJ) as part of EDEE failed; EUS -Hepaticogastrostomy (HGS) was conducted. One month later, a Hot-Axios LAMS (15mm x 15mm) EUS-GJ was placed, and prior 15 mm balloon dilatation, the second part of the EDEE operation was conducted, accessing the surgical HJ with a paediatric colonoscope and placing a Nagi stent (16mm x 20mm) towards the substenosis. The LAMS completely buried itself during the 6-month Nagi removal follow-up, making it impossible to determine its gastric mucosal location. We placed a fully covered self-expandable metal stent (10mm x 8cm) on the HGS for antegrade Nagi stent extraction. Recurrent HJ substenosis and bile duct stones induced cholangitis in 2024. EUS-guided identification and cannulation of the buried LAMS involved passing a 19-G fine needle biopsy needle through the LAMS, advancing a Jagwire deep into the jejunum, and bridging it with a second Hot-Axios LAMS (15mm x 15mm) using a non-cautery enhanced (cold LAMS-in-LAMS) technique.A frontal scope was used to remove bile duct stones before the latest 15 mm balloon was expanded, and a third 15 mm x 10 mm LAMS was placed across the substenotic HJ. EUS-guided management of buried LAMS was safe and effective, with normal liver function tests and clinical outcomes.

References

1) Nayar, M., Leeds, J. S., UK & Ireland LAMS Colloborative, & Oppong, K. (2022). Lumen-apposing metal stents for drainage of pancreatic fluid collections: does timing of removal matter?. Gut, 71(5), 850–853. https://doi.org/10.1136/gutjnl-2021-325812
2) Bazaga Pérez de Rozas, S., Chahal, P., Sánchez-Ocaña, R., García-Alonso, F. J., Carbajo, A. Y., de la Serna-Higuera, C., & Manuel, P. M. (2019). Buried lumen-apposing metal stent (LAMS) in esophagogastric anastomosis: the LAMS-in-LAMS rescue treatment. Endoscopy, 51(6), 600–601. https://doi.org/10.1055/a-0861-99074)
3) Ligresti, D., Cipolletta, F., Amata, M., Cimavilla, M., Traina, M., & Tarantino, I. (2018). Buried lumen-apposing metal stent (LAMS) following endoscopic ultrasound-guided gallbladder drainage: the LAMS-in-LAMS rescue treatment. Endoscopy, 50(8), 822–823. https://doi.org/10.1055/a-0624-2050
4) Honan, B. M., Mulki, R., & Sánchez-Luna, S. A. (2024). Bridging the Buried GATE: LAMS-in-LAMS Rescue Technique for Endoscopic Ultrasound-Directed Transgastric ERCP. ACG case reports journal, 11(9), e01497. https://doi.org/10.14309/crj.0000000000001497