Introduction

Lenvatinib (LEN) remains an important treatment option for unresectable hepatocellular carcinoma (uHCC) patients in the present immunotherapy era. Based on the recognized impact of nutritional status and systemic inflammatory response on cancer treatment outcomes, this study evaluated uHCC patients treated with LEN to determine the prognostic significance of a newly developed combination of geriatric nutritional risk index (GNRI) and the systemic inflammatory response marker C-reactive protein (CRP), known as GNRI-C score.

Aims & Methods

This multicenter retrospective study included 484 patients with uHCC who received LEN between 2018 and 2022. Initially, GNRI score was calculated to assess nutritional status based on serum albumin level, height, and body weight, with the cohort categorized into three groups; score 0 (GNRI >98), score 1 (GNRI 92–98), and score 2 (GNRI <92). Next, GNRI-C score, which integrates GNRI-based risk stratification with CRP level, with an additional 1 point assigned for CRP ≥1 mg/dL, used to classify the patients into four groups (score 0, 1, 2, or 3). In this manner, GNRI-C score was considered to provide a comprehensive assessment by incorporating both nutritional status and inflammation caused by the presence of a hepatocellular carcinoma. Treatment outcomes, including objective response rate (ORR), disease control rate (DCR) determined using RECIST v.1.1, progression-free survival (PFS), overall survival (OS), and impact of GNRI-C score on prognosis, were subsequently analyzed.

Results

The median follow-up period was 12.9 months. Patient median age was 73 years and 79.3% were male. A GNRI-C score of 0 was noted in 220, 1 in 109, 2 in 106, and 3 in 49 patients. For GNRI-C scores of 0, 1, 2, and 3, treatment response analysis showed ORR values of 51.3%, 45.7%, 50.0%, and 38.9%, respectively, and DCR values of 84.8%, 83.0%, 85.1%, and 83.3%, respectively, with no significant differences (p = 0.517, p = 0.963, respectively). Similarly, adverse event incidence rates did not significantly differ among the patient groups formed by GNRI-C score. On the other hand, for patients grouped based on GNRI-C score of 0, 1, 2, and 3, median PFS was significantly different at 10.79, 7.46, 5.75, and 3.68 months, respectively (p <0.001), as was median OS at 28.61, 19.64, 10.25, and 8.21 months, respectively (p <0.001). Even for patients who received lenvatinib as first-line therapy, significant differences for PFS (9.86, 7.46, 6.43, and 4.25 months, respectively) and OS (34.57, 20.14, 10.75, and 8.21 months, respectively) were noted when divided using GNRI-C score (p <0.001). Finally, comparative prognostic analysis demonstrated the superiority of GNRI-C over other scoring systems, as the Akaike Information Criterion score for OS prediction was lowest for GNRI-C (2887.19), outperforming GNRI, mALBI grade, NLR, O-PNI, and neo-GPS.

Conclusion

GNRI-C score, which integrates nutritional and inflammatory markers, is considered to be a superior prognostic tool for assessing uHCC patients undergoing LEN treatment. This simple and objective scoring system may aid clinicians in identifying high-risk patients and also optimizing treatment strategies.

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.

Introduction

Upper gastrointestinal bleeding (UGIB) is a major cause of mortality in the United States (US). This study aimed to investigate the contemporary trends in the management and outcomes of these patients as well as factors associated with in-hospital mortality, using national data.

Aims & Methods

The US National Inpatient Sample was queried from 2016-2020. Using International Classification of Diseases 10th Revision Codes, all adults >18 admitted with a principal discharge diagnosis of UGIB were extracted along with data about demographics, management and outcomes. Categorical variables were compared using chi-squared and expressed as percentages (%). Logistic regression was performed, adjusting for variables associated with adverse outcomes and reported as adjusted odds ratios (aOR) with 95% confidence intervals (CI). Data were considered significant if p<0.001.

Results

There were 918,925 hospitalizations for UGIB in the study period. Variceal bleeding occurred in 36,050 (3.9%) of admissions. Endoscopy was performed in 451,450 (49.1%) of admissions, with 10,160 (1.1%) of admissions and 9,355 (1.0%) of admissions requiring interventional radiology and gastrointestinal surgery to control blood loss respectively. The crude rate of all-cause in-hospital mortality was 1.9%. Factors associated with death included variceal bleed (aOR 2.84 CI 2.67-3.02), age (aOR 1.03 CI 1.03-1.03), history of cancer (aOR 2.45 CI 2.35-2.56), ulcer disease (aOR 1.44 CI 1.39-1.49), chronic renal failure (aOR 1.34 CI 1.29-1.37), chronic obstructive pulmonary disease (aOR 1.29 CI 1.24-1.34), receipt of endoscopy (aOR 1.33 CI 1.29-1.38), surgery (aOR 3.92 CI 3.63-4.24) and interventional radiology (aOR 3.33 CI 3.09-3.58).

Conclusion

UGIB remains a significant cause of hospitalisation in the US. Knowledge of the contemporary trends and outcomes of this patient group is important to improve management in this at-risk patient group.