Clinical Case Summary

An 82-year-old man with Child B alcoholic cirrhosis, complicated by portal hypertension, underwent surveillance upper digestive endoscopy (UDE), revealing large esophageal varices and a 20 mm exophytic lesion, 40 cm from the dental arch, with an infiltrative and ulcerated appearance. Biopsies were inconclusive. Endoscopic ultrasound identified a heterogeneous, amorphous lesion with poorly defined borders and disruption of all wall layers, complicated by numerous large varices, preventing biopsy due to hemorrhagic risk. Computed tomography revealed parietal thickening in the distal esophagus and multiple varices, complicating lesion delineation. An oncology consultation recommended clinical surveillance, considering the patient's age, comorbidities, indeterminate nature of the esophageal lesion, and low suspicion for adenocarcinoma on ultrasound. One year later, surveillance UDE showed regression of the lesion.Histological samples were reviewed, revealing changes consistent with pyogenic granuloma. Pyogenic granuloma is a rapidly growing capillary hemangioma that may occur within the lumen of a pre-existing vessel (intravascular variant). The case is supported by appropriate iconography.

This case is presented with imaging, highlighting the challenge due to the macroscopic appearance suggestive of a neoplastic lesion and the pyogenic granuloma's growth within esophageal varices, limiting diagnostic and therapeutic management.

References

Clinical Case Summary

Background: Endoscopic ultrasound (EUS)-guided cystogastrostomy with lumen-apposing metal stents (LAMS) is a widely accepted treatment for symptomatic pancreatic pseudocysts, particularly in cases of walled-off necrosis (WON). While the procedure is generally safe, delayed bleeding can occur. This report presents a novel approach to managing massive upper gastrointestinal bleeding following LAMS placement when interventional radiology (IR) embolization is not feasible.
Case presentation: A 51-year-old male with a history of pancreatitis and a large pancreatic pseudocyst underwent successful EUS-guided placement of an Axios stent. The patient was discharged on the second day of the procedure with no adverse events. Three days later, the patient developed significant melena, pallor, and a dramatic drop in hemoglobin levels, necessitating urgent blood transfusions. Diagnostic upper endoscopy revealed active pulsatile bleeding from the cyst wall behind the stent edge, which is inaccessible to conventional endoscopic methods. Two attempts of angiography by two different IR consultants failed to locate the bleeding source.
Given the critical situation and after resuscitation with IV blood transfusion, a multidisciplinary team proposed a novel technique: injection of Purastat, a hemostatic agent, into the cyst through the stent, followed by stent removal and additional application of glue over the cyst orifice. This approach successfully controlled the bleeding, stabilized the patient’s condition, and eliminated the need for surgery. Follow-up imaging revealed a small splenic artery aneurysm without active bleeding.
Conclusion: This case highlights the potential of Purastat as an effective tool for managing life-threatening gastrointestinal bleeding following LAMS placement. The successful use of this technique in sealing the cyst and stopping the bleeding suggests it could be a definitive management option in similar cases.

References

1. Shamah S, et al. Delayed bleeding after lumen-apposing metal stent placement for pancreatic fluid collections: Incidence, risk factors, and management. *Endoscopy International Open*. 2023;11(2):E158-E163.
2. Varadarajulu S, et al. Hemostasis in gastrointestinal endoscopy: Emerging techniques and devices. *Gastrointestinal Endoscopy Clinics of North America*. 2022;32(3):421-439.

Introduction

Phase Angle (PA) represents a useful bioimpedance analysis-assessable marker of sarcopenia, accurately predicting liver-related hospitalizations in advanced chronic liver disease (ACLD), correlating with C-reactive protein levels. Clinically significant portal hypertension (CSPH) and systemic inflammation constitute the main hepatic decompensation drivers. A relevant proportion of Metabolic dysfunction-associated steatotic liver disease (MASLD) patients present sarcopenia (configuring the paradox of “sarcopenic obesity”), as well as compensated ACLD (cACLD)-MASLD individuals more rapidly progress to decompensation (dACLD) rather than other etiologies. However, the clinical applications of PA have never been specifically investigated in the setting of MASLD.

Aims & Methods

Considering the background, in MASLD, we primarily aimed to evaluate the trend of PA values across the different liver disease progression stages, investigating the relationship with the hepatic decompensation drivers; in dACLD-MASLD, we aimed to estimate the accuracy of the novel PA/C-reactive protein (CRP) index (PAC-I) in predicting 3-month further liver-related events (LREs)-determining hospitalizations.
In this observational study, between December 2023 and January 2025, MASLD patients were consecutively enrolled and stratified according to current LSM and eventual previous LREs in < F3 fibrosis (AF) (n.50), cACLD (n.50), and dACLD (n.50) patients. At baseline, anthropometrical, biochemical, nutritional, and clinical data [including the endoscopic assessment of CSPH and the relative severity (F1, F2, F3) of esophageal varices (OEVs)] were collected. Bioimpedance analysis was adopted to assess body composition parameters. Sarcopenia was diagnosed according to the European Working Group on Sarcopenia (EGWSOP2) criteria. MASLD-dACLD patients were followed up, and further acute decompensation (AD)-LREs-determining hospitalizations [severe ascites, severe hepatic encephalopathy (HE), OEV bleeding, and any acute bacterial infections] in the subsequent 3 months were recorded.

Results

In MASLD patients, PA (°) values inversely correlated with LSM [R: -0.711; p<0.0001], progressively decreasing according to the worsening of liver disease stages, emerging as statistically significantly lower in dACLD compared with cACLD individuals (p<0.0001). In dACLD patients, PA inversely correlated with CRP levels [R: -0.945; p:0.001]. Focusing on CSPH, PA values were significantly lower in > F2-OEV-affected individuals (p<0.0001). Multivariate analysis revealed CSPH (aHR 1.221, p<0.0001), CRP (aHR: 1.112, p:0.002), and PA (aHR: 1.178, p:0.003) as the variables significantly associated with 3-month further LREs’ occurrence in dACLD patients.
ROCy analysis revealed an elevated accuracy and superiority compared to PA alone (AUC PA:0.717; AUC PAC-I: 0.893; p:0.003) of PAC-I in predicting 3-month further LREs’ occurrence, identifying PAC-I < 2.35 as the best cut-off. Consistently, dACLD patients showing baseline PAC-I < 2.35 presented a higher risk [HR: 2.287, p: 0.032] of further LREs.

Conclusion

In MASLD, PA correlates with the main driver of progression, and the PAC-I represents a useful noninvasive tool in predicting short-term liver-related hospitalizations in dACLD patients.

References

1. Espirito Santo Silva DD, Waitzberg DL, Passos de Jesus R, Oliveira LPM, Torrinhas RS, Belarmino G. Phase angle as a marker for sarcopenia in cirrhosis. Clin Nutr ESPEN. 2019 Aug;32:56-60. doi: 10.1016/j.clnesp.2019.05.003. Epub 2019 May 31. PMID: 31221291.
2. Saueressig C, Glasenapp JH, Luft VC, Alves FD, Ferreira PK, Hammes TO, Dall'Alba V. Phase Angle Is an Independent Predictor of 6-Month Mortality in Patients With Decompensated Cirrhosis: A Prospective Cohort Study. Nutr Clin Pract. 2020 Dec;35(6):1061-1069. doi: 10.1002/ncp.10584. Epub 2020 Oct 15. PMID: 33058222.

Introduction

Acetaminophen (APAP) is a major cause of drug-induced liver injury (DILI), once the latter evolves into liver failure, it significantly impacting clinical outcomes. Urokinase plasminogen activator receptor (uPAR) is a membrane protein that is distributed on various immune-active cell membranes, which is not only associated with cell adhesion, invasion and migration, but also can regulate the immune microenvironment. However, uPAR specific roles in the regulation of myeloid cell innate immunity and the maintenance of hepatic homeostasis during DILI remains unclear.

Aims & Methods

The expression pattern of uPAR in both mouse DILI models and DILI patients was determined. Multiplex Immunohistochemistry (mIHC), flow cytometry, spatial transcriptomics (ST), single-cell RNA sequencing (scRNA-seq), intravital 3D imaging, luciferase reporter gene assay and Cleavage Under Targets and Tagmentation (CUT&Tag) were used to explore molecular mechanisms. uPAR^-/-, Lyz2^creuPAR^f/f and AXL^-/- mice, various mouse primary cells, human liver and serum samples were used to verify the discoveries of bioinformatics analysis.

Results

We found that the expression level of uPAR in the liver of both mouse DILI models and DILI patients was significantly high, systemic and myeloid deficiency of uPAR could alleviate liver inflammation in mice after challenged with APAP. mIHC, flow cytometry, ST, scRNA-seq and intravital 3D imaging multidimensionally elucidated that macrophage efferocytosis in both uPAR^-/- and Lyz2^creuPAR^f/f mice was enhanced due to the upregulation of the AXL, leading to the accelerated clearance of senescent neutrophils and thereby promoting the resolution of liver inflammation. Luciferase reporter gene assay and CUT&Tag confirmed that transcription factor IRF7 directly bound to the promoter region of AXL in macrophages. Mechanistic studies showed that uPAR regulated AXL mediated efferocytosis through the STAT3/IRF7 pathway. Macrophage-specific overexpression of IRF7 in vivo enhanced macrophage efferocytosis and promoted the attenuation of liver inflammatory response in both mouse DILI and liver ischemia-reperfusion injury models. AXL^-/- mice had exacerbated phenotype, while AXL activator GAS-6 protein could alleviate liver injury.

Conclusion

uPAR/STAT3/IRF7/AXL signaling is critical to regulate macrophage efferocytosis and maintain hepatic tissue homeostasis in the progression of DILI. Its dual functionality as a liver homeostatic regulator and DILI therapeutic target warrants further investigation.

Introduction

Inflammatory Bowel Disease (IBD) patients carry a high risk of malnutrition, independently of disease activity. Screening for malnutrition in IBD is currently recommended since malnutrition, as well as low Fat-Free Mass Index (FFMI), have been associated to poor disease outcomes. However, due to a non-universal definition of malnutrition, most Nutritional Screening Tools (NSTs) have been validated compared to different reference methods and do not consider patients’ body composition. Moreover, the ability of most NSTs to predict malnutrition over time has not been explored.

Aims & Methods

The aim of this study was to compare the efficacy of different NSTs to predict malnutrition, as defined by the ESPEN 2015 and GLIM criteria, and a low FFMI in a cohort of inactive/mildly active IBD patients.
This is a prospective, single center, cohort study enrolling Crohn’s disease (CD) and ulcerative colitis (UC) patients in clinical remission or with mildly active disease as defined by Harvey-Bradshaw Index and partial Mayo Score, respectively. MUST, MIRT, MNA, NRS-2002 and SaskIBD-NR questionnaires and Bioelectrical Impedance Analysis (BIA) were performed at baseline and after six months follow-up. A low FFMI was defined as <18 kg/m2 in males and <15 kg/m2 in females. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the accuracy of the different NSTs for the detection of malnutrition and low FFMI at six months were calculated.

Results

Sixty-six (CD: 32; UC: 34) IBD patients were enrolled. Median age was 55.5 years (IQR 34-62.8), median disease duration was 10 years (IQR 6-17). At baseline, all CD and 30/34 (88%) UC patients were in clinical remission; median C-reactive protein was 0.8 mg/L (IQR 0-3.8), median fecal calprotectin was 55.2 mcg/g (IQR 12.9-326). Of the entire cohort, 6/66 (9%) and 17/66 (26%) patients were malnourished according to GLIM and ESPEN criteria, respectively, [(GLIM CD:3, UC: 3)(ESPEN: CD: 3; UC:14)] and 5/66 (8%) had low FFMI (CD:1; UC: 4). At 6 months follow-up, all CD and 31/34 (91%) UC patients were in clinical remission. Ten out of 66 (15%) and 32/66 (48%) patients were malnourished according to GLIM and ESPEN criteria, respectively [(GLIM CD:5, UC: 5)(ESPEN: CD: 15; UC:17)], 11/66 (17%) patients had low FFMI (CD: 3; UC: 8). Baseline MIRT showed the highest sensitivity for the diagnosis of both ESPEN and GLIM-defined malnutrition at 6 months (ESPEN: 40.5%; GLIM: 50%). For ESPEN, MIRT and NRS2002 were the most accurate NSTs (MIRT: 50%, NRS2002: 51.5%), while SaskIBD (75.8%) showed the highest accuracy in detecting GLIM-malnourished patients at 6 months follow up. Among all NSTs, baseline MIRT, MNA and NRS2002 had the highest sensitivity for the detection of low FFMI at six months (MIRT, MNA, NRS2002: 45.5%), while SaskIBD_NR was the most accurate (80.3%).

Conclusion

MIRT might be the NSTs of choice to predict defined malnutrition and low Fat-Free Mass Index at 6 months follow-up in a cohort of inactive/mildly active IBD patients.

References

Huang S, Niu Y, Liu X, Gu Z, Huang A, Wu J. Characteristics of malnutrition according to Global Leadership Initiative on Malnutrition criteria in non-surgical patients with inflammatory bowel disease. Nutrition. 2022;94:111514. doi:10.1016/j.nut.2021.111514

Jensen GL, Cederholm T, Correia MITD, et al. GLIM Criteria for the Diagnosis of Malnutrition: A Consensus Report From the Global Clinical Nutrition Community. JPEN J Parenter Enteral Nutr. 2019;43(1):32-40. doi:10.1002/jpen.1440

Cederholm T, Bosaeus I, Barazzoni R, et al. Diagnostic criteria for malnutrition - An ESPEN Consensus Statement. Clin Nutr. 2015;34(3):335-340. doi:10.1016/j.clnu.2015.03.001

van Bokhorst-de van der Schueren MA, Guaitoli PR, Jansma EP, de Vet HC. Nutrition screening tools: does one size fit all? A systematic review of screening tools for the hospital setting. Clin Nutr. 2014;33(1):39-58. doi:10.1016/j.clnu.2013.04.008

Ding NS, Tassone D, Al Bakir I, et al. Systematic Review: The Impact and Importance of Body Composition in Inflammatory Bowel Disease. J Crohns Colitis. 2022;16(9):1475-1492. doi:10.1093/ecco-jcc/jjac041

Introduction

Pancreatic exocrine insufficiency (PEI) is a condition characterized by inadequate secretion or activity of pancreatic enzymes, resulting in the maldigestion and malabsorption of nutrients. While PEI is most commonly associated with chronic pancreatitis and cystic fibrosis, it also occurs frequently in the context of pancreatic and peri-pancreatic malignancies. In patients with pancreatic cancer PEI arises due to direct tumor infiltration, ductal obstruction, parenchymal destruction, or as a consequence of surgical resection. Other gastrointestinal malignancies, such as ampullary or biliary tree cancers, may also contribute to PEI through similar mechanisms. Importantly, PEI in cancer patients is often under-recognized, despite its significant impact on nutritional status, quality of life, and overall prognosis. Timely identification and management of PEI in malignancy-associated cases is crucial to optimize clinical outcomes and support ongoing cancer therapies.

Aims & Methods

The objective of this study is to assess the incidence of PEI in patients with biliopancreatic and ampullary tumors, to explore potential differences in PEI occurrence based on tumor location and to investigate possible associations between PEI and relevant biomarkers.
We conducted a retrospective observational analysis of a consecutively recruited patient cohort including patients diagnosed with biliopancreatic and ampullary tumors at a tertiary care hospital between 2016 and 2024.
PEI was defined as fecal elastase-1 (FE-1) levels below 100 µg/g.
At the time of diagnosis, we collected data on demographic characteristics, tumor-related variables, the incidence of PEI, and serum nutritional markers.

Results

We included 408 patients with malignancies potentially associated with PEI. Of these, 54.2% were male, with a mean age of 72 years (range: 38–101) and a mean body mass index (BMI) of 25.45 (SD ± 4.28).
The types of malignancies included were pancreatic ductal adenocarcinoma (PDAC) in 63.5% of patients, cholangiocarcinoma (CCA) in 23.8%, ampullary tumors in 9.8%, and gallbladder tumors in 2.9%. The overall incidence of PEI at the time of diagnosis was 38.2%. Among subgroups, the incidence was 51.4% in PDAC patients, 13.4% in those with CCA, and 25% in those with ampullary tumors. PEI incidence was significantly associated with elevated HbA1c (>5.8%, p<0.01) and Ca 19-9 levels (>37 U/mL, p<0.01).
In PDAC, tumors located in the pancreatic head were associated with a significantly higher incidence of PEI (58.8%) compared to tumors in the body (27.8%) and tail (21.7%) (p<0.01). In this subgroup, PEI was significantly associated with elevated HbA1c (>5.8%, p=0.03), elevated Ca 19-9 (>37 U/mL, p=0.04), and elevated bilirubin (>1.2 mg/dL, p<0.01).
In contrast, among CCA patients, no significant differences in PEI incidence were observed based on tumor location, and no significant associations were found between PEI and the clinical or laboratory variables analyzed .

Conclusion

• PEI is observed not only in patients with PDAC but also in those with CCA and ampullary tumors at the time of diagnosis.
• Given the high incidence of PEI in tumors located in the pancreatic head, empirical pancreatic enzyme replacement therapy should be considered in this subgroup.
• In PDAC patients, the presence of PEI is significantly associated with endocrine dysfunction, hyperbilirubinemia secondary to biliary obstruction and elevated Ca 19-9 levels.