Clinical Case Summary

Necrotizing pancreatitis, which is associated with an 8 to 39% rate of death, develops in approximately 20% of patients. One of its rare complications is the formation of pancreatic pseudoaneurysms, which can result in life-threatening gastrointestinal bleeding. Pancreatic pseudoaneurysm is a rare but potentially life-threatening vascular complication of chronic or necrotizing pancreatitis (4% to 17%). In this case, we describe the successful management of a pancreatic pseudoaneurysm in a patient with necrotizing pancreatitis using mesenteric angiography and embolization. This case report presents the management of a 57-year-old male with a history of hypertension & dyslipidemia with good functional capacity and health seeking behavior. He had no other significant medical, family, and psycho-social history. The patient came in for severe epigastric pain radiating to the back and was initially managed as a case of gallstone pancreatitis. Weeks later he developed overt gastrointestinal bleed (melena). Further work up revealed progression to necrotizing pancreatitis with subsequent pancreaticoduodenal fistula and hemorrhagic complications seen on imaging and esophagogastroduodenoscopy. He underwent successful mesenteric angiography with coil embolization; however, the fistula persisted, draining necrotic fluid and delaying the initiation of oral feeding. To promote fistula healing, an endoscopically placed nasoduodenal tube was advanced to the fourth part of the duodenum, allowing enteral nutrition while bypassing the second part of the duodenum. This case highlights the clinical presentation, diagnostic imaging, interventional techniques, and the multidisciplinary approach essential for effective management.

References

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Introduction

Cardiovascular diseases (CVDs) are often a limiting factor in cancer treatment. In our systematic review and meta-analysis we evaluated the prevalence and incidence of CVDs in pancreatic ductal adenocarcinoma (PDAC).

Aims & Methods

We conducted the systematic search on 5 February 2024 in three databases (PubMed, EMBASE, CENTRAL). Studies reporting the prevalence or incidence of CVDs in PDAC were included. Subgroup analyses based on cancer stage and treatment type were performed. Pooled proportions with the 95% confidence interval (CI) were calculated using a random effect model. We evaluated the risk of bias using the Joanna Briggs Institute Prevalence Critical Appraisal. (PROSPERO CRD42023482295).

Results

We included 198 articles. The prevalence of CVDs other than thrombotic events at PDAC diagnosis was similar to the one in the general population: hypertension 33 % (95%CI:27-40%), ischemic heart disease 6% (95%CI:3-12%), heart failure, arrhythmia, and stroke affecting each 2-3% of cases. Their incidence during treatment was low (1%-10% overall). Thrombotic events other than embolism affected 11% (95%CI: 7%-18%) of cases at diagnosis and the incidence during treatment was between 8-10% regardless of cancer stage or treatment type. Pulmonary embolism affected 3% of cases at diagnosis and occurred in a similar proportion during treatment. The included studies had an overall low-moderate risk of bias.

Conclusion

Thrombotic events affect around 10% of PDAC patients at baseline. A similar proportion develop thrombotic events during follow-up regardless of disease stage or treatment type. The prevalence of CVDs other than thrombotic events is equivalent to the one in the general population.

Introduction

Acetaminophen (APAP) overdose is a primary cause of drug-induced liver injury (DILI). Although the inflammatory microenvironment plays a critical role in APAP-induced liver injury (AILI), its cellular interaction network and molecular regulatory mechanisms remain incompletely elucidated. Krüppel-like factor 4 (KLF4), a zinc finger transcription factor, is known to regulate monocyte differentiation, but its functional role in the AILI inflammatory microenvironment remains unclear. This study aims to investigate the regulatory effects of myeloid KLF4 deletion on the AILI microenvironment.

Aims & Methods

By integrating multidimensional omics analysis and a myeloid-specific Klf4 knockout mouse model, we dynamically dissected microenvironmental remodeling during AILI progression. Liver samples were collected for RNA sequencing, combined with single-cell transcriptomics, flow cytometry, and molecular interaction validation to clarify the KLF4-dependent cellular subpopulation interaction network. In vivo liver imaging, histology, biochemical assays, and molecular experiments were performed to validate KLF4-dependent intercellular interactions. Primary hepatocytes and hepatocyte cell lines were used for in vitro verification.

Results

Myeloid-specific KLF4 deletion led to an increase in CXCL2⁺CXCL3⁺CD24⁺ monocytes, which activated the NF-κB signaling pathway to secrete CXCL2/CXCL3 chemokines. These chemokines bound to the CXCR2 receptor on neutrophils, driving neutrophil infiltration and neutrophil extracellular traps (NETs) formation, while amplifying the TNF-α signaling pathway. Concurrently, myeloid KLF4 knockout induced enrichment of CXCL1⁺IL17RA⁺ endothelial cells. Neutrophil-derived NETs promoted endothelial phenotypic switching toward pro-inflammatory polarization, while endothelial-derived CXCL1 further recruited neutrophils, establishing a "monocyte-neutrophil-endothelial" cellular subpopulation interaction that perpetuated microenvironmental inflammation.

Conclusion

This study reveals the molecular mechanism by which KLF4 drives inflammatory cascades in the AILI microenvironment through regulation of the myeloid-endothelial interaction network. We propose therapeutic strategies targeting NETs formation or the CXCL2/CXCL3-CXCR2 axis, providing novel targets for precise intervention in AILI.