Clinical Case Summary

A 51-year-old male presented to the emergency department with acute back pain, suspicious for renal colic. An abdominal CT scan incidentally revealed a 30 mm hypodense lesion in the pancreatic uncinate process with central calcifications (see Fig. 1).
An endoscopic ultrasound (EUS) demonstrated a hypoechoic, heterogeneous mass in the uncinate process, with irregular margins and a huge posterior acoustic shadowing. No signs of vascular or ductal involvement were noted. Therefore, EUS-guided fine needle biopsy (FNB) with a 22-G Franseen-tip needle was performed via transduodenal and transgastric approaches, obtaining an adequate histological sample after macroscopic on-site examination (MOSE).
Histological analysis revealed spindle cells positive for CD34, BCL2, STAT6, and CD99, and negative for CKIT, DOG1, desmin, actin, S100, and cytokeratins, with Ki-67 index > 5%, suggesting for solitary fibrous tumor (SFT) of the pancreas (see Fig.2). Immunohistochemical confirmation was obtained at a tertiary referral pathology laboratory. A multidisciplinary tumor board advised conservative follow-up based on the benign histology and absence of local invasion.
Conclusion: Pancreatic SFTs are extremely rare, with only 34 cases reported to date. They are more frequently located in the pancreatic head and are slightly more common in females. Most are discovered incidentally. This case highlights the critical diagnostic value of EUS-FNB, which enabled accurate tissue acquisition for advanced immunohistochemical analysis, informing a non-surgical, surveillance-based approach. Because of the non-specific clinical presentation and radiological features of pancreatic SFTs, diagnosis is particularly challenging using preoperative imaging and laboratory tests alone. Therefore, histopathological and immunohistochemical evaluation is essential for definitive diagnosis.

References

References and Illustrative Material:

Figure 1: Abdominal CT scan showing a pancreatic mass in the uncinate process with central calcification.

Figure 2: On the left, tissue sample stained with hematoxylin and eosin. Spindle cell proliferation with disorganized architecture. The lesion is hypercellular, composed of elongated mesenchymal cells with scant cytoplasm and oval-to-tapered nuclei, suggesting a spindle cell neoplasm, such as SFT. On the right, the same tissue sample was analyzed using immunohistochemistry: strong and diffuse nuclear positivity for STAT6 was found in tumor cells.

Selected References:

1. Ronchi A et al. Solitary fibrous tumors: an update on diagnosis and management. Pathol Oncol Res.

2020;26(2):597-605.

2. Wang WW, Zhou SP, Wu X, Wang LL, Ruan Y, Lu J, Li HL, Ni XL, Qiu LL, Zhou XH. Imaging, pathology, and diagnosis of solitary fibrous tumor of the pancreas: A case report and review of literature. World Journal of Clinical Cases. 2024;12(5):995–1003.

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

Systemic sclerosis (SSc) is a rare autoimmune disease marked by multisystemic fibrotic and vascular involvement, mainly affecting the skin, lungs, and upper digestive tract. Skin involvement may serve as a marker for visceral severity, particularly regarding pulmonary and upper digestive manifestations. This study examined its correlation with these systemic complications in SSc patients.

Aims & Methods

A retrospective, descriptive, bicentric study was conducted on SSc patients followed in the internal medicine department between 2004 and 2024. Clinical evaluation included cutaneous involvement via modified Rodnan score, pulmonary assessment by clinical examination, imaging, and pulmonary function tests. Upper digestive involvement was explored through symptoms, esophagogastroduodenoscopy, and esophageal manometry performed in the gastroenterology department to assess motility and mucosal integrity. Statistical analysis (descriptive and analytical) was performed using SPSS (version 26) with the Chi-square test and a significance threshold of p <0.05.

Results

A total of 160 patients were included, mostly female (91.2%), with a median age of 50 years (range:13–81). Localized scleroderma was diagnosed in 76.2%. Skin involvement was assessed in 121 patients using the Rodnan score (mean:15.31; range:0–51), categorized as mild (0–10) in 35%, moderate (11–20) in 15%, severe (21–30) in 16.3%, and very severe (>30) in 9.4%.
Upper digestive involvement was observed in 31.4%, 14.9%, 18.2%, and 9.1% of patients with mild to very severe skin involvement, respectively. Among associated symptoms: epigastric pain was present in 8.4%, 5%, 5%, and 3.4%; gastroesophageal reflux disease (GERD) in 21.2%, 9.3%, 16.9%, and 8.5%; and dysphagia in 15.3%, 7.6%, 13.6%, and 6.8%, respectively.
Esophageal manometry was performed in 36.2%, showing lower esophageal sphincter (LES) hypotonia in 5%, 2.5%, 5%, and 3.3% of mild to very severe cases, respectively. Aperistalsis was noted in 3.3%, 1.7%, 0.8%, and 0.8%, with rare ineffective motility and hypocontractility. No significant association was found between skin severity and upper digestive involvement, either clinically (p=0.458) or manometrically (p=0.98).
Similarly, no correlation was found between skin and pulmonary involvement. Lung disease was observed in 56.3% of localized and 19.4% of diffuse forms. Among these, interstitial lung disease was present in 26.3%, 12.7%, 16.1%, and 9.3%; pulmonary fibrosis in 15.6%, 6.4%, 8.3%, and 1.8%; and restrictive syndrome in 15%, 9.3%, 13.1%, and 5.6%, across increasing skin severity (all p >0.3).
However, pulmonary involvement was noted in 60% of patients with upper digestive symptoms. Dyspnea was reported in 66.9%, crackles in 29.4%, cough in 27.5%, and chest pain in 6.3%. Radiology showed interstitial lung disease in 58.8% and pulmonary fibrosis in 28.8%. Among these, GERD was present in 46.5%, dysphagia in 36.1%, epigastric pain in 19.2%, and isolated abdominal pain in one case. Manometry revealed LES hypotonia in 13.1%, aperistalsis in 5%, and ineffective motility in 0.6%. In contrast to skin involvement, a significant association was found between pulmonary and upper digestive manifestations (p<0.01).

Conclusion

No correlation was found between the severity of cutaneous involvement and digestive disorders. However, a significant link was observed between pulmonary involvement and upper digestive symptoms, suggesting that uncontrolled acid reflux may contribute to pulmonary fibrosis in SSc patients. This highlights the need for early management and multidisciplinary monitoring.

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.