Introduction

Nanoliposomal irinotecan plus fluorouracil with folinic acid (NFF) is a standard regimen after gemcitabine-based therapy for patients with unresectable pancreatic cancer (urPC). However, there are almost no reports on the effectiveness and safety of NFF regarding the presence or absence of biliary drainage (BD) prior to NFF. Therefore, we analyzed whether they impacted on the efficacy and safety of NFF in the real-world (the NAPOLEON-2).

Aims & Methods

We prospectively collected the data of consecutive urPC patients treated with NFF who had received at least one previous chemotherapy in 17 hospitals in Japan from June 2021 to October 2023. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), relative dose intensity (RDI) and adverse events (AEs). We analyzed the data on patient characteristics, treatment efficacy, and AEs between non-BD group and BD group.

Results

A total of 150 urPC patients who received NFF regimen were prospectively enrolled. All patients received gemcitabine before NFF. The median follow-up period was 7.2 months (95% confidence interval [CI], 6.3–8.8); median age, 72 years (range, 45–85), with 81 male patients (54%). One-hundred and thirteen patients were included in non-BD group, and 37 were in BD group. There were several clinically significant differences in the patient characteristics, such as tumor location and duration time of previous chemotherapy. There was no significant difference in OS between non-BD and BD group (8.6 vs 6.8 months; hazard ratio (HR), 1.25; 95% CI, 0.83–1.89; P = 0.29). Also, there was no significant difference in PFS between non-BD and BD group (3.7 vs 3.6 months; HR, 1.05; 95% CI, 0.71–1.55; P = 0.81). The ORR was 11% and 11% in non-BD group and BD group, respectively. The DCR was 58% and 51% in the non-BD group and BD group, respectively. The median number of treatment cycles was 7 (range, 1–44) in non-BD group and 6 (1-30) in BD group, respectively. The median RDIs for nal-IRI were 72.7% in non-BD group and 75.0% in BD group, respectively, and for fluorouracil were 78.4% in non-BD group and 82.7% in BD group, respectively. Hematological AEs of grade ≥3 were observed in 34% of non-BD group and 38% of BD group, while nonhematological AEs of grade ≥3 were observed in 40% and 68%, respectively. The rate of biliary tract infection was clinically higher in BD group (30% vs 4%). The rate of pancreatic head cancer was higher in the BD group than non-BD group (95% vs 24%), however, there was no significant difference in OS between non-BD and BD group among patients with pancreatic head cancer (9.7 vs 7.1 months; HR, 1.33; 95% CI, 0.76–2.34; P = 0.32).As for the treatments followed by NFF, 55 (54%) patients in the non-BD group and 25 (76%) patients in the BD group received best supportive care alone.

Conclusion

Although biliary tract infection occurred more frequently in the BD group, therapeutic efficacies of NFF were comparable between both groups. We need to pay attention to nonhematological AEs in the biliary drainage group in daily clinical practice.

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer that poses significant therapeutic challenges. In this regard, the identification of prognostic biomarkers is crucial to improve the prediction of clinical outcomes and guide therapeutic decisions. Tumour-associated autoantibodies (TAAbs) have been identified as prognostic biomarkers in several types of cancer, as they can be generated before the first clinically detectable signs of disease.

Aims & Methods

The aim of this study was to identify TAAbs that can be used as prognostic biomarkers in PDAC. 80 sera from patients with PDAC, divided into four groups according to disease stage, were included in the study: patients with premalignant lesions (n = 20), patients undergoing curative resection after diagnosis (CR) (n = 20), patients with unresectable advanced locoregional disease (LA) (n = 20) and patients with metastatic disease (MT) (n = 20). Sera from each group were analysed divided into 4 pools of 5 samples each using the HuProt Human Protreome microarray v4.0 (CDI Laboratories, Baltimore, MD). Candidate TAAbs with high specific reactivity in MT and/or LA samples were selected according to the following criteria: z-score ≥ 3 in at least 2/4 pools and fold-change > 1.2. The RNAseq data collected in the Human Protein Atlas were used to determine protein expression levels and prognostic value. The GSE15471, GSE28735 and GSE16515 databases were used to compare expression levels with those of healthy subjects without the disease.

Results

43 TAAbs demonstrated high levels of specific reactivity in samples from MT and/or LA patients. Of these highly recognised proteins, 15 were selected for showing notable levels of expression in tumour tissue from PDAC patients and prognostic capacity in some types of cancer. Of these 15, 2 proteins involved in tumour development were identified. Survival analyses showed that six of the 15 selected proteins were significantly associated with a worse prognosis in PDAC patients (p < 0.05). Finally, in the comparison with control tumour tissue, 5 proteins were identified with significantly higher expression in patients diagnosed with the disease (p < 0.05 in at least 2 of the cohorts used).

Conclusion

15 TAAbs have been identified as promising candidates for prognostic biomarkers in PDAC. Further validation studies are required to confirm their prognostic value and to develop a robust biomarker signature with potential for clinical application and market translation.

Introduction

The aetiology of acute pancreatitis remains elusive in 10-30% of patients after clinical, biological and morphological investigations. Endoscopic ultrasound has shown promise and is particularly effective in exploring the bilio-pancreatic region.

Aims & Methods

The aim of our study was to evaluate the contribution of endoscopic ultrasound to the aetiological diagnosis of unexplained acute pancreatitis.
This is a retrospective descriptive study of 89 patients who underwent endoscopic ultra sound for unexplained acute pancreatitis between January 2010 and January 2025.

Results

The mean age of our patients was 55 +/- 16.3 years, with extremes ranging from 17 to 89 years. The sex ratio (M/F) was 0.81, with a slight female predominance of 55.1%. A history of previous acute pancreatitis was found in 31.9% of cases, and 16.3% of patients had undergone cholecystectomy. The diagnostic yield in our study was 68%. Biliary origin was retained in 40.4% (n=36) of patients, 19 of whom underwent complementary ERCP at the same anaesthetic time. Neoplastic pathology was found in 32.5% of cases (n=30). Chronic pancreatitis was reported in 22.4% of patients (n=20). Two cases of pancreas divisum, one case of sphincter of Oddi dysfunction and one case of choledocele were found. In the remaining 32% of cases, the endoscopic ultrasound was normal and no cause could be found.

Conclusion

Endoscopic ultrasound is currently an indispensable tool in the etiological investigation of unexplained acute pancreatitis. In our study, the diagnostic efficiency was around 68%.

Introduction

Acute pancreatitis (AP) is a common acute inflammatory disease of the abdomen. ATP citrate lyase (ACLY) has been shown to play a critical role in mitigating acute pancreatitis-associated injury. Lentinan, a multifunctional polysaccharide derived from shiitake mushrooms, exhibits biological activities such as anti-inflammatory, antioxidant, and immunomodulatory effects, and is widely used in clinical settings. However, the role of Lentinan in acute pancreatitis remains unclear.

Aims & Methods

This study aimed to investigate the protective effects of Lentinan against acute pancreatitis and whether this protection depends on ATP citrate lyase. Adult healthy male C57BL/6 mice were randomly divided into control group, acute pancreatitis group, and Lentinan + acute pancreatitis group. The cerulein-LPS induced AP model was established by intraperitoneal injection of cerulein solution (100 μg/kg body weight) 10 times at hourly intervals, followed by a single injection of lipopolysaccharide (5 mg/kg) immediately after the last cerulein injection. In the lentinan + acute pancreatitis group, mice were pretreated with intraperitoneal injections of of Lentinan solution (50 mg/kg, 100 mg/kg, or 200 mg/kg) for three consecutive days before AP induction. The severity of pancreatitis was assessed by comparing plasma activities of amylase, lipase, alanine aminotransferase, aspartate aminotransferase, and plasma levels of urea, and creatinine, as well as pancreatic histopathological scores. Systemic inflammatory response was evaluated by measuring plasma IL-1β and TNF-α levels through enzyme-linked immunosorbent assay. Pancreatic infiltration of macrophages and neutrophils was detected by immunofluorescence, and protein levels of ACLY, NLRP3, and IL-1β in pancreatic tissues were measured by Western blot. To further validate the critical role of ACLY, AP was induced in mice with pancreas-specific ACLY knockout, with Lentinan pretreatment.

Results

Lentinan significantly alleviated pancreatic histopathological damage caused by AP, including edema, necrosis, and inflammatory cell infiltration. It also reduced plasma aminotransferase activity, creatinine, and urea levels, but did not significantly decrease plasma amylase or lipase activity. A higher dose of Lentinan (200 mg/kg) was less effective than lower doses in reducing plasma aminotransferase, creatinine, and urea in AP mice, possibly due to greater hepatorenal toxicity. Therefore, a moderate dose of Lentinan (100 mg/kg) provided effective protection against acute pancreatitis and was therefore selected for subsequent experiments. Additionally, Lentinan reduced pancreatic infiltration of macrophages and neutrophils, decreased plasma pro-inflammatory cytokine levels, upregulated pancreatic ACLY protein expression, and downregulated the levels of NLRP3 inflammasome and IL-1β proteins in pancreatic tissues. In mice with pancreas-specific ACLY knockout, both local pancreatic injury and systemic inflammation caused by AP were significantly exacerbated, and the protective effect of Lentinan against acute pancreatitis was diminished.

Conclusion

Lentinan exerts protective effects against acute pancreatitis by improving local and systemic inflammatory responses. The expression of pancreatic ACLY is indispensable for mediating this protective effect, which was partially achieved through the inhibition of the NLRP3 inflammasome pathway. The present study establishes a novel mechanism for this clinically available immunomodulator, which could have potential therapeutic implications in acute pancreatitis.

Introduction

The learning curve for EUS-guided Gastroenterostomy (EUS-GE) has been assessed through retrospective studies involving few elite senior endoscopists (SE), using procedural time as the main surrogate outcome. This study aims to evaluate the training course of junior endoscopists (JE) approaching EUS-GE using the WEST technique, considering both technical efficiency and clinically relevant patient outcomes.

Aims & Methods

From a prospective single-centre registry of EUS-GE (PROTECT, ClinicalTrials.gov NCT04813055) using the Wireless Simplified Technique (WEST), the learning curve of 3 JE, experienced in pancreatobiliary endoscopy (PBE) was analysed to identify inflection points (“knots”), applying adaptive regression and cumulative sum control chart (CUSUM) on several continuous and dichotomous variables. EUS-GE performed by a SE and those on post-surgical anatomy were excluded.

Results

From a prospective database of 165 EUS-GE, 100 were performed by a JE with previous EUS-GE training (JE1) and 26 by two naïve JEs.
In JE1’s curve, neither procedural nor fluoroscopy time showed any improvement while radiation dose (mean Air Kerma: 392 ± 317 Gy) significantly decreased (F-test p=.0005) after 57 (adaptive regression) and 72 interventions (CUSUM), stabilizing thereafter. The need for supervision/backup from a SE showed a significant knot after 32 procedures (p<.0001). Technical success (100%), clinical success (95.0%), adverse events (AEs; 6.0%) and moderate/severe AEs (4.0%) remained constant through the learning curve, clustered according to the aforementioned knots. Conversion from EUS-GE to enteral stenting was rare (7.2%) and non-significantly decreased over time.
Despite requiring significantly higher fluoroscopy time (234 vs. 187 seconds, p=.009) and procedural time (55 vs. 43 minutes, p=.002), naïve endoscopists achieved efficacy and safety outcomes comparable to the remaining cohort.

Conclusion

From the analysis of a prospective learning curve, performing ≈ 30 EUS-GE seems required for independent practice, and ≈ 70 to stabilize the fluoroscopy usage. EUS-GE training of naïve PBE endoscopists in high-volume institutions, using a standardized technique, does not compromise clinical and safety standards.

Introduction

The revised Atlanta Classification delineates the local complications of acute pancreatitis, categorizing them as acute (peri)pancreatic fluid collections (PFCs), acute necrotic collections, pancreatic pseudocysts, and walled-off pancreatic necrosis (WOPN). Various endoscopic interventions are employed for the management of WOPN, notably including direct transluminal endoscopic necrosectomy (DEN) following the placement of an endoscopic ultrasound-guided (EUS) lumen-apposing metal stent (LAMS). This study aims to assess the clinical outcomes and safety profile of DEN in patients diagnosed with pancreatic WOPN.

Aims & Methods

This single-center retrospective analysis encompasses patients with pancreatic WOPN who underwent DEN at Semmelweis University between October 1, 2021, and October 1, 2024. The procedures were performed by three seasoned specialists in EUS and endoscopic retrograde cholangiopancreatography (ERCP). Comprehensive data on patient demographics, procedural specifics, and follow-up outcomes were collected, with adverse events classified according to the AGREE criteria.

Results

We successfully placed LAMS in 31 patients (61% female, mean age 66.3 years, SD 9.4). The primary indications for intervention included the dimensions of WOPN, exacerbation of gastric outlet obstruction, and signs of infection. The mean dimensions of WOPN were recorded as 98 mm in the anteroposterior direction (SD 35.6), 90 mm laterolateral (SD 44), and 88 mm craniocaudal (SD 27.4), with a predominant occurrence in the head of the pancreas (60%). Alcohol consumption emerged as the leading etiological factor for WOPN in 92% of male patients, whereas biliary causes were identified in 67% of female patients.
In total, we conducted 83 DEN procedures across the 31 patients (51 males and 32 females). The average number of DEN sessions was three for both male and female groups (range: 2-6). The technical success rate achieved was 100%, accompanied by a clinical success rate of 97%. One patient succumbed to the condition; however, three of the surviving 30 required intensive care due to multiorgan failure. To enhance the resolution of infection between DEN sessions, we employed 7 Fr/250 cm nasocystic tubes for irrigation of the WOPN with a saline solution in all patients, with no adverse events reported as a result of this intervention.

Conclusion

DEN can be performed safely in experienced medical centers and demonstrates a high success rate in the treatment of infected WOPN, effectively alleviating symptoms and decreasing enzyme levels. The predominant etiology of WOPN formation in male patients is attributed to alcohol consumption, while biliary factors are more prevalent in female patients.

Introduction

While pancreatic cancer is traditionally associated with older age, its incidence is rising in adults under 50. This younger population often falls outside standard screening and triage pathways, contributing to delayed diagnosis. In the absence of risk factors, early symptoms may be overlooked or misattributed, delaying imaging and leading to advanced-stage discovery. Although a minority of patients carry hereditary risk, the majority of young cases present without identifiable predispositions.

Aims & Methods

This study aimed to describe the clinical, biological, and diagnostic profile of pancreatic cancer in adults under 50, with a focus on diagnostic delays, tumor marker levels, disease stage, and the presence of traditional risk factors.
A retrospective monocentric analysis was conducted on all patients diagnosed with pancreatic cancer between January 2020 and December 2024 at a regional reference center. Patients were divided into two age groups: <50 and ≥50 years. Variables included age, sex, BMI, smoking status, diabetes, CA 19-9 levels, time from symptom onset to diagnosis, and tumor stage (resectable, borderline, locally advanced, metastatic). Statistical analyses used chi-square and non-parametric tests.

Results

Among 293 patients, 24 (8.2%) were under 50 years (range: 31–49; median age: 46.5 years).

• This younger group had a male predominance (62%) and lower median BMI (22.3 kg/m²).
• Diagnostic delays >30 days were more frequent in younger patients (71%) vs. older adults (56%) (p = 0.04), with a longer median delay (45 vs. 35 days).
• Median CA 19-9 was higher in the younger group (970 vs. 503 U/mL), and values >1000 U/mL were observed in 41% vs. 24% of older adults.
• Stage at diagnosis in younger patients:
  • Resectable: 8.3%
  • Borderline: 20.8%
  • Locally advanced: 33.3%
  • Metastatic: 37.5% (no significant difference vs. older group; p = 0.61).
• Only 4.2% of younger patients had traditional risk factors (smoking, obesity, diabetes).
• Among those without any risk factor, 78% presented with advanced-stage disease.

Conclusion

Pancreatic cancer in adults under 50 is an emerging and underrecognized challenge. In our cohort, younger patients experienced longer diagnostic delays and more frequent advanced-stage presentations—despite lacking classical risk factors. These findings expose a diagnostic blind spot, likely shaped by age-related bias.
Clinicians should not dismiss elevated CA 19-9 values in younger adults, even in the setting of cholestasis, and should maintain a high index of suspicion in those presenting with persistent abdominal symptoms or unexplained weight loss. Earlier imaging and broader clinical vigilance could help reduce missed opportunities for curative intervention in this vulnerable group.

Disclosure

The authors declare no conflict of interest