Introduction

IgG4-related disease (IgG4-RD) is a chronic fibro-inflammatory multi-systemic disease. Pancreato-biliary involvement is reported in up to 60%, which can lead to exocrine and endocrine pancreatic insufficiency. Glucocorticoids can be used to control active inflammation but are associated with substantial toxicity. B-cell depletion with anti-CD20 chimeric Rituximab (RTX) and anti-CD19 humanised Inebilizumab (INEB) are steroid-sparing and used to control disease flares. INEB is the only FDA-approved medication for the treatment of IgG4-RD.

Aims & Methods

Our aim was to compare B-cell depleting agents for the treatment of IgG4-RD. We searched PubMed, Cochrane Central Register of Clinical Trials and Embase databases for studies of maintenance therapy in IgG4-RD with a pre-defined strategy and performed a network meta-analysis to assess relapse at 12 months, occurrence of infections and infusion-related reactions.

Results

96 out of 2545 manuscripts underwent full text review after exclusions. Three studies met eligibility for the meta-analysis, two reporting the use of RTX and one of INEB (Table 1).

For the primary outcome of disease relapse at 12 months, INEB had a risk ratio (RR) of 5.8 (95% CI 0.29 - 115.02) and RTX had an RR of 2.29 (95% CI 0.19 - 28.21), with INEB being superior in preventing relapses. The RR for infections with INEB was 0.81 (95% CI 0.19 - 3.41) whilst with RTX was 0.62 (95% CI 0.13 - 3.04). The RR for infusion-related reactions with INEB was 1.27 (95% CI 0.09 - 18.76) and for RTX was 0.93 (95% CI 0.11 - 8.19). These must be interpreted in the context of study design; INEB in a phase 3 randomised trial following a stringent safety protocol for reporting of adverse events, and RTX in retrospective observational studies.

Conclusion

This Network Meta-analysis demonstrates that INEB is superior to RTX at preventing disease relapses in patients with IgG4-RD at 12 months. Adverse events, such as infection and infusion-related reactions, were comparable in lieu of the methodological differences between studies.

Disclosure

Emma L Culver has received speaker fees from Albireo/IPSEN, Advanz/Intercept, Dr Falk, Amgen, GSK, Mirum Pharma, Gilead, Chemomab, Zenus Bio, and Advisory/consultancy fees from Advanz/Intercept, IPSEN, Mirum, GSK, Dr Falk Pharma, Amgen, Zenus Bio, Sanofi, Moderna and Sail BioPharma. MC has received speaker fees from Albireo/IPSEN, Advanz/Intercept, Amgen, GSK, Mirum Pharma, Gilead, and Advisory/consultancy fees from Advanz/Intercept, Alphasigma, Albireo/IPSEN, Mirum, GSK, Dr Falk Pharma, Amgen, Mayoly, Echosens, Kowa, Moderna, Zydus.

Introduction

Differentiating mucinous (MPCLs) from non-mucinous pancreatic cystic lesions (NMPCLs) remains critical for appropriate therapeutic decisions. While carcinoembryonic antigen (CEA) levels >192 ng/mL have been the conventional benchmark, their limited sensitivity underscores the need for more accurate alternatives. Recent data suggest intracystic glucose levels may be a promising biomarker. This study prospectively evaluated the diagnostic performance of intracystic glucose compared to CEA in pancreatic cyst fluid obtained via EUS-guided fine needle aspiration (EUS-FNA).

Aims & Methods

From July 2018 to October 2024, 24 patients with pancreatic cystic lesions undergoing EUS-FNA using a 22G needle were included. Glucose and CEA concentrations were measured using standard biochemical protocols. Final diagnosis was based on surgical pathology (n=5), cytopathology (n=9), or consensus radiologic/endoscopic evaluation by two blinded expert pancreatologists (n=10). All procedures and analyses were performed in a tertiary academic gastroenterology center in Morocco.

Results

Mean patient age was 59.8 years. Diagnoses comprised 13 mucinous cysts (54.2%; including 9 IPMNs and 4 MCNs), 7 serous cystadenomas (29.2%), 2 cystic neuroendocrine tumors (8.3%), 1 pseudocyst, and 1 simple cyst.
The mean intracystic glucose level in MPCLs was 14.1 mg/dL (95% CI: 5.6–22.6), versus 90.3 mg/dL (95% CI: 82.1–98.6) in NMPCLs (p < 0.0001). A glucose threshold of ≤30 mg/dL yielded an AUC of 0.94 (95% CI: 0.84–0.99), with 92.3% sensitivity and 100% specificity.
For CEA ≥192 ng/mL, AUC was 0.71 (95% CI: 0.54–0.86), with 46.1% sensitivity and 100% specificity. No significant correlation was found between glucose levels and either CEA or cyst size.

Conclusion

Intracystic glucose represents a simple, cost-effective, and highly accurate marker for distinguishing mucinous from non-mucinous pancreatic cystic lesions. It demonstrates superior sensitivity compared to CEA and can be a valuable adjunct in the diagnostic algorithm of pancreatic cysts, particularly in resource-conscious settings.

References

 Carrara S, Ceriello A, Arcidiacono PG. Glucose in pancreatic cyst fluid: a reliable test for mucinous cysts? Endoscopy. 2022;54(1):63–70.
 Köker D, Tevethia H, Madhoun MF. Intracystic glucose: a promising low-cost tool in differentiating pancreatic cysts. Gastrointest Endosc. 2023;97(4):832–9.
 Alomari F, Hammad T, Khasawneh MA, et al. Diagnostic performance of EUS-FNA glucose vs CEA in pancreatic cysts. Pancreas. 2021;50(5):661–6.

Introduction

EUS-guided drainage using lumen-apposing metal stents (LAMSs) and direct endoscopic necrosectomy (DEN) are primary treatment modalities for symptomatic pseudocysts and walled-off pancreatic necrosis (WOPN). However, bleeding is a frequent and serious adverse event associated with these procedures, often requiring radiological or surgical interventions also due to the limitations of conventional endoscopic hemostatic techniques. PuraStat is a novel topical hemostatic agent that has demonstrated excellent results in managing gastrointestinal bleeding.

Aims & Methods

Our aim was to evaluate the efficacy and safety of PuraStat in managing bleeding secondary to EUS-guided drainage and DEN of pancreatic fluid collections (PFCs). In this multicenter, retrospective, observational study we described 27 patients who underwent PuraStat treatment because of active bleeding during or after EUS-guided drainage or DEN sessions of pseudocysts or WOPN between 2017 and 2024.

Results

38 bleeding episodes were recorded (10 patients with WOPN experienced multiple bleeding events). The bleeding type was oozing in 36 cases and spurting in 2 cases. PuraStat was successfully applied in 100% of patients and achieved successful hemostasis in 96.5% of cases. No re-bleeding occurred. No PuraStat-related adverse events were recorded.

Conclusion

PuraStat is a safe, effective, and easy-to-use hemostatic agent for managing oozing hemorrhages related to PFCs EUS-guided drainage or DEN. Prospective and comparative studies are needed to confirm these preliminary data.

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

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

At present, the resection of the pancreatic body and tail generally requires invasive surgical treatment. Laparoscopic resection of the pancreatic body and tail is the predominant methodology to remove lesions in these locations; its safety and surgical planning are relatively mature, but it remains a complex and high-precision surgical operation, requiring abundant experience and skills in laparoscopic surgery, with a 10% rate of complications. Therefore, we use an endoscopic treatment to remove lesions in the pancreatic body or tail directly through animal experiments.

Aims & Methods

Five swine with body weight of 35 ± 2.1 kg were used in this study. First, we used EUS to locate pancreatic body. EUS - guided fine-needle injection was used to label the pancreatic and gastric puncture site using methylene blue. An endoscope with water-jet function and a distal attachment cap was then introduced and a full-thickness incision of approximately 1.5 cm was created on the middle posterior wall of gastric body using Hook/IT knives to get access into the peritoneum. After entering the peritoneum, pancreas was identified following methylene blue. A 2 cm of parenchyma of the pancreatic lobule was then dissected, avoiding the parenchyma around the main pancreatic duct. Electrocoagulation was used to deal with the bleeding of pancreatic duct lobule. Finally, the pancreatic tissue was removed with the assistance of a snare. The endoscope was withdrawn and wound was closed using endoclips.

Results

All the procedures were performed successfully in all the study animals, and there were no perioperative complications. The technical success rate and the survival rate of the pigs were both 100%. After the procedure, routine blood, inflammatory factors, amylase, blood glucose were measured and all the animals recovered well. Endoscopic reexamination and specimen collection of all experimental animals were performed postoperatively based on the study design. In this experiment, a total of 5 pancreatic tissues were removed by endoscopy, in which the resection size of was approximately 2.2 ± 0.8 cm. All the animals survived for 12 weeks until they were euthanized.

Conclusion

The pilot experiment demonstrated that pure flexible endoscopic lobular resection of the pancreas is a feasible and safe approach for removing pancreatic lesions in a porcine model. All animals recovered well without adverse effects, indicating that this minimally invasive technique could serve as an effective alternative to traditional invasive surgical methods for managing lesions in the pancreatic body and tail. This study suggest further exploration and potential application of endoscopic techniques in clinical settings for pancreatic surgeries, potentially leading to improved patient recovery times and reduced surgical risks.

Introduction

Infections in acute pancreatitis are associated with increased morbidity, mortality, and healthcare costs. Early diagnosis is essential to improve prognosis and reduce mortality. The aim of the present study is to evaluate the distribution of infectious complications according to the underlying etiology.

Aims & Methods

A retrospective analysis was conducted on a prospective database comprising a cohort of 526 patients with acute pancreatitis, consecutively included between March 2017 and June 2019 at a tertiary care hospital. All patients underwent systematic blood testing at admission and at 48 hours. Clinical management adhered to standard clinical practice guidelines. Diagnosis and classification were based on the revised 2012 Atlanta classification. Infectious complications were analyzed in patients with biliary and alcohol-related acute pancreatitis.

Results

Variable	Overall (n = 526)	Biliary (n = 304)	Alcohol-related (n = 39)	p-value
Acute cholangitis (Tokyo-18)
Suspected and/or confirmed	173 (37.6%)	140 (53.8%)	8 (20.4%)	0.001 **
Confirmed cases only	49 (29.2%)	43 (30.7%)	0	0.059
Antibiotic therapy	165 (36.1%)	123 (41.3%)	9 (23.7%)	0.037 **
Extrapancreatic infections (Total)	48 (14.3%)	34 (15.2%)	3 (13%)	1.000
Pneumonia	16 (4.8%)	8 (2.6%)	1 (2.6%)	1.000
Urinary tract infection	28 (8.4%)	25 (8.2%)	1 (2.6%)	0.335
Phlebitis / Catheter-related infection	4 (1.2%)	1 (0.3%)	1 (2.6%)	0.215
Infected pancreatic necrosis	11 (2.4%)	6 (2.1%)	2 (5.3%)	0.230

The distribution of infectious complications occurring during hospitalization is shown in Table 1. Up to 53.8% of patients with biliary acute pancreatitis presented with acute cholangitis according to the Tokyo-18 criteria, whereas this occurred in only 20.4% of alcohol-related cases. All cases of cholangitis in the alcoholic pancreatitis group, as well as the majority of those in the biliary group, met only the criteria for suspected acute cholangitis (100% vs. 53.8%, respectively). Antibiotic therapy was used in 41.3% of biliary pancreatitis cases, with a statistically significant difference compared to alcohol-related pancreatitis (23.7%). No significant differences were observed in the rates of extrapancreatic infections between the two groups, occurring in 15.2% and 13% of biliary and alcohol-related cases, respectively.

Conclusion

Extrapancreatic infections play a key role in the clinical course of acute pancreatitis, particularly in moderate and severe cases. The most frequent sites of infection include the respiratory and urinary tracts, as well as bloodstream infections. These infections are associated with an increased risk of complications, prolonged hospital stays, and higher mortality.
The characteristics of infections vary according to the etiology of pancreatitis. In our cohort, biliary pancreatitis was significantly more often associated with acute cholangitis, which is consistent with the pathophysiology of biliary-origin pancreatitis. Among patients with alcohol-related pancreatitis, up to 20% met criteria for suspected cholangitis; however, none fulfilled the criteria for confirmed cholangitis. This may be explained by the presence of acute-phase reactants and transient cholestasis, potentially leading to the administration of unnecessary antibiotic therapy.
Although previous studies have reported higher rates of respiratory infections in alcohol-related acute pancreatitis, our data showed no significant differences in these infections—or in infectious complications overall—between the two etiologies.

References

1. Petrov, M. S., Shanbhag, S., Chakraborty, M., Phillips, A. R. J., & Windsor, J. A. (2010). Organ Failure and Infection of Pancreatic Necrosis as Determinants of Mortality in Patients With Acute Pancreatitis. Gastroenterology, 139(3), 813–820.
2. Siriwardena, A. K., Jegatheeswaran, S., Mason, J. M., Siriwardena, A. K., Jegatheeswaran, S., Mason, J. M., Baltatzis, M., Sheen, A. J., O’Reilly, D. A., Jamdar, S., Deshpande, R., De Liguori Carino, N., Satyadas, T., Qamruddin, A., Hayden, K., Parker, M. J., Butler, J., & McIntyre, B. (2022). A procalcitonin-based algorithm to guide antibiotic use in patients with acute pancreatitis (PROCAP): a single-centre, patient-blinded, randomised controlled trial. The Lancet Gastroenterology & Hepatology, 7(10), 913–921.
3. Valverde-López, F., Martínez-Cara, J. G., & Redondo-Cerezo, E. (2022). Pancreatitis aguda. Medicina Clínica, 158(11), 556–563.