Introduction

Autoimmune pancreatitis (AIP) is a chronic, relapsing form of pancreatitis, often affecting multiple organs. Although the exact pathomechanism is incompletely understood, plasmacytoid dendritic cells (pDC) and their cytokines IL-33 and interferon alpha-1 (IFNA1) are known to play a central role in AIP pathophysiology. Through activation of IFN-regulatory factors 3 and 7 (IRF3/IRF7) in pDC, IFNA1 transcription is initiated, likely offsetting the inflammatory cascade. AIP often leads to exocrine atrophy and insufficiency, however it is currently unknown whether pDCs affect acinar cell regeneration or their cell death.

Aims & Methods

This study aims to understand the effect of the IFN-cascade offset by pDCs on acinar regeneration capacity and cell death in AIP. The MRL/Mp mouse model for AIP was used to first characterize the immune cell infiltrate in AIP compared to acute pancreatitis (AP) via immunohistochemistry (IHC) staining. To test the impact of pDCs and Ifna1 release on pancreatic acinar cells, pDCs were generated from bone marrow of wild type (WT) and Irf3/7-knock out (Irf3/7-KO) mice and murine acinar cells were incubated with supernatant of WT and Irf3/7-KO pDCs, or pDC-related cytokines IL-33 and IFN-a. Gene expression via qPCR, cell stress via LDH assay and cytokine array were performed to measure the effects on acinar cells.

Results

AIP in MRL/Mp mice exhibited a stronger immune infiltrate in comparison to mice with an AP. The immune infiltrate in AIP was characterized by a dense invasion of CD8+ T cells, presence of CD11c+ cells (pDCs) and complete absence of neutrophils. Furthermore, Irf3 and Irf7 expressions were increased not only in immune but also acinar cells in AIP, whereas decreased in acinar cells and not at all expressed in immune cells in AP. Proliferation markers were not expressed in acinar cells in AIP, whereas showed some expression in acinar cells in AP. Acinar cells treated with pDC supernatant of WT revealed an increase in apoptosis signaling genes, whereas acinar cells treated with pDC supernatant of Irf3/7-KO mice showed a downregulation of apoptotic genes.

Conclusion

This study reveals that pDCs dictate acinar cell death signaling by regulating apoptosis via the IFN-cascade. This might be a distinct feature of AIP, in which the clinical course is moderate and only apoptosis is present, compared to AP, in which the disease course is much more severe and necrosis is a prominent feature. Further studies are needed to examine the role of pDC in necrosis and acinar regeneration.

References

1. Hart PA, Zen Y, Chari ST. Recent Advances in Autoimmune Pancreatitis. Gastroenterology. 2015;149(1):39–51.
2. Watanabe T, Yamashita K, Arai Y, Minaga K, Kamata K, Nagai T, et al. Chronic Fibro-Inflammatory Responses in Autoimmune Pancreatitis Depend on IFN-α and IL-33 Produced by Plasmacytoid Dendritic Cells. J Immunol. 2017;198(10):3886–96.
3. Minaga K, Watanabe T, Arai Y, Shiokawa M, Hara A, Yoshikawa T, et al. Activation of interferon regulatory factor 7 in plasmacytoid dendritic cells promotes experimental autoimmune pancreatitis. J Gastroenterol. 2020;55(5):565–76.

Introduction

Despite EUS-guided drainage (EUS-FCD) is the preferred modality for management of peripancreatic fluid collections (PFCs), factors predicting the need for step-up to additional procedures (including radiology, surgery or additional endoscopies) are retrospectively explored in studies restricted to Lumen Apposing Metal Stents (LAMS) or excluding pseudocysts and post-surgical collections, which might require a step-up as well.

Aims & Methods

All consecutive candidates to EUS-FCD with either LAMS or Double-pigtail Plastic Stents (DPPS) between 2020-2023 were included in a Prospective Registry of Therapeutic EUS (PROTECT). The role of baseline clinical and morphological factors, including the Quadrant / Necrosis / Infection (QNI) score, in predicting the need for any step-up to additional procedures was evaluated by stepwise logistic regression.

Results

Twenty-three post-surgical PFCs, 19 pseudocysts and 18 walled-off necrosis [WOPN]) were included, 42% treated with LAMS and 58% with DPPS based on morphology. Clinical success was 92.9%, but 38% of patients required a step-up to necrosectomy (26.7%) or additional procedures. Patients requiring step-up versus those sufficing drainage had a higher number of quadrants involved (OR=3.6 [1.5-8.4]), a more frequent paracolic extension (OR=6 [1.4-26]), a higher necrosis content (>30%, OR=7.2 [1.8-28.4] ; >60% OR=25.2 [4.2-153]) and were in the high-risk group according to the QNI score, with no difference in the diameter and rate of superinfection. At multivariate analysis, being in the high-risk QNI group was the only independent predictor of step-up (OR=9.8 [2.9-32.9]). The score however was not able to stratify in analyses restricted to WOPN only or LAMS only. High-risk QNI patients presented also a longer hospital stay (17.5 [8-45] vs 4 [2-6.5], p=0,001), without any difference in ICU stay and nutritional support.

Conclusion

In this prospective series of consecutive non-selective PFCs undergoing EUS-FCD, QNI score was the only independent predictor of any need for step-up to additional procedures, and strongly correlated to the EUS-FCD allocation to LAMS versus DPPS, unravelling a potential additional utility.

Disclosure

GV reports travel grants from Pentax Medical, Boston Scientific and Euromedical, and lecture fees by Boston Scientific.
All the other authors ​declare no conflict of interest.

Introduction

Increased lipase level is a serological hallmark of the diagnosis of acute pancreatitis (AP) but can be detected in various other diseases associated with lipase leakage due to inflammation of organs surrounding the pancreas or reduced renal clearance and/or hepatic metabolism. This non-pancreatic hyperlipasemia (NPHL) is puzzling for attending physicians during the diagnostic procedure for AP. It would be clinically beneficial to identify the clinical and laboratory variables that hinder the accuracy of lipase diagnosis with the aim of improve it. A more precise description of the NPHL condition could potentially provide prognostic factors for adverse outcomes which is currently lacking.

Aims & Methods

We aimed to provide a detailed clinical and laboratory characterization of a large prospective NPHL patient cohort and assess parameters determining disease outcomes.
A Hungarian patient cohort with serum lipase levels at least three times higher than the upper limit of normal (ULN) was prospectively evaluated over 31 months. Patients were identified using daily electronic laboratory reports developed to support an ongoing observational, multicenter, prospective cohort study called the EASY trial (ISRCTN10525246) to establish a simple, easy, and accurate clinical scoring system for early prognostication of AP. Diagnosis of NPHL was established based on ≥ 3 × ULN serum lipase level in the absence of abdominal pain or abdominal imaging results characteristic of pancreatitis.

Results

A total of 808 patients [male, n = 420 (52%); median age (IQR): 65 (51-75) years] were diagnosed with ≥ 3 × ULN serum lipase levels. A total of 392 patients had AP, whereas 401 had NPHL with more than 20 different etiologies. Sepsis and acute kidney injury (AKI) were the most prevalent etiologies of NPHL (27.7% and 33.2%, respectively). The best discriminative cut-off value for lipase was ≥ 666 U/L (sensitivity, 71.4%; specificity, 88.8%). The presence of AKI or sepsis negatively affected the diagnostic performance of lipase. NPHL was associated with a higher in-hospital mortality than AP (22.4% vs 5.1%, P < 0.001). In multivariate binary logistic regression, not lipase but increased amylase level (> 244 U/L) and neutrophil-to-lymphocyte ratio (NLR) (> 10.37, OR: 3.71, 95%CI: 2.006-6.863, P < 0.001), decreased albumin level, age, and presence of sepsis were independent risk factors for in-hospital mortality in NPHL.

Conclusion

NPHL is a common cause of lipase elevation and is associated with high mortality rates. Increased NLR value was associated with the highest mortality risk. The presence of sepsis/AKI significantly deteriorates the serological differentiation of AP from NPHL.

Introduction

Pain in acute pancreatitis is the symptom to be treated urgently. There are currently no recommendations for analgesic management. Intravenous lidocaine has both analgesic and anti-inflammatory effects. Its use has never been evaluated for analgesia in acute pancreatitis. The aim of our study was therefore to evaluate the efficacy and safety of intravenous lidocaine in the management of acute pancreatitis resistant to level I and II analgesics.

Aims & Methods

We conducted a retrospective, monocentric study between January 2015 and December 2021. Patients visiting the emergency department for proven acute pancreatitis and presenting with pain resistant to group I and II analgesics, hospitalized in the hepato-gastroenterology department and treated with intravenous lidocaine, were included. Pain was assessed by retrospective collection of numerical pain scales (NPS) at the emergency department, and at each analgesic re-evaluation. Treatment efficacy was defined as the absence of need for a Level III analgesic (opioids).

Results

154 patients, hospitalized in our gastroenterology unit for acute pancreatitis and presenting with pain refractory to level I and II analgesics treated with intravenous lidocaine were included. Patients were predominantly male, with a median age of 48.5 years [37.0; 58.0]. The main etiology of acute pancreatitis was ethylic in 36% of cases. Acute necrotizing pancreatitis was present in 69% of patients. 44/154 patients received a bolus of opioid morphine in the emergency department before the administration of lidocaine. Lidocaine was prescribed in a continuous way at the dose of 2g/24h (intravenous administration with electric syringe). The median NPS before prescription of lidocaine was 8.0 [7.00; 9.00]. Lidocaine treatment was effective in 88.7% of patients (136/154). 1.3% of patients experienced lidocaine-related adverse events such as skin rash and dysgeusia. In univariate analysis, patients requiring intensive care or developing an acute respiratory distress syndrome were significantly more likely to fail lidocaine (respectively OR = 5.83; CI [1.69; 20.06]; p=0.01 and OR = 4.23; CI [1.44; 12.43]; p=0.009).

Conclusion

Intravenous lidocaine administration appears to be effective and safe for pain control in 89% of patients failing to level I and II analgesia. Further prospective studies are needed to confirm these results.
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Introduction

This study aimed to analyze the correlation between different attributes of doctors who prescribe colonoscopies and the cleanliness of the intestine to guide the development of colonoscopy application protocols.

Aims & Methods

Data on colonoscopy cases conducted in the gastroenterology department of Hangzhou First People's Hospital between April 2018 and March 2021 were collected. The gender, age, professional attributes of the prescribing doctors, and Boston Bowel Preparation Scale (BBPS) score were recorded. In addition, the correlation between the prescribing doctors' characteristics and the intestine's cleanliness was analyzed.

Results

The study included 22,522 patients with a mean BBPS score of 6.83±1.94. There were 16,459 male and 6,063 female doctors with similar BBPS scores (P = 0.212). The study found no significant difference in BBPS scores between 19,338 physicians and 3,184 non-physicians (P = 0.154). However, BBPS scores differed significantly between 18,168 gastroenterologists and 4,354 non-gastroenterologists (P = 0.016) and between 19,990 intestinal-related specialties and 2,532 non-intestinal-related specialties (P = 0.000). In addition, BBPS scores were significantly different between 18,126 prescribing doctors with colonoscopy ability and 4,352 without (P = 0.014). However, there was no significant difference in BBPS scores among doctors of different ages (P = 0.190). The study found significant differences in BBPS scores between male and female patients and those under or over 40 years (P = 0.000).

Conclusion

To improve colonoscopy preparation quality, priority should be given to doctors in gastroenterology, intestinal-related specialties, and with colonoscopy operation ability. Their expertise may result in better education and improved bowel cleanliness.